Circulation: Arrhythmia and Electrophysiology On the Beat

Om Circulation: Arrhythmia and Electrophysiology On the Beat

Each podcast will include key highlights from the journal's current issue and a report on new research published in the field of arrhythmia and electrophysiology.

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Circulation: Arrhythmia and Electrophysiology November 2020 Issue13.01.2021 (00:46:14)
Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue. In our first paper, Danielle Haanschoten, Hein Wellens and Associates aim to examine survival benefit of prophylactic implantable cardioversion defibrillator (ICD) implantation in early selected high-risk patients with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). A randomized, multicenter, controlled trial compared ICD versus conventional medical therapy in high-risk primary PCI patients based on one of the following factors: Left ventricular ejection fraction (LVF) less than 30% within four days of STEMI, primary ventricular fibrillation, Killip class 2 or greater and/or TEMI flow less than three after PCI. ICD was implanted 30 to 60 days after MI, myocardial infarction, primary endpoint was all cause mortality three years of follow-up. The trial was prematurely ended after inclusion of 266 patients, 38% of the calculated sample size. Additional survival assessments was performed in February 2019 for the primary endpoint. A total of 266 patients, 78.2% male with a mean age of 60.8 years were enrolled. 131 were randomized to the ICD arm and 135 patients to the control arm. All cause mortality was significantly lower in the ICD group, five versus 13, hazard ratio of 0.37 after three years follow-up. Appropriate ICD therapy occurred in nine patients at three years follow-up, 5 within the first eight months after implantation. After median long-term follow-up of nine years, total mortality (18% versus 38%, hazard ratio of 0.58) and cardiac mortality (hazard ratio of 0.52) was significantly lower in the ICD group. Non-cardiac death was not significantly different between the groups. LVEF increased 10% or more in the 46.5% of patients during follow-up and the extent of improvement was similar in both study groups. The authors concluded that in this prematurely terminated and thus underpowered randomized trial early prophylactic ICD implantation demonstrated lower total and cardiac mortality in high-risk STEMI patients treated with primary PCI. In our next paper Felipe Bisbal, Eva Benito and Associates aim to test the efficacy of ablating, cardiac magnetic resonance, CMR detected atrial fibrosis plus pulmonary vein isolation (PVI). This was an open label, parallel group, randomized controlled trial. Patients with symptomatic drug refractory AF paroxysmal or persistent undergoing first or repeat ablation were randomized one-to-one basis to receive PVI plus CMR-guided fibrosis ablation, the CMR group or PVI alone, the PVI alone group. The primary endpoint was a rate of recurrence greater than 30 seconds at 12 months of follow-up using a 12-lead ECG and Holter monitoring at 3, 6 and 12 months. The analysis was conducted by intention to treat. In total 155 patients, 71% male, age 59, CHADS2-VASc 1.3, 54% paroxysmal AF were allocated to the PVI group alone (n=76) or CMR group(n=79). First ablation was performed in 80% and 71% in the PVI alone and CMR groups respectively. The mean atrial fibrosis burden was 12%, only approximately 50% of patients had fibrosis outside the pulmonary vein area. 100% and 99% of patients received the assigned intervention in the PVI alone and CMR group. Primary outcome was achieved in 21 patients (27.6%) in the PVI alone group and 22 patients (27.8%) in the CMR group (Odds ratio 0.01, P=0.976). There was no differences in the rate of adverse events, three in the CMR group and two in the PVI alone group. The authors concluded that a pragmatic ablation approach targeting CMR detected atrial fibrosis plus PVI was not more effective than PVI alone in an unselected population undergoing AF ablation with low fibrosis burden. In the next paper, Vivek Reddy and Associates tested a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. 15 subjects admitted for defibrillator implantation (ejection fraction≤35%) on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 hertz, 4 ms pulse width, and less than or equal to 20 milliamperes. Changes in the maximum positive dP/dt, the dP/dtMax indicated change in ventricular contractility. Of 15 enrolled patients, five were not studied due to equipment failure or abnormal pulmonary artery anatomy. In the remaining patients dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt, dP/dtMin, mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. In this first-in-human study, the authors demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. In our next paper, Jorge Romero, Luigi Di Biase, and Associates, in their study investigated the incremental benefit of left atrial appendage electrical isolation (LAAEI) in patients undergoing catheter ablation for nonparoxysmal atrial fibrillation (AF). Propensity score-matched analysis was performed using a prospective registry database from 2010 to 2014. All patients in the LAAEI group were matched based on baseline characteristics, echocardiographic parameters, and procedural ablation techniques. Authors identified 1842 patients who underwent catheter ablation for nonparoxysmal atrial fibrillation. Propensity score matching yielded 1092 patients, 546 with LAAEI, and 546 without LAAEI. At five years follow-up, overall freedom from all arrhythmia recurrence, off-antiarrhythmic drugs, in patients who underwent LAAEI was 68.9% versus 50.2% in those who underwent standard ablation (p In the next paper, Niraj Varma and Associates postulated that left ventricular (LV) epicardial pacing results in slowly propagating pace wave fronts effect that may limit cardiac resynchronization therapy (CRT) efficacy in patients with left ventricular (LV) enlargement using conventional biventricular or bi-V pacing and single LV pacing, but may be mitigated by LV pacing by two widely spaced sites using MultiPoint pacing (MPP) with anatomic separation (AS) of 30 millimeters or more. They tested this hypothesis in the multi-centered MPT IDE trial. Following implant, quadripolar biventricular pacing was activated in all patients (n=506). From 3 to 9 months post implant among patients with available baseline LV and diastolic volumes LVEDV measures and 188 received bi-V pacing and 43 receiving MPP-AS. Patients were dichotomized by median baselines LVEDV indexed to height. Outcomes were measured by the clinical composite score (CCS) as the primary endpoint, quality of life, left ventricular remodeling, EF greater than 5% and systolic volume decreased 10% in heart failure event or cardiovascular death. LVEDVI median was 1.4 millimeters per centimeter. Baseline characteristics differed in patients with LVEDVI greater than median versus LVEDVI less than or equal to median. Among patients with LVEDVI greater than median, bi-V was less efficacious compared to patients with LVEDVIs less than or equal to median. Clinical composite scores 65% versus 79%. In contrast, MPP-AS programming generated greater composite score response (92% versus 65%, P=0.03) and improved quality of life (31 versus -15.7, P=0.38) versus bi-V pacing with LVEDV greater than median. Reverse remodeling trended better with MPP-AS programming. When LVEDVI was greater than median, heart failure event rate increased following the three months randomization point in bi-V but no heart failure event occurred in patients with MPP-AS programming between three and six months in LVEDVI greater than median. All measured outcomes did not differ in patients receiving MPP-AS and bi-V pacing with LVEDVI less than or equal to median. The authors concluded that conventional biventricular pacing even with a quadripolar lead has reduced efficacy in patients with left ventricular enlargement however in patients with larger hearts and programmed to MPP-AS the greatest response rate was observed. In our next paper, Chih-Min Liu, Shih-Lin Chang, Hung-Hsun Chen and Associates, applied deep learning to pre-ablation pulmonary vein computed tomography (PVCT) geometric slices to create a predictive model for non-pulmonary vein (NPV) triggers in patients with paroxysmal atrial fibrillation (PAF). They retrospectively analyzed 521 PAF patients who underwent catheter ablation of PAF. Among them, PVCT geometric slices from 358 nonrecurrent AF patients one to three millimeters interspace per slice, 20 to 200 slices per each patient, ranging from the upper border of the left atrium to the bottom of the heart, for a total of 23,683 images of slices were used in the deep learning process, the ResNet34 of the neural network, to create the predictive model of the NPV trigger. There were 298 (83.2%) of patients with only pulmonary vein (PV) triggers and 60 (16.8%) with non-PV triggers plus or minus PV triggers. The patients were randomly assigned to either training, validation, or test groups, and their data was allocated according to those datasets. The image datasets were split into training (N=17,340), validation 3491, and testing 2852 groups, which had completely independent set of patients. The accuracy of prediction in each PVCT image for non-pulmonary vein trigger was 82.4%. The sensitivity and specificity were 64.3% and 88.4%, respectively. For each patient, the accuracy of prediction for a non-pulmonary vein trigger was 88.6%. The sensitivity and specificity were 75.0% and 95.7%, respectively. The area under the curve (AUC) for each image was 0.82 and 0.88, respectively. The authors concluded that the deep learning model using pre-ablation PVCT can be applied to predict trigger origins in PAF patients receiving catheter ablation. The applications model may identify patients at a high risk for non-pulmonary vein trigger before ablation. In our next paper, Brian Zenger and Associates aim to understand the relationship between physician social media influence and their scholarly and clinical activity. Authors identified attending US electrophysiologists on Twitter. They compared physician Twitter activity to A) scholarly publication record H-index and B) clinical volume according to CMS. The ratio observed versus expected Twitter followers, observed to expected ratio was calculated based on each scholarly K-index and clinical activity. Authors identified 284 physicians with mean Twitter age of 5.0 years and median 568 followers. They had a median of 34.5 peer-reviewed papers, 401 citations, and H-index 9. The median K-index was 0.4. The median EP procedures was 77 and E and M visits 264. The top 1% electrophysiologists for followers accounted for 20% of all followers, 70% of status updates, and a mean H-index of six versus 15 for others (P=0.3) and accounted for 1% of procedural and E and M volumes. They had a mean K-index of 21 versus 0.77 for others (P In our next paper, Soroosh Kiani and Associates identified four explanted hearts in the context of transplant who received stereotactic body radiation therapy (SBRT) as part of an 11 patient compassionate use series at their institution. Clinical ventricular tachycardias (VTs) and CT defined target volume of SBRT were correlated to the anatomic specimen. Gross pathological, histological, and ultrastructural examination of tissue in the target area of SBRT were performed. All patients had nonischemic cardiomyopathy, and 3 had left ventricular assist devices. In all cases, patients had recurrent sustained ventricular tachycardia (VT) and had multiple failed antiarrhythmics and radiofrequency ablation. Four patients underwent five SBRT therapy sessions with 25 gray single-fraction dose delivered to the area of culprit scar. The time from SBRT to explant was 12 to 250 days. Histopathological features following radiation were comparable in all patients and were characterized by area of subendocardial necrosis surrounded by a rim of fibrosis. In one patient, the surrounding myocardium showed cytoplasmic vacuolization in myocytes and in another patchy interstitial fibrosis. Vascular changes consisted of myointimal thickening with prominence of endothelial cells. Electron microscopy (EM) of myocardium showed irregular, convoluted intercalated disc regions, loss of contractile elements with disrupted and haphazardly arranged myofibrils, and edematous mitochondria with loss of cisternae. The authors reported the first series of findings in human tissue in four patients after SBRT. Histopathological features were consistent across all four patients and were indicative of cell injury, death, and to a lesser extent fibrosis. EM demonstrated features consistent with acute injury. These specimens may provide radiobiological evidence of acute cellular injury during SBRT for VT, which may have an antiarrhythmic effect prior to the onset of fibrosis. In our next paper, Job Verdonschot, Stephane Heymans, Mark Hazebroek and Associates in their study aimed to depict the underlying cardiac pathophysiologic process of nonresponse to cardiac resynchronization therapy (CRT) in dilated cardiomyopathy (DCM) using endomyocardial biopsies (EMB). Within the Maastricht and Innsbruck registries of DCM patients, 99 patients underwent EMB before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as greater than 14 infiltrating cells per millimeter squared. Echocardiographic left ventricular end-systolic volume (LVESV) reduction of 15% or greater after six months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders; 67 patients responded (68%), whereas in 32 (32%) did not respond to CRT. Cardiac inflammation prior to implantation was negatively associated with response to CRT (25% of responders and 47% of nonresponders, odds ratio 0.3, P=0.01). EMB fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test, P In our next paper, Mohit Turagam, Daniel Musikantow, and Associates extracted data from a registry regarding consecutive patients with confirmed COVID-19 who are receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death. Between patients who died versus discharged, they compared a primary composite endpoint of cardiac arrest from ventricular tachycardia, ventricular fibrillation or bradyarrhythmias such as atrioventricular block. Among 800 COVID-19 patients at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring and either died (52) or were discharged (88); the median age was 61 years, 73% men, and ethnicity was Caucasian at 34%. Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%. Compared to discharged patients, those who had died had elevated peak troponin levels 0.27 versus 0.02 nanograms per milliliter and more primary endpoint events (17% versus 4%, P=0.01), a difference driven by tachyarrhythmias. Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, whereas atrioventricular block was largely an independent primary event. The authors concluded that hospitalized COVID-19 patients who die experience malignant cardiac arrhythmias more often than those who survive to discharge. However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement. In our next paper, Sarah Ghonim and Associates examine whether adults with repaired tetratology of Fallot (RTOF) die prematurely for ventricular tachycardia (VT) and sudden cardiac death inducible VT predicts mortality. Ventricular scar, the key substrate for VT, can be noninvasively defined with late gadolinium enhancement, cardiac magnetic resonance (CMR) but whether this relates to inducible VT is unknown. 69 consecutive RTOF patients (43 male, mean 40 years) clinically scheduled for invasive programmed VT-stimulation were prospectively recruited for prior 3D late gadolinium enhancement LGE CMR. Ventricular LGE was segmented and merged with reconstructed cardiac chambers and LGE volume was measured. VT was induced in 22 of 31 patients. Univariable predictors of inducible VT include increased RV LGE (OR 1.15), increased nonapical ventricular LV LGE (OR 1.09), older age (OR 1.6), QRS duration≥180 milliseconds (OR 3.5), history of nonsustained VT (OR 3.5), and previous clinical sustained VT (OR 12.8). Only prior sustained VT (OR 8.02) remained independent in bivariable analyses after controlling for RV LGE volume (OR 1.14) and RV LGE volume of 25 centimeter cubed had 72% sensitivity and 81% specificity for predicting inducible VT (AUC 0.81). At the extreme cutoffs for ruling-out and ruling-in inducible VT, RV LGE>10 cubic centimeters was 100% sensitive and 36 centimeters cubed was 100% specific for predicting inducible VT. Authors conclude that 3D LGE CMR defined scar burden is independently associated with inducible VT and may help refine patient selection with programmed VT-stimulation when applied to at least intermediate clinical risk cohort. In our next paper, Moussa Saleh, the Northwell COVID-19 Research Consortium and Associates performed a comprehensive search of the electronic medical records using a proprietary python script to identify any mention of QT prolongation, ventricular tachyarrhythmias and cardiac arrest. COVID-19 positive patients that received hydroxychloroquine±azithromycin across 13 hospitals between March 1st and April 15th were included in this study. The primary outcome of torsade de pointes was observed in one (0.015%) out of 6476 hospitalized COVID-19 patients receiving hydroxychloroquine±azithromycin. 67 (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to average QT prolongation of 60 milliseconds from a baseline QTc of 473.7 milliseconds to a peak QTc of 532.6 milliseconds. Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%) while one or more doses of therapy were held in the remaining nine (13.4%). A simplified approach to monitoring for QT prolongation arrhythmia was implemented on April 5th. There were no deaths related to the medications with the simplified monitoring approach and hydroxychloroquine exposure was reduced. The author concluded that the risk of torsade de pointes is low in hospitalized COVID-19 patients receiving hydroxychloroquine±azithromycin therapy. In our next paper, Yoshiaki Kaneko and Associates studied 22 consecutive patients with superior fast-slow AV nodal reentrant tachycardia (AVNRT) among which 3 patients had an apparent, but not typical slow-fast AVNRT characterized by a long AH interval and tachycardia (long AH). The diagnosis of superior AV nodal reentrant tachycardia was based on the standard criteria in two patients and the occurrence of Wenckebach AV block during tachycardia, which was attributed to a block at the lower common pathway below the circuit of the AVNRT, detected owing to the lower common pathway potentials in one patient. As with typical slow-fast AVNRT, tachy-long-AH was induced after a jump in the AH interval. In contrast, typical slow-fast AVNRT fluctuation in the ventriculoatrial interval was observed during the tachy-long-AH. Ventricular overdrive pacing was unable to entrain or terminate the tachy-long-AH. Moreover, the tachy-long-AH reciprocally transited to/from superior fast-slow AVNRT spontaneously or was triggered by ventricular contractions while the atrial cycle length and EAA remained unchanged. Both tachycardias were cured by ablation at a single site in the right-side para-Hisian region of two patients and the noncoronary aortic cusp of one patient. Collectively, the essential circuit of both tachycardias was identical, and the tachy-long-AH was diagnosed as another phenotype of superior fast-slow AVNRT accompanied by sustained antegrade conduction via another bystander slow pathway breaking through the His-bundle owing to the repetitive antegrade block at the lower and common pathway, thus presenting as a long AH interval during the ongoing superior fast-slow AVNRT. The authors concluded that an unknown superior fast-slow AVNRT phenotype exists that apparently mimics the typical slow-fast AVNRT and is also an unknown subtype of apparent slow-fast AVNRT. In our next paper, Tinuola Ajayi, Christy Remein and Associates designed and implemented a virtual atrial fibrillation (AF) Strategically Focused Research Network (SFRN) Cross-Center Fellowship program to enhance the competencies of early-stage AF basic, clinical, and population health researchers through experiential education and mentorship. The pedagogical model involves significant cross-center collaboration to produce a curriculum focused on enhancing AF scientific competencies, fostering career and professional development, and cultivating grant writing skills. Outcomes for success involved clear expectations for fellows to produce manuscripts, presentations, and for those at the appropriate career stage, grant applications. Authors evaluated the effectiveness of the fellowship model versus mixed methods formative and summative surveys. In the two years of the fellowship, fellows generally achieved productivity metrics sought by our pedagogical model, with outcomes for the 12 fellows including 50 AF-related manuscripts, 7 publications, 28 presentations, and 3 grant awards applications. Participant evaluations reported that the fellowship effectively met educational objectives. All fellows reported medium to high satisfaction with the overall fellowship, webinar content and facilitation, staff communication and support, and program organization. The authors concluded that the fellowship model represents an innovative educational strategy by providing a virtual AF training and mentoring curriculum for early career basic, clinical, and population health scientists working across multiple institutions, which is particularly valuable in the pandemic era. In our next paper, Audrey Dionne and Associates hypothesize that atrioventricular reentrant tachycardia is common in children. Catheter ablation is increasingly used as first-line therapy with a high acute success, but recurrence during follow-up remains a concern. The aim of this study was to identify risk factors for recurrence after accessory pathway (AP) ablation. Cox proportional hazard models were used to examine the association between patient and procedural characteristics and recurrence during follow-up. In 558 accessory pathway ablation procedures, 542 (97%) were acutely successful. During a follow-up of 0.4 years, there were 42 (8%) patients with documented recurrence. On univariate analysis, early recurrence was associated with younger age, congenital heart disease, multiple accessory pathways, accessory pathway location, right sided and posteroseptal versus left sided, cryoablation versus radiofrequency (RF), empiric ablation, the lack of full power RF lesions In a research letter, Kevin Makati and Associates developed a hybrid epicardial endocardial procedure to address suboptimal treatment outcomes for persistent atrial fibrillation (AF) and longstanding persistent atrial fibrillation. The hybrid convergent procedure combines minimally invasive epicardial radiofrequency (RF) ablation of the left atrial posterior wall and pulmonary vein (PV) antrum with endocardial PV isolation (PVI) and has shown favorable results in achieving sinus rhythm with and without antiarrhythmic drugs including in longstanding persistent atrial fibrillation and with longer follow-up. This investigation used a retrospective analysis of 226 consecutive patients enrolled in the registry TRAC-AFib which collects data and surgical and hybrid ablation procedures. The patients underwent convergent procedures with endocardial cryothermy PVI between November 2011 and May 2018. A total of 201 patients had available follow-up after blanking period for primary effectiveness. 75% of all patients were free of ATAF or atrial tachycardia on previously ineffective antiarrhythmic drugs and 70% were free of AF, atrial flutter, atrial tachycardia off amiodarone. At last follow-up, 77% of patients were off antiarrhythmic drugs and 69% of these patients were free of atrial fibrillation, atrial flutter, or atrial tachycardia. Thus freedom from atrial fibrillation, atrial flutter or atrial tachycardia off antiarrhythmic drugs was 53%. 85% of persistent atrial fibrillation and 70% of longstanding persistent atrial fibrillation were free of atrial fibrillation, atrial flutter, atrial tachycardia with a mean 14.7 and 16.8 months follow-up. 84% of persistent AFib and 64% of longstanding atrial fibrillation patients were free of atrial fibrillation, atrial flutter, atrial tachycardia off amiodarone. This is the largest study using endocardial cryothermy in convergent procedures providing insight in the safety and effectiveness of this alternative energy source after epicardial RF ablation. Results indicate that the cryoconvergent procedure provides a promising solution for persistent atrial fibrillation and longstanding persistent atrial fibrillation evidenced by relatively low atrial fibrillation recurrence rates and marked AF burden reduction after treatment even in longstanding persistent atrial fibrillation. In this research letter by Sergio Conti and Associates, they sought to determine the impact of various monitoring strategies and procedural success. In STAR AF II, patients with persistent AF were randomized one to four to four fashion to pulmonary vein isolation PVI alone, PVI plus complex fractionated atrial electrograms or PVI plus linear ablation. Patients were followed for 18 months with a visit ECG and 24-hour Holter at 3, 6, 9, 12, and 18 months. In addition, transtelephonic monitoring transmission was performed weekly for 18 months and whenever symptoms were reported. After initial three month blanking, recurrences were defined as any arrhythmia greater than 30 seconds. The pool procedural success rate was reported assuming five different monitoring scenarios, Holter recordings at six and 12 months (group A); Holter at three, six and 12 months (group B); Holter at three, six, nine, and 12 months (group C); Holter at three, six, nine, 12 and 18 months (group D); Holter at three, six, nine, 12, 18 months plus all transtelephonic transmissions (group E). Comparisons of procedural success obtained by each of the following scenarios was performed using Cochran's Q test. 549 patients completed the ablation and 18 month followup. Compliance with the visits with 90%, for followup Holter monitor 85%, for weekly transtelephonic monitoring 75%. The pool of success for all three aims in the study was 44% including all of the Holter recordings and transtelephonic transmissions group E. The pool of success rate for the other monitoring scenarios were as follows: Group A 73.5%, group B 64.6%, group C 62.2%, and group D 58.2%. Cochran's Q test showed a significant difference between the four screening strategies (P In a research letter, Alessandro Vicentini and Associates in their study aim to investigate the relationship between baseline QTc and mortality. Authors performed retrospective analysis of ECGs of 318 patients admitted to the Policlinico San Mateo Hospital in Pavia, Italy between February 22, 2020 and April 24, 2020. Patients were defined as infected by a positive nasopharyngeal swab for COVID-19 or by clinically diagnosed infection. QT interval was mainly measured from 12-lead ECG using Bazzett's formula. The authors found that the QTc interval in COVID-19 patients is higher than expected in a normal population. They hypothesized that one of the mechanisms explaining this phenomenon is inflammatory cytokines activation which can suppress ITR in heterologous cells and myocytes resulting in prolonged repolarization. Moreover COVID-19 patients were more susceptible to pulmonary thromboembolism which is known to be linked to QT prolongation. Furthermore, prolonged QTc was found to be a strong predictor in hospital mortality with the highest risk in patients with prolonged baseline QTc and further prolongation with a value of greater than or equal to 500 milliseconds observed during hospitalization. In a research letter, Saverio Iacopino and Associates investigated the arrhythmic complications of patients hospitalized with COVID-19 pneumonia in the intensive care unit or general medicine department at their institution between April 1 and 26, 2020. The authors collected baseline characteristics, laboratory findings, and therapy. All patients were on continuous telemetry during hospitalization. New diagnosis of atrial fibrillation (AF) lasting more than 30 seconds, atrial tachycardia (AT) lasting more than 30 seconds, sustained greater than 30 or nonsustained greater than three beats of ventricular tachycardia (VT) and symptomatic bradycardia requiring permanent cardiac pacemaker that occurred during hospitalization were verified. A daily electrocardiogram (ECG) was also analyzed to measure corrected QT interval and evaluated potential prolongation QT greater than 500 milliseconds. Continuous variables were reported as mean standard deviation. The authors found that patients with arrhythmias had higher inflammatory markers such as peak white blood counts, C-reactive protein and creatinine phosphokinase (CPK) suggesting a more extended inflammatory stress that probably also effected the cardiovascular system. In hospital mortality was also higher in these patients, 50% versus 11%. With a limited number of patients, the authors findings should be considered as preliminary observations that need to be confirmed in larger controlled studies. In a research letter, Akira Matsumori and Associates found that circulating immunoglobulin free light chains (FLCs) were increased in mice with heart failure due to myocarditis. The authors tested their hypothesis that their differences in concentration of FLCs among patients with lone AFib who are in AFib when they took the samples, heart failure with sinus rhythm in age matched healthy volunteers. FLC kappa and lambda were assayed. Patients with amyloidosis, renal insufficiency and autoimmune disorders were excluded. FLCs have benefits because they are very stable and do not change after long-term storage and up to three freeze-thaw cycles. Separately, after amassing the lone AF (N=28), in heart failure (N=16), with sinus rhythm groups (N=110), group by propensity score using age and sex, all statistics were performed. The median concentrations of circulating FLC lambda and kappa in patients with lone AF and atrial fibrillation in sinus rhythm were significantly different from the healthy volunteer group (P In a special report, Timothy Markman and Associates aim to investigate the patient and procedural characteristics associated with worsening tricuspid regurgitation after right ventricular (RV) lead placement as well as a time course of these changes. The authors used a prolapse technique, a straight stylet was withdrawn several centimeters from the lead tip to create atraumatic portion that was advanced across the floor of the right atrium creating a loop which crossed the tricuspid valve. They also used a direct method, a curved stylet used to advanced the lead across the tricuspid valve. The authors identified 1599 patients who underwent first time placement of the right ventricular (RV) lead. Of these 583 met study inclusion criteria, including 105 implanted with cardiac resynchronization (CRT) devices. Baseline echocardiograms were performed 47 days prior to implantation and followup echocardiograms 249 days following implantation. By two months, the tricuspid regurgitation (TR) severity increased by mean grade of 0.8 while tricuspid severity remained unchanged over the remainder of the first year in non-CRT patients. Among CRT patients, tricuspid regurgitation progressively decreased to levels lower than pre-device implantation. In univariable ordinal logistic regression, worsening TR severity was positively associated with the prolapse technique (OR 1.49), and inversely associated with CRT implantation (OR 0.59). There was no association between ventricular pacing percentage among non-CRT patients. In multivariable ordinal logistic regression increased TR severity was positively associated with baseline pulmonary artery systolic pressure (OR 1.03) and inversely associated with CRT implantation (OR 0.43). The authors found that TR rapidly increased with a mean 0.8 grade within the first two months. TR steadily improved over the following year in CRT patients. In a review article, Khaldoun Tarakji and Associates discuss that the field of cardiac electrophysiology has been on the cutting edge of advanced digital technology for many years. More recently, medical device development through traditional clinical trials has been supplemented by direct to consumer products with advancement of the wearables and healthcare apps. The rapid growth of innovation along with mega data generated has created challenges and opportunities. This review summarizes a regulatory landscape applications to clinical practice, opportunities for virtual clinical trials, the use of artificial intelligence to streamline, interpret data, and integration into the electronic medical records and medical practice. Preparation of the new generation of physicians, guidance and promotion by professional societies and the advancement of research in the interpretation and application of big data and the impact of digital technology and healthcare outcomes will help to advance the adoption and future of digital healthcare. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright and American Heart Association 2020.
Circulation: Arrhythmia and Electrophysiology October 2020 Issue12.01.2021 (00:37:09)
Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation, Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue. In our first paper, Bruce Wilkoff and associates evaluated antibacterial envelope cost effectiveness compared to standard of care infection prevention strategies in the US healthcare system. Decision tree model was used to compare costs and outcomes of the antimicrobial envelope used adjunctive to standard of care infection prevention versus standard of care alone over a lifelong time horizon. The analysis was performed from an integrated payer provider network perspective. Infection rates, antimicrobial envelope effectiveness, infection treatment costs and patterns, infection related mortality and utility estimates were obtained from the WRAP-IT study. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality life adjusted years were discounted at 3%. An upper willingness-to-pay threshold of $100,000 per quality adjusted life year was used to determine cost-effectiveness in alignment with the American College of Cardiology and American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. The base case incremental cost-effectiveness ratio (ICER) of the antibacterial envelope compared with standard-of-care was $112,603 per quality-adjusted life year. The ICER remained lower than the threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. The authors concluded that the absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of CIED infection. In our next paper, Peter Loh and associates in this study aim to investigate the feasibility and safety of single pulse irreversible electroporation (IRE) pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). Ten patients with symptomatic paroxysmal or persistent AF underwent single pulse IRE pulmonary vein isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping of the left atrium and pulmonary veins were performed using a conventional circular mapping catheter. Pulmonary vein isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 Joule direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16–27 millimeters). A deflectable sheath was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if pulmonary vein potentials were abolished after the first application. Bidirectional pulmonary vein isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing was used to reveal dormant pulmonary vein conduction. All 40 pulmonary veins could be successfully isolated with a mean of 2.4 IRE applications per pulmonary vein. Mean delivery peak voltage and peak current were 2154 volts and 33.9 amperes. No pulmonary vein reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. The authors concluded that in 10 patients in this first in-human study, acute bidirectional electrical pulmonary vein isolation could be achieved safely using single pulse IRE ablation. In our next paper, Christian Sohns and associates studied the relationship between left ventricular ejection fraction (LVEF) New York Heart Association (NYHA) class on presentation and the end points of mortality and heart failure (HF) admissions in the CASTLE-AF study population. Furthermore, predictors for LVEF improvement were examined. The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function in NYHA class were assessed at baseline after randomization and at each follow-up visit. In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to greater than 35% at the end of the study (odds ratio, 2.17; P In the next paper, Milena Leo and associates conducted a randomized study to compare risk of esophageal heating and acute procedure success of different LSI-guided ablation protocols combining higher or lower radiofrequency power or different target LSI values. Eighty consecutive patients were prospectively enrolled and randomized to one of 4 combinations of radiofrequency (RF) power and target LSI for ablation of the left atrial posterior wall (that is 20 watts LSI 4, 20 watts LSI 5, 40 watts LSI 4, and 40 watts LSI 5). The primary end point of the study was the occurrence and number of esophageal temperature alerts (ETAs) per patient during ablation. Acute indicators of procedure success were considered as secondary end points. Long-term follow-up data was also collected for all patients. Esophageal temperature alerts (ETAs) occurred in a similar proportion of patients in all groups. Significantly, shorter RF durations was required to achieve the target LSI in the 40 watt groups. Less than 50% of the RF lesions reached the target LSI of 5 when using 20 watts despite a longer RF duration. A lower rate of first-pass pulmonary vein isolation and a higher rate of acute pulmonary vein reconnection were recorded in the group 20 watts LSI 5. A lower AF recurrence rate was observed in the 40 watt groups compared with the 20 watts groups at 29 months follow-up. The authors concluded that when guided by LSI, posterior wall ablation with 40 watts is associated with a similar rate of ETAs and a lower AF recurrence rate at follow-up if compared with 20 watts. These data will provide a basis to plan future randomized trials. In the next paper, Shohreh Honarbakhsh and associates in this study aimed to determine whether STAR mapping using sequential recordings from conventional pulmonary vein mapping catheters could achieve similar results. Patients with persistent AF less than 2 years were included. Following pulmonary vein isolation (PVI), AF drivers were identified on sequential STAR maps created with PentaRay, IntellaMap Orion, or Advisor HD Grid catheters. Patients had a minimum of 10 multipolar recordings of 30 seconds each. These were processed in real-time and AF drivers were targeted with ablation. An ablation response was determined as AF termination or cycle length slowing greater than or equal to 30 milliseconds. Thirty patients were included, 62.4 years old, AF duration 14.1 months, of which 3 had AF terminated on pulmonary vein isolation, leaving 27 patients that underwent STAR-guided AF driver ablation. Eighty-three potential AF drivers were identified 3.1 per patient of which 70 were targeted with ablation (2.6 per patient). An ablation response was seen at 54 AFDs, 77.1% of AF drivers with 21 AF termination and 33 cycle length slowing and occurred in all 27 patients. No complications occurred. At 17.3 months, 22 out of 27 or 81.5% of patients undergoing STAR-guided ablation were free from atrial fibrillation, atrial tachycardia off antiarrhythmic drugs. The authors concluded that STAR-guided AF driver ablation through sequential mapping with a multipolar catheter effectively achieved an ablation response in all patients. AF termination in a majority of patients, with a high freedom from atrial fibrillation atrial tachycardia off antiarrhythmic drugs at long-term follow-up. In our next paper, Takashi Kaneshiro and associates sought to evaluate the characteristics of esophageal injuries in atrial fibrillation (AF) ablation using high power short duration setting. After exclusion of 5 patients with their esophagus at the right portion of left atrium and 21 patients with additional ablations such as box isolation and/or low voltage area in left atrium posterior wall, 271 consecutive patients, 62 years, 56 women, who underwent pulmonary vein isolation (PVI) by radiofrequency catheter ablation were analyzed. In the 101 patients, high power short duration setting at 45 to 50 watts with an Ablation Index module was used. In the remaining 170 patients, before introduction of the high power short duration setting, a conventional power setting of 20 to 30 watts with contact force monitoring was used, that is the conventional group. They performed esophagogastroduodenoscopy after pulmonary vein isolation in all patients and investigated the incidence and characteristics of esophageal thermal injury. Although the incidence of esophageal thermal injury was significantly higher in the high power short duration group compared with the conventional group (37% versus 22%, P=0.011), the prevalence of esophageal lesions did not differ between the groups (7% versus 8%). Multivariate logistic regression analysis revealed that the use of the high power short duration setting (odds ratio 6.09, P In our next paper, Prasongchai Sattayaprasert, Sunil Vasireddi and associates hypothesize that in disease the inflammatory secretome of cardiac human mesenchymal stem cells remodels and can regulate arrhythmia substrates. Human cardiac mesenchymal stem cells were isolated from patients with or without heart failure from tissue attached to extracted device leads and from samples taken from explanted donor hearts. Failing human cardiac mesenchymal stem cells or nonfailing human cardiac mesenchymal stem cells were cocultured with normal human myocytes derived from induced pluripotent stem cells. Using fluorescent indicators, action potential duration (APD), calcium alternans, and spontaneous calcium release, incidence was determined. Failing and nonfailing human cardiac mesenchymal stem cells from both sources exhibited similar trilineage differentiation potential and cell surface marker expression as bone marrow human cardiac mesenchymal stem cells. Compared to nonfailing human cardiac mesenchymal stem cells, failing human cardiac mesenchymal stem cells prolonged action potential duration by 24% (P In the next paper, Atsushi Suzuki and associates conducted this study to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiological outcomes, and characterize the process of lesion formation in a porcine model using particle therapy. Twenty-five animals received scanned proton beam irradiation. ECG-gated computed tomography (CT) scans were acquired at end-expiration breath hold. Structures, the atrioventricular junction (AV junction), or left ventricular myocardium (LV), and organs at risk were contoured. Doses of 30, 40, and 55 gray were delivered during expiration to the AV junction (n=5) and left ventricular myocardium (n=20) of intact animals. In this study, procedural success was tracked by pacemaker interrogation in the AV junction group, time-course magnetic resonance imaging (MR) in the left ventricular group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55 gray caused slowing and interruption of cardiac impulse propagation at the AV junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance imaging after 12 weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation but not after 20 weeks. . The authors concluded that scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation. In the next paper, Philippe Maury and associates sought to study surface ECG waveforms and effect of ablation in long-lasting ventricular fibrillation (VF) in patients with left ventricular assist devices. Continuous 12-lead ECG of 5 episodes of long-lasting VF occurring in 3 patients with left ventricular assist devices were analyzed. Spectral analysis (dominant frequency or DF) and quantification of waveform amplitude regularity (URI), and complexity (NDI) were performed over a median of 24 minutes of VF. Radiofrequency (RF) ablation was performed during VF in 2 patients. There was a significant increase in dominant frequency between VF onset and termination but none of the other parameters significantly changed. Some VF parameters varied from patient to patient and from lead to lead. DF decreased after RF ablation in both cases and VF terminated spontaneously shortly after ablation in one case. The previously incessant VFs in these 2 patients did not recur afterward. The authors concluded that VF rate increases over time with left ventricular assist devices and is lowered by ablation. Long-lasting VF may be modified or even terminated by ablation. In the next paper, Taisuke Ishikawa and associates aim to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with Emery-Dreifuss muscular dystrophy (EMD) mutation. Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). The authors identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction, but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of left ventricular noncompaction and Emery-Dreifuss muscular dystrophy has never been reported, they further genetically screened 102 left ventricular noncompaction patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and left ventricular noncompaction without complications of muscular dystrophy. All six male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas two female carriers were asymptomatic. Notably, a strong family history of stroke was observed in these patients was probably due to the increased risk of thromboembolism attributed to both atrial standstill and left ventricular noncompaction. The authors concluded that cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with left ventricular noncompaction and increased risk of thromboembolism. In our next paper, Min Gu, Hongxia Niu, Yiran Hu and associates in their study aim to compare his bundle pacing (HBP) implantation with a novel imaging technique versus the standard implantation technique. This study included 50 patients with standard pacing indications randomized to HBP with visualization of the tricuspid valve annulus (n=25, the visualization group) or with the standard method (n=25, the control group). In the visualization group, the tricuspid valve annulus (TVA) was imaged by contrast injection in the right ventricle using fluoroscopy. The site of HBP was identified in relationship to the tricuspid septal leaflet and interventricular septum. Permanent his bundle pacing was successful in 92% in the visualization group and 88% in the control group. The fluoroscopic time in his bundle lead placement was significantly shorter in the visualization group (7.1 minutes) compared to control group (10.1 minutes, P=0.03). Total procedural and fluoroscopic times were also significantly shorter in the visualization group (91 minutes and 9.6 minutes) than the control group (104 minutes and 12.7 minutes, P=0.01 and P=0.04, respectively). There was no significant difference in capture threshold between the groups. In the visualization group, there was a quantitative association between the his bundle pacing site and the tricuspid valve annulus. The authors concluded that visualization technique shortens the procedural and fluoroscopic times for his bundle implantation. Moreover, anatomic localization of his bundle pacing sites is strongly associated with physiological characteristics of pacing, which can help optimize lead placement. In our next paper, Ethan Rowin and associates study cohort comprises 207 consecutive hypertrophic cardiomyopathy (HCM) patients with primary prevention implantable cardioverter defribillators (ICDs) implanted prior to 2008 and followed for 10 years or more (mean 12 years; range to 31). Patients were 38 years at implant and 45 or 21% experienced appropriate interventions terminating ventricular tachycardia (VT) or ventricular fibrillation (VF). The majority of ICD discharges occurred 5 years or more after implant (29 patients or 64%), including 10 or more years in 16 patients (36%). Initial device therapy increased in frequency from 2.3% of patients at less than 1 year to 8.5% of patients at 10 years or more post implant (P=0.005). Inappropriate ICD shocks in 39 patients occurred most commonly less than 5 years after implant (54%) and decreased in frequency with increasing time from implant from 9.7% of patients at less than 5 years to 3.8% at 10 years or more, P=0.02). Other major device complications including infection and/or lead fractures and dislodgement occurred in 27 patients (12%) but did not increase in frequency over follow-up (P=0.47). There were no arrhythmic sudden death events among the 217 ICD patients. The authors concluded that HCM primary prevention ICD therapy increased progressively over time after implant including substantial proportion with prolonged periods of device dormancy including two thirds of patients five years or more and 10 years or more in one-third. Frequency of inappropriate shocks decreased over follow-up, likely reflecting changes in device programming, while occurrence of device complications, such as lead fractures or infection, did not increase over follow-up. In the next paper, Alexander Zolotarev, Dmitry Dylov, Vadim Fedorov and associates hypothesize that application of machine learning (ML) to electrogram frequency spectra may accurately automate driver detection by multielectrode mapping (MEM) and add some objectivity to the interpretation of MEM findings. Temporally and spatially stable single atrial fibrillation (AF) drivers were mapped simultaneously in explanted human atria (n=11) by subsurface near-infrared optical mapping 0.2 mm2 resolution and 64-electrode multielectrode (higher density [HD] or lower density [LD] with 3 mm2 and 9 mm2 resolution, respectively). Unipolar MEM and near infrared optical mapping recordings (NIOM) were processed by Fourier transform analysis into 28,407 total Fourier spectra. Thirty-five features of ML were extracted from each Fourier spectrum. Targeted driver ablation and NIOM activation maps efficiently defined the center and periphery of AF driver preferential tracks and provided validated classifications for driver versus nondriver electrodes in MEM arrays. Compared with analysis of single electrogram frequency features, averaging the features from each surrounding 8 electrodes neighborhood, significantly improved classification of AF driver electrograms. The classification metrics increased when less strict annotation, including driver periphery electrodes, were added to driver center annotation. Notably, f1-score for the binary classification of HD catheter data set was significantly higher than that of the LD catheter (0.81 versus 0.66, p In our next paper, Deborah Friedman and associates provide data regarding any potential fetal/neonatal cardiotoxicity, leveraged an opportunity that is unique in which neonatal electrocardiograms (ECGs) and hydroxychloroquine (HCQ) blood levels were available in a recently completed study evaluating the efficacy of HCQ 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro antibodies. Forty-five ECGs were available for QTc measurements, and levels of HCQ were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of HCQ and the neonatal QTc (R=0.02, P=0.86) or the mean of HCQ values obtained through each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11%) neonates had prolongation of the QTc>2 standard deviations above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. The authors concluded that in aggregate, these data provide reassurance that the maternal use of HCQ is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. In a research letter, James Hummel and associates sought to examine the time course of QTc prolongation in their database of COVID-19 patients treated with hydroxychloroquine. This study demonstrates that QTc prolongation in hospitalized patients with COVID-19 infection is common and can occur very late, well after the initiation of therapy. Vigilance to minimize multiple concurrent drugs and careful monitoring of renal function and cardiac rhythm are required for hospitalized COVID-19 patients. This, however, should not be extrapolated to non-COVID-19 patients with no comorbidities and who are not using concurrent QT-prolonging medications. In a research letter, Melissa Moey, Prasanna Sengodan and associates aim to characterize the electrocardiographic characteristics and incidents of patients admitted with SARS-CoV-2. Their study had several limitations. It was a single study observational retrostudy of a small population of patients with SARS-CoV-2 without a comparison group. Data are limited to index hospital admission followup data to see whether EKG electrocardiogram intervals revert to baseline following recovery from infection are lacking. Approximately 70% of patients in their study received hydroxychloroquine (HCQ) and/or azithromycin. However, the latest data have shown ineffectiveness and possible harm with these drugs in treatment of SAR-CoV-2. QRS widening has been previously documented in critically ill intensive care unit ICU patients. Hence, this finding may not be specific to SARS-CoV-2. Additional prospective studies with a larger population and longer follow up period are recommended to validate and further elucidate their findings. In a research letter, Hikmet Yorgun and associates aim to report their experience in patients with mechanical aortic mitral prosthesis who underwent endocardial ventricular tachycardia (VT) ablation as an index or redo procedure. The author's findings expand the literature regarding the safety and efficacy of transapical approach with limited left ventricular (LV) access, and emphasize the importance of close collaboration between cardiac electrophysiologist and surgeons during the procedure. Limitations include small sample size and short follow-up duration, as well as lack of pre-procedural magnetic resonance imaging, mainly due to the presence of implantable cardioverter defibrillator. In a research letter, Bradley Peltzer and associates sought to define the incidence and risk factors for arrhythmias among patients hospitalized with COVID-19 and to evaluate associated arrhythmias with outcomes, including mortality. The authors studied all patients with COVID-19, who were admitted consecutively to New York Presbyterian Weill Cornell medicine and New York-Presbyterian Lower Manhattan hospital between March 3rd and April 6th, 2020. The primary outcome of the study was a 30 day all cause mortality. Arrhythmias were identified by review electrocardiograms and telemetry data obtained during hospitalization. There were several limitations to this study. This was a retrospective study with data obtained via chart abstraction, which may be subject to error or misinterpretation. Variation telemetry monitoring systems across hospital units may have led to possible underdetection of arrhythmias in some cases. Because this study focuses on hospital outcomes. Out of hospital deaths following discharge of COVID-19 were not examined. In this analysis of rhythmic complications of over a thousand consecutive patients hospitalized with COVID-19, atrial fibrillation flutter was seen in over 15% and more than 60% of these occurring in patients without any prior history of atrial fibrillation while ventricular tachycardia ventricular fibrillation occurred in less than 3% of patients. Age, male, sex and hypoxia and presentation were independently associated with the occurrence of arrhythmia. The presence of arrhythmia is tracked with markers of disease severity and elevated markers of myocardial injury, inflammation, and fibrinolysis. While there are likely myriad factors that lead to COVID-19 associated arrhythmias, their findings suggests that arrhythmias may predominantly be a marker of COVID-19 severity. Further studies to elucidate the mechanism COVID-19 associated arrhythmias and assess whether treatments targeting SARS-CoV-2 infection and its associated inflammatory response can reduce arrhythmia occurrence or warrant. In a perspective, Bryce Alexander and Adrian Baranchuk discuss that in the current area of medicine, many patients with terminal illnesses have preexisting cardiac disease that required implantable cardioverter (ICD) placement. The world is currently in the midst of an unprecedented COVID-19 pandemic. While data are still being collected and analyzed, there appears to be significantly increased mortality in older and more comorbid patients with current process of deactivation, the requirement for the physical presence of the electrophysiology (EP) team with the patient may disrupt the dying process and may serve as a vector for transmission of infection back into the community or hospital. Most modern ICDs currently have the ability of unidirectional communication through remote monitoring network. These allow for followup of patients through interrogation device independent of a physical program. Currently there is no capacity for bi-directional remote communication of a program or implanted device. The potential perceived barrier to implementation to strategies, concerns related to cybersecurity of implantable electronic devices (CIECD). While cyber security threats from any network connected medical device cannot be eliminated, the benefits of the features provided may outweigh the possible dangers. In the case of remote deactivation of ICDs, there are several important benefits. For patients, benefits will include preservation of the dying process without outside interruption, as well as possible faster deactivation of the ICD eliminating unwanted shocks. For healthcare providers, this approach could eliminate barriers to ICDs deactivated early in terminal patients and help to develop a structured approach to routine deactivation. On a system level, this approach may reduce costs and allow for less utilization of hospital or clinic space. Given the benefits of remote monitoring and the increased demand to transform practice into tele-health, the authors propose a stepwise approach to remote programming capability, starting with remote deactivation. If able to be accomplished, the inactivation of ICD's at Distance for Dignity of Dying project, the 4D project, will allow for a less interrupted dying process in the palliative patient. And it reduced the risk of infection transmission in the setting of ongoing or future pandemic. If this approach were to prove feasible, it could potentially open the door for future applications of remote reprogramming, including, but not limited to: 1) allowing increased input in the case of loss of capture, 2) adjusting sensitivity, 3) reprogramming to the MRI magnetic resonance imaging mode, 4) asynchronous pacing, tachy detection off prior to electric cardiac response, and 5) lower rate cutoff for slow ventricular tachycardia. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association, 2020.
Circulation: Arrhythmia and Electrophysiology September 2020 Issue12.01.2021 (00:34:30)
Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-chief, with some of the key highlights from this month's issue. In our first paper, Zak Loring and associates examined 3,139 patients undergoing atrial fibrillation (AF) ablation, between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation Registry from 24 US centers. Patients undergoing AF ablation were predominantly male (63.9%) and Caucasian (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and persistent atrial fibrillation patients had more comorbidities than paroxysmal AF patients. Drug refractory, paroxysmal AF was most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radio-frequency, RF ablation, with contact force sensing was the most common ablation modality (70.5%) and 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations. The most common adjunctive lesion included left atrial roof or posterior/inferior lines and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases. In our next paper, Brian Howard and associates hypothesize that pulse field ablation (PFA) would reduce pulmonary vein stenosis risk and collateral injury compared to irrigated radiofrequency ablation (IRF). IRF and PFA deliveries were randomized in eight dogs with two superior pulmonary veins (PVs), ablated with using one technology and two inferior PVs ablated with the other technology. IRF energy (25-30 watts) or PFA with delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography (CT scans) were collected at 0, 2, 4 and 8, and 12 week, including termination time points to monitor PV cross-sectional area at each PV ablation site. Maximum average change in normalized cross-sectional area at 4 weeks was 46.1%±45.1% post IRF compared to -5.5±20.5% for PFA (P≤ to 0.001). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites compared to more confined and often incomplete lesions after IRF. At the distal PV sites only IRF ablations were grossly identified based on focal fibrosis. Mild pulmonary chronic parenchymal hemorrhage was noted in three left superior pulmonary vein lobes after IRF. Damage to vagus nerves, as well as evidence of esophagus dilation, occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites. In our next paper, Mohamed Diab and associates aimed to assess the safety of ablation for atrial fibrillation (AF) with trans-esophageal (TEE) screening on intracardiac echocardiography (ICE) imaging of the appendage in direct oral anticoagulant (DOAC) compliant patients. They studied 900 patients with a medium CHA2DS2-VASc score of two. Interquartile range one to three. All consecutive patients presenting with AF or atrial flutter on DOAC were included. All were on DOACs (333 Rivaroxaban, 285 Dabigatran, 281 Apixaban and one Edoxaban). Thromboembolic complications occurred in four patients (0.3%), two ischemic strokes, one transient ischemic attack without residual deficit and one splenic infarct, all with no further complications. Bleeding complications incurred in 5 patients (0.4%), including 2 pericardial effusions (1 intraoperative, 1 after 30 days, both drained), and 3 groin hematomas (1 due to needing heparin for venous thrombosis, none requiring intervention). No patients required emergent surgeries. In our next paper, Alexios Hadjis and associates aim to explore the role of complete diastolic pathway activation mapping on ventricular tachycardia (VT) recurrence. They studied 85 consecutive patients who underwent VT ablation using and guided by high-density mapping. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway or no diastolic pathway map performed. Recurrences of VT were defined as appropriate IC therapies or on the basis of EC documented arrhythmia. Complete recording of the diastolic pathway was achieved in 36 of 85 (42.4%). Partial recording of the diastolic pathway of clinical VT was achieved in 24 of 85 (28.2%). No recording of the diastolic pathway of clinical VT was feasible in 25 of 85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrences was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88% in patients who had full diastolic activity recorded, 50% of partial diastolic activity recorded and 55% in those who underwent substrate modification (P=0.02). The authors concluded that mapping of the entire diastolic pathway was associated with a higher freedom from VT occurrence compared to partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies. In our next paper, Hui-Nam Pak and associates investigated whether electrical posterior box isolation (POBI) may improve rhythm outcome of catheter ablation in patients in whom persistent atrial fibrillation changes to paroxysmal atrial fibrillation after antiarrythmic drug medication and cardioversion. They prospectively randomized 114 patients, 75% male, 59.8 years old to circumferential pulmonary vein ablation (CPVI) alone (n=57) and an additional POBI group (n=57). Primary endpoint was AF recurrence after a single procedure, and secondary endpoints were recurrence pattern, cardioversion rate and response to antiarrhythmic drugs (AAD). After a mean follow-up of 23.8 months, the clinical recurrence rate did not significantly differ between the CPVI alone and additional POBI group (31.6% versus 28.1%; P=0.682). The recurrence rate as atrial tachycardias, 5.3% versus 12.3% (P=0.14) and cardioversion rates, 5.3% versus 10.5% (P=0.25) were not significantly different between the CPVI and POBI group. At the final follow-up, sinus rhythm was maintained without antiarryhthmic drug in 52.6% of CPVI group and 59.6% of the POBI group (P=0.45). No significant difference was found in major complications between the two groups, 5.3% versus 1.8% (P=0.618). But the total ablation time was significantly longer in the POBI group (4187 seconds versus 5337 seconds; P In our next paper, Dan Musat and associates assess the incidents and predictors of very late occurrence (VLR) when atrial fibrillation occurs 12 months or more after ablation in patients who underwent cryoballoon pulmonary vein isolation alone (PVI), had an ILR and were confirmed AF free (atrial fibrillation free) for at least one year. They included 188 patients, mean 66 years, 62% male and 54% paroxysmal atrial fibrillation with CHA2DS2-VASc 2.6. After one year post PVI, 49% of patients remained AF free. During subsequent follow-up, 32% had very late recurrence of atrial fibrillation. The only independent risk factor for very late recurrence was an elevated CHA2DS2-VASc score (hazard ratio 1.317; P=0.06). Patients with CHA2DS2-VASc score greater than four represented a quarter of the population and were at highest risk. In our next paper, Daniele Pastori, Danilo Menichelli, Gregory Yip and associates in the ATHERO-AF Study Group investigate the association between family history of atrial fibrillation (AF) in cardiovascular events (CVEs), major adverse events (MACE), and cardiovascular mortality. They conducted a multicenter prospective observational cohort study, including 1,722 nonvalvular AF patients from February 2008 to August 2019 in Italy. Family history of AF was defined as the presence of AF in a first-degree relative: mother, father, sibling, or children. Primary outcome was a composite of CVEs, including fatal/non-fatal ischemic stroke and myocardial infarction and cardiovascular death. Second, they analyze the association with MACE. Mean age 74.6 years, 44% women. Family history of AF was detected in 368 or 21.4% of patients, and 3.5% had two or more relatives affected by AF. Age of AF onset progressively decreased from patients without family history of AF compared to those with single and multiple first-degree affected relatives (P In our next paper, Louise Reilly and associates created the first patient-inspired KCNJ2 transgenic mouse and studied the effects of this mutation on cardiac function, IK1 and calcium handling to determine the underlying cellular arrhythmic pathogenesis. A cardiac specific KCNJ2-R67Q mouse was generated and bred for heterozygosity. That's R67Q+/-. Echocardiography was performed at rest and under anesthesia. In vivo electrocardiogram, ECG recording, and whole heart optical mapping of intact hearts was performed before and after adrenergic stimulation in wild-type littermates and R67Q+/- mice. In IK1 measurements and action potential AP characterization, intracellular calcium imaging from isolated ventricular myocytes at baseline and after adrenergic stimulations were performed in wild-type and R67Q+/- mice. R67Q+/- mice (n=17) showed normal cardiac function structure baseline electrical activity compared to wild-type (n=10). Following epinephrine and caffeine, only the R67Q+/- mice had bidirectional ventricular tachycardia, frequent ventricular ectopy and/or bigeminy and optical mapping demonstrated high prevalence of spontaneous and sustained ventricular arrhythmia. Both R67Q+/- (n=8) and wild-type myocytes (n=9) demonstrated typical n-shaped IK1 IV relationship. However, following isoproterenol, max outward IK1 increased by about 20% in wild-type, but decreased by 24% in R67Q+/- (P In our next paper, Michael Liu and associates use computational modeling to simulate 1D, 2D and 3D tissue under a variety of conditions to test the ability of genetically engineered non-arrhythmogenic stabilizer cells to suppress triggered activity due to delayed or early afterdepolarization. Due to source-sink relationships in cardiac tissue, a minority (20 to 50%) of randomly distributed stabilizer cells engineered to be non-arrhythmogenic can suppress the ability of arrhythmogenic cells to generate delayed or early afterdepolarization related arrhythmias. Stabilizer cell gene therapy strategy can be designed to correct a specific arrhythmogenic mutation such as in CPVT mice studies, or more generally to suppress delayed or early afterdepolarization from any cause by overexpressing the inward rectifier potassium, Kir2.1 in stabilizer cells. The authors propose this as a promising antiarrhythmic strategy. In our next paper Wei Hu, Dongchen Zhou, and associates used high resolution mapping to study the determinants of flutter wave morphology on surface ECG in patients with peri-mitral atrial flutters (PMAFLs) that develops post atrial fibrillation (AF) ablation or post-cardiac surgery. The mean tachycardia cycle length (TCL) was 264 milliseconds with right atrial RA activation time, 155 milliseconds, 60.8% of the tachycardia cycle length, and the flutter wave duration, 107 milliseconds or 41.6% of the tachycardia cycle length. The overlap between the RA activation time and the flutter wave duration was 102 milliseconds, which takes 68.5% of the RA activation time and 95.7% of the flutter wave duration respectively. The authors found that the ECG flutter wave morphology of PMAFLs is mainly dependent on RA activation pattern. Quantitative analysis also showed that during the flutter wave duration, more percentage of the endocardial area was activated in the RA than in the LA (70.0% versus 45.2%: P In our next paper, Peter van Dam, Emanuela Locati and associates sought to localize electric activity in Brugada syndrome using novel CINeECG method, which creates an inverse electrocardiogram (IECG) from standard 12-lead electrocardiogram (ECG). They studied 15 spontaneous Brugada syndrome patients and 18 ajmaline-induced Brugada syndrome patients at baseline and after ajmaline in whom epicardial potential duration maps (PDM) were available. 17 type-3 Brugada syndrome patients not showing type-1 Brugada syndrome after ajmaline, that is ajmaline-negative, in 47 normal subjects. In 18 right bundle branch block (RBBB) patients in spontaneous or ajmaline-induced Brugada syndrome patients CineECG localized the terminal forces in the RVOT congruent with arrhythmogenic substrate location detected by epicardial potential duration maps (PDM). The RVOT location was never observed in normal right bundle branch block or ajmaline-negative patients. In most ajmaline-induced Brugada syndrome patients (78%), the RVOT location with already evident at baseline. The CineECG classified all normal subjects and ajmaline-negative patients at baseline as normal or undetermined and all right bundle branch block patients as RBBB while all spontaneous ajmaline-induced Brugada syndrome patients as Brugada. Compared to a standard 12-lead ECG, CineECG at baseline had 100% positive predictive value and an 81% negative predictive value in predicting ajmaline test results. In our next paper Zhen Wang and associates examined the circadian cardiac electrophysiology properties in relationship to age. The authors examined adult male mice hearts, 12 to 18 weeks, that were isolated during light, ZT4 and ZT9 and dark, ZT14 and ZT21 from adult male mice and aged (18 - 20 months) male hearts. They were isolated at ZT4 and ZT14. All hearts were Langendorff-perfused for optical mapping with voltage and calcium channel sensitive dyes (n=4-7 per group). Cardiac gene and protein expression was assessed using real time PCR (four to six per group) and Western blot, three to four per group. Adult hearts showed circadian differences in actual potential duration (APD) and calcium transient duration with the shortest values at ZT14. The pacing frequency at which calcium T alternans emerge was faster, and average calcium T alternans magnitude was significantly reduced at ZT14 compared to other time points. There was a trend for decreased spontaneous PVCs, premature ventricular contractions, and pacing-induced ventricular arrhythmias at ZT14, and the hearts at ZT14 had diminished responses to isoproterenol compared to ZT4 (ZT4: 49.5% versus ZT14: 22.7% decrease in action potential duration, P In our next paper, Christopher Cheung and associates reported on the patients who underwent repeat ablation procedures for symptomatic atrial tachyarrhythmia with the objective of evaluating pulmonary vein (PV) reconnections in this CIRCA-DOSE study. This study was a multi-center randomized trial that demonstrated that pulmonary vein isolation (PVI) performed by second generation or contact force (CF-RF) resulted in comparable freedom from atrial tachyarrhythmia as measured by continuous cardiac monitoring using an implantable loop. Among the 346 patients randomized in the CIRCA-DOSE trial, 52 patients, or 15%, underwent a repeat ablation procedure. There were no significant differences in baseline characteristics between patients undergoing repeat ablation and the remaining cohort, apart from higher baseline atrial fibrillation (AF) burden, percent time in AF, and those who underwent a repeat procedure (10.1% versus 1.6%; P=0.002). At the repeat procedure, PV reconnection was noted in 4,752 or 90.4% of patients with no significant difference between the two groups (14 out of 16 or 97.5% after CF-RF and 17 out of 18 or 94.4% after CRYO 4, and 16 out of 18 or 88.9% after CRYO 2, P=0.64). The median number of reconnected PVs per patient was two after CF-RF and two after CRYO 2 and one after CRYO 4 (P=0.46). A total of 89 out of 201 PVs, that's 44.3%, were reconnected. This included 23 out of 52 or 44.2% right superior, 27 out of 52 (51.9%) right inferior, 17 out of 42 (40.5%) left superior and 15 out of 42 (35.7%) left inferior. One out of three or 33% right middle and six out of 10 or 60% of left common. There was no difference in the pattern of reconnection between the CF-RF and cryoballoon groups. In our next paper, a research letter, Joshua Payne and associates examine how well low energy shock impedance is correlated with high energy shock impedance with subcutaneous implantable cardioverter defibrillator, S-ICD implantation. Consecutive patients received pair 10 and 65 joule shocks were studied. The 65 joule shock was delivered either during induced VF or synchronously during sinus rhythm. All 10 joule shocks were delivered synchronously in sinus rhythm. There were 28 patients in this study, including 24 who underwent new device implantation. Defibrillation threshold testing was performed in 21 or 75% of patients. All but one, 96%, were successfully defibrillated at 65 joules. There was a significantly higher impedance for 10 joule shocks compared to 65 joule shocks, 73.1 ohms versus 70.3 ohms respectively (P=0.023) with a mean difference of 2.8 ohms. The impedances for the two shock energies were highly correlated (R-squared=0.97; P In our next research letter, Paolo Compagnucci and associates conducted a single center retrospective observational study by enrolling patients in electrophysiologic (EP) procedures at a tertiary level referral center in Italy during the COVID-19 pandemic. They examined all consecutive patients who underwent EP procedures since March 9, 2020 when the novel health care measures were taken in the cardiology department due to the COVID-19 outbreak until April 26, 2020. These patients were compared to those undergoing EP procedures in the preceding six months. During the COVID emergency, only non deferrable procedures were performed giving priority to electrical storm, refractory device infections requiring lead or device extraction, pacemaker or defibrillator implantations and generator changes. During the COVID-19 emergency 79 EP procedures were performed. The most common interventions included generator changes, pacemaker implantation to (2 with leadless devices), defibrillator implantations, catheter ablations and device extractions. In the six months before the lockdown 592 EP procedures were performed, most commonly pacemaker implementations (three with leadless devices), generator change and catheter ablations for atrial fibrillation. Their findings suggest three key messages. One, overall there's a drastic reduction in the numbers of EP procedures due to postponement of non-urgent interventions. Two, EP laboratory model and extensively adopting personal protective equipment (PPE) and other preventative measures proved safe for healthcare professionals. And three, weekly rates of electrical storm catheter ablation significantly increased. In our next research letter, Seigo Yamashita and associates examine the risk of coronary sinus ablation during mitral isthmus ablation. Out of 712 patients who underwent mitral isthmus (MI) linear ablation in their institution, epicardial ablation within the coronary sinus (CS) was performed in 446 or 62.6% because of incomplete block by endocardial ablation only. 126 of 446 (28.3%) patients had redo procedures due to AF/AT recurrence, and they were retrospectively included in this study. Age 55 years, persistent AFib in 117. The coronary sinus post procedure (CS post) diameter was 5.6 millimeters with a mean reduction in 11.1% compared to coronary sinus pre diameter (CS pre) 6.0 millimeters. Among 126 patients, 15 or 12% demonstrated coronary sinus (CS) stenosis located at three to four or four o'clock in the LAO view in 33%, 20% and 40% of patients respectively with a mean reduction of 61.0%, but all were asymptomatic. These three cases demonstrated severe stenosis with a 5 Fr CS mapping catheter impossible to cross. The severe stenosis was located at the level of three o'clock on the LAO in all. On multi-variable analysis adjusted for age, atrial fibrillation type, minimum CS diameter, and TactiCath use, narrower coronary sinus diameter was the only independent predictor of coronary sinus stenosis (odds ratio 0.07 or P In our next research letter, Min-Young Kim, Belinda Sandler and associates compare the anatomical distribution of ectopic-triggering ganglionated plexus (GP) to that of atrial ventricular dissociating GP in patients with atrial fibrillation. The highest probability of ectopic-triggering ganglionated plexus greater than 30% were in the roof mid anterior wall around all pulmonary vein ostia except for the right inferior pulmonary vein in the posterior wall, suggesting that they inadvertently ablated during conventional pulmonary vein isolation procedures for atrial fibrillation, possibly explaining why some patients remain symptom-free with reconnected pulmonary veins. On the other hand, the majority of atrial ventricular dissociating GP lie outside the pulmonary vein isolation target regions. In our next special report, Arwa Younis, May Goldenberg and associates aim to evaluate the yield of MADIT-CRT response score to predict the long-term risks of clinical events and life-threatening ventricular arrhythmias by QRS morphology. Among patients with left bundle branch block, the rate of life-threatening ventricular tachyarrhythmias or death at three years was lowest (8%) among CRTD patients with a high response score and highest among ICD patients with a low response score (22%). Log rank P-value for the difference during follow-up, P In our next special report, Alexandra Benz and associates prospectively collected data from asymptomatic atrial fibrillation, stroke evaluation, and pacemaker patients in the Atrial Fibrillation Reduction Atrial Pacing Trial, or ASSERT Trial found that implementation of inactive fixation atrial lead was not associated with a higher incidence of atrial fibrillation compared to implantation of a passive fixation atrial lead both early post implantation and over long-term followup. In our next special report, Siddharth Trivadi and associates conducted a longitudinal follow-up study of speckle tracking strain echocardiography and assessment of myocardium mechanics in patients with idiopathic ventricular arrhythmia. They were able to demonstrate subtle abnormalities in myocardial mechanics and dispersion that persist for prolonged periods of time, despite successful abolishment of the inciting arrhythmia or the absence of overt cardiomyopathy or established arrhythmia-related cardiomyopathy. The study suggests that patients with idiopathic ventricular arrhythmias are not truly idiopathic and that subtle subclinical myocardial changes exist. In a perspective piece, Pietro Enea Lazzerini and associates provide recommendations about electrocardiographic QTC monitoring along with this decisional guide for optimizing risk-benefit ratio when exploratory drugs are administered. The document also highlights that severely ill COVID-19 patients are frequently burdened by comorbidities, especially electrolyte imbalances, concomitant QT prolonging drugs in the high grade systemic inflammatory state, further increasing torsades de pointes susceptibility. They comment that specifically dampening inflammation-driven arrhythmic risk via IL-6 blockade could reduce the need for withholding or withdrawing potentially useful COVID-19 repurposed pharmacotherapies. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.
Circulation: Arrhythmia and Electrophysiology July 2020 Issue23.12.2020 (00:19:47)
Paul J. Wang: Welcome to the monthly podcast, On the BEAT, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor in Chief, with some of the key highlights from this month's issue. Albert Feeny and Associates used unsupervised machine learning of electrocardiogram [ECG] waveforms to identify cardiac resynchronization therapy [CRT] subgroups to differentiate outcomes beyond QRS duration and left bundle branch block. They retrospectively analyzed 946 CRT patients with conduction delay. Principal component analysis [PCA] dimensionality reduction obtained a 2-dimensional representation of pre-CRT 12-lead QRS waveforms. K-means clustering of the 2-dimensional PCA representation of 12-lead QRS waveforms identified two patient subgroups [QRS PCA groups]. Vectorcardiographic QRS area was also calculated. They examined two primary outcomes: (1) composite endpoint of death, left ventricular assist device, or heart transplant, and (2) degree of echocardiographic left ventricular ejection fraction [LVEF] change after CRT. Compared to QRS PCA group 2 (n = 425), Group 1 (n=521) had a lower risk for achieving the composite endpoint (hazard ratio of 0.44, P In our next paper, Julie Shade, Rheeda Ali and Associates combined machine learning [ML] and personalized computational modeling to predict, prior to pulmonary vein isolation [PVI], which patients are most likely to experience atrial fibrillation [AF] recurrence after PVI. The single center retrospective proof of concept study included 32 patients with documented paroxysmal AF who underwent PVI and had pre-procedural late gadolinium enhanced magnetic resonance imaging [LGE MRI]. For each patient, a personalized computational model of the left atrium simulated AF induction via rapid pacing features were derived from pre-PVI LG MRI images and from results of simulations [SIM] AF. The most predictive features used to input to a quadratic discrimination analysis ML classifier, which was trained, optimized, and evaluated with a 10-fold nested cross validation to predict the probability of AF recurrence post PVI. In the cohort, the ML classifier predicted probability of AF recurrence with an average validation, sensitivity, and specificity of 82% and 89% respectively, and a validation AUC of 0.82. Dissecting the relative contributions of simulations SIM AF and raw images to the predictive capability of the ML classifier, they found that only when features from simulation SIM AF were used to train the ML classifier, its performance retained similar (validation AUC equals 0.81). However, when only features classified from raw images were used for training, the validation AUC significantly decreased (0.47). In our next paper, Sarah Vermij and Associates examined sodium channel NaV 1.5 localization and function mutations in the gene and coding the sodium channel NaV 1.5 caused various cardiac arrhythmias. The authors use novel single-molecule localization [S-M-L-M] and computational modeling to define nanoscale features of NaV 1.5 localization and distribution at the lateral membrane [L-M], the LM groove, and T-tubules in cardiomyocytes from wild-type (N=3), dystrophin-deficient (mdx; N=3) mice, and mice expressing C-terminally truncated NaV 1.5 (ΔSIV; N=3). The authors assessed T-tubules sodium current by recording whole-cell sodium currents in control (N=5) in detubulated (N=5) wild-type cardiomyocytes. The authors found that NaV 1.5 organizes as distinct clusters in the groove and T-tubules which density, distribution, and organization partially depend on SIV and dystrophin. They found that overall reduction in NaV 1.5 expression expressed in mdx and ΔSIV cells result in a non-uniform distribution with NaV 1.5 being specifically reduced at the groove ΔSIV and increased in T-tubules of mdx cardiomyocytes. A T-tubules sodium current could, however, not be demonstrated. The authors concluded that NaV 1.5 mutations may site-specifically affect NaV 1.5 localization and distribution at the lateral membrane and T-tubules, depending on site-specific interacting proteins. In our next paper, Sharan Sharma, Mohit Turagam, and associates studied strategies to improve patient comfort related to pericardial access. They conducted a multi-centered retrospective study, including 104 patients who underwent epicardial ventricular tachycardia [VT] ablation and Lariat left atrial appendage occlusion. They compared 53 patients who received post-procedural intrapericardial liposomal bupivacaine (LB)+oral colchicine (LB group) and 51 patients who received colchicine alone (non-LB group). Lyposomal bupivacaine was associated with significant lowering of median pain scale at 6 hours (1.0 versus 8.0, P In our next paper, Sergio Callegari, Emilio Macchi, and Associates characterize the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting atrial fibrillation [AF] (group 1; 59 males; 60 years of age; 91 mitral disease-related AF, 30 nonmitral disease-related AF) and 39 patients in sinus rhythm with mitral valve regurgitation (group 2; 32 males; 59 years of age). 10 autopsy hearts served as controls. Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which the authors arbitrarily divided into four stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and in a more advanced stage in group 1 versus group 2 and within group 1, in patients with rheumatic disease versus non-rheumatic cases. In AF patients with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69–150 cells/mm2, depending on the areas in AF biopsies). A few fibrocytes, circulating and bone marrow-derived mesenchymal cells, were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization. In our next paper, Shijie Zhou and Associates tested an automated localization system to identify the site of origin of left ventricular [LV] activation in real time using 12-lead ECG. The automated site of origin, solo system, consists of three steps: (1) localization of ventricular segment based on population templates, (2) population-based localization within a segment, and, (3) patient-specific site localization. Localization error was assessed by the distance between the known reference site and the estimated site. In 19 patients undergoing 21 catheter ablation procedures of scar related VT, solo accuracy was estimated using 552 LV left endocardial pacing sites pooled together and 25 VT-exit sites identified by contact mapping. For the 25 VT-exit sites, localization error of the population-based localization steps was within 10 mm. Patient-specific site localization achieved accuracy of within 3.5 mm after including up to 11 pacing (training) sites. Using 3 remotes (67.8 mm from the reference VT-exit site), and then 5 close pacing sites, resulted in localization error of 7.2 mm for the 25 identified VT-exit sites. In 2 emulated clinical procedure with 2 induced VT's, the solo system achieved accuracy within 4 mm. In our next paper, Ryan Koene and associates examined outcomes of use of dofetilide in atrial fibrillation [AF] patients with left ventricular ejection fraction [LVEF]≤35% without prior implantable cardioverter defibrillator [ICD] cardiac resynchronization therapy [CRT], or AF ablation. An analysis of 168 consecutive patients from 2007 to 2016 was performed. Incidences of adverse events, drug discontinuation, ICD, or CRT implementation, LVEF improvement (>35%) and recovery (50% or greater), AF recurrence, and AF ablation were determined. Multi-variate regression analysis to identify predictors of LVEF improvement/recovery was performed. The mean age was 64 years. Dofetilide was discontinued prior to hospital discharge in 46 (27%) because of QT prolongation (14%), torsades de pointe or polymorphic ventricular tachycardia/ventricular fibrillation (6% [sustained 3%, nonsustained 3%]), in effectiveness (5%), and other causes (3%). At one year 43% remained on dofetilide. Freedom from AF was 42% at 1 year and 40% underwent future AF ablation. LVEF recovered to 50% or greater in 45% and an improved to greater than 35% in 73%. Predictors of LVEF improvement included presence of AF during echocardiogram (odds ratio 4.22, P=0.002), coronary artery disease (odds ratio 0.35, P=0.01), left atrial diameter (odds ratio, 0.52 per 1 cm increase, P=0.01), and LVEF (odds ratio, per 1% increase, 1.09, P=0.006). The C statistic was 0.78. Our next paper is a research letter by Giuseppe Ciliberti, Gherardo Finocchiaro, and Associates. Myocardial infarction with nonobstructive coronary arteries, MINOCA, accounts for one to 10% of all causes of acute myocardial infarction [MI]. The authors examine 37, that is 0.7% of the entire study population, sudden cardiac death cases of MINOCA. The majority of decedents were male (N=23, 62%), mean age at death was 34 years, age range 13 to 96 years. Death occurred at rest or during daily activities in 36, that is 97% of individuals. Coronary thrombosis was found at 9 out of 13 at a 69% with nonobstructive atherosclerosis. Drug use was reported in 10 or 27%. Our next paper is a special report entitled HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for tele-health and arrhythmia monitoring during and after a pandemic. This document discusses how digital health may facilitate electrophysiology practice in patients with arrhythmia. Electrophysiology is well placed for virtual consultation. Digital tools such as direct to consumer mobile ECG and wireless blood pressure devices can be used to further compliment the tele-health visit without in-person contact C-I-E-D wearable mobile health and clinical data can be integrated into clinician workflow. Wearable and smart flow based devices allow convenient real-time monitoring for arrhythmias. Remote CID monitoring has a continue important role. Our special report is entitled Guidance for Rebooting Electrophysiology Through COVID-19 Pandemic from the Heart Rhythm Society and the American Heart Association, Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology endorsed by the American College of Cardiology. Dhanunjaya Lakkireddy, Mina Chung and Associates in this joint document for representatives of the Heart and Society, American Heart Association, American College of Cardiology, provide guidance for clinicians, institutions establishing safe electrophysiological care. To achieve the same they address regional and local COVID-19 disease status, the role of viral screening, and serologic testing, return to work considerations for exposed and infected healthcare workers, risk stratification and management strategy based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures and development of outpatient and periprocedural care pathways. In a special report, Philip Krisai and Associates reported the results of CONVERT-AF (Canakinumab for the Prevention of Recurrences After Electrical Cardioversion in Patients With Persistent Atrial Fibrillation) is a randomized double blind placebo control trial enrolling patients with persistent A-Fib, atrial fibrillation, AF undergoing electrical cardioversion, or ECV with HS CRP levels of two mg/L or greater. Age, greater than 50 years of age women needed to be post-menopausal. After sinus rhythm restoration, patients were randomly assigned within 60 minutes to a single subcutaneous injection of 150 mg of Canakinumab or matching placebo. 11 and 13 patients were randomized to Canakinumab and placebo rest respectively mean overall age was 66 years, 24% women. AF recurrence in six months occurred in 10 (77%) and four (36%) in patients with the placebo or Canakinumab groups, respectively (hazard ratio 0.36, P=0.09). At one month AF recurred in six (46%) and four (36%); at three months in eight (62%) and four (36%) patients respectively. The hazard ratios for first time redo ECV and hospitalization-free survival were 0.29 (P=0.27) and 0.74 (P=0.75) respectively and antiarrhythmic drug use at 6 months were used in 7 (54%) and 9 (82%) of patients in the placebo and the Canakinumab group respectively. Odds ratio 3.86 P equals 0.16 log transform high sensitivity CRP was 31% lower in the Canakinumab group. At six months, adverse events occurred in 3 (23%) and 3 (27%) in the placebo and Canakinumab groups, respectively. Infections occurred in 2 (15%) and 2 (18%) in the placebo and Canakinumab groups respectively. In a special report Amr Barakat and associates reported that the number of implants of SelectSecure 3830 [SS3830] increase greater than 4-fold in 2017 (9,145) and 2018 (9,895) compared to 2016 (1,972 implants). The yearly number of his bundle pacing related publications increased approximately 4-fold in 2015 and approximately 25-fold in 2018, compared to 2014. 140 medical device reports related to SS3830 lead use were made for permanent his bundle pacing. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time... this program is copyright American heart association, 2020.
Circulation: Arrhythmia and Electrophysiology August 2020 Issue22.12.2020 (00:36:14)
Paul J. Wang: Welcome to the monthly podcast! On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief. With some of the key highlights from this month's issue. In our first paper, Demilade Adedinsewo and associates assess the accuracy of an artificial intelligence-enabled electrocardiogram [AI-ECG] to identify patients presenting with dyspnea who have left ventricular LV systolic function (defined as LV ejection fraction ≤35%) in the emergency department [ED]. Patients were included if they had at least one standard 12-lead electrocardiogram [ECG] acquired on the date of the ED visit and an echocardiogram performed within 30 days of presentation. Patients with prior LV systolic dysfunction were excluded. A total of 1,606 patients were included. Meantime from ECG echocardiogram was one day. The AI-ECG algorithm identified LV systolic dysfunction with an area under the curve [AUC] of 0.89 and accuracy of 85.9%. Sensitivity was 74%, specificity 87%, negative predictive value 97%, and positive predictive value 40%. To identify an ejection fraction less than 50%, the AUC was 0.85, sensitivity 86%, sensitivity 63%, and specificity 91%. NT-proBNP alone with a cutoff greater than 800 identified LV systolic function with an AUC of 0.80 by comparison. In our next paper, Mahmood Alhusseini and associates hypothesize that convolutional neural networks [CNN] may enable objective analysis of intracardiac activation in atrial fibrillation [AF]. They perform panoramic recording of bi-atrial electrical signals in AF and use the Hilbert-transform to produce 175,000 image grids in 35 patients labeled for a rotational activation by experts who showed consistency, but with variability (kappa [κ]=0.79). In each patient, ablation terminated atrial fibrillation. A CNN was developed and trained on 100,000 AF image grids validated on 25,000 grids, and then tested on a separate 50,000 grids. They found in a separate test cohort of 50,000 grids, CNN reproducibly classified AF image grids into those with or without rotational sites with 95.0% accuracy. This accuracy exceeded that of support vector machines, traditional linear discriminant, and k-nearest neighbor statistical analyses. To probe the CNN, they applied gradient weighted class activation mapping, which revealed that the decision logic closely mimicked rules used by experts (C statistic 0.96). The authors concluded that convolutional neural networks improve the classification of intercardiac AF maps compared to other analyses and agreed with expert evaluation. In our next paper, Kenji Okubo and associates examined whether late potential LP, abolition and ventricular tachycardia [VT] non-inclusive ability predicted long-term outcomes in patients with non-ischemic cardiomyopathy [NICM] undergoing VT ablation. The total 403 patients with NICM (523 procedures) who underwent VT ablation from 2010 to 2016 were included. The underlying structural disease consists of dilated cardiomyopathy (DCM, 49%), arrhythmogenic right ventricular cardiomyopathy (ARVD 17%), postmyocarditis (14%), valvular heart disease (8%), congenital heart disease (2%), hypertrophic cardiomyopathy (2%), and others (5%). Epicardial access was performed in 57% of patients. At baseline, the LPs were present in 60% of patients, and a VT was either inducible or sustained/incessant in 85% of the cases. At the end of the procedure LP abolition was achieved in 79% of cases in VT noninducability in 80%. After a multivariate analysis, the combination of LP abolition and VT noninducibility was independently associated with free survival from VT (hazard ratio, 0.45, p = 0.0002) and cardiac death (hazard ratio 0.38, P = 0.005). The benefit of LP abolition of preventing the VT recurrence in ARVD and postmyocarditis appeared superior to that observed for DCM. In our next paper, Domenico Corradi, Jeffrey Saffitz and associates hypothesize that structural molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict postoperative atrial fibrillation [POAF] may identify new molecular pathways and targets for prevention of this common morbid complication. Right atrial appendage [RAA] samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial. 35.2% of patients experienced POAF compared to the non-POAF group. They were significantly older and more likely to have chronic obstructive pulmonary disease or heart failure. They had a higher Euro score and more often underwent valve surgery. No differences in atrial size were observed between POAF and non-POAF patients. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen storage, or connection 43 distribution at the time of surgery, was not significantly associated with the incidents of POAF. None of these histopathological abnormalities were correlated with level of NT pro-BNP, hs-cTnT, CRP, or oxidative stress biomarkers. The authors concluded that in sinus rhythm patients undergoing cardiac surgery, histopathological changes in RAA do not predict POAF. They did not also correlate with biomarkers of cardiac function, inflammation, and oxidative stress. In our next paper, Mark McCauley, Liang Hong, Arvind Sridhar, and associates hypothesize that obesity decreases sodium channel NAF 1.5 expression via enhanced oxidative stress, thus reducing the sodium current and enhancing susceptibility to atrial fibrillation [AF]. They studied a diet induced obese [DIO] mouse model. Pacing induced AF in 100% of DIO mice versus 25% in controls (P In our next, paper Hirosuke Yamaji and associates conducted a randomized control trial to examine the impact of electrophysiological evaluation of the left atrium on atrial fibrillation [AF] outcome. They examined consecutive persistent and patients with, in 33, and without, 111 patients left atrial [LA] low voltage areas [LA-LVA]. Patients without LA-LVA were randomly assigned to EP test-guided (n=57) and control (n=54). In the EP test-guided group, an adjunctive posterior wall isolation [PWI] was performed in those with positive results (PWI subgroup; n=24) but not those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, ERP > 20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia during measurements. LVA ablation was performed in the LA-LVA patients during the follow-up period of a mean of 62 weeks, the EP test-guided group had a significantly lower recurrence rate (19%,11/57 versus 41%, 22/54, P=0.012) and a higher Kaplan-Meier AF/AT-free survival curve compared with controls (P=0.01). No significant differences in the recurrence, and AF/AT-free survival curves between PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test-guided group. A stepwise Cox proportional hazard analysis identified EP test-guided ablation as a factor, reducing recurrence rates. The recurrence rates in LA-LVA ablation group and EP test-guided group were similar. In our next study, Jinxuan Lin and associates assess whether simultaneous pacing of the left and right bundle branch areas may achieve more synchronous ventricular activation than just bundle pacing alone. In symptomatic bradycardia patients, the distal electrode of the bipolar pacing lead was placed at the left bundle branch area via a transventricular-septal approach. This was used to pace the left bundle branch area, while the ring electrode was used to pace the right bundle branch area. Bilateral bundle branch area pacing [BBBP] was achieved by stimulating the cathode and anode in various configurations. BBBP was successfully performed in 22 out of 36 patients. Compared with LBBP, BBBP resulted in greater shortening of QRS duration (109.3 vs 118.4 ms, P In our next paper, Ramanathan Parameswaran, Jonathan Kalman, Geoffrey Lee and associates recorded 2-minute long segments of simultaneous inter-operative mapping of endo- and epicardial lateral right atrial [RA] wall in patients with persistent atrial fibrillation [AF] using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms [EGMS] of continuous 2-minute AF recordings and electrodes locations were exported for phase analysis. They defined endocardial-epicardial dissociation [EED] as phase differences of ≥20 ms between paired endo- and epi electrodes. Wavefronts [WF] were classified as single rotations, that is single wavefront, focal waves, or disorganized activity as per standard criteria. Endo-Epi wave fronts were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with directional changes occupying at least 70% of the sample area. 14 patients with persistent AF underwent cardiac surgery are included. EED was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (endo 41.3%, epi 46.8%, P = 0.0194) and single wave (endo 31.3 versus epi 28.1, P = 0.129) were the dominant patterns. Transient rotations (endo 22%, epi 19.2%, P = 0.169, mean duration 590 ms) and non-sustained focal waves (endo 1.2% and epi 1.6%, P = 0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. EGM fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P In our next paper, Andrew Beaser and associates hypothesize that intravascular ultrasound [IVUS] could accurately visualize and quantify intravascular lead adherence and degree of intravascular lead adherence correlates with transvenous lead extraction difficulty. Serial imaging of leads occurred prior to transvenous lead extraction using IVUS. Intravascular lead adherence areas were classified as high or low grade. Degree of extraction difficulty was assessed using 2 metrics and correlated with intravascular lead adherence grade. Lead extraction difficulty was calculated for each patient and compared to IVUS findings. 158 vascular segments in 60 patients were analyzed: 141 (89%) low grade versus 17 (11%) high grade. Median extraction time (low = 0 versus high grade 97 seconds, P In our next paper, András Bratincsák, and associates sought to create the foundation of normative ECG standards in the young using Z-scores. 102 ECG variables were collected from a retrospective cohort of 27,085 study subjects with no known heart conditions, age zero to 39 years. The cohort was divided into 16 age groups by gender. Median interquartile range and range were calculated for each variable adjusted to body surface area. Normative standards were developed for all 102 ECG variables, including heart rate; P, R, and T axis; R-T axis deviation; PR interval, QS duration, QT, and QTc interval; P, Q, R, S, and T amplitudes in 12 leads; as well as QRS and T wave integrals. Incremental Z-score values between negative 2.5 and 2.5 were calculated to establish the upper and lower limits of normal. Historical ECG interpretive concepts were reassessed and new concepts observed. The author summarized that electronically acquired ECG values based on the largest pediatric and young adult cohort ever compiled provide the first detailed, standardized, quantitative foundation of traditional and novel ECG variables. In our next paper, Jungmin Hwang and associates hypothesize that suppressing the late sodium current may counterbalance the reduced repolarization reserve in long QT syndrome [LQTS] and prevent early depolarization [EAD] and polymorphic ventricular tachycardia [PVT]. They tested the effects of selective late sodium channel blocker GS967 on polymorphic ventricular tachycardia [PVT] induction in a transgenic rabbit model of type two using intact heart optical mapping, cellular electrophysiology, and confocal calcium imaging and computer modeling. They found that GS967 reduced ventricular fibrillation [VF] induction under a rapid pacing protocol (7 out of 14 hearts in control versus 1 out of 14 at 100 nanomolar) without altering action potential duration [APD] or restitution and dispersion. GS967 suppressed PVT incidents by reducing calcium mediated EADs and focal activity during isoproterenol perfusion (at 30 nanomolar, 7 out of 12 and a 100 nanomolar, 8 out of 12 without EADs and PVTs). Confocal calcium imaging of LQT myocytes revealed GS967 shortened calcium transient duration by accelerating sodium calcium exchanger mediated calcium efflux from cytosol, thereby reducing EADs. Computer modeling revealed the inward late sodium current potentiates EADs in the LQT setting through providing additional depolarizing currents through action potential plateau phase, and increasing intracellular sodium that decreases the depolarizing sodium calcium exchanger, thereby suppressing the action potential plateau and delaying the activation of slowly activating delayed rectifier current, IKS. Suggesting important roles in the late sodium current in regulating intracellular sodium. Thus, the authors concluded that selective late sodium channel blockade by GS967 prevents EADs and abolishes PVT in LQT rabbits by counterbalancing the reduced repolarization reserve and normalizing intracellular sodium. In our next paper, Pietro Lazzerini, Mohamed Boutjdir and associates, hypothesize that systemic inflammation per se can significantly prolong QTc during infection via cytokine-mediated changes in potassium channel expression. They found in patients with acute infections, regardless of concomitant QT-prolonging anti-microbial therapy, QTc was significantly prolonged but rapidly normalized in parallel to C-reactive protein [CRP] and cytokine level reduction. Consistently, in Torsades de Pointes cohort, concomitant acute infections were prevalent 30% despite only a minority (25%) of these cases were treated with QT-prolonging anti-microbials. KCN J2, potassium channel expression in peripheral blood mononuclear cells was strongly correlated to that in ventricles, inversely associated to CRP and interleukin one changes in acute infection patients. The authors concluded that acute infection, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless of concomitant antimicrobial therapy. In a research letter, Christophe Beyls and associates examined the risk of bradycardia and critically ill COVID-19 patients treated with Lopinavir [LPV], a protease inhibitor of HIV-1, and Ritonavir [RTV], another protease inhibitor that strongly inhibits hepatic cytochrome P 450 [CYP3A4] activity in order to increase the Lopinavir plasma concentration. During the first month of the outbreak, patients admitted to the ICU with positive PCR for COVID-19 received LPV (200 mg)/RVT (50 mg) twice daily for 10 days. Bradycardia was defined as heart rate below 60 for a period of more than 24 hours. All patients were monitored 24 hours a day for all hemodynamic parameters, including heart rate with a five-lead ECG. Monitors were linked to a computerized system allowing to extract hemodynamic data. LPV/RTV plasma concentration was monitored using analytic method, combining high propensity performance, liquid chromatography and tandem mass spectrometry at 72 hours and every 72 hours. They prospectively included 41 COVID-19 patients who received LPV/RTV treatment. Nine or 22% patients experienced bradycardia. No patients had a pre-existing nodal pathology on the ECG on admission. Among the 9 patients with bradycardia, 8 or 88% were sinus bradycardia and one (12%) third-degree AV block. Causality may be considered as bradycardia occurred at least 48 hours after LPV/RTV initiation, bradycardia resolved after discontinuation or dose reduction and no alternative cause was found. Patients who presented with bradycardia were older, had a higher RTV plasma concentration and a lower lymphocyte count. In our study, no correlation was found between RTV plasma concentration, LPV plasma concentration, and mean heart rate at day three. No patient had bradycardia in the first 48 hours after LPV/RTV administration. For patients with LPV RTV plasma level overdose, the dose of LPV RTV was divided by two until the next dose. For the patient with third degree AV block LPV/RTV was stopped. None of the patients had any known cytochrome CYP3A4-inhibiting drugs. The authors concluded that the results suggest that RTV plasma overdose in elderly critical ill patients may increase the risk of bradycardia. In a research letter, Emily Zeitler and associates surveyed cardiac implantable device [CID] patients. A total of 109 patients were approached to participate, nine declined. Most respondents were white (79%), male (60%) with a mean age of 73 years. The median number of correct responses to the 11 factual questions was six. Respondents held some common misconceptions. For example, 25% of respondents believe that FDA determines the cost of the device. Trust in the FDA was high; 67% of respondents agreed "I trust the FDA". Respondents mostly agreed "the FDA would not approve my device unless it was a hundred percent safe". Only 6% of respondents agreed, "we would be better off if there was no FDA," and a similarly small fraction disagreed with "when it comes to medical devices, the U.S. does the best job in the world at keeping people safe". Most respondents, 69% demonstrated fear of device recalls by agreeing with "if there was a recall of all are part of my device, I think I would be worried or scared." On average, respondents were comfortable sacrificing some privacy for device surveillance, 75% agreed with "once the device has been approved, the FDA should continue to monitor for signs that there are problems with the device even if it means that private health information about me is collected". Respondents seemed to believe that the FDA was risk averse; 56% believed that the FDA does not approve devices unless they're a hundred percent safe. This is in contrast to trends shifting the demonstration of safety to post-approval settings and expanding acceptable forms of data for regulatory approval. In a research letter, Laura Rottner, Christoph Sinning and associates examined novel high resolution imaging system based on a wide band dielectric technology, and reports the first clinical experience of feasibility and reliability of cryoballoon [CB] occlusion tool as compared to fluoroscopic and 3D transesophogeal [TEE] assessment during pulmonary vein isolation [PVI]. In consecutive patients with symptomatic atrial fibrillation [AF], cryoballoon-based ablation was performed with a novel 3D wide-band dielectric imaging system. Pulmonary vein [PV] occlusion was assessed with fluoroscopy in 3D-TEE and concomitantly correlated with the novel CB occlusion tool. The endpoint was defined as persistent PV isolation verified by spiral mapping catheter recordings 30 minutes after the last CB application. A total of 36 (90%) of PVs in 10 patients with paroxysmal (40%) and persistent (60%) were analyzed. In all patients, a normal PV anatomy with four separate PVs was documented. Visualization via 3D-TEE was feasible in 80% septal PVs and 100% of lateral PVs. In 67% of PVs, total PV occlusion was confirmed by all 3 imaging modalities. In 17% of PVs, incomplete PV occlusion was initially demonstrated by TEE and 3D dielectric imaging, whereas fluoroscopy suggested complete occlusion in initial analysis. After repositioning of the CB at 3 PVs, complete PV occlusion was verified by all three modalities. In 3 out of 36 (8%), no occlusion was initially seen by any imaging modality, for which the CB was repositioned resulting in total PV occlusion as confirmed by all three modalities. Two out of 36 PVs (6%) were confirmed to be occluded via fluoroscopy in 3D-TEE, but not by the CB occlusion tool. There was only one out of 36 PVs (3%), which were confirmed to be included by the CB tool and 3D-TEE, but not by fluoroscopy. A negative and positive predictive value of 1.0 and 0.6 was seen when comparing PV occlusion by the novel occlusion tool compared to PV collusion, verified by fluoroscopy and 3D-TEE. In a special report, Jun Hirokami, and associates aim to clarify the spatial correlations between fractionated potential detected by Lumipoint with non-PV trigger. They enrolled 30 symptomatic atrial fibrillation [AF] patients who underwent non pulmonary vein [PV] foci ablation. 4 patients underwent the first procedure, 17 underwent second procedure and eight underwent third procedure, and one underwent a fourth procedure. They highlighted the fractionated signal area in atrial muscle [FAAM] during sinus rhythm and atrial pacing, thereby producing a digital FAAM map. They retrospectively applied Lumipoint to 30 patients in order to clarify the relationship between FAAM and non-pulmonary vein [PV] foci. Non-PV foci were successfully identified in all patients. They identified four patients with multiple non-PV foci. Of these four patients, one had non-PV foci at the superior vena cava and left arterial anterior wall. One had non-PV foci at the SVC and LA bottom wall. And two had non-PV foci at the SVC and interatrial septum. They only analyze 30 non-PV foci unrelated to SVC because the SVC isolation was routinely performed for non-PVC foci at the SVC. In order to analyze the correlation between FAAM and location of non-PV triggers, they determined the cutoff points of peaks slider, which non-PV triggers were completely located within the FAAM in. The accuracy of predicting location of the non-PV triggers was summarized using area under the receiver operating curve, a UROC curve. The optimal cutoff point of peak sliders to predict the location of non-PV was determined by the Youden Index. The Youden Index established the optimal cutoff point of the maximum peaks slider was 7; sensitivity was 0.906 and specificity 0.770. The peaks slider 7 was the most accurate predictor fractionated signals location area to the location of non-PV triggers. (area under the curve 0.902). The mean area of peaks slider 7 was six centimeters squared or 4.3% of the atrium. The authors concluded that the proof-of-concept observational study demonstrated that novel visualization tool of FAAM map successfully identified non-PV triggers that did not induce atrial fibrillation and/or non-PV foci, which potentially serve as substrates for AF maintenance. In a special report, Leslie Saxon and associates update their prior publication providing further detail on mitigation adoption rates for the entirety of the U.S. patient population with implanted cardiac rhythm management devices falling under FDA cyber security advisories from any device manufacturer. They also provided limited data on known cybersecurity mitigation adoption outside the U.S. They report a unique complication resulting for introducing firmware to already implanted devices. Discuss how evolving FDA policies towards firmware mitigation adoption may increasingly determine how and when updates occur. They found that patients under 50 years of age and those over 80 years were less likely to receive the software upgrades, and male versus females had greater rates of upgrades. The upgrade rates varied according to U.S. Region and date of implant. Resynchronization devices were less likely to receive the upgrade, as were pacemaker dependent patient. Those ICD patients initially falling under the battery advisers were upgraded more frequently. The number of advisory patients followed in clinic was a significant predictor for firmware upgrade adoption, particularly for pacemakers that were often upgraded in smaller size clinics. Overall, only 24% of devices for all groups, and 22% of devices not impacted by the battery advisory were upgraded. For Abbott devices, the home communicator cyber security vulnerabilities were mitigated with an automatic software patch that was updated using the Merlin network, and adoption rates were nearly a hundred percent. For the entire patient cohort with impacted pacemaker and ICDs, U.S. and global adoption rates remain low at 24 to 35% with a low rate of complications. Most reported complications for pacemakers and ICD were symptoms (transient palpitations, dizziness, or syncope) that resulted from the temporary change in mode to VVI or transient loss of programmer telemetry while performing the upgrade (pacemaker 0.05%; ICD 0.01%). Globally, a total of 9 pacemakers and 8 ICDs required replacement, as a result of performing the firmware upgrade due to irreversible reversion to a backup pacing mode and loss of defibrillation therapy (ICDs). Analysis of the returned ICD pulse generaotrs found at 7 cases, the cause related to a capacitor bond failure that was exposed only when extended telemetry as required by the upgrade. The failure mechanism was an isolated component failure in the remaining ICD. The programmer based test has recently been FDA approved and can be performed prior to firmware upgrade to identify ICD patients at risk for capacitor bond failure. A total of 256 ICDs were susceptible to loss of RF telemetry after receiving a firmware update, and this has since been mitigated with a software patch. For Medtronic programmers, the initial mitigation responses of cybersecurity advisory was to take the programmers off the network. The network connection was enhanced with one or more security protections provided to the programmers using a flash drive, so the programmers can now be secured from potential cyber intrusion when connected to the network. Medtronic ICDs are currently being upgraded. The upgrade is being provided to impacted patients automatically when the device is interrogated with the programmer during follow-up. Metronic is introducing upgrades in phased approach with all expected to be completed by the beginning of 2021. There are 9% or 55,000 ICDs under this advisory that cannot receive the update due to design or safety constraints. Since the 2017 Abbott advisories identify cybersecurity vulnerabilities in pacemakers and ICDs with the potential for exploits have been increased, including 2 additional FDA advisories issued for another manufacturer. Medtronic's connected communication product and implantable defibrillators in the past 12 months. The authors comment that a recent report and a smaller number of Abbott impacted pacemaker and ICD patients from Canada reported marked differences in mitigation adoption rates between pacemakers and ICDs. This was due to an increase incremental clinical familiarity and comfort with performing the updates as experience and education surrounding these issues evolve. The authors indicate that automating cybersecurity updates without process in place for determining safety, for alerting patients or clinicians that have been delivered, may also be associated with yet unknown risks. Newer generation devices and communication protocols may render cyber security, advisories less frequent as cybersecurity integration is considered an essential aspect of device design. In a review article, Albert Feeny and associates discuss the use of artificial intelligence [AI] and machine learning [ML] in medicine, which are currently areas of intense exploration showing potential to automate human tasks or even perform tasks beyond human capabilities. The first objective of this review is to provide the novice reader with a literacy of AI/ML methods, and to provide a foundation of how one may conduct an ML study. The review provides a technical overview of some of the most commonly used terms, challenges in AI/ML studies with reference to recent studies in cardiac electrophysiology to illustrate key points. The second objective of this review is to use examples from the recent literature to discuss how AI and ML are changing clinical practice and research in cardiac electrophysiology with emphasis on disease detection and diagnosis, prediction, and patient outcomes and novel characterization of disease. The final objective is to highlight important considerations and challenges for appropriate variation, adoption, and deployment of AI technologies and practice. That's it for this month! We hope that you will find the journal to be the go-to place for everyone interested in the field! See you next time! This program is copyright American Heart Association 2020. Thank you.
Circulation: Arrhythmia and Electrophysiology June 2020 Issue22.12.2020 (00:19:19)
Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Vivek Reddy and associates studied a novel, 7.5, French lattice tip catheter with the compressible 9 mm nitinol tip that is able to deliver either focal radio frequency ablation [RFA] or pulsed field ablation [PFA], 2 to 5 second lesions. In a 3 center, single-arm, first in human trial, the catheter was used with a custom mapping system to treat paroxysmal or persistent atrial fibrillation. Toggling between energy sources, point by point, pulmonary vein [PV] encirclement was performed using biphasic pulsed field ablation, posteriorly, and either temperature controlled irrigated RFA or pulse field ablation, anteriorly (RF/PF or PF/PF) respectively. Linear lesions were created with either PFA or RFA. The 76 patient cohort included 55 paroxysmal and 21 persistent atrial fibrillation [AF] patients undergoing either RF/PF [pulse field ablation] 40 patients or PF/PF ablation in 36 patients, pulmonary vein isolation therapy duration was 22.6 minutes per patient with a mean of 50.1 RF/PF ablation lesions per patient. Linear lesions included 14 mitral, 34 left atrial roof and 44 cavo-tricuspid isthmus lines with therapy duration times of 5.1, 1.8 and 2.4 min/patient respectively. All lesion sets were acutely successful using 4.7 minutes of fluoroscopy. There were no device-related complications, including no strokes. Post-procedure esophagogastroduodenoscopy revealed minor mucosal thermal injury in two of the 36 RF/PF and zero of the 24 PF/PF patients. Post-procedure brain MRI revealed DWI positive flair, negative and DWI positive flare positive asymptomatic lesions in 5 and 3 of the 51 patients respectively. In our next paper, Moussa Saleh and associates examined whether chloroquine, hydroxychloroquine plus or minus azithromycin lead to a prolongation of the QT interval, possibly increasing the risk of torsades de pointes and sudden death in a hospitalized population of patients with COVID-19. 201 patients were treated for COVID-19 with chloroquine/hydroxychloroquine. 10 patients or 5% received chloroquine, and 191 or 95% received hydroxychloroquine and 119 or 59% also received azithromycin. The primary outcome of Torsades de pointes was not observed in the entire population. Baseline QTC interval did not differ between patients treated with chloroquine or hydroxychloroquine monotherapy versus those treated with combination group chloroquine/hydroxychloroquine and azithromycin (440 ms versus 439.9 ms). The maximum QT during treatment was significantly longer in the combination versus the monotherapy group, 470 ms versus 453 ms (P = 0.004). Seven patients (3.5%) required discontinuation of these medications due to QTC prolongation. No arrhythmic deaths were reported. In our next paper, Mikko Tulppo and associates examine whether the association between leisure time physical activity and the risk of sudden death and non-sudden cardiac death in coronary artery disease patients. 1,946 patients with angiographically verified coronary artery disease were classified into four groups: inactive, irregularly active, active exercise regularly two to three times per week, and highly active, exercise four times or more weekly. During follow-up, median 6.3 years, 52 sudden cardiac death and 49 non-sudden cardiac deaths occurred. Inactive patients had increased risk for sudden cardiac death compared to active patients, hazard ratio 2.45. Leisure time was not associated with sudden cardiac death in patients with Canadian cardiovascular class one, 18 events in 1,107 patients. Among patients with Canadian cardiovascular society, class two or higher, 34 events in 839 patients. An increased risk for sudden cardiac death encountered in highly active patients, hazard ratio 7.46 (P In our next paper, Jacob Koruth and associates examined the preclinical feasibility and safety of a 9mm lattice tip catheter with focal biphasic pulse field [PF] based thoracic vein isolation and linear ablation combined focal biphasic pulse field and radio-frequency [RF] focal ablation and vocal biphasic pulse field delivered directly on top of the esophagus. They treated two cohorts of six swine with pulse fields at low dose and high dose followed for four weeks and two weeks, respectively to isolate 25 thoracic veins and to create five right atrial low dose PF, six mitral high dose PF, and six roof lines with combined RF and high dose PF. Baseline and follow-up voltage mapping, venus potentials, ostial diameters and phrenic nerve viability were assessed. High dose PF in RF lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviate esophagus. 100% of thoracic veins, 25 out of 25, were successfully isolated with 12.4 applications per vein with a mean pulse field times of less than 90 seconds per vein. Durable isolation improved from 61.5% in the low dose pulse field to 100% with a high dose pulse field (P = 0.04). And all linear lesions were successfully completed without incurring venous stenosis or phrenic injury. High dose pulse field sections had higher trans mortality rates than low dose pulse field (98.3% versus 88.1%, P = 0.03). Despite greater thickness, 2.5 versus 1.3 mm, pulse field lesions demonstrated homogeneous fibrosis without epicardial fat, nerve or vessel involvement. In comparison, combined RF plus high dose PF sections revealed similar transmurality, but expectedly more necrosis, inflammation and epicardial fat, nerve and vessel involvement. Significant ablation related esophageal and necrosis inflammation and fibrosis were seen in all RF sections as compared to no PF sections. In our next paper, Hagai Yavin and associates investigated the effects of a novel, lattice tip catheter designed for focal radiofrequency ablation [RFA] or pulse field ablation in 25 swine. In 14 animals, they examined in step one (n = 14) the feasibility to create atrial line of block and described as acute effects on the phrenic nerve and esophagus. In step two (n = 7), they examined the subacute effects of pulse field ablation on block durability, phrenic nerve, and esophagus 2 or more weeks. In 4 animals in step three, they compare the effects of pulse field ablation and RFA on the esophagus using a mechanical deviation model, approximating the esophagus through the right atrium in 4 and direct ablation honest lumen in 4. The effects of endocardial PFA and RFA on the phrenic nerve were also compared (n = 10). Histological analysis were performed. Pulse field ablation produced acute block in 100% of lines achieved with 2.1 applications per centimeter line. Histological analysis following a mean of 35 days showed 100% transmurality (thickness range 0.4 to 3.4 mm) with a lesion width of 19.4 mm. Pulse field ablation selectively affected cardiomyocytes, but spared blood vessels and nervous tissue. Pulse field ablation applied from the posterior atrium to the approximated esophagus produced transmural lesions without esophageal injury. Pulse field ablation applied within the esophageal lumen produced mild edema compared to radiofrequency ablation (13 applications) which produced epithelial ulcerations. Pulse field ablation resulted in no or transient stunning of the phrenic nerve, less than 5 minutes without histological changes while radiofrequency ablation produced paralysis. In our next paper, Elad Anter and associates investigated the optimal methods to identify arrhythmogenic substrate of scar related VT. They examine how often sites of activation slowing during sinus rhythm co localize with ventricular tachycardia VT circuit. In a multicenter study in patients with infarct-related VT, the left ventricle was mapped during activation from three directions, sinus rhythm, or atrial pacing, right ventricular and left ventricular LV pacing at 600 ms. Ablation was applied selectively to the cumulative area of slow activation defined as a sum of all regions with activation time of 40 ms or greater per 10 mm. Hemodynamically tolerated ventricular tachycardias or VT were mapped with activation or entrainment. The primary outcome was a composite of appropriate ICD therapies and cardiovascular death. In 85 patients, the left ventricle was mapped during activation from 2.4 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spacial overlap of activation slowing between sinus rhythm and right ventricular RV pacing was 84.2%, between sinus rhythm and LV pacing was 61.4%, and between right ventricular and left ventricular pacing, 71.3% (P In our next paper, Georg Gussak and associates identified a novel form of abnormal calcium wave activity in normal and failing dog atrial myocytes, which occurs during the action potential and is absent during diastole. The goal of this study was to determine if triggered calcium waves affect cellular electrophysiological properties. The authors use simultaneous recordings of intracellular calcium, and action potentials for the measurement of maximum diastolic potential and action potential duration during triggered calcium waves in isolated dog atrial myocytes. Computer simulations then explored electrophysiological behavior arising from triggered calcium waves at the tissue scale. At 3.3 to five Hertz, triggered calcium waves occurred during the action potential and outlasted several action potential cycles. Maximum diastolic potential was reduced and actual potential duration was significant prolonged during trigger calcium waves. All electrophysiological responses that triggered calcium waves were abolished by using SCA 0400 and ORM 10103, indicating that sodium calcium exchange current caused depolarization. The time constant recovery from inactivation of calcium current was 40 to 70 ms in atrial myocytes, depending on the holding potential. This current could be responsible for action potential (AP) activation during repolarization induced by triggered waves. Modeling studies demonstrate the characteristic properties of triggered calcium waves are potentially arrhythmogenic by promoting both conduction block and reentry arising from the repolarization induced by triggered calcium waves. The authors concluded that triggered calcium waves activate inward sodium calcium exchange and dramatically reduce atrial maximum diastolic potential and prolonged action potential duration establishing the substrate for reentry that could contribute to initiation and maintenance of atrial arrhythmias. In our next paper Faisal Merchant and Omid Sayadi and associates evaluate the ability of a real-time, closed loop system to record and analyze repolarization alternans from multiple intracardiac leads and deliver dynamically R-wave triggered pacing stimuli during the absolute refractory period. They examined the ability of this system to control repolarization alternans and reduce arrhythmia susceptibility, in vivo. R-wave trigger pacing can induce repolarization alternans, the magnitude of which can be modulated by varying the amplitude, pulse width, or size of the pacing vector. Using a swine model (n = 9), the authors demonstrated that to induce 1 microvolt change in the alternans voltage on the body surface, coronary sinus or left ventricle, requires a delivery charge of 0.04, 0.05 and 0.06 microcoulombs, respectively, while to induce one unit change of the case score requires a delivery charge of 0.93, 0.32 and 0.33 microcoulombs, respectively. For all body surface and intracardiac leads a Delta alternans voltage and Delta K score between baseline and R-wave triggered pace peaks increases consistently with an increase in the pacing pulse amplitude, pulse width and vector spacing. Additionally, the author showed that the proposed method can be used to suppress spontaneously occurring alternans (n = 7), in the presence of myocardial ischemia. Suppression of repolarization alternans by pacing during the absolute refractory period results in a significant reduction in arrhythmia susceptibility, evidenced by lower S rank score during program ventricular stimulation compared to baseline prior to ischemia. In a perspective outlining the cardiovascular effects of chloroquine and hydroxychloroquine, Ohad Oren and associates describe their belief that the use of chloroquine and hydroxychloroquine in COVID-19 should be limited to randomized, controlled trials. For critically ill patients, unable to enroll in a trial, selective in-hospital use could be considered with careful clinical monitoring in keeping with the FDA's emergency use authorization. The authors suggested that studies evaluating chloroquine and hydroxychloroquine should systematically collect baseline demographic data, results from electrocardiographic and echocardiographic monitoring prior to and during treatment and rates of adverse cardiovascular events in both the near and long-term. In a research letter, Federico Migliore and Alessandro Zorzi and associates found a 28% decrease in the number of urgent pacemaker implantations during the six weeks after the first COVID-19 case, from 122 to 88 (P = 0.02), compared to the six weeks before the first COVID-19 case. The proportion of female patients requiring urgent pacemaker implantation after the COVID-19 outbreak decreased from six out of 122 (49%) to 30 out of 88 (34%) (P = 0.03). In a special report Stephanie Kochav and associates described 4 cases of cardiac arrhythmias in COVID-19, including AV block, atrial fibrillation, polymorphic ventricular tachycardia, and pulseless electrical activity arrest. In a year in review, Suraj Kapa and associates discuss a number of the many advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies in the past year. Data suggests that secretoneurin may be a marker for patients at risk of ventricular arrhythmias, while natriuretic peptide receptor C may have a role in atrial fibrosis. In atrial specific 2-pore potassium channel TASK-1 may be a therapeutic target for atrial fibrillation. Sensory neurons may play a key role in sleep apnea related to atrial fibrillation. Bariatric surgery is associated with improved atrial fibrillation outcome. Artificial intelligence applied to electrocardiography has yielded estimates of age, gender, and overall health. We've seen new tools for collection of patient centered outcomes following catheter ablation. There's been significant advances in the ability to identify ventricular tachycardia termination sites through high density mapping of deceleration zones. We've learned that right ventricular dysfunction may be a predictor of survival benefit after ICD implantation in non ischemic cardiomyopathy patients. We've seen further insights in the role of his bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advance, we have new tools to predict arrhythmic event rates in gene carriers. And finally, we've seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.
Circulation: Arrhythmia and Electrophysiology May 2020 Issue16.12.2020 (00:17:49)
Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, Bruce Wilkoff and associates examine the impact of cardiac implantable electronic device [CIED] infections on mortality, quality of life, healthcare utilization, and cost in the U.S. Healthcare system. They found that the majority CIED infection was associated with increased all-cause mortality, 12-month risk-adjusted hazard ratio 3.41, P The quality of life was reduced, P = 0.004, and did not normalize for six months. Disruptions in CIED therapy were observed in 36% of infections for a median duration of 184 days. The authors reported that the mean hospital costs were $55,547. In our next paper, Songwen Chen, Xiaofeng Lu and associates examine the ability to eliminate premature ventricular complexes [PVCs] originating from the proximal left anterior fascicle, safely from the right coronary sinus. The authors mapped the the right coronary sinus and left ventricle in 20 patients with left anterior fascicle PVCs. They found that the earliest activation site with Purkinje potential during both PVC and sinus rhythm was localized at proximal left anterior fascicle in eight patients, the proximal group, or non-proximal left anterior fascicle in 12 groups, the non-proximal group. The Purkinje potentials proceeded PVC-QRS at the earliest activation site in proximal group 32.6 milliseconds was significantly earlier than that in non-proximal group, 28.3 milliseconds P = 0.025. Similar difference in the Purkinje potentials proceeding sinus QRS at the earliest activation site was also observed between proximal and non-proximal group, 35.1 milliseconds versus 25.2 milliseconds, P In proximal group, the distance between the earliest activation site to the left His-bundle into the right coronary sinus were shorter than that of the non-proximal group 12.3 millimeters versus 19.7, P = 0.002, and 3.9 millimeters versus 15.7 millimeters, P Electrocardiographic analysis showed that when compared to non-proximal group, the PVCs proximal group had a narrower QRS duration, smaller S wave in leads one, V five,and V six; lower R waves in leads one, aVL, aVR, V one, V two, and V four and smaller q wave in leads three and aVF. The QRS duration difference [PVC-QRS and sinus rhythm QRS] In our next paper, Benjamin Steinberg and associates examined the factors that are associated with large improvements in health-related quality of life in patients with atrial fibrillation. The authors assessed factors associated with a one-year increase in quality of life, measured by AFEQT of one standard deviation that is greater and equal to 18 points, three times clinically important difference among patients in the ORBIT-AF one registry. They found that 28% of patients had such a health-related quality improvement compared with patients not showing large health-related quality of life improvement. They were similar age, (median 73 versus 74 years of age), equally likely to be female, (44% versus 48%), but more likely to have newly diagnosed atrial fibrillation [AF] at baseline (18% versus 8%, P = 0.0004) prior antiarrhythmic drug use (52% versus 40%, P = 0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P = 0.045), and more likely to undergo AF related procedures during follow-up (AF ablation 6.6% versus 2.0%, cardioversion 12.2% versus 5.9%). In multivariate analysis, a history of alcohol abuse has a ratio 2.4 and increased baseline diastolic blood pressure has a ratio 1.23 per 10 point increase and greater than 65 millimeters of mercury were associated with large improvements in health-related quality of life at one year. Whereas patients with prior stroke, chronic obstructive pulmonary disease and peripheral artery disease were less likely to improve. In our next paper, Eiichi Watanabe and associates studied safety and resource consumption of exclusive remote follow-up in pacemaker patients for two years. Consecutive pacemaker patients committed to remote pacemaker management were randomized to either remote follow-up or conventional in-office follow-up at twice yearly intervals. Remote follow-up patients were only seen if indicated by remote monitoring, all returned to hospital after two years. In 1,274 randomized patients (50.4% female, age 77 years), 558 remote follow-up or 550 conventional in office follow-up patients reached either the primary end point or 24 months follow-up. The primary end point, a composite of death, stroke, or cardiovascular events requiring surgery occurred in 10.9% and 11.8% respectively in the two groups (P = 0.0012) for non-inferiority. The median number of in-office follow-ups was 0.5 in the remote follow-up group and 2.01 in the conventional in-office follow-up per patient year (P In our next paper, Sarah Strand and associates use fetal magnetocardiography from the University of Wisconsin biomagnetism laboratory to study 39 fetuses with pathogenic variants in long QT syndrome, LQTS genes. 27 carried the family variant, 11 had de novo variants, and one was indeterminant. De novo variants, especially de novo SCN5A variants were strongly associated with a severe rhythm phenotype and perinatal death. Nine or 82% showed signature LQTS rhythms, six showed torsade de pointes, five were still born, and 9% died in infancy. Those that died exhibited novel fetus rythms, including AV block with 3:1 conduction ratio, QRS alternans in 2:1 AV block, long cycle length, torsade de pointes, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with torsade de pointes and perinatal death. Fetuses with familiar variants showed a lower incidence of signature LQTS rhythm, six out of 27 or 22%, including torsade de pointes, and 3 out of 27 or 11% all were live born. The authors concluded that the malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth. In our next paper, Corina Schram-Serban and associates compare the severity of extensiveness of conduction disorders between obese patients and non-obese patients measured at high resolution scale. They studied 212 patients undergoing cardiac surgery (male:161, mean 63 years of age), who underwent epicardial mapping of the right atrium, Bachmann's bundle, and left atrium during sinus rhythm. Conduction delay [CD] was defined as interelectrode conduction time seven to 11 milliseconds and conduction block [CB] as conduction time ≥ 12 milliseconds. In obese patients, the overall incidence of conduction delay was 3.1% versus 2.6% (P = 0.002), conduction block 1.8% versus 1.2%, and continuous CDCB 2.6% versus 1.9% higher in the obese patients, conduction delay (P = 0.012) and continuous CDCB lines are longer. There were more conduction disorders at Bachman's bundle, and this area has a higher incidence of conduction delay 4.4% versus 3.3% (P = 0.002), conduction block 3.1% versus 1.6% (P In our next paper, Ricardo Cardona-Guarache and associates describe five patients with concealed, left-sided nodoventricular in four patients and nodofascicular in one patient accessory pathways. They proved the participation of accessory pathway in tachycardia by delivering His-synchronous premature ventricular complexes that either delayed the subsequent atrial electrogram or terminated the tachycardia, and by observing an increase in ventricular atrial interval coincident with left bundle branch block in two patients. The accessory pathways were not atrioventricular pathways because the septal ventricular atrial interval during tachycardia was less than 70 milliseconds in 3, 1 had spontaneous AV dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing. Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of accessory pathways was suspected after failed ablation of the right inferior extension of the AV node in 3 cases and by observing VA increase in left bundle branch block in 2 cases. The nodofascicular in 3 of the 4 nodoventricular accessory pathways were successfully ablated from within the proximal coronary sinus guided by recorded potentials at the roof of the coronary sinus, and nodoventricular accessory pathway was ablated via a transseptal approach near the coronary sinus os. In our next paper, Pierre Qian and associates examined whether an open irrigated microwave catheter ablation can achieve deep myocardial lesions endocardially and epicardially through fat while acutely sparing nearby coronary arteries. Epicardial ablations via subxiphoid access in pigs were performed at 90 to 100 Watts at four minutes at sites near coronary arteries and produced mean lesion depth of 10 millimeters, width 18 millimeters, and length 29 millimeters through median epicardial fat thickness of 1.2 millimeters. Endocardial ablations at 180 Watts achieved depths of 10.7 millimeters, width of 16.6 millimeters, and length of 20 millimeters. Acute coronary occlusion or spasm was not observed at median separation distance of 2.7 millimeters. In our next paper, Jad Ballout and associates examined 21 consecutive patients with cardiogenic shock and refractory ventricular arrhythmias undergoing bailout ablation due to inability to wean off of mechanical support. Mean age was 61 years, 86% were males, median left ventricular injection fraction 20%, 81% ischemic cardiomyopathy. The type of mechanical support in place prior to the procedure was intra-aortic balloon pump in 14 patients, Impella in 2, ECMO in 2, ECMO and intra-aortic balloon pump in 2, and ECMO and Impella in 1. In the cardio voltage maps with myocardial scar in 90% (19 patients), the clinical ventricular tachycardias VTs were inducible in 13% (62 patients), whereas 6 patients had PVC induced ventricular fibrillation, VT (29%), and VT could not be induced in 2 patients (9%). Activation mapping was possible in all 13 patients with inducible clinical VTs, substrate modification was performed in 15 patients with scar in 79%. After ablation and scar modification, the arrhythmia was noninducible in 19 patients (91%). Seventeen (81%) were eventually weaned off mechanical support successfully with the majority of patients being discharged home and surviving beyond one year. However, 6 (29%) died during the index admission with persistent cardiogenic shock. In a research letter, Parveen Garg and associates examined the multi-ethnic study of atherosclerosis [MESA] incident atrial fibrillation a population with 50% African-American or Hispanic. After adjusting for age, race, ethnicity, sex education, income, clinic site, height, body, mass index, cigarette, smoking, diabetes, systolic and diastolic blood pressure, and hypertensive medications, physical activity, alcohol consumption, lipid parameter to lipid lowering therapy, the baseline lipoprotein A level greater or equal to 30 milligram per deciliter was inversely associated with developing atrial fibrillation compared those with lower levels (hazard ratio 0.84). However, the mechanism of this paradoxical association is unclear. In another research letter, Yoshihide Takahashi and associates reported that 49 patients undergoing ablation of persistent atrial fibrillation had at least one focal site and rotational activation in 57%. Of these, 19 patients underwent a repeat ablation for recurrent atrial fibrillation. AF was mapped in 17 patients and 131 focal activation sites were ablated. There were 105 displayed focal activation sites during the de novo ablation and 89 focal activation sites during the repeat ablation. During the de novo ablation, rotation activation was observed in 19 sites. Of the 19 sites, 12 (63%) displayed rotational activity, also with the repeat ablation. The author suggested focal or rotational activation sites can be classified into two types, ones critical for AF recurrence and the ones that are bystander. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association, 2020. Correction: In the study by Pierre Qian and associates, the epicardial ablations via subxiphoid access were performed in sheep, not pigs, as previously stated.
Circulation: Arrhythmia and Electrophysiology April 2020 Issue16.12.2020 (00:12:56)
Paul J. Wang: Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, David Okada and associates assess the ability of a novel machine learning approach for quantifying 3D spatial complexity of gray scale patterns on late gadolinium-enhanced cardiac magnetic resonance images to predict ventricular arrhythmias in patients with ischemic cardiomyopathy. They examined 122 consecutive ischemic cardiomyopathy patients with left ventricular ejection fraction of 35%, without prior history of reentrant ventricular arrhythmias. These patients underwent late gadolinium-enhanced cardiac magnetic resonance imaging. From raw gray scale data, the authors generated graphs encoding the 3D geometry of the left ventricle. They then assess the global regularity of signal intensity patterns using Fourier-like analysis and generated a substrate spatial complexity profile for each patient. A machine learning statistical algorithm was employed to discern which substrate spatial complexity profiles correlated with ventricular arrhythmic events. That is appropriate ICD firings and arrhythmic sudden cardiac death. At five years of follow-up from the statistical machine learning results, a complexity score ranging from zero to one was calculated for each patient that was tested using multivariate Cox regression models. At five years of follow-up, 40 patients had ventricular arrhythmia events. The machine learning algorithm classified with overall 81% accuracy and correctly classified 86% of those without ventricular arrhythmia. Overall negative predictive value was 91%. Average complexity score was significantly higher in patients with ventricular arrhythmia events versus those without P In our next paper, Henry Chubb and associates examine the outcomes of cardiac resynchronization therapy studies in pediatric and or congenital heart disease patients using a propensity score match analysis. They examined 63 matched CRT control pairs. Heart transplant or death occurred in 12 subjects or 19% or 37 controls or 59% with a median follow-up of 2.7 years. Cardiac resynchronization therapy was associated with markedly reduced risk of heart transplant or death. Hazard ratio is 0.24 P In our next paper Pachon-M and associates examined whether AF nest ablation eliminates the atropine response and decreases RR variability suggesting that they're related to vagal innervation. The authors perform prospective control longitudinal randomized study enrolling 62 patients in two groups, AF nest group that is 32 patients with functional or reflex Bradyarrhythmias or vagal AF treated with AF Nest ablation and a control group, 30 patients with anomalous bundles, ventricular prematures, atrial flutter, AV nodal reentry and atrial tachycardias who were treated with a conventional ablation approach. In the AF nest group, ablation was delivered at the AF nest detected by fragmentation or fractionation of the endocardial electrograms and by 3D anatomical location of the ganglionated plexus. Vagal response was evaluated before, during and post ablation by five seconds non-contact vagal stimulation at the jugular foramen through the internal jugular veins, analyzing 15 seconds mean heart rate, longest RR pauses and AV block. A pre-ablation non-contact vagal stimulation due sinus pauses, asystole, and transient AV block in both groups showing a strong vagal response. Post-ablation non-contact vagal stimulation in the AF nest showed complete abolishment of the cardiac vagal response in all cases, P In our next paper, Domingo Uceda and Xiang-Yang Zhu and associates examined whether progressive increases in pericardial fat volume and inflammation, prospectively dampens the heart rate variability in hypercholesterolemic pigs. The author studied wild type or PCSK9 gain-of-function Ossabaw mini-pigs in-vivo before and after three and six months of a normal diet. Four in the wild type group and six in the PKSK9 group. Or high-fat diet, wild type three, in PCSK9, six. At diet completion, they found that the hypercholesterolemic PCSK9 had significantly depressed heart rate variability, and both high fat diet groups had higher sympathovagal balance compared to the normal diet. P In our next paper, Konstantinos Aronis and Rheeda Ali and associates examined myocardial conduction velocity and myocardial fibrosis density on late gadolinium enhanced cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy. The author studied six patients with ischemic cardiomyopathy undergoing VT ablation, and five with structurally normal left ventricle serving as controls. All patients underwent late gadolinium enhanced cardiac magnetic resonance, and electroatomic mapping in sinus rhythm. Median conduction velocity in ischemic cardiomyopathy patients and controls was 0.41 meters per second and 0.65 meters per second respectively. In ischemic cardiomyopathy patients conduction velocity in areas with no visible fibrosis was 0.81 meters per second. For each 25% increase in normalized late gadolinium-enhanced intensity conduction velocity decreased by 1.34 fold. Dense scar areas have an average of 1.97 to 2.66 fold slower conduction velocity compared to areas without dense scar. Ablation lesions that terminate at VT were localized in areas of slow conduction on conduction velocity maps. The authors found that conduction velocity is inversely associated with late gadolinium enhanced cardiac magnetic resonance fibrosis density in patients with ischemic cardiomyopathy. In our next paper, Bence Hegyi and associates examined whether the IKR current or the sodium L-type current play counterbalancing roles in the ventricular action potential. The authors found that a comparable amount of net charge carried by these two currents during the physiological action potential, suggesting that the outward potassium current via IKR and the inward sodium current via the sodium L-type current are in balance during physiological repolarization. These two current integrals in control myocytes were highly correlated, but this close correlation was lost in heart failure myocytes. Pretreatment with E-4031 to block IKR mimicking long QT syndrome 2, or ATX II to impair a sodium channel inactivation mimicking long QT3 prolong the action potential duration. However, using GS-967 to inhibit sodium L-type current sufficiently restored action potential control to control in both cases. Furthermore, the sodium L-type inhibition significantly reduced the beat to beat and short-term variabilities of action potential duration. Sodium L-type current inhibition also restored action potential duration in repolarization stability in heart failure. Conversely, pretreatment with GS-967 shortened action potential duration mimicking short QT syndrome and E-4031 reverted APD shortening. Furthermore, the amplitude of action potential alternans occurring at high pacing frequency was decreased by sodium L-type inhibition, increased by IKR inhibition and restored by a combination of sodium L-type and IKR inhibitions. The author suggests that targeting these two ionic currents to normalize or balance may have significant therapeutic potential in heart diseases with repolarization abnormalities. In our next paper, Derek Chew and associates examine the impact of the duration between first diagnosis of atrial fibrillation and ablation or diagnosis to ablation time on AF recurrence following catheter ablation by conducting a systematic review and meta analysis of observational studies. They found six studies that met inclusion criteria with a total of 4,950 participants undergoing atrial fibrillation ablation for symptomatic AF. A shorter diagnosis to ablation time of one year or less was associated with a lower relative risk of AF recurrence compared to diagnose to the ablation time greater than one year. Relative risk 0.73 P The authors concluded that the duration between time to first day of AF and AF ablation is associated with an increased likelihood of atrial fibrillation ablation procedural success. In a research letter by Kapuaola Gellert and associates, 48 hour continuous ECG was found to have an association between sleep apnea and atrial fibrillation in the community-based population study, the ARIC study. In a special report, Francesco Notaristefano reported that the risk of device pocket hematoma 10 days after CIED surgery showed an independent association with the type of interventional procedure such as device implementation, odds ratio 3.5, implantable cardioverter defibrillator 4.4, cardiac resynchronization therapy, odds ratio 11.7, and antithrombotic treatment, but not with novel oral anticoagulants. In an interesting review article Nicholas Tan and associates describe the current and future perspectives of left bundle branch block. That's it for this month. We hope that you'll find the Journal to be the go-to place for everyone interested in the field. See you next time. Copyright American Heart Association 2020.
Circulation: Arrhythmia and Electrophysiology March 2020 Issue16.12.2020 (00:16:05)
Paul J. Wang: Welcome to the monthly podcast On the Beat for circulation, arrhythmia, and electrophysiology. I'm Dr. Paul Wang, Editor In Chief, with some of the key highlights from this month's issue. Elizabeth Wang and Associates examined the relationship between acute precipitants of atrial fibrillation and long-term recurrence of atrial fibrillation, AF, from a multi-institutional, longitudinal electronic medical record database. Among 10,723 patients with newly diagnosed Afib, age 67.9 years, 41% women, the authors found that 19% had an acute AF precipitant, the most common of which were cardiac surgery in 22%, pneumonia in 20% and non-cardiothoracic surgery in 15%. The cumulative incidence of AF recurrence at five years was 41% among individuals with a precipitant, compared to 52% in those without a precipitant. Adjusted hazard ratio 0.75 P In the next paper, Jacob Koruth and associates examine the effect of pulse field ablation on the esophagus in a novel in-vivo porcine esophageal injury model. The authors studied 10 animals under general anesthesia while the lower esophagus was deflected towards the inferior vena cava using an esophageal deviation balloon and ablation was formed from within the inferior vena cava at areas of esophageal contact. Six animals received eight pulse field ablation applications per site and four animals received six clusters of irrigated radio frequency ablation applications at 30 Watts for 30 seconds. All animals survived to 25 days, sacrificed, and the esophagus was submitted for a pathological examination including 10 discreet histological sections of the esophagus. The authors found that zero out of six pulse field ablation animals demonstrated esophageal lesions while esophageal injury occurred in all four radio frequency ablation animals, P = 0.005. A mean of 1.5 mucosal lesions per animal, length 21.8 millimeters with 4.9 millimeters were observed, including one esophageal pulmonary fistula, and deep esophageal ulcers in the other animals. Histological examination demonstrated tissue necrosis surrounded by an acute and chronic inflammation and fibrosis. The necrotic radio frequency ablation lesions involved multiple esophageal tissue layers with evidence of arteriolar medial thickening and fibrosis of peri-esophageal nerves, abscess formation and full thickness esophageal wall disruption were seen in the areas of perforation or fistula. In our next paper, Peter Noseworthy and associates examine whether the ability of deep learning algorithms to detect low left ventricular ejection fraction using the 12 lead electrocardiogram varies by race or ethnicity. The authors used a retrospective cohort analysis and included 97,829 patients with paired electrocardiograms and echocardiograms and used a convolutional neural network to identify patients with a left ventricular ejection fraction less than or equal to 35% from the 12 lead electrocardiogram. The convolutional neural network was previously derived in a homogeneous population, 96.2% non Hispanic white, N = 44,959 which demonstrated consistent performance to detect low left ventricular ejection fraction across a range of racial ethnic subgroups in a separate cohort of 52,870 patients (Non-Hispanic white 44,524 patients with an AUC of 0.93; Asian 557 with an AUC of 0.96; Black/African American N = 651 with an AUC of 0.937; in Hispanic/Latino N = 331 AUC of 0.937; in Native American/Alaskan N = 223 AUC of 0.938). In secondary analysis, a separate neural network was able to discern racial subgroup category, Black/African American AUC 0.84 and white non-Hispanic AUC 0.75 in a five-class classifier. In a network trained only in non-Hispanic whites, from the original derivation cohort, performed similarly well across a range of racial ethnic subgroups in the testing cohort with at least an AUC of 0.93 in all racial ethnic subgroups. The authors concluded that while ECG characteristics vary by race, this did not impact the ability of a convolutional neural network to predict low left ventricular ejection fraction from the ECGs. They recommend reporting of performance against diverse ethnic, racial, age, and gender groups for all new artificial intelligent tools. In our next paper, Benjamin Shoemaker and associates examine the association between atrial fibrillation or AF genetic susceptibility and recurrence after de novo AF ablation, using a comprehensive polygenic risk score for AF in the 10 centers from the AF genetics consortium. AF genetic susceptibility was measured using a previously described a polygenic risk score, N = 929 snips. The overall arrhythmia recurrence rate between 3 and 12 months was 44% in 3,259 patients. Patients with a higher AF genetic susceptibility were younger and have fewer clinical risk factors for atrial fibrillation. Persistent atrial fibrillation has a ratio of 1.39, left atrial size has a ratio of 1.32, and left ventricular ejection fraction per 10% has a ratio of 0.88, were associated with increased risk of occurrence. In unit varied analysis, the authors found that AF genetic susceptibility had a hazard ratio of 1.08 P = 0.07 and in multivariate analysis hazard ratio 1.06 with a P value 0.13. In our next paper, Mohit Turagam and associates reported the outcomes of the first inhuman value trial, which uses low intensity collimated ultrasound or LICU guided anatomical mapping in robotic ablation to isolate the pulmonary veins for atrial fibrillation ablation. In 52 paroxysmal atrial fibrillation patients, ultrasound M-mode based left atrial anatomies were successfully created and ablation was performed under robotic control along an operated defined lesion path. The operatives found that acute pulmonary vein isolation was achieved in 98% of pulmonary veins using LICU only in 77% of pulmonary veins and requiring touch-up with a standard radio frequency ablation catheter in 23% of the pulmonary veins. The touch up rate decreased to 5.8% in patients undergoing LICU ablation with an enhanced software. Freedom from atrial relational recurrence was 79.6% at 12 months or 92.3%, 12 out of 13 patients with the enhanced software. Major adverse events occurred in three patients or 5.8%. One had transient diaphragmatic paralysis, one vascular access complication and one had transient ST segment elevation from air-embolism without sequelae. In our next paper, Miguel Rodrigo and associates mapped electrical patterns of disorganization and reasons of reentrant activity in atrial fibrillation, or AF, from the body surface using electrocardiographic imaging. The author examined the bi-atrial intracardiac electrograms of 47 patients at ablation (30 persistent, 29 males, age 63 years) obtained using 64-pole basket catheters while simultaneously recording 57-lead body surface electrocardiogram. The authors found the body surface mapping showed greater atrial fibrillation organization near intracardiac detected drivers and elsewhere, both in phase singularity density in numbers of drivers, they found that complexity defined as a number of stable AF reentrant sites was concordant between the noninvasive and invasive methods. The subset receiving targeted ablation, AF complexity, showed lower values in those in whom AF terminated than in those in whom AF did not terminate, P In our next paper, Krystien Lieve and Veronica Dusi and associates examined whether heart rate reduction immediately after exercise is regulated by autonomic reflexes, particularly vagal tone and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia, CPVT. In a retrospective observational study, the authors studied 187 patients mean age 36 years, 68 or 36% symptomatic before diagnosis, pre-exercise stress test heart rate and maximal heart rate were equal amongst symptomatic and asymptomatic patients. Patients that were symptomatic prior to diagnosis had a greater delta HRR one prime after a maximum exercise, 43 versus 25, P In our next paper, Balvinder Handa and associates examined whether low spatial resolution, sequentially acquired data can be used to examine the global fibrillation organization, characterizing dominant propagating patterns and identifying rotational drivers. The authors employed ranger causality analysis, an econometric tool for quantifying causal relationships between complex time series, which was developed as a novel fibrillation mapping tool and adapted to low spatial resolution sequentially acquired data. Ventricular fibrillation, or VF, optical mapping was performed and Langendorff-perfused Sprague Dawley rat hearts, N = 18. And novel algorithms were developed using Granger causality analysis to quantify causal dependence of neighboring signals and plot Granger causality analysis vectors, quantify global organization using causality pairing index, a measure of neighboring causal signal pairs, and localize rotational drivers by quantifying the circular interdependence of neighboring signals with the circular interdependence value. Granger causality analysis based mapping tools were optimized for low spatial resolution by down sampled optical mapping data validated against high resolution phase mapping analysis and further tested in previous VF optical mapping recordings of coronary perfused donor heart LV wedge preparations, N = 12, and adaptive for sequentially acquired intracardiac electric Grande during human persistent atrial relation mapping, N=16. The authors found that global VF organization quantified by causality pairing index showed a negative correlation at progressively lower resolutions in organized VF with high causality pairing index values. Ranger causality analysis vector mapping characterize dominant propagating patterns and localized stable rotational drivers with the circular interdependence value showing a significant difference in driver versus non driver regions, P = 0.0002. These findings were further confirmed in human VF in persistent atrial fibrillation, a positive correlation was found between causality peri-index and presence of stable rotational drivers. 50% of patients had rotational drivers with a low incidence of 0.9 rotational drivers per patient. In a special report, Piotr Futyma and associates report on the use of bipolar radiofrequency ablation of ventricular arrhythmias originating in the vicinity of the His bundle. Bryce Alexander and associates report in a research letter the patient acceptance of cybersecurity upgrade in ICDs. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.
Circulation: Arrhythmia and Electrophysiology February 2020 Issue09.04.2020 (00:12:57)
Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Ling Kuo and associates examine the association between left atrial high-resolution late gadolinium enhancement on cardiac magnetic resonance and electrogram abnormalities in patients with atrial fibrillation or AF. They found that in 40 AF patients age 63.2 years with a mean of 1312 electrogram points per patient. Lower bipolar voltage was associated with higher signal intensity Z score in patients who had undergone previous ablation coefficient equals -0.049 P P = 0.7. Left atrial high-resolution late gadolinium enhancement activation delay was associated with signal intensity z-score in patients with previous ablation, signal intensity Z score coefficient = 0.004, P P = 0.03, and left atrial high-resolution late gadolinium enhancement coefficient 0.035, P The authors concluded that the association of left atrial late gadolinium enhancement with voltage is modified by ablation in ablation naive patients. Atrial late gadolinium enhancement is associated with electrogram fractionation even in the absence of voltage abnormality. In our next paper, Laila Staerk and associates examine the associations between 85 protein biomarkers and incident atrial fibrillation or AF in patients 50 years of age or greater, from the Framingham Heart Study Offspring and Third Generation cohorts. Out of 3378 participants, 54% women, mean age 61.5 years, 401 developed AAF over a mean follow-up of 12.3 years. They observed a lower hazard of incident atrial fibrillation associated with mean higher levels of incident like growth factor hazard ratio per one standard deviation increment in protein level equals 0.84, and higher hazard ratio of incident atrial fibrillation associated with higher mean levels of both insulin-like growth factor-binding protein and N-terminal pro-B-hormone type a natriuretic peptide. In our next paper, Eoin Donnellan and associates examine changes in atrial fibrillation or AF type following bariatric surgery in 220 morbidly obese patients body mass index ≥40 kilograms per meter square. They observed a reduction in body mass index following bariatric surgery from 49.7 to 37.2 kilograms per meter square. Weight loss was greatest in the gastric bypass group with a mean percentage loss of 25% compared to 19% in patients underwent sleeve gastrectomy, and 16% following gastric banding. P P = 0.004. They found that on Cox proportional hazards analysis percent weight loss was significantly associated with AFib reversal, P = 0.0002. In our next paper, Thomas Pezawas and associates examine the role of diastolic function assessment to predict arrhythmic death. They prospectively enrolled 120 patients with ischemic, 60 patients with dilated cardiomyopathy, and 30 patients with normal left ventricular ejection fraction. After an average of 7.0 years, arrhythmic death or resuscitated cardiac arrest was observed in 28 (or 13.3%) and 33 (or 15.7%) of patients respectively. Non-arrhythmic death was found in 41 (or 19.5%) of patients. On Kaplan Meier analysis patients with dysfunction grade III had the highest risk of arrhythmic death or resuscitated cardiac arrest, P This finding was independent from the degree of left ventricular ejection fraction and was observed in patients with ejection fraction ≤ 35%, P = 0.001 and with a left ejection fraction > 35%, P = 0.014. Non-arrhythmic mortality was highest and patients with dysfunction grade III. This was true for patients with left ventricular ejection fraction ≤to 35%, or > 35%. In an adjusted model for relevant confounding factors, grade III dysfunction was associated with a 3.5-fold, increased risk of arrhythmic death or resuscitated cardiac arrest in the overall study population hazard ratio of 3.52, P In our next paper, because asthma and atrial fibrillation share an underlying inflammatory pathophysiology, Matthew Tattersall and associates hypothesize that persistent asthmatics would be at higher risk for developing atrial fibrillation or AF and this association would it be attenuated by adjust for baseline markers of systemic inflammation. The authors examined 6,615 patients mean age 62.0 years, 47% male, 27% African American, 12% Chinese, 22% Hispanic. In the MESA, or multiethnic study of atherosclerosis study, a prospective longitudinal study of adults free of cardiovascular disease at baseline, AF incident rates were 0.11 events per ten person-years for non-asthmatics, 0.11 events per ten person-years for intermittent asthmatic, and 0.19 events per ten person-years for persistent asthmatic. Log rank P value = 0.008. In risk factor adjusted models, persistent asthmatic had a greater risk of incident atrial fibrillation has a ratio of 1.49 P = 0.03. Interleukin six tumor necrosis factor and D-dimer predicted incident atrial fibrillation, but the relationship between asthma and incident AFib was not attenuated by adjustment for any inflammation marker. In our next paper, Deepak Pasupula and associates examine the survival trends in out-of-hospital cardiac arrest patients before and after the introduction of the 2010 AHA CPR guidelines in the United States. They sought to assess survival trends in out-of-hospital cardiac arrest patients before and after the introduction of the 2010 AHA CPR guidelines. Using the retrospective observational study from the National Emergency Department sample, they found that the change in the 2010 AHA CPR guidelines was associated with only small improvement in Emergency Department survival and survival-to-discharge trends among US out-of-hospital cardiac arrest patients, and only one out of six out-of-hospital cardiac arrest patients survive to discharge. They studied 1,282,520 patients presenting to the emergency department after out-of-hospital cardiac arrest, meaning age 65.8 years, 62% males. The average survival after emergency department care increased only 1%, 22% before 2010 in 23% after 2010, P In our next paper, Julian Stewart and associates examine the changes in cardiac output, inappropriate sinus tachycardia, postural tachycardia syndrome, vasovagal syncope in the presence of symptomatic excessive heart rate. They studied 12 healthy controls, nine inappropriate sinus tachycardia, 30 vasovagal syncope and 30 postural tachycardia syndrome patients, selected randomly by disorder. Subjects were instrumented for electrocardiography, beat-to-beat blood pressure, respiratory rate, CO-Model flow algorithm, and central blood volume from impedance cardiography. At baseline heart rates, diastolic and mean arterial pressure in inappropriate sinus and tachycardia postural tachycardia syndrome were higher versus controls. Upright mean heart rate increased most in postural tachycardia syndrome. Then in inappropriate sinus tachycardia, in vasovagal syncope with diverse changes in cardiac output, systemic or vascular resistance, and central blood volume. Each patient grouping was separately and collectively analyzed for heart rate change following transition from in-phase to anti-phase as heart rate increased. Heart rates transition =115 for inappropriate sinus tachycardia, 123 for postural orthostatic tachycardia syndrome and 124 for vasovagal syncope. P=ns. Controls never reached the transitional heart rate. The authors concluded that excessive heart rate independently and equivalently reduces upright cardiac output in inappropriate sinus tachycardia, vasovagal and postural tachycardia syndrome patients. In our next paper, Adam Graham, Michele Orini, and associates examined the accuracy of non-invasive ECG imaging or ECGI in localizing the origin of arrhythmias during catheter ablation of ventricular tachycardia and structurally abnormal hearts. In 18 patients, 29 ventricular tachycardias were examined. The distance between the site of origin and sites of earliest activation in ECGI were 22.6 millimeters with a first quartile of 13.9, and third quartile of 36.2 millimeters. ECGI mapped ventricular sites of origin onto the correct AHA segment with a higher accuracy than a validated 12-lead ECG algorithm, 83.3% versus 38.9%, P=0.015. In a research letter, Shadi Yaghi and associates report about the ability of left atrial appendage morphology to improve prediction of stagnant flow and stroke risk in atrial fibrillation. In an interesting review article, Charles Swerdlow and associates provide an in depth look at how impedance may provide insights into lead performance. That's it for this month. We hope that you will find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.
Circulation: Arrhythmia and Electrophysiology January 2020 Issue03.04.2020 (00:16:47)
Paul J. Wang: Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief with some of the key highlights from this month's issue. In our first paper in the real time mapping of AF drivers RADAR study, Subbarao Choudry and associates examined in a single arm first in human investigator-initiated FDA IDE study, a novel system for real time, high resolution identification of atrial fibrillation, AF drivers, in persistent or long-standing persistent AF. They enrolled 64 subjects at four centers, 73% male age, 64.7 years, BMI 31.7. LA size 54. Longstanding AF, 83% longstanding persistent, 17%. prior AF ablation, 41%. After 12.6 months of follow-up, 68% remained AF free off all antiarrhythmics. 74% remained AF free and 66% remained AF, AT and A-flutter free on or off antiarrhythmic drugs. AF terminated with atrial fibrillation ablation in 35 patients, 55% overall. And in 23 out of 38, 61% of de novo ablation patients. For patients with AF termination during atrial ablation, 82% remained AF free and 74% AF, AT or A-flutter free during follow-up on or off antiarrhythmic drugs. Patients undergoing first time AFib ablation had higher rates of freedom from AF than the redo group. In our next paper, David Briceño and associates examined 19 consecutive patients presenting with left bundle branch block ventricular tachycardia in the setting of arrhythmogenic right ventricular cardiomyopathy, ARVC, with procedures separated by at least nine months and a mean of 50 months. The authors found there was no significant progression of voltage bipolar 38 centimeters squared versus 53 centimeters squared, p=0.09 or unipolar 116 centimeters squared versus 159 centimeters squared, p=0.36 for the entire group. There was a significant increase in right ventricular RV volumes, percentage increase 28%. 206 milliliters versus 263 milliliters, P less than 0.001 for the entire study population. Larger scars at baseline but not changes over time were associated with a significant increase in RV volume, p=0.006 for bipolar and p=0.03 for unipolar. Most patients with progressive RV dilatation, 57%, had moderate in two patients or severe in six patients, tricuspid regurgitation recorded either at initial or repeat ablation procedure. The authors found that in patients with ARVC presenting with recurrent ventricular tachycardia, more than 10% increase in right ventricular endocardial surface area of bipolar voltages consistent with scar is uncommon during intermediate follow-up. Most recurrent ventricular tachycardias are localized to regions of prior defined scar. In our next paper, Susan Heckbert and associates examined detection of atrial fibrillation in 1,556 individuals participating in an ancillary study involving ambulatory ECG monitoring part of the cross-sectional analysis in the multiethnic study of atherosclerosis, MESA, a community based cohort study that enrolled 6,814 Americans free of clinically recognized cardiovascular disease in 2000 to 2002. Among 1,556 participants, 41% were white, 25% African American, 21% Hispanic, 14% Chinese, 51% were women mean age 74 years. The prevalence of clinically detected atrial fibrillation after 14.4 years follow-up was 11.3% in whites, 6.6% in African Americans, 7.8% in Hispanics and 9.9% in Chinese and was significantly lower in African Americans than in whites in both unadjusted and risk factor adjusted analyses, p less than 0.001. By contrast, in the same individuals, the proportion of monitor detected atrial fibrillation using a 14-day ambulatory ECG monitor was similar in the four race or ethnic groups. 7.1%, 6.4%, 6.9% and 5.2% compared with white, all p greater than 0.5. The authors concluded that the prevalence of clinically detected atrial fibrillation was substantially lower in African Americans than white participants with or without adjustments for atrial fibrillation risk factors. However, unbiased atrial fibrillation detection by ambulatory monitoring the same individuals reveal little difference in the proportion with atrial fibrillation by race, ethnicity, supporting the hypothesis of differential detection by race, ethnicity in the clinical recognition of atrial fibrillation. In our next paper, Maria Teresa Barrio-Lopez and associates examined the presence of epicardial connections between pulmonary veins and other anatomical structures. The authors considered an epicardial connection was present if one, the first pass around the pulmonary vein antrum did not produce pulmonary vein isolation. And two, subsequent atrial activation during pulmonary vein pacing showed that the earliest site was located away from the ablation line and later activation sites were obscured near the ablation line. Out of the 534 patients included, 72 or 13.5%, were found to have 81 epicardial connections. There was a significant association between the presence of epicardial connections in structural heart disease, 15.3% in patients without epicardial connections versus 36.5% in patients with epicardial connections, p less than 0.001. In patent foramen ovale, 4.6% versus 13.5%, p=0.002. The presence of a left common trunk was significantly associated with the absence of epicardial connection. 29.6% in patients without epicardial connections versus 16.2% in patients with epicardial connections, p=0.014. Patients with epicardial connections had a lower acute success of pulmonary vein isolation compared to patients with epicardial connection, 99.1% versus 86.1%, p less than 0.001. After adjusting for age, sex, type of atrial fibrillation, left atrial area, hypertension, structural heart disease, presence of left common trunk, patent foramen ovale and time for atrial fibrillation and diagnosis to the ablation, the authors found a significantly higher risk of atrial tachyarrhythmia recurrences in patients with epicardial connections compared to patients without epicardial connections, hazard ratio 1.7, p=0.04. In our next paper, Benzy Padanilam and associates examined the role of premature His complexes to differentiate AV nodal reentry tachycardia from atrioventricular reentry tachycardia high output pacing at the distal His location delivered premature His complexes. Atrioventricular reentrant tachycardia was predicted when late premature His complexes perturbed tachycardia or when early premature His complexes led to atrial advancement by amount equal or greater than the degree of premature His complex prematurity. Among the 73 SVTs, the test accurately predicted atrioventricular reentry tachycardia, n=29 in AV nodal reentry tachycardia, n=44 in all cases. Late premature His complexes advanced the circuit in all 29 atrioventricular reentry tachycardias in none of the AV nodal reentry tachycardias, sensitivity and specificity 100%. With earlier premature His complexes, the degree of atrial advancement was equal or greater than the premature His complex prematurity in 26 out of 29 atrioventricular reentrant tachycardia and none of the AV nodal reentrant tachycardias, 90% sensitivity and a 100% specificity. The mean prematurity of the premature His complex required to perturb AV nodal reentry tachycardia was 48 milliseconds, range 28 to 70 milliseconds. And the advancement less than the prematurity of the premature His complex, mean 32 milliseconds range, 18 to 54 milliseconds. In our next paper, Masateru Takigawa and associates examined the recurrence rate and mechanisms of atrial fibrillation ablation related atrial tachycardia recurrence among 147 patients with atrial tachycardias treated with arrhythmia system. 46.3% had recurrence at a mean of 4.2 months and 44 patients received a redo procedure. Atrial tachycardia circuits in the first procedure were compared to those in the redo procedure. Although mappable atrial tachycardias were not observed in seven patients, 68 atrial tachycardias were observed in 37 patients during the first procedure, perimitral flutter in 26 patients, roof-dependent macroreentrant atrial tachycardia in 18, peritricuspid flutter in 10, non-macro atrial tachycardia in 14 and focal atrial tachycardia in three. During the redo atrial tachycardia procedure, 54 atrial tachycardias were observed in 41 patients, perimitral flutter in 24, roof-dependent macroreentrant atrial tachycardia in 14, peritricuspid flutter in one, non-macroreentrant tachycardia in 14, and focal atrial tachycardia in one. Recurrence of perimitral flutter and roof-dependent macroreentrant atrial tachycardia were observed in 57.7% and 44.4% respectively, while peritricuspid flutter did not recur. Either the same focal atrial tachycardia nor the same non-macroreentrant tachycardia were observed except in one case with septal scar related to biatrial tachycardia. Epicardial structure related to atrial tachycardia were involved in 18 out of 24 or 75% in perimitral flutter, in 28.6% in roof-dependent macroreentry atrial tachycardia, in 28.6% in non-macroreentry tachycardia. Out of the 21 patients with a circuit including epicardial structures, six patients treated with ethanol infusion in the vein of Marshall did not show any atrial tachycardia recurrence although 53.3% treated with radiofrequency showed atrial tachycardia recurrence, p=0.04. In our next paper, Yaya Yu, Xuecheng Wang and associates compared the incidence and characteristics of ablation related asymptomatic cerebral emboli between high resolution diffusion weighted DWI and conventional DWI image. They examined 55 consecutive atrial fibrillation ablation patients undergoing high resolution DWI one day prior to ablation and repeated high resolution DWI and conventional DWI within 48 hours of post ablation. The authors found that high resolution DWI revealed a higher incidence of acute asymptomatic cerebral emboli compared to conventional DWI, 67.3% versus 41.8%, p less than 0.001. And significantly more asymptomatic cerebral emboli, 106 versus 45 lesions, p=0.001. For asymptomatic cerebral emboli, seen on both scans, the size measured by high resolution DWI was larger, 5.42 versus 4.21 millimeters, p less than 0.001. No patients had any impaired neurocognitive performance during follow-up. Impaired left ventricular ejection fraction, p=0.012 and low interoperative activated clotting time ACT p=0.009, level was associated with occurrence of asymptomatic cerebral emboli in a multivariate analysis. In our next paper, Ahmed AlTurki and Mariam Marafi and associates performed a systematic review and meta-analysis to assess the risk of stroke, myocardial infarction and death following postoperative atrial fibrillation after non-cardiac surgery. The authors included 28 studies, enrolling 2,612,816 patients in their final analyses. At one month, in ten studies, postoperative atrial fibrillation with associated with approximately three-fold increased risk of stroke, odds ratio 2.82, p less than 0.001. Postoperative atrial fibrillation was associated with ≈4-fold increase in the long-term risk of stroke, odds ratio 4.12, p ≤ to 0.001. In eight studies with 12 months or greater follow-up, there was a significant increase in the risk of stroke and myocardial infarction associated with postoperative atrial fibrillation, odds ratio 3.44, p value, p less than 0.001. And odds ratio for myocardial infarction 4.02, p less than 0.001. Postoperative atrial fibrillation was associated with a threefold increase in all of cause mortality 30 days, 15.0% versus 5.4%, odds ratio 3.36. In a research letter, Zhiyong Qian, Xiaofeng Hou, Yao Wang and associates validated physiological left bundle branch block pacing using high density ventricular mapping in a swine model. In another research letter by Shinsuke Miyazaki and associates, the authors examined whether the durability of pulmonary vein isolation can be predicted by the time to isolation in second generation cryoballoon ablation. That's it for this month. We hope that you will find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.
Circulation: Arrhythmia and Electrophysiology December 2019 Issue03.04.2020 (00:16:53)
Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief with some of the key highlights from this month's issue. In our first paper, Jacob Koruth and Associates examine the ability to produce ablation lesions using pulse field ablation, which is tissue specific and non-thermal in swine compared to radio frequency ablation. All 46 targeted veins were successfully isolated on the first attempt in all cohorts. Pulmonary vein isolation durability was assessed in 28 veins, including the SVC. Durability was higher in the pulsed field ablation bipolar group, 18 out of 20 in the bipolar group, 10 out of 18 in the monopolar group, and 3 out of 6 in the radio frequency group. P = 0.002. Transmit morality rates were similar across groups with evidence of nerve damage only with radiofrequency. In our next paper, Vivek Reddy and Associates is part of the multicentered first-in-human study, RADIANCE, examine the ability of a novel compliant radio frequency balloon catheter with 10 irrigated flexible electrodes to simultaneously and independently deliver energy. At four sites, 39 patients with paroxysmal atrial fibrillation underwent pulmonary vein isolation using energy delivery simultaneously from all electrodes up to 30 seconds posteriorly, and 60 seconds anteriorly. 152 of 152 targeted pulmonary veins were isolated. 79.6% with a single application. Electrical reconnection occurred in only 7 out of 150 pulmonary veins or 4.7% upon adenosine isoproterenol challenge. Esophageal temperature was monitored in all patients. The esophagus was also mechanically deviated in ten patients. At three months, imaging revealed no pulmonary vein stenosis and early atrial recurrence occurred in only 10 out of 39 or 25.6% of patients. In our next paper Takeshi Kitamura and Associates examine the effect of substrate based ventricular tachycardia ablation targeting local abnormal ventricular activity on recurrent ventricular fibrillation events in patients with structural heart disease. In a retrospective two center study of a total of 686 patients with incident ventricular tachycardia ablation procedure targeting local abnormal ventricular activity, 21 patients, age 57 years left ventricular ejection fraction 30%, had both ventricular tachycardia and ventricular fibrillation. A total of 80 ventricular fibrillation events were recorded in the ICD logs, the six months preceding ablation. Complete and partial local abnormal ventricular activity elimination was achieved in 11 or 52%, in 10 or 58% of patients respectively. Catheter ablation was associated with a highly significant reduction in ventricular fibrillation recurrences. P less than 0.0001 which were limited to three or 14 patients at six months. The total number of ventricular events therefore, decreased from 80 to three with a median of 1.0 to 0.0 in the six months prior to and following ablation respectively. The reduction in ventricular fibrillation events was significantly greater in patients with catheter ablation compared to 21 match controls during a 6- month period preceding and following a baseline assessment. The authors concluded that substrate guided ventricular tachycardia ablation, targeting local abnormal ventricular activity, may be associated with a significant reduction in recurrent ventricular fibrillation, suggesting that ventricular tachycardia and ventricular fibrillation share overlapping arrhythmogenic substrate in patients with structural heart disease. In our next paper, Feng Hu and Associates examine the effect of right anterior ganglion aided plexi ablation on vagal response during circumferential pulmonary vein isolation. 80 patients with paroxysmal atrial fibrillation who underwent first time ablation were prospectively enrolled and randomly assigned to two groups. Group A (n = 40) circumferential pulmonary vein isolation starting with the right pulmonary veins at the right anterior ganglion plexi site. In group B (n = 40) circumferential pulmonary vein isolation starting with the left pulmonary veins first, and the last ablation site being the right anterior ganglionic plexi site. During circumferential pulmonary vein isolation, the positive vagal response was observed in only one patient in group A, in 25 patients in group B. P less than 0.001. A total of 21 patients with positive vagal response in group B needed temporary ventricular pacing during the procedure, while the only patient with positive vagal response in group A did not need temporary ventricular pacing, P less than 0.001. Compared with baseline basic cycle length, sinus node recovery time, and AV node Wenckebach pacing cycle length were decreased significantly after pulmonary vein isolation procedure in both groups, all P less than 0.05 and without differences between the two groups. In our next paper, Karl-Heinz Kuck and Associates reported the results of the randomized atrial fibrillation management and congestive heart failure with ablation, AMICA trial. Patients with persistent or long standing persistent atrial fibrillation and left ventricular ejection fraction ≤ 35%, were randomly allocated to catheter ablation of atrial fibrillation or best medical therapy. The primary study endpoint was the absolute increase in left ventricular ejection fraction from baseline at one year. Pulmonary vein isolation was the primary ablation approach. Best medical therapy comprised rate or rhythm control. All patients were discharged after index hospitalization with a cardioverter defibrillator or resynchronization therapy defibrillator implanted. This study was terminated early for futility of 140 patients, 65 years, 90% men available for endpoint analysis, 68 and 72 patients were assigned to ablation in best medical therapy respectively. At one year, left ventricular ejection fraction had increased in ablation patients by 8.8% and in medical therapy by 7.3%, P = 0.36. Sinus rhythm was recorded on 12-lead electrocardiograms at 1 year. In 61 of 83 ablation patients, or 73.5%, and 42 out of 82 best medical therapy patients or 50%. Device-recorded atrial fibrillation at one year, was 0% or maximally 50% of the time in 28 of 39 ablation patients, so 72% in 16 out of 36 best medical therapy patients or 44%. There were no differences in secondary endpoint outcomes of six-minute walk tests, quality of life or NT pro BNP between the ablation and best medical therapy patients. In our next paper, Dhanunjaya Lakkireddy and Associates examined the association between unrecognized inflammation and premature ventricular contraction. In a single-center prospective study, 107 patients with 5,000 or more PVCs per 24 hours, which were symptomatic, and no known ischemic heart disease, underwent combination of laboratory testing including FDG or 18F-fluorodeoxyglucose pet scan, cardiac magnetic resonance imaging, and biopsy. The mean age cohort was 57 years, 41% were males, a left ventricular ejection fraction was 47%. Positive pet scan was seen in 51%, and 51% had preserved left ventricular function. Based on clinical profile, FDG pet imaging, cardiac magnetic resonance imaging, and histological data, 58% received immunosuppressive therapy alone and 25% received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% over a mean follow-up of six months in patients with left ventricular systolic dysfunction, 37% showed a mean improvement in left ventricular ejection fraction of 13%. In our next paper, Clare Atzema and Associates examined the association of rapid (3 days), early (7 days), and basic (30 days), outpatient physician follow-up with short and long-term outcomes in atrial fibrillation patients discharged from an emergency department. In 163 emergency departments in Ontario, Canada with a diagnosis of atrial fibrillation, they use landmark analysis with propensity score matching. In the 10,657 patients with rapid follow-up care who are propensity score matched to a patient with follow-up between 4 and 7 days, the hazard of a return emergency visit was reduced by 11%. In the 17,234 patients with early follow-up who are matched to a patient with care between 8 and 30 days, the 1-year mortality was 11% lower, and 1-year hospitalization was 6% lower. Relative to no 30-day care, basic follow-up care was associated with an increased hazard ratio of 90-day hospitalization, but no longer was associated with mortality. The authors concluded that compared to follow-up care between 8 and 30 days, follow-up care within a week after discharge from an emergency department with atrial fibrillation, was associated with a reduction in death, in hospitalization at 1 year, in association not present with 30-day follow-up. In our next paper, James Freeman and Associates evaluate outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding hospitalization in patients undergoing atrial fibrillation ablation compared with a propensity score match cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) I and II registries. Among 21,595 patients, 6% underwent de novo atrial fibrillation ablation. The propensity score matched cohort included 1087 patients who underwent atrial fibrillation matched one-to-one with 1087 patients treated with an antiarrhythmic medication only. There were no significant differences in the risk of all-cause and cardiovascular death in most other major cardiovascular and neurologic events. Atrial fibrillation catheter ablation was associated with an increased risk of all cause hospitalization hazard ratio 1.24 particularly in the 3 months after the procedure. Among those who underwent atrial relation ablation with CHA2DS2 VAS score, 2 for men and 3 for women, 23% had oral anticoagulation discontinued after ablation. Among those with discontinue oral anticoagulation, the median time to discontinuation was 6.2 months. Thus, the authors found no difference in adjusted rates of cardiovascular and all-cause death, between patients treated with atrial fibrillation catheter ablation and antiarrhythmic medications only. In our next paper, Michael Liu and Associates examined R-from-T as a common mechanism of arrhythmia initiation in long QT syndrome. In their study, spontaneous initiation of polymorphic ventricular tachycardia was elicited by gradually ramping up ICa,L to simulate the early phase of sympathetic surge or changing the heart rate, reproducing the different genotype-dependent clinical electrocardiographic features in LQTS type 2 and 3, T-wave alternans was observed followed by premature ventricular complexes. Compensatory pauses occurred resulting in short-long sequences, as ICa,L increased further polymorphic ventricular tachycardia episodes occurred, always proceeded by short-long-short sequences. However, in LQTS type 1 once a PVC occurred, it almost immediately led to an episode of polymorphic ventricular tachycardia. Arrhythmias in LQT2 and 3 were bradycardia dependent, whereas LQT1 was not. In all 3 genotypes, PVCs always originated spontaneously from the steep repolarization gradient region and manifested on ECG as R-on-T. the authors called this mechanism R-on-T to distinguish it from the classic explanation of R-on-T arrhythmogenesis when an exogenous PVC coincidentally encounters a repolarization region. In R-from-T, the PVC and the T wave are causally related, where the steep repolarization gradients combine with enhanced ICa,L leading to the PVCs emerging from the T wave. Since enhanced ICa,L was required for R-from-T to occur, suppressing window ICa,L effectively prevented arrhythmias in all 3 genotypes. In our next paper, Dhani Dharmaprani and Associates hypothesized phase singularity formation and destruction in fibrillation could be modeled as a self-regenerating Poisson renewal processes, producing exponential distributions of inter event times governed by constant rate parameters defined by prevailing properties of each system. The authors studied 5 systems, human persistent atrial fibrillation in 20 cases, tachypaced atrial fibrillation in sheep in 5 cases, rat atrial fibrillation in 4 cases, and rat ventricular fibrillation in 11 cases, as well as computer simulated fibrillation. Phase singularity time to event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of phase singularity formation and destruction were determined. A systematic review is conducted to cross validate with sources from the literature. In all systems phase singularity lifetime and inter formation times were consistent with underlying Poisson renewal processes. The authors conclude that Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation. In our issue, there was a very interesting special report on hypothermia outcomes after transvenous lead extraction complications requiring cardiothoracic surgery by Peter Hu and Associates. In addition, there is a very interesting review of atrial fibrillation mediated cardiomyopathy by Kevin Heist and Associates. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology November 2019 Issue19.11.2019 (00:15:24)
Dr Paul Wang: Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Leroy Joseph and associates examined whether an increase in dietary saturated fat could lead to abnormalities of calcium homeostasis and heart rhythm, by an NADPH oxidase 2, NOX2-dependent mechanism. In mice on high fat diets, they found that saturated fat activates NOX, whereas polyunsaturated fat does not. The high saturated fat diet increased repolarization heterogeneity in ventricular tachycardia, VT inducibility in perfused hearts. Pharmacologic inhibition or genetic deletion of NOX2 prevented arrhythmogenic abnormalities in vivo during high saturated fat diet and resulted in less inducible VT. On the other hand, high saturated fat diet activates calcium calmodulin dependent protein kinase in the heart, which contributes to abnormal calcium handling, promoting arrhythmia. This work suggests that a molecular mechanism links cardiac metabolism to arrhythmia and it suggest that NOX2 inhibitors could be a novel therapy for heart rhythm abnormalities caused by cardiac lipid overload. In our next paper, Misha Regouski and associates examined whether the relationship between endurance exercise and atrial fibrillation, or AF, is dependent on atrial myopathy. They examined six cardiac specific TGFβ1 transgenic and six wild type goats. Pacemakers were implanted in all animals for continuous arrhythmia monitoring and AF inducibility. AF inducibility was evaluated using five separate ten second bursts of atrial pacing. At baseline sustained AF greater than 30 seconds was induced with 10 seconds of atrial pacing in 4 out of 6 transgenic goats, compared to zero out of six wild type controls, P less than 0.05. No spontaneous AF was observed at baseline, three months of progressive endurance exercise up to 90 minutes at 4.5 miles per hour was performed. The authors observed that between two to three months of exercise, three out of six transgenic animals developed self-terminating spontaneous atrial fibrillation compared to zero out of six wild type animals, (P less than 0.05). There was an increase in AF inducibility in both transgenic and wild type animals during the first two months of exercise with partial normalization at three months. These changes in AF susceptibility were associated with a decrease in circulating micro RNA 21 and micro RNA 29 during the first two months of exercise, with partial normalization three months in both transgenic and wild type animals. The authors concluded that endurance exercise appears to increase inducible AF secondary to altered expression of key profibrotic biomarkers that is independent of the presence of an atrial myopathy. In our next paper, Seokhun Yang and associates examined whether there is an association between lifetime exposure to endogenous sex hormone, and incident atrial fibrillation, or AF, in subsequent ischemic stroke. They studied nearly five million natural postmenopausal women aged 40 years or greater without prior history of AF and with breast cancer. The primary end point was incident AF and the secondary end point was subsequent ischemic stroke once AF is developed. During the mean follow up of 6.3 years, shorter total reproductive years ( For the secondary endpoint analysis, the risk of ischemic stroke after AF development significantly decreased with each five-year increment in total reproductive years with less than 30 years as a reference. (Adjusted hazard ratio 0.93, for 30 to 34 years 0.84, for 35 to 39 years is 0.88, for 40 years or greater. P for trend less than 0.001) the authors concluded that women with natural menopause shortened lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. In contrast, prolonged exogenous hormone replacement therapy increased the risk of incident AF. In our next paper, Stephan Hohmann and associates examine the accuracy of electrocardiographic imaging, ECGi, in a closed chest porcine model. A total of 109 endocardial and nine epicardial locations were paced in nine pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal location. (97% versus 79% P=0.01) Absolute distances in space between true and predicted pacing locations were 20.7 millimeters. In the next paper, Ayelet Shapira-Daniels and associates examine the lesion formation produced by a novel expandable lattice electrode radio frequency, RF catheter with an expanded lattice electrode in a larger surface area. The eight French bi-directional irrigated catheter (Sphere-9 Affera Inc) has a nine-millimeter spherical lattice tip with an effective surface area 10-fold larger than standard linear catheter. In 11 ex vivo bovine hearts unipolar ablation lattice produce deeper lesions at 60, 30 and 126 application duration. 6.7 versus 4.8 millimeters. 8.3 versus 5.3 millimeters and 10.0 versus 6.2 millimeters respectively. (P less than or equal 0.001) In five porcine hearts bipolar ablation was compared between the catheters. T max 60 degrees centigrade versus 40 Watts, 60 seconds bipolar lesions were deeper, 15.8 versus 10.5 millimeters, (P less THA 0.001) and we're more likely to be transmural (80% versus 0% P equals 0.002) in vivo lattice produced deeper lesions, 10.5 versus 6.5 millimeters. (P less than or equal to 0.001) Tissue temperature at seven millimeters was higher with lattice. (P less than 0.001) The steam pop occurrence was lower with lattice. (4% versus 18% P equals 0.01) (in vivo, 0% versus 14.2% P equals 0.13) the authors concluded that this novel RF system produces larger ventricle lesions compared to standard irrigated catheters and at a lower risk of tissue overheating. In our next paper, Jinlin Zhang and associates used an ultra-high-density mapping system to identify the characteristics and precise mechanisms of atrial tachycardia with cycle length alternans. They identified seven atrial tachycardias with alternating cycle length in a total of 478 atrial tachycardias from two institutions mapped with an ultra-high-density mapping system. Activation maps were performed for long cycle length (289 milliseconds; mapping points 21,520) in short cycle length, (251 milliseconds; mapping points, 17,594) separately. The authors classified atrial tachycardias with cycle length alternans into two types. Type one: There existed two potential loops with different routes. Cycle length alternans resulted from an intermittently 2:1 conducting block within the channel of the smaller loop. Type two: Cycling alternans resulted from different conduction velocity through two closely spaced gaps within preexisting linear lesions. Catheter ablation successfully terminated all seven atrial tachycardias. In our next paper Marine Cacheux and associates examine the role of stromal interaction molecule one STIM1, a calcium sensor that regulates cardiac hypertrophy by triggering store operated calcium entry on arrhythmias. Binding to phospholamban STIM1 increases sarcoplasmic reticulum calcium load independent of store operated calcium entry. They hypothesize that STIM1 controls electrophysiological function in arrhythmias in the adult heart. Inducible myocyte restricted STIM1 knockdown was achieved in adult mice. STIM1 knocked down mice (n=23) exhibited poor survival compared to STIM control (n=22). In Cre recombinase control (n=11) with greater than 50% mortality after only eight days of cardiomyocyte restricted STIM1 knock down. STIM1 knock down but not STIM1 control or CRE recombinase control hearts exhibited increased arrhythmias, such as frequent ectopy to pacing induced VTVF. There was decreased conduction velocity, increased action potential duration heterogeneity in STEM one knocked down mice. These features however, were comparable in VTVF positive and VTVF negative hearts. They also uncovered a marked increase in the magnitude of action potential duration alternans during rapid pacing and the emergence of a spatially discordant alternans profile in STIM1 knock down hearts. Unlike conduction velocity slowing and actual potential duration of heterogeneity, the magnitude of action potential alternatives was greater. (80%, P less than 0.05 in VTVF positive versus VTVF negative STIM1 knock down hearts) The authors concluded that an adult murine model with inducible and myocyte specific STIM1 depletion. The regulation of spatially discord alternans was mediated by STIM1. In our next paper Charlotte Houck and associates examined arrhythmia mechanisms and procedural and long-term outcomes in pediatric congenital heart disease patients undergoing catheter ablation. The authors studied 232 patients, (11.7 years, 33.5 kilograms). The most common diagnoses were Ebstein's anomaly (n=44), septal defects (n=39) and single ventricle (n=36). Arrhythmia Mechanisms included atrioventricular reentry tachycardia (n=104 in 90 patients), atrioventricular nodal reentry tachycardia (n=33 in 29 patients). Twin atrioventricular nodal tachycardia (n=3 in two patients), macroreentrant atrial tachycardia (n=59 in 56 patients). Focal atrial tachycardia (n=33 in 25 patients). Ventricular ectopy (n=10 in eight patients) and ventricular tachycardia (n=15 in 13 patients). 56 arrhythmias in 39 patients were undefined, outcomes included complete success (n=189 in 81%), partial success n=7 in 33%), failure. (n=16 in 7%), or empiric ablation (n=20 in 9%). Over 3.6 years, arrhythmia recurred in 49%. In 23 out of 51 repeat procedures, or 45%, a different arrhythmia a substrate was found. Overall adverse event rate was 9.4% although only 1.6% (n=4) were of major severity and 0.8% (n=2) of moderate severity. In our next paper, Babikir Kheiri and associates conducted a systematic review and meta-analysis, randomized controlled trials, to evaluate the efficacy and safety of antiarrhythmic drugs and catheter ablation in the treatment of ventricular tachyarrhythmias in patients with an ICD. They identified 22 randomized controlled trials with 3,828 total patients (age 64.3 79% males). The use of amiodarone was associated with a significant reduced rate of VT recurrence compared to control (hazard ratio 0.34). Sotalol was associated with increased risk of VT recurrence compared to amiodarone (hazard ratio 2.88). Compared to control, amiodarone had a hazard ratio of 0.33, and catheter ablation (hazard ratio 0.52) were associated with significant reduced ICD shocks. Compared with amiodarone, sotalol was associated with significant increase ICD shocks (hazard ratio 2.70). The rate of death was not significantly different between the competing strategies. Also, in this issue, Michele Orini and associates wrote a research letter on further evidence on how to measure local repolarization time using intracardiac unipolar electrograms in the intact human heart. Also in this issue, Christopher Andrews and associates wrote a special report on electro-mechanics of normal human heart in situ. In this issue, Arvindh Kanagasundram and associates wrote a review on sustained monomorphic ventricular tachycardia and non-ischemic heart disease, the arrhythmia substrate correlation that informed the approach to ablation That's it for this month. We hope that you will find the journal, the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology October 2019 Issue21.10.2019 (00:16:00)
Dr Paul Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, in a single‐center observational cohort study, Owen Donnellan and Associates compared arrhythmia recurrence rates in morbidly obese patients who underwent prior bariatric surgery, with those of non-obese patients following atrial fibrillation ablation. In addition to morbidly obese patients who did not undergo bariatric surgery, they matched 51 morbidly obese patients' body mass index, 40 kilograms per meter squared, who had undergone prior bariatric surgery in a two to one manner with 102 non-obese patients, and 102 morbidly obese patients without bariatric surgery on the basis of age, gender, and timing of atrial fibrillation ablation. From the time of bariatric surgery to ablation, bariatric surgery was associated with a significant reduction in BMI. 47.6 to 36.7 and reduction in systolic blood pressure, 145 to 118, P During a mean follow up of 29 months following ablation, recurrent arrhythmia occurred in 10 out of 51 or 20 patients in a bariatric surgery group, compared to 25 out of 102 patients, 24.5% in a non-obese group, and 56 out of 102 or 55% in the non-bariatric surgery morbidly obese group. No procedural complications were observed in the bariatric surgery group. In our next paper, Martin Andreas and Associates examined whether noninvasive, low-level, transcutaneous electrical stimulation of the greater auricular nerve reduced the risk of postoperative atrial fibrillation, in a pilot of patients undergoing cardiac surgery. After cardiac surgery, electrodes were applied in the triangular fossa of the ear. Stimulation, amplitude 1-million-amp frequency, one Hertz for 40 minutes, followed by a 20-minute break, was performed for up to two weeks after cardiac surgery. Patients were randomized into sham, N equals 20 or treatment group, N equals 20, for low- level, transcutaneous electrical stimulation. Patients receiving low-level, transcutaneous stimulation had a significant reduced incidence of postoperative atrial fibrillation. Four out of 20, compared to controls 11 out of 20. P equals 0.02. The median duration of postoperative atrial fibrillation was comparable between the treatment group and control group. No effect on low-level stimulation on CRP or IL-6 levels was detectable. In our next paper, Kazuki Iso and Associates examine whether the vagal response phenomenon is common to patients without atrial fibrillation. Continuous, high- frequent stimulation of the left atrial ganglion and plexus was performed in 42 patients, undergoing ablation for atrial fibrillation. In 21 patients undergoing ablation for left-sided accessory pathway, the high frequency stimulation, 20 Hertz at 25 milliamps of 10 millisecond pulse duration, was applied for five seconds at three sites within the presumed anatomical area of each of the five major left atrial ganglion plexus, for a total of 15 sites per patient. The authors define vagal response to high frequency stimulation, as prolongation of the R interval by > 50% in comparison to the mean pre-high-frequency stimulation RR interval, average over 10 beats. In active ganglion plexus areas, is areas in which vagal response was elicited. Overall, more active ganglion plexi or GP areas were found in the atrial fibrillation group patients, than in the non-atrial fibrillation group patients. And in all five major GPS, the maximum R interval during high-frequency stimulation was significantly prolonged in atrial fibrillation patients. After multivariate adjustment, association was established between the total number of vagal response sites and the presence of atrial fibrillation. The authors concluded that the significant increase in vagal responses elicited in patients with atrial fibrillation, compared to responses in non-atrial fibrillation patients, suggests that the vagal responses is to hypercan stimulations, reflect an abnormally increased ganglion plexi activity, specific to atrial fibrillation substrates. In our next paper, Vidal Essebag and Associates combine the data from the Bruise Control One and Two studies to evaluate the effect of concomitant antiplatelet therapy on clinically significant hematomas, and to understand the relative risk of clinically significant hematomas in patients treated with DOAC versus continued Warfarin. The Bruise Control study demonstrated that perioperative Warfarin continuation, reduced clinically- significant hematomas by 80%, compared to Heparin bridging. 3.5% versus 16%. Bruise Control Two observed a similarly low risk of clinically-significant hematomas when comparing continued versus interrupted direct oral anticoagulant. 2.1% in both groups. A total of 1,343 patients were included in Bruise Control One and Bruise Control Two, the primary outcome for both trials with clinically-significant hematomas. There are 408 patients identified as having continued either a single or dual antiplatelet agent at the time of device surgery. Anti-platelet use versus non-use was associated with clinically-significant hematomas in 9.8% versus 4.3%. P less than 0.001 and remained a strong independent predictor with multi-variate adjustment. Odds ratio 1.965, however, multivariate analysis adjusting for anti-platelet use, there was no significant difference in clinically-significant hematomas observed between direct oral anticoagulant use, compared with continued Warfarin. In our next paper, Markus Rottmann and associates examine the relationship between activation slowing during sinus rhythm, and vulnerability for reentry, and correlated the areas with components of the circuit. In a porcine model of healed infarction, of 15 swine, nine had inducible ventricular tachycardia, 5.2 per animal. While in six swine, VT could not be induced despite stimulation from four RV and LV sites at two drive trains in six extra stimuli down to refract refractoriness. Infarcts with ventricular tachycardia had a greater magnitude of activation slowing, during sinus rhythm, a minimal endocardial activation velocity cutoff, less than 0.1 meters per second. Differentiated inducible from non-inducible infarctions. P equals 0.15. Regions of maximal endocardial slowing during the sinus rhythm corresponded to the VT isthmus. Area under the curve equals 0.84 while bystander sites exhibited near normal activation during sinus rhythm. VT circuits were complex, with 41.7 exhibiting discontinuous propagation with intramural bridges of slow conduction in delayed quasi -simultaneous endocardial activation. Regions forming the VT isthmus borders had facts or activation during sinus rhythm, while regions forming the inner isthmus were activated faster during ventricular tachycardia. In our next paper, Mary Rooney and Associates sought to define the prevalence of subclinical atrial fibrillation in a community-based elderly population, and to characterize subclinical atrial fibrillation and the incremental diagnostic yield of four versus two weeks of continuous ECG monitoring. They conducted a cross-sectional analysis within the community- based, multi-centered observational atherosclerosis risk in communities. Erik Study, using visit five, 2016 to 2017 data. The 2,616 Erik Study participants who wore a lead-less ambulatory ECG monitor for up to two weeks were age 79 years, 42% men and 26% black. In its subset, 386 participants without clinically-recognized atrial fibrillation wore the monitor twice, each time for two weeks. They characterize the prevalence of subclinical atrial fibrillation, atrial fibrillation detected without clinically recognized atrial relation. Over two weeks of monitoring and the diagnostic yield of four versus two weeks, the authors found that the prevalence of subclinical atrial relation was 2.5%. the prevalence of subclinical each relation was 3.3% among white men, 2.5% among white women, 2.1% among black men and 1.6% among black women. Subclinical A Fib was mostly intermittent, 75%. Among those with intermittent subclinical atrial fibrillation, 91% had an AF burden of less than or equal to 10%, during the monitoring period. In a subset of 386 patients without clinical atrial fibrillation, 78% more subclinical atrial fibrillation was detected by four weeks versus two weeks of ECG monitoring. In this study, the prevalence of subclinical A Fib was lower than previously reported. And monitoring beyond two weeks provided substantial incremental diagnostic yield. In our next study, Rafael Ramirez and Yoshio Takemoto and Associates investigated arrhythmic mechanisms of Ranolazine in sheet models, in paroxysmal and persistent atrial fibrillation. Paroxysmal atrial fibrillation was maintained during acute stretch and persistent atrial relation was induced by long-term atrial tachypacing. Isolated Langendorff-perfused sheet parts were optically mapped. In paroxysmal atrial fibrillation, Ranolazine 10 micromolar reduced dominance frequency from 8.3 to 6.2 Hertz. P less than 0.01, before converting to sinus rhythm, decreased singularity point density for 0.07 to 0.039 and left atrial epicardium and prolonged atrial fibrillation cycling. Road or duration tip trajectory in variants of Afib cycle lengths were unaltered. In persistent atrial fibrillation, Ranolazine reduced dominance frequency, prolonged atrial fibrillation cycle length, increased the variance of atrial fibrillation cycling and had no effect on singularity point density, and failed to convert atrial fibrillation to sinus rhythm. Doubling the Ranolazine concentration or supplementing with Dofetilide failed to convert persistent atrial fibrillation to sinus rhythm. In computer simulations or rotors, reducing the sodium current decreased dominant frequency, increased tip meandering, and produce vortex shedding upon wave interaction with un-excitable regions. Thus, the authors concluded that paroxysmal atrial fibrillation and persistent atrial relation respond differently to Ranolazine. Cardioversion in the paroxysmal atrial fibrillation can be attributed partly to decrease dominant frequency and singularity point density and prolongation of atrial fibrillation cycling. In persistent atrial fibrillation, increased dispersion of atrial-like cycle length and likely vortex shedding, contributes to rotor formation, compensating for any rotor loss, and may underline the inefficacy of Ranolazine to terminate persistent atrial fibrillation. In our next paper, Pyotr Platonov and Associates assess the risk of atrial fibrillation and its relationship to Long-QT syndrome genotype, and the long-term prognosis in Long-QT syndrome patients. Genotype- positive patients with Long-QT syndrome. 784 with LQT1. 746 with LQT2, and 233 with LQT3, were compared with 2043 genotype-negative family members. In patients followed from birth to 60 years, LQT3 patients had an increased risk of atrial fibrillation compared to genotype-negative family members. Hazard ratio 6.62. While neither LQT1 or LQT2 demonstrated increased atrial fibrillation risk. After the age of 60 years, LQT2 patients had significant lower risk of atrial fibrillation compared with genotype-negative controls. Hazard ratio of 0.07. Atrial fibrillation was a significant predictor of cardiac events in LQT3 patients, through the age of 60. Hazard ratio, 5.38. The authors concluded that there's an increased risk of early-age atrial fibrillation in LQT3 patients and a protective effect of LQT2 genotype, resulting in a decreased risk of atrial fibrillation after the age of 60. In our next paper, Julia Ramírez and Associates evaluated the cardiovascular prognostic value of T-waves morphology restitution in 55,222 individuals undergoing an exercise stress test in the UK biobank, and identify any genetic contribution. They found that 1,743 or 3.2% of individuals had a cardiovascular event. T-wave morphology restitution during recovery from exercise was significantly associated with cardiovascular events. Hazard ratio 1.11. Independent of clinical variables and other ECG markers, T-wave morphology restitution during recovery from exercise was also associated with all-cause mortality. Hazard ratio 1.1. And ventricular arrhythmias, hazard ratio 1.16. They identified 12 genetic loci, in total for T-wave morphology restitution during exercise, in T wave morphology restitution during recovery, of which nine are associated with another ECG marker. Individuals with the top 20% of T-wave morphology restitution during recovery, genetic risk scores, were significantly more likely to have a cardiovascular in the full UK biobank. 5.3% than individuals in the bottom percent, a 20% hazard ratio of 1.07. We have two other research letters in a special report. Wassim Mosleh, Sharma Kattel report that Galectin-3 is a predictor of mortality after cardiac arrest. In the next research letter, Jerry Jez and Associates report on remotely-navigated ablations in ventricular myocardium, that result in acute lesion-size, comparable to force sensing manual navigation. In a special report, Sohaib Virk and Saurabh Kumar report on a meta-analysis of remote magnetic versus manual catheter navigation for atrial fibrillation ablation. That's it for this month. We'll hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright, American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology September 2019 Issue19.09.2019 (00:14:31)
Dr Wang: Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, Ying Tian and associates examine the effects and long-term outcomes of percutaneous stellate ganglion blockade in the setting of drug refractory electrical storm due to ventricular arrhythmia. They studied 30 consecutive patients over nearly a five-year period. They used bupivacaine alone, or in combination with lidocaine injected into the neck with good local anesthetic spread in the vicinity of the left stellate ganglion in 15 patients, or both stellate ganglion in 15 patients. The mean left ventricular ejection fraction was 34%. At 24 hours, 60% of patients were free of ventricular arrhythmia. Patients whose ventricular arrhythmia was controlled had a lower hospital mortality rate than patients whose ventricular arrhythmia continued. 5.6 versus 50%, P equals 0.009. Implantable cardioverter-defibrillator interrogation showed a significant 92% reduction in ventricular arrhythmia episodes from 26 to 2 in the 72 hours after stellate ganglion blockade, P less than 0.001. Patients who died during the same hospitalization, N equals 7, were more likely to have ischemic cardiomyopathy, 100% versus 43.5%. And recurrent ventricular arrhythmias within 24 hours, 85.7% versus 26.1%. There were no procedure related complications. In our next paper, Zachi Attia and associates hypothesized that a convolutional neural network could be trained through a process called 'deep learning' to predict a person's age and gender using only 12-lead electrocardiogram signals. They trained convolutional neural network using 10 second samples of 12-lead ECG signals from 499,727 patients to predict gender and age. The networks were tested on a separate cohort of 275,056 patients. For gender classification, the model obtained 90.4% classification accuracy with an area under the curve of 0.97. In the independent test data, age was estimated as a continuous variable with an average error of 6.9 years, R squared equals 0.7. Among 100 hundred patients with multiple ECGs over the course of at least two decades of life, most patients, 51%, had an average error between real age and convolutional neural network predicted age of less than seven years. Major factors seen amongst patients with convolutional neural network predicted age that exceeded chronologic age by greater than seven years included low ejection fraction, hypertension, and coronary disease, P less than 0.1. In the 27% of patients whose correlation was greater than 0.8, between convolutional neural network predicted and chronological age, no incident events occurred over follow up 30 years. The authors concluded that applying artificial intelligence to the ECG allows prediction of patient, gender, and estimation of age. The ability of artificial intelligent algorithm to determine physiological age with further validation may serve as a measure of overall health. In our next paper, Zain Ul Abideen Asad and associates performed a meta-analysis of randomized control trials in order to compare the efficacy and safety of catheter ablation with medical therapy for atrial fibrillation with the primary outcome being all-cause mortality. They examined 18 randomized controlled trials comprising 4,464 patients. Catheter ablation resulted in significant reduction in all-cause mortality, relative risk of 0.69 that was driven by patients with atrial fibrillation and heart failure in reduced ejection fraction, relative risk 0.52. Catheter ablation resulted in significantly fewer cardiovascular hospitalizations, hazard ratio of 0.56, and fewer recurrences of atrial arrhythmia, relative risk 0.42. Subgroup analysis suggested that younger patients, age less than 65 years, and men derived more benefit from catheter ablation compared to medical therapy. In our next paper, Felipe Kazmirczak, Ko-Hsuan Amy Chen, and associates examined patients with cardiac sarcoidosis meeting guideline criteria for implantable defibrillator implantation in a large retrospective cohort study of patients with biopsy proven sarcoidosis and known or suspected cardiac sarcoidosis undergoing cardiovascular magnetic resonance imaging. The authors found that in 290 patients, the class one and class 2A recommendation identified all patients who experienced a composite endpoint of significant ventricular arrhythmia or sudden cardiac death over a mean follow-up of three years. Patients meeting class one recommendations had a significantly higher incidence of composite endpoint than those meeting class 2A recommendations. Left ventricular ejection fraction greater than 35% with greater than 5.7% late gadolinium enhancement and cardiovascular negative residence imaging was as sensitive as or significantly more specific than left trigger ejection frack greater than 35% with any late gadolinium enhancement. Patients meeting two class 2A recommendations left ventricular ejection fraction greater than 35% would need for a pacemaker, and left ventricle rejection at greater than 35% with late gadolinium enhancement. Greater than 5.7% had high annualized event rates. Excluding two class 2A recommendations, left ventricular ejection fraction greater than 35% with syncope, and left ventricular ejection fraction greater than 35% with inducible ventricular [inaudible] resulted in improved discrimination for the composite endpoint. In our next paper, Kenji Okubo, Antonio Frontera, and associates examined the ability of a new grid mapping catheter for performing substrate and ventricular tachycardia activation mapping during ventricular tachycardia ablation procedures, identifying the low voltage areas and visualizing diastolic pathways. The authors studied 41 consecutive patients undergoing ventricular tachycardia ablation procedure. The grid mapping catheter was used to create three different maps with three bipolar configurations along the spine, across the spine, high density wave solution. The median low voltage area drawn by the high-density wave configuration was 28.9 centimeters squared, but it was 13% and 15% smaller with a low voltage area identified by along and across. The late potential areas identified by the three configurations did not differ. Ventricular tachycardia activation mapping visualizes the full diastolic pathway in 22 out of 40, or 55%. The authors found that identifying the full diastolic pathway led to a higher ongoing VT termination rate during the ablation than in the case of partial recordings, 88% versus 45%, P equals 0.03. In addition, when the full diastolic pathway's identified, the targeted VTS were always non-inducible. In our next paper, Masateru Takigawa, and associates examined whether the spacing orientation, the bipoles of high-density mapping catheters impacts the accuracy of scar detection. The authors analyze the electrograms using high-density HD grid catheter and determine the optimal cutoff for scar detection in six infarcted sheep. For using bipolar voltages to detect MRI defined scar, the area under the receiver operating curve dependent on the spacing and orientation of the bipoles and range from 0.89 to 0.923. The area under the receiver operating curve was significantly larger, P less than 0.01, when only the best points on each site were selected for analysis compared to when all points were used. In our next paper, Darren Tsang and associates examine the impact of prior sternotomy on transvenous lead extraction outcomes. Of 1,480 patients, 455 had prior sternotomy. When compared to patient with no prior sternotomy, those with prior tsunami were more likely to be older, male, and present with more comorbidities and leads targeted for extraction. No statistical difference was identified in major and minor complication rates, clinical success rates, or in hospital mortality. In patients with prior sternotomy, there were no instances of pericardial effusion following extraction. Patients with sternotomies prior to lead extraction experienced vascular cardiac perforation, presented clinically with hemothoraces rather than pericardial effusions. In our next paper, Babak Nazer and associates highlight the electrophysiologic properties in sites of ablation for manifest nodofascicular and nodoventricular accessory pathways that connect the atrial ventricular node and the Purkinje system or ventricular myocardium respectively. Concealed nodoventricular and nodofascicular pathways participate as the retrograde limb of supraventricular tachycardia. Manifest nodofascicular and nodoventricular accessory pathways comprise the antegrade limb of wide complex supraventricular tachycardia but are quite rare. The authors report on eight patients who underwent electrophysiologic studies for wide complex tachycardia three, narrow complex tachycardia one, and for pre-excitation in four patients. The authors found nodofascicular and nodoventricular accessory pathways were an integral part of the supraventricular tachycardia in three patients. In these three cases, cases one and two revealed wide complex tachycardia due to manifest supraventricular tachycardia. Case three with a bi-directional nodofascicular and nodoventricular accessory pathway that conducted retrograde during supraventricular tachycardia, and antegrade causing pre-excitation during atrial pacing. The nodofascicular or nodoventricular accessory pathway with a bystander during AV nodal reentry and tachycardia, atrial fibrillation, atrial flutter, and orthodromic AV reentrant tachycardia in four cases, and caused only pre-excitation in one. Successful accessory pathway ablation was achieved empirically in the slow pathway region in one case. In five cases, the ventricular insertion was mapped to the slow pathway region in two cases, or septal right ventricle in three cases. The accessory pathway was not mapped in cases five and seven due to its bystander role. The QRS morphology of pre-excitation predicted the right ventricular insertion sites in four to five cases in which it was mapped. During follow-up, one patient noted recurrent palpitations but no documented supraventricular tachycardia. The authors recommend that ablation should initially target the slow pathway region with mapping of the right ventricular insertion site if slow pathway ablation is not successful, and that the QRS morphology of maximal pre-excitation may be used to predict the successful right ventricular ablation site. In our next paper, Constanze Schmidt and associates sought to determine if gene therapy targeting TASK-1 atrial specific potassium channel gene would suppress atrial fibrillation and correct cellular electrophysiological modeling in a porcine model of atrial fibrillation. The authors induced atrial fibrillation in pigs using atrial burst stimulation via implanted pacemakers and injected into both atria adeno-associated viral vectors carrying anti TASK-1 SIRNA for gene transfer to suppress TASK-1 channel expression. After 14 days, porcine cardiomyocytes were isolated from the right and left atrium. The authors found that anti TASK-1 adeno-associated viral vector application significantly reduced atrial fibrillation burden in comparison to pigs. Arrhythmic effects of anti TASK-1 SIRNA were associated with reduction of TASK-1 currents and prolongation of action potential durations in cardiomyocytes to sinus rhythm values. The authors concluded that suppression of atrial fibrillation through selective reduction of TASK-1 currents may represent a new option for anti-arrhythmic therapy. We have two excellent research letters this month. Jordana Kron and associates reported the presence of Inflammasome within the granulomas in hearts of three cardiac sarcoidosis patients. Providing additional support for the role of IL-1 in the pathogenesis of cardiac sarcoidosis and raising the possibility of ion targeted therapies to treat cardiac sarcoidosis. Walid Barake and associates examine 549 patients with left bundle branch block, left ventricular ejection fraction greater than 50% at baseline, and a follow-up echocardiogram. Of these, 134, 24.4% had a greater than 10% drop in left ventricular ejection fraction. The patients with possible left bundle branch block induced cardiomyopathy were more likely to be younger and male. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology August 2019 Issue27.08.2019 (00:13:34)
Dr Paul Wang: Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, Mark McCauley, Flavia Vitale and associates report that carbon nanotube fibers may improve impaired myocardial conduction. In three sheep, radiofrequency ablation was used to create epicardial conduction delay. In addition, in a rodent model, carbon nanotube fibers were sewn across the atrial ventricular junction. They demonstrated acute ventricular preexcitation, but in chronic studies at four weeks, atrial pacing was required for resumption of AV conduction. Carbon nanotube fibers are conductive, biocompatible with no gross or histopathological evidence of toxicity. In our next paper, Koichiro Ejima and associates compared outcomes of circumferential pulmonary vein isolation for atrial fibrillation ablation randomized to contact force monitoring or unipolar signal modification in 136 patients with paroxysmal atrial fibrillation. In the unipolar signal modification-guided group, each radiofrequency application was delivered until the development of completely positive unipolar electrograms. In the contact force monitoring-guided group, a contact force of 20 grams, ranged 10 to 30 grams, and a minimum force time integral of 400 gram seconds were the targets for each radiofrequency application. The freedom from atrial tachyarrhythmia recurrence at 12 months was 85% in the unipolar signal modification-guided group and 70% in the contact force monitoring-guided group, P equals 0.031. The radiofrequency time for pulmonary vein isolation was shorter in the unipolar signal modification-guided group than contact force monitoring-guided group, but was not statistically significant, P equals 0.077. The incidence of time-dependent in ATP-provoked early electrical reconnections between the left atrium and pulmonary veins, procedural time, fluoroscopic time, and average force-time integral did not significantly differ between the two groups. In our next paper, Vishal Luther and associates tested whether ripple mapping is superior to conventional annotation-based local activation time mapping for atrial tachycardia diagnosis. Patients with atrial tachycardia were randomized, either ripple mapping or local activation time mapping. The primary endpoint was atrial tachycardia termination with delivery of the planned ablation lesion set. The inability to terminate atrial tachycardia with the first lesion set, the use of more than one entrainment maneuver, or the need to cross over to the other mapping arm were defined as failure to achieve the primary endpoint. The primary endpoint occurred in 38 of 42 patients or 90% in the ripple mapping group, and 29 of 41 patients, 71%, in the local activation time mapping group, P equals 0.45. The primary endpoint was achieved without any entrainment in 31 out of 42 patients or 74% with ripple mapping, and 18 out of 41 patients or 44% with local activation time mapping, P equals 0.01. Of those patients who failed to achieve the primary endpoint, atrial tachycardia termination was achieved in 9 out of 12 patients or 75% in the local activation time mapping group following crossover to ripple mapping with entrainment, but zero out of four patients, 0%, in ripple mapping group crossing over to local activation time mapping with entrainment, P equals 0.04. In our next paper, Franziska Fochler and associates examined whether anatomical targeting of late gadolinium enhancement MRI-detected gaps and superficial atrial scar is feasible and effective to treat recurrent atrial arrhythmias post-atrial fibrillation ablation. The authors studied 102 patients who underwent initial atrial fibrillation ablation and repeat ablation for recurrent atrial arrhythmias within one-year. 46 patients or 45% with atrial fibrillation recurrence were assigned to group one and underwent fibrosis homogenization as the second procedure. 56 patients or 55% with atrial tachycardia recurrence were assigned to group two and underwent late gadolinium enhancement MRI detected scar-based dechanneling. Both groups underwent re-isolation of pulmonary veins, if necessary. In the first 25 patients from group two, the atrial tachycardia was electroanatomically mapped and a critical isthmus was defined. It was found that those isthmi were located in the regions with non-transmural scarring detected by late gadolinium enhancement MRI. In the last 31 patients from group 2, an empirical late gadolinium enhancement MRI-based dechanneling was performed solely based on late gadolinium enhancement MRI results. During one-year follow-up after the second ablation, 67% of patients group one and 64% of patients group two were free from occurrence. In group two, 64% in the electroanatomic-guided and 65% in the late gadolinium enhancement MRI dechanneling group were free from recurrence. The authors concluded that homogenization of existing scar is appropriate treatment for recurrent atrial fibrillation while dechanneling of existing isthmi seem the appropriate approach for patients recurring with atrial tachycardia. In our next paper, George Leef, Fatemah Shenasa, Neal Bhatia and associates examined whether wave front field mapping of persistent atrial fibrillation can reveal an underlying network of a small number of spatially anchored rotational and focal sites. They examined unipolar atrial fibrillation electrograms from 64-pole baskets in 54 patients from an international registry in whom persistent atrial fibrillation was terminated by targeted ablation. They identified 4.0, plus or minus 2.1, spatially anchored rotational focal sites in atrial fibrillation that were a single in seven patients type I or paired chiral-antichiral type II rotational drivers that controlled most of the atrial area. Ablation of one or two large drivers terminated all cases of these types of atrial fibrillation. Third, interaction of three to five drivers type III, n equals 42, was present with changing areas of control. Targeted ablation at driver center terminate atrial fibrillation and required more ablation in type III versus I, P equals 0.02 in the left atrium. In our next paper, Ryan Azarrafiy and associates examined survival after superior vena cava tear using an endovascular balloon. Data were prospectively collected from both a United States Food and Drug Administration-maintained database and physician reports of adverse events as they occurred. Confirmed superior vena cava tears were analyzed for patient demographics, case details, and index hospitalization mortality. Over a period of two years, 116 confirmed superior vena cava events were identified, of which 44% involve proper balloon use and 50% involve no use or improper use. When an endovascular balloon was properly used, 45 of 51 patients, or 88.2%, survived in comparison to 37 out of 65, or 56.9%, when a balloon was not used or improperly used; P equals 0.0002. Furthermore, multivariate regression modeling found that proper balloon deployment was an independent, negative predictor of in-hospital mortality for patients who experienced a superior vena cava laceration, odds ratio of 0.13; P value less than 0.001. In our next paper, Bharatraj Banavalikar and associates examined 28 patients with focal atrial tachycardia, mean age 34.6 years, females 60.7%, were included in the study. Most common symptoms were palpitations, 85.7%, followed by shortness of breath, 25%. The mean atrial tachycardia rate was 170 beats per minute and mean left ventricular ejection fraction was 54.7%. Overall, 18 or 64.3% patients responded within six hours of the first dose of ivabradine; 13 out of the 18 ivabradine responders subsequently underwent catheter ablation. Focal atrial tachycardia originating in the atrial appendages was a predictor of ivabradine response compared with those arising from other atrial sites, P equals 0.46. In our next paper, Takumi Yamada and associates studied 26 consecutive patients with idiopathic origins that were identified at the left ventricular summit. The authors studied 26 consecutive patients with idiopathic left ventricular summit ventricular arrhythmias in the basal and apical left ventricular summit in 15 and 11 patients, respectively. Radiofrequency ablation of the apical left ventricular summit ventricular arrhythmias were successful in the great cardiac vein in nine patients and in the apical left ventricular outflow tract in two. Ablation of the basal left ventricular summit was successful in the aortomitral continuity in nine patients, at the junction of the left and right coronary cusp in 4 and the left coronary cusp in two. Three apical left ventricular summit ventricular arrhythmias exhibited an eccentric endocardial pattern that was from basal to apical left ventricular outflow tract. In 11 basal left ventricular summit ventricular arrhythmias, the activation pattern was eccentric because ventricular activation within the great cardiac vein in the apical left ventricular summit was earlier than that in the basal left ventricular outflow tract. In two left ventricular summit ventricular arrhythmias, the activation was eccentric because a relatively early ventricular activation was recorded at multiple sites away from the successful ablation site. The authors concluded that eccentric activation patterns often occurred during idiopathic left ventricular, ventricular arrhythmias, which could mislead catheter ablation of those arrhythmias. In our next paper, Anand Thiyagarajah and associates performed a systematic review and meta-analysis of studies performing posterior wall isolation for atrial fibrillation. Of 17 studies, 13 employed box isolation, 3 single ring isolation, and 2 debulking ablation, and included 1,643 patients, of which 31% had paroxysmal atrial fibrillation. The acute procedural success for achieving posterior wall isolation was 94%. Single-procedure 12-month freedom from atrial arrhythmias was 65% overall and 61.9% for persistent atrial fibrillation. Randomized control trials comparing posterior wall isolation to pulmonary vein isolation, three studies in 444 patients, yielded conflicting results and could not confirm incremental benefit to posterior wall isolation; 15 major complications, 0.1%, including two atrio-esophageal fistulas, were reported. In a research letter, Tadashi Hoshiyama and associates examined the effect of contact vector direction on the ability of pulmonary vein isolation. In a review article, Belinda Gray and associates describes sudden cardiac death in the young, ages 35 years or less. A significant proportion of sudden cardiac deaths in this group may be precipitated by underlying inherited cardiac conditions, including both heritable cardiomyopathies and inherited arrhythmic syndromes. Tragically, sudden deaths may be the first manifestation of disease in a family. Both clinical and genetic evaluation of surviving family members becomes important. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology July 2018 Issue15.07.2019 (00:15:30)
Paul Wang: Welcome to the monthly podcast On The Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Moo-Nyun Jin, Tae-Hoon Kim, and associates examined the 1-year serial changes in cognitive function, with or without atrial fibrillation catheter ablation. They used the Montreal cognitive assessment score in 308 patients undergoing atrial fibrillation ablation, the ablation group and 50 atrial fibrillation patients on medical therapy who met the same indication for atrial fibrillation ablation, the control group at baseline three months and 12 months. Cognitive impairment was defined as a published cutoff score of less than 23 points. Pre-ablation cognitive impairment was a detected in 18.5%. The Montreal cognitive assessment score significantly improved one year after radio frequency ablation. In both the overall ablation group, 24.9 to 26.4 p less than 0.001, and the propensity matched ablation group 25.4 to 26.5, but not in the control group. 25.4 to 24.8 p equals 0.012. Pre-ablation cognitive pyramid odds ratio 13.7, was independently associated with an improvement in one-year post ablation cognitive function. In our next paper, Zian Tseng, James Salazar and associates studied World Health Organization defined sudden cardiac deaths autopsied in the POstmortem Systemic InvesTigation of sudden cardiac death, the POST SCD study to determine whether premortem characteristics could identify autopsy defined sudden arrhythmic death among presumed sudden cardiac deaths. They prospectively identified 615 World Health Organization defined sudden cardiac deaths, of which 144 were witnessed. Autopsy defined sudden arrhythmic death had no extra cardiac or acute heart failure cause of death. Of the 615 presumed sudden critic deaths, 348 or 57% were autopsy defined, sudden arrhythmic deaths. For witness cases, using an emergency medical system model area under the receiver operator curve 0.75, included presenting rhythm of ventricular tech or cardiac fibrillation, pulseless electrical activity, while the comprehensive model, adding medical record data and depression, area under the curve 0.78. If only VTVF witness cases, 48 of those were classified as sudden arrhythmic death. The sensitivity was 0.46, and specificity 0.90. For unwitnessed cases, the emergency medical system model, area under the curve 0.68, included black race, male sex, age, time since last seen normal, while the comprehensive, area into the curve 0.75, added the use of beta blockers, antidepressants, QT prolonging drugs, opiates, illicit drugs and dyslipidemia. If only unwitnessed cases, less than one hour, n equals 59, were classified as sudden arrhythmic deaths, the sensitivities were 0.18, and specificity was 0.95. The authors concluded that models could identify pre-mortem characteristics to better specify autopsy defined sudden arrhythmic deaths, among presumed sudden cardiac arrests. The authors suggest that the World Health Organization definition can be improved by restricting witnessed sudden cardiac deaths to ventricular tachycardia fibrillation or non-pulseless electrical activity rhythms in unwitnessed cases to less than one hour since last normal, at a cost of sensitivity. In our next paper, Rafael Jaimes III and associates performed optical mapping of trends, membrane, voltage and pacing studies on isolated Langendorff-perfused rat hearts to assess the cardiac electrophysiology after mono-2-ethylhexyl phthalate, a phthalate with documented exposure in intensive care patients. The authors found that a 30-minute exposure to mono-2-ethylhexyl phthalate increased the atrioventricular node effector in period 147 milliseconds compared to 170 milliseconds in controls and increased the ventricular effective refractory periods of 117 milliseconds compared to 77.5 milliseconds in controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths. Mono-2-ethylhexyl phthalate exposure also slowed epicardial conduction velocity, 25 centimeters per second compared to 60 centimeters per second in controls. The authors concluded that acute mono-2-ethylhexyl phthalate exposure, at clinically relevant doses, has a significant effect on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications and lead to cardiac arrhythmias. In our next paper, Stephan Willems and associates report the use of a novel, non-contact imaging and mapping system that uses ultrasound to reconstruct atrial chamber anatomy and measure timing and density of dipolar, ionic activation or charge density across the myocardium to guide ablation of atrial arrhythmias. They conducted a prospective non-randomized study, the UNCOVER AF trial which was conducted at 13 centers across Europe and Canada. In 127 patients with persistent atrial fibrillation who underwent mapping and catheter ablation, acute procedural efficacy of 98% was seen. At 12 months, the single procedure freedom from atrial fibrillation, on or off antiarrhythmic drugs, was 72.5%, with 23% undergoing retreatments following one or two procedures. Freedom from atrial fibrillation was 93.2%. The primary safety outcome was 98% was no device related major adverse events reported. In our next paper, Anne-Floor Quast, Niek Beurskens, and associates describe a novel, completely extracardiac pacing system, with a lead in the anterior mediastinum, outside the pericardium and circulatory system. A total of 166 or 95% out of 174 patients had a viable lead access path through the fourth, fifth, or sixth intercostal space. Access to the targeted implant location using delivery tool was successful in all five cadavers and three humans, without use of fluoroscopy, with an average lead delivery time of 121 seconds. No damage to the lung, pericardium, heart or internal thoracic vessels occurred. Pacing performance in six human subjects showed a voltage threshold of 4.7 volts in a threshold pulse width of 1.8 milliseconds. In our next paper, Yasuhiro Shirai and associates compare the ability to identify ventricular tachycardia isthmuses in ischemic and nonischemic cardiomyopathies. Of 445 patients, 228 with ischemic cardiomyopathy and 217 with nonischemic cardiomyopathy, undergoing VT ablation. Detailed entrainment mapping of at least one tolerated VT was performed in 111 patients, 71 with ischemic cardiomyopathy and 40 with nonischemic cardiomyopathy. Of 89 nonischemic cardiomyopathy VTs, the isthmus could be identified by endocardial entrainment in 55 or 62%, compared to only eight out of 47 or 17% nonischemic cardiomyopathy VTs, p less than 0.01. With combined endocardial and epicardial mapping, the isthmus could be identified in 56 or 63% ischemic cardiomyopathy VTs, and 12 or 26% of nonischemic cardiomyopathy VTs, p less than 0.01, while a similar proportion of patients any critical component, defined as entrance, isthmus or exit, could be identified in 85% of ischemic cardiomyopathy VTs and 79% of nonischemic cardiomyopathy VTs, p equals 0.3. Complete success, no inducible VT at the end of the procedure was 82% versus 65%, p equals 0.04 and a one-year single procedure VT survival, 82% versus 55%, p less than 0.01. Both higher in patients with ischemic cardiomyopathy. The authors concluded that among mappable ischemic cardiomyopathy VTs, critical circuit components can be usually identified on the endocardium. In contrast, among mappable nonischemic cardiomyopathy VTs, although some critical components can be typically identified with the addition of epicardial mapping, the isthmus is less commonly identified, possibly due to midmyocardial location. In our next paper, Miki Yokokawa and associates targeted documented but non-inducible clinical VTs, based on stored, implantable cardioverter defibrillator electrograms. Radio frequency ablation was performed in a consecutive group of 66 postinfarction VTs, in whom clinical VTs were non-inducible during an ablation procedure. In the first 33 patients, the control group, only inducible VTs were targeted. In the second 33 patients, non-inducible clinical VTs were targeted by pace mapping based on stored ICD-electrograms, the ICD electrogram guided ablation group. VT recurred in five patients or 15% in the ICD-electrogram guided approach, and in 13% or 39% in the control group. Freedom from recurrent VT was higher, p equals 0.04, in the ICD-electrogram-guided group, but there was no difference in ventricular fibrillation or total mortality between groups. In our next paper, Albert Feeny and associates examined whether machine learning could predict cardiac resynchronization therapy or CRT response. A training cohort was created from all Johns Hopkins patients and an equal number of randomly sampled Cleveland Clinic patients. All remaining patients comprise the testing cohort. Response was defined as greater than or equal to 10% increase in left ventricular ejection fraction. Machine learning models were developed to predict CRT response using different combinations of classification algorithms in clinical variable sets on the training cohort. 925 patients were included. On the training cohort, the best machine learning model was a naive Bayes classifier using nine variables, QRS morphology, QRS duration, New York Heart Association classification, left ventricular ejection fraction and end-diastolic diameter, sex, ischemic cardiomyopathy, atrial fibrillation, and epicardial LV lead. On the testing cohort, machine learning demonstrated better response prediction than guidelines, area under the curves 0.7 versus 0.65, p equals 0.012, and greater discrimination of event-free survival, concordance index 0.61 versus 0.56, p less than 0.001. The fourth quartile of machine learning model had greatest risk of reaching the composite endpoint, while the first quartile had the least, hazard ratio of 0.34, p less than 0.001. The authors found that machine learning with nine variables incrementally improved prediction of CRT response and survival beyond guidelines, but its performance with not improved by incorporating more variables. In our next paper, Bernhard Kaess, Charlotte Andersson and associates examine the familial clustering of cardiac conduction defects in the Framingham heart study, using multivariable-adjusted logistic regression models to investigate the association of parental AV block, complete bundle branch block, or a pacemaker insertion with occurrence of cardiac conduction abnormalities on offspring. Individuals with at least one effected parent with a conduction defect had at 1.65-fold odds for manifesting AV block, and 1.62-fold odds for developing complete bundle branch block. If at least one parent had any electrocardiographic conduction defect or pacemaker insertion, the offspring had 1.62-fold odds for experiencing any of these conditions. The Danish and nationwide administrative registries of nearly 3 million individuals and about five thousand incident pacemaker implantations, individuals with at least one first degree relative with a history of pacemaker insertion, had a multivariable-adjusted 1.68-fold incident rate ratio of undergoing pacemaker insertion. If the affected relative was less than or equal to 45 years of age, the incident rate ratio was markedly increased to 51.0. In our final paper, a review article, Venkat Nagarajan, Siew Ho Yen, and Sabine Ernst provide a detailed discussion of anatomic landmarks and considerations that will aid in his bundle pacing lead implantation. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology June 2019 Issue18.06.2019 (00:17:20)
Dr. Wang: Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wong, editor-in-chief, with some of the key highlights from this month's issue. In our first paper, Jeremy Wasserlauf and associates compare the accuracy of an atrial fibrillation sensing smartwatch with simultaneous recordings from an insertable cardiac monitor. The authors use smart rhythm 2.0, a convolutional neuro-network, trained on anonymized data of heart rate, activity level and EKGs from 7500 AliveCor users. The network was validated on data collected in 24 patients with insertable cardiac monitor, and a history of paroxysmal atrial fibrillation who simultaneously wore the atrial fibrillation sensing smart watch with smart rhythm 0.1 software. The primary outcome was sensitivity of the atrial fibrillation sensing smart watch for atrial fibrillation episodes of greater than equal to one hour. Secondary end points include sensitivity of atrial fibrillation sensing smart watch for detection of atrial fibrillation by subject and sensitivity for total duration across all subjects. Subjects with greater than 50% false positive atrial fibrillation episodes on insertable cardiac monitor were excluded. The authors analyzed 31,349 hours meaning 11.3 hours per day of simultaneous atrial fibrillation sensing smart watch and insertable cardiac monitor recordings in 24 patients. Insertable cardiac monitor detected 82 episodes of atrial fibrillation of one hour duration or greater while the atrial fibrillation sensing smartwatch was worn. With a total duration of 1,127 hours. Of these, the smart rhythm 2.0 neural network detected 80 episodes. Episode sensitivity 97.5% with total duration 1,101 hours. Duration sensitivity 97.7%. Three of the 18 subjects with atrial fibrillation of one hour or greater had atrial fibrillation only when the watch was not being worn. Patient sensitivity 83.3% or 100% during the time worn. Positive predictive value for atrial fibrillation episodes was 39.9%. The authors concluded that an atrial fibrillation sensing smartwatch is highly sensitive to detection of atrial fibrillation and assessment of atrial fibrillation duration in an ambulatory population when compared to insertable cardiac monitor. In our next paper, Liliana Tavares and associates examine the autonomic nervous system response to apnea in its mechanistic connection to atrial fibrillation. They study the effects of ablation of cardiac sensory neurons with resiniferatoxin, a neurotoxic transient receptor potential vanilloid one agonist. In a canine model, apnea was induced by stopping ventilation until oxygen saturation decreased in 90%. Nerve recordings from bilateral vagal nerves left stellate ganglion and anterior right ganglion plexi were obtained before and during apnea, before and after resiniferatoxin injection in the anterior white ganglion plexi in seven animals. Each refractory period and atrial fibrillation inducibility upon single extra stimulation was assessed before and during apnea, before and after intrapericardial resiniferatoxin administration in nine animals. The authors found that apnea increased anterior wide ganglion plexi activity followed by cluster crescendo vagal bursts synchronized with heart rate and blood pressure oscillation. Upon further oxygen desaturation, a tonic increase in left stellate ganglion activity in blood pressure oscillations ensued. Apnea induced atrial effective refractory shortening from 110 to 90 milliseconds, P less than 0.001 and atrial fibrillation induction in nine animals vs. zero out of nine at baseline. After resiniferatoxin administration increases in ganglion plexi and left stellate ganglion activity, and blood pressure during apnea were abolished, in addition, the atrial effector refractory period increased to 127 milliseconds, P=0.0001 and atrial fibrillation was not induced. Vagal bursts remain unchanged. Ganglion plexi cells showed cytoplasmic microvacuolation and apoptosis. The authors concluded that apnea increased ganglion plexi activity followed by vagal bursts and tonic left stellate ganglion firing. Resiniferatoxin decreases sympathetic and ganglion plexi nerve activity, abolishes apnea's electrophysiotic response and atrial fibrillation inducibility indicating that sensory neurons play a role in apnea induced atrial fibrillation. In our next paper, Thomas Pambrun and associates examined whether using unipolar signal modification as a local end point would improve the safety and efficacy of high-power ablation during pulmonary vein isolation. They studied four swine and 100 consecutive patients referred for pulmonary vein isolation with the first 50 patients in a control group using 25 to 30 watts and the last 50 patients in a study group with 40 to 50 watts. Atrial radiofrequency applications were stopped two seconds in the study group and swine or five seconds in the control group after unipolar signal modification. Ventricular radiofrequency applications of 500 joules were performed at the swine epicardium. The authors found that swine did not show any extracardiac damage related to atrial lesions. At equal energy of 500 joules, 50 watt lesions were deeper, three vs. 2.6 millimeters, P=0.3 and wider, 6.2 vs. five millimeters, P=0.006 and 25 watt lesions. In a clinical study, there were no complications occurring at either power output. The study group displayed higher first pass pulmonary vein isolation, 92% vs. 73%, P less than 0.001. In addition, the study group had a lower acute pulmonary vein reconnection, 2% vs. 17%, P less than 0.001 as well as reduced procedure time, 73.1 vs. 107.4 minutes and ablation team, 13 vs. 30.3 minutes. Sinus rhythm maintenance at 12 months was similar, 90% and 88%. The authors concluded that high power pulmonary vein isolation guided by unipolar signal modification safely decreases procedural burden while achieving similar 12-month outcomes. In our next paper, Toshiaki Sato and associates attempted to identify predictors of low his-bundle pacing threshold. They studied 51 patients, 53% with atrial ventricular block undergoing his-bundle pacing for bradycardia with an intrinsic QRS duration of less than 120 milliseconds. His-bundle pacing lead positioning was guided by unipolar his-bundle electrograms recorded with an electrophysiology recording system. In total, 153 attempts at anchoring the his-bundle pacing lead were made, of which 45 achieved acceptable his-bundle pacing thresholds, less than or equal to 2.5 volts at one millisecond. The amplitude of negative deflection in unipolar his-bundle electrograms and the selective his-bundle pacing at fixation where independently associated with achieving a acceptable threshold. A negative amplitude of greater than or equal to 0.06 millivolts in the his-bundle electrograms was determined as the optimal value for identifying acceptable threshold. This deep negative his-bundle electrogram was recorded with a his-bundle pacing threshold of 1.4 volts in 34 attempts, significantly lower than the positive his-bundle electrogram without deep negative deflection, 2.8 volts in 31 trials or greater than five volts in 38 trials. The permanent his-bundle pacing lead remained with a deep negative, greater than or equal to 0.06 millivolts or positive his-bundle electrogram in 28 or 14 patients respectively and with a positive or negative his-bundle pacing injury current in 19 and 23 patients respectively. During follow-up, increased his-bundle pacing threshold of greater than one volt was significantly more prevalent in the positive his-bundle electrogram group. The his-bundle pacing threshold of deep negative his-bundle electrogram and his-bundle injury current but not of selective his-bundle pacing group were significantly lower than other sub-groups during follow-up. In the next paper, Claire Martin and associates examined whether altering activation wavefront affects activation timing and local abnormal ventricular activity characterization in patients with ischemic cardiomyopathy. They use the ultra-high density arrhythmia to generate maps for all stable ventricular tachycardias and with pacing from the atrium, right ventricular apex and left ventricular branch of the coronary sinus. 56 pace maps and 23 ventricular tachycardia circuits were mapped in 22 patients. In 79% of activation maps, there was one or greater lines of block in the pace conduction wavefront with 93% having fixed block and 32% showing functional partial block. Bipolar scar was larger with atrial than right ventricular, 31.7 centimeters squared vs. 27.6 centimeters squared, P = 0.003 or left ventricular pacing, 31.7 centimeters squared vs. 27.0 centimeters squared, P = 0.009. Local abnormal ventricular activities areas were smaller with atrial than right ventricular pacing, 12.3 centimeters squared vs. 18.4 centimeters squared or left ventricular pacing, 12.3 centimeters squared vs. 17.1 centimeters squared. Local abnormal ventricular activities were larger with wavefront propagation perpendicular vs. parallel to the line of block along isthmus boundaries, 9.3 vs. 13.6 centimeters squared P = 0.01. All patients had successful tachycardia isthmus ablation in 11 months follow-up, two patients had a recurrence. In our next paper, Andrew Tseng and Katie Kunze and associates conducted a systematic review and network meta-analysis on the effect of medication device therapies and reduced ejection fraction on all-cause mortality. Randomized control trials published between January 1980 and July 2017 were identified. The authors found that combination therapy of angiotensin converting enzyme inhibitors or angiotensin receptor blockers with beta blockers alone or in addition to implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillators demonstrated significant reduction in all cause of mortality when compared to placebo. By probability rank, implantable cardio defibrillator plus angiotensin receptor blockers plus beta blockers plus mineralocorticoid receptor blockers, implantable cardioverter defibrillators plus angiotensin receptor blockers plus beta blockers and angiotensin receptor-neprilysin inhibitor plus beta blockers and mineralocorticoid receptor antag as combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitors plus beta blockers plus mineralocorticoid receptor antagonist to ICD plus optimal pharmacologic combination therapy. In our next paper, Karl-Heinz Kuck and associates examined repeat ablation in the fire and ice trial, which examined efficacy and safety of pulmonary vein isolation using cryoballoon vs. radio-frequency current ablation in patients with drug refractory symptomatic paroxysmal atrial fibrillation. Patients with re-ablation procedures during fire and ice were retrospectively consented and rolled at 13 trial centers. 89, 36 cryo-balloon and 53 radio-frequency patients were studied. Paroxysmal atrial fibrillation was the predominant recurring arrhythmia, 69% prior to re-ablation. Re-ablations occurred at the median of 173 and 182 days in the cryoballoon and radio frequency cohorts. The number of reconnected pulmonary veins was significantly higher in the radio frequency than the cryo-balloon, 2.1 vs. 1.4 P = 0.01, which was significantly driven by more connected left superior pulmonary veins and markedly more reconnected right superior pulmonary veins. The number of predominantly radio frequency lesions applied during re-ablation was significantly greater in patients originally treated with radio frequency, 3.3 vs. 2.5, P=0.015 with no difference in overall acute success. After re-ablation, no differences in procedure related rehospitalization or antiarrhythmic drug utilization was observed between cohorts. In the next paper, Ayelet Shapira-Daniels and Michael Barkagan and associates examined the ability of reducing baseline impedance to improve ventricular ablation success. In 16 patients with ventricular tachycardia or frequent ventricular premature complexes with failed rate of frequency ablation with irrigated catheters, the impedance was modulated by adding or repositioning return patches. Ablation was repeated at similar location and power settings. The authors studied six patients with idiopathic ventricular premature complexes originated from the left ventricular summit, N=4 or papillary muscles, N=2. Six patients with non-infarct related ventricular tachycardia and four patients with infarc related ventricular tachycardia. Prior unsuccessful radio frequency ablation at critical sites had a number of 10.4 applications, power of 43.3 watts, duration 55.3 seconds and impedance reduction, 14.6 Ohms in low ionic solution was used in 81%. Modulating the return patches resulted in reduced baseline impedance, 111.7 vs. 34.7 ohms, P less than 0.0001. Increased current output 0.6 vs. 0.56 amps, P also less than 0.0001. And impedance dropped 16.8 ohms. Repeat ablation at similar locations had successful effect in 12 out of 16 or 75% patients. During a follow-up duration of 13 months, 10 out of 12 or 83% patients remained free of arrhythmia occurrence. The frequency of steam pops was similar between higher and lower baseline impedance settings. The authors concluded that in patients with deep ventricular substrate, reducing the baseline impedance is a simple, safe and effective technique for increasing the effect of radio frequency ablation. However, the combination with low ionic solutions may increase the risk for steam pops and neurological events. Our last paper is a review by Robert Anderson and associates. The authors summarize all of the published 12 lead ECD algorithms used to localize ventricular arrhythmias from the right ventricular and left ventricular outflow tracks. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time! This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology May 2019 Issue21.05.2019 (00:11:29)
Dr Paul Wang: Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. In our first article, Daniel Alyesh, Konstantinos Siontis and associates described myocardial calcifications in patients with ischemic cardiomyopathy undergoing ventricular tachycardia ablation in comparison to a control group of patients without ventricular tachycardia. They found that in 56 consecutive post-infarction patients, myocardial calcifications were identified in 39 or 70% of post-infarction ventricular tachycardia patients compared to 6 or 11% of patients without ventricular tachycardia. A calcification volume of 0.538 centimeters cube distinguished patients with calcification-associated ventricular tachycardia from patients without calcification-associated ventricular tachycardias; area under the curve, 0.87; sensitivity, 0.87; specificity, 0.88. A non-confluent calcification pattern was associated with ventricular tachycardia target sites independent of calcification volume, P equals 0.01. Myocardial calcifications corresponding to areas of electrical non-excitability forming a border for re-entry were found in 33% of all ventricular tachycardias for which target sites were identified, and in 62% of patients with myocardial calcifications. In our next paper, Mia Fangel and associates examined whether glycemic status evaluated by hemoglobin A1c has an effect on the risk of thromboembolism among patients with atrial fibrillation and Type 2 diabetes. They used a cohort study from 5,386 patients with incident non-valvular atrial fibrillation and Type 2 diabetes in Danish registries. Compared with patients with hemoglobin A1c of less than or equal to 48 millimole per mole, they observed a higher risk of thromboembolism among patients with hemoglobin A1c 49 to 58 millimoles per mole with a hazard ratio of 1.49 and a hemoglobin A1c greater than 58 millimole per mole with a hazard ratio of 1.59 after adjusting for confounding factors. Surprisingly, in patients with diabetes duration of 10 years or more, higher hemoglobin A1c levels were not associated with a higher risk of thromboembolism. In our next paper, Niek Beurskens and associates compared tricuspid valve dysfunction in leadless pacemaker therapy to dual chamber transvenous pacing systems. They studied 53 patients receiving a leadless pacemaker, including 28 with a Nanostim and 25 with a Micra device. Of these 53 patients, 23 or 43% had tricuspid regurgitation that was graded as being more severe at 12 months. Compared with an apical position, a right ventricular septal position of the leadless pacemaker was associated with increased tricuspid valve incompetence, odds ratio, 5.20; P equals 0.03. An increase in mitral valve regurgitation was observed in 38% of patients. Leadless pacemaker implantation resulted in a reduction of right ventricular function. Leadless pacemaker implantation was further associated with a reduction in left ventricular ejection fraction and elevated LV TI index. The changes in tricuspid regurgitation in leadless pacing group was similar to the changes in dual-chamber transvenous pacemaker group, 43% versus 38% respectively; P equals 0.39. In our next paper, Jurgen Duchenne and associates examined whether regional left ventricular glucose metabolism correlates with regional work in an animal model with reversible dyssynchrony due to pacing. In 12 sheep, after 8 weeks of right atrial and right ventricular free wall pacing, there is evidence of left ventricular dilatation and thinning of the septum and thickening of the lateral wall. The authors employed motion compensation and anatomical correction in order to provide reliable regional estimates of myocardial glucose metabolism. They found that in homogenous regional distribution of myocardial workload due to left bundle branch block triggers adaptive remodeling of the left ventricle, leading to a more homogenous load distribution per volume unit myocardium. In reverse, cardiac resynchronization therapy leads acutely to an inhomogeneous distribution of workload, which homogenizes over time due to reverse remodeling. The authors concluded that redistribution of regional loading appears as a mode of action of cardiac resynchronization therapy so that myocardial mechanics should be the main treatment target of cardiac resynchronization therapy. In our next paper, Jihye Jang and associates examined the association between local conduction velocity and late gadolinium enhancement and myocardial thickness in a swine model of healed left ventricular infarction. They studied six swine with healed myocardial infarction and two controls. The authors found a significantly slower conduction was found in late gadolinium enhancement regions, 0.33 versus 0.54 meters per second, P less than 0.001, and regions of wall thinning, 0.38 versus 0.55 meters per second, P also less than 0.001; areas with greater late gadolinium enhancement heterogeneity and wall thickness gradient exhibited slower conduction velocity. In our next paper, Xi Zhang and Xiaohui Kuang and associates studied whether restricting contact force to less than 20 grams reduces the risk of esophageal injury in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. In a prospective, single-center, randomized study, 89 consecutive patients, mean age 57.2 years, 57% men, with atrial fibrillation, 68.5% paroxysmal and 31.5% persistent were randomized to restrictive contact force group or non-contact force group. The primary end point was a rate of esophageal injury post ablation. The same power setting, similar ablation time, and average measured catheter tip temperature during posterior wall ablation just opposite to the esophagus were present in both groups, there were no cases of esophageal injury in the restricted contact force group versus 9 or 20% of cases of esophageal injury post ablation in the non-contact force group. There are similar rates of freedom from atrial tachyarrhythmias at a mean of 31.3 months follow-up, 68.2% versus 64.4%. In our next paper, J. Martijn Bos and associates examined whether sodium channel blockers like mexiletine may have a potential role in LQT1 and LQT2, two forms of potassium channel mediated long QT syndrome. They retrospectively studied 12 patients, 5 females, median age at diagnosis 14.1 years with genetically established long QT2 in 10 or a combination of LQT1/LQT2 in 1 or LQT2/LQT3 in 1, who all received mexiletine. Prior to diagnosis, six patients were symptomatic and prior to initiation of mexiletine, four patients experienced one breakthrough cardiac event on beta blocker therapy. Median age at first mexiletine dose was 24.3 years. After mexiletine, the median QTc decreased by 65 milliseconds from 547 milliseconds pre-mexiletine to 470 milliseconds post-mexiletine, P equals 0.0005 for all patients. In eight patients or 67%, the QTc decreased by 40 milliseconds with a mean decrease in QTc of 91 milliseconds, P less than 0.008. For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up. In our final paper, Andrea Mazzanti and associates assessed whether low dose quinidine in Brugada Syndrome patients reduces the occurrence of life-threatening arrhythmic events in this population. They compared the clinical course of 53 Brugada Syndrome patients treated with quinidine to that of 441 untreated controls, matched by sex, age, symptoms, and duration of observation. The 53 Brugada Syndrome patients, 89% males, median age 39.8 years, received quinidine at 439 milligrams per day for 5.0 years. Therapy was stopped in three cases or 6% for side effects. Quinidine reduced by 26% the risk of experiencing life-threatening arrhythmic events in cases versus controls; hazard ratio, 0.74; P equals 0.62. In 27 of 123 Brugada Syndrome patients symptomatic for life-threatening arrhythmic events who were treated for 7.0 years, the annual rate of life-threatening arrhythmic events decreased from 14.7% while off-quinidine to 3.9% while on-quinidine, P equals 0.03. The authors noted that recurrent life-threatening arrhythmic events were recorded in 4 or 15% of cardiac arrest survivors while on-quinidine, underscoring the importance of implantable defibrillator therapy. That's it for this month. We hope that you will find the Journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology April 2019 Issue16.04.2019 (00:11:37)
Dr Paul Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor in Chief, with some of the key highlights from this month's issue. In our first paper Lucas Boersma and associates examined the final two-year outcome data from 47 centers, in 1,020 patients receiving the left atrial appendage occlusion watchman devices. Their study population had a mean age of 73.4 years, with 311 having prior ischemic stroke or TIA, 153 having prior hemorrhagic stroke, and 318 having prior major bleeding. 49% had a CHAS II vast score of 5 or greater, and 40% had a HAS-BLED score of three or greater. Oral anticoagulation was contraindicated in 72%. During follow up, 161 patients, or 16.4% died, 22 strokes were observed or 1.3 per 100 patient years representing an 83% reduction versus historic data. And 47 major non-procedural bleeding events were observed, or 2.7 per 100 patient years representing a 46% reduction versus historic data. Device thrombus was observed in 34 patients or 4.1%, and was not correlated to the drug regimen during follow up. P=0.28. In our next paper, Anish Amin and Associates examined whether high voltage impedance and subcutaneous or SICD system implant position are associated with ventricular fibrillation or VF conversion success with a sub-maximal joule shock. In the SICD investigational device exemption study, a successful conversion test required two consecutive VF conversions at 65 joules in either shock vector. Sub-optimal device position was defined as an inferior electrode or pulse generator, or electrode coil depth of greater than three mm anterior to the sternum, based on chest radiograph. Of 314 patients who underwent SICD implantation, 282 patients were included in this analysis. There were 637 inductions to test defibrillation at 65 joules. 62 conversion failures, or 9.7%, occurred in 42 or 14.9% of patients. Lower body mass index or BMI, and lower shock impedance, were associated with higher conversion success rate. Whereas white race was associated with lower conversion success rate. Sub-optimal position was more common in obese patients. Inferior electrode and greater distance between the lead and sternum were associated with a higher impedance. When appropriate system position was achieved, conversion failure was not associated with high BMI. In our next paper, Je-Wook Park and associates examined the left atrial pressure after repeat radiofrequency catheter ablation procedures. Among 1,848 patients who underwent atrial fibrillation or AF catheter ablation, the authors measured the left atrial pressure, LAP, immediately following the transseptal puncture in sinus rhythm in 1,687 patients before De novo ablation, median age 59 years, 72.4% male and 72.8% paroxysmal AF, and in 142 with second procedures. In the same 142 patients, the degree of left atrial stiffness, reflected by LAPP, the difference between LAP peak and LAP nater, was significantly higher in the second procedure than in the De novo procedure. P An increase LAPP during repeat procedures was independently associated with a reduced diastolic function. P=0.041. However, the EQ5D symptom score did not change after de novo ablation. In our next paper, Adam Graham and associates examined a median of 711 electrocardiographic imaging, or ECGI, in cardiopirin points per patient to compare simultaneous epicardial mapping using CARTO and ECGI after geometrical co registration in 8 patients. They found that the correlation coefficient measuring the similarity of activation times we equal to 0.66, and the correlation coefficient for repolarization times was 0.55. The minimum distance between epicardial pacing sites, and the region of earliest activation in ECGI was 13.2 mm. Range 0 to 28.3 mm, from 25 pacing sites with stimulation to cuirass interval less than 40 milliseconds. In our next paper, Michael Barkagan and associates examined high-current, short-duration radiofrequency energy delivery using and expandable spheroid-shaped lattice electrode with effective service tenfold larger than standard irrigated electrodes. It incorporated nine surface temperature sensors, with ablation performed in temperature control mode. In phase one of the study, the authors found that six thigh muscle preparation experiments, ablation with the lattice catheter resulted in wider lesions at both low and high energy settings, 8.7 vs 12.2 mm. P In phase two of the study, in Eighth Swan, the authors found that right atrial lines created in the posterior lateral walls using low and high-energy settings with the lattice catheter were wider, posterior 14.7 versus 9.2 mm, P On phase three of the study, the authors found at 30 days, 100% of the ablation lines created with lattice catheter remained contiguous, compared to only 14.3% of lines created with a standard irrigated catheter. The authors reported that there were no steam pops or collateral tissue damage. In our next paper, Anett Ottesen and associated hypothesized that because circulating [inaudible] neuron concentrations are increased in patients with myocardial dysfunction, and predict poor outcome. And because secretive neuron inhibits calcium calmodulin dependent protein kinase ii delta activity, the up regulation of secretive neuron in patients protects against cardiomyocytes mechanisms arrhythmia. The authors found this secreting neuron levels were elevated in 8 patients with catecholaminergic polymorphic ventricular tachycardia, or in 155 patients after cardiac arrest. AAV9 induced over expression of secretive neuron, attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies map secreta neuron binding to the sub straight binding sight in catalyst region of calcium calmodulin dependent protein kinase ii delta. Secreta neuron attenuate in isoproterenol induced autophosphorylation of 3NE287 calcium calmodulin dependent protein kinase ii delta, in laying [inaudible] hearts, in inhibited calcium calmodulin dependent kinase ii dependent [inaudible] receptor phosphorylation. Secretor neuron treatment decreased calcium spark frequency in dimensions in cardiomyocytes during isoproterenol challenge, and reduced the instance of calcium wave delayed depolarizations in spontaneous action potentials. Secreta neuron treatment also lowered the incidence of early after depolarizations during isoproterenol paralleling a reduced magnitude of L type calcium current. Thus, the authors demonstrated that secreta neuron production is upregulated in conditions with cardiomyocytes calcium dysregulation and may provide compensatory protection against cardiomyocytes mechanisms of arrhythmia. In our final paper, Ne Gang and Shu Wang and associates examined whether Sorting Nexin-17, SNX17, regulates the trafficking process of protein voltage gated channel subfamily A member 5, which has been proposed as a target of interventions for atrial fibrillation. The authors curated a Sorting Nexin-17 knockout rat line. Sorting Nexin-17 hetero zygotes rat survived, and the level of Sorting Nexin-17 protein in the atrium was decreased by 50%. Sorting Nexin-17 deficiency increased the membrane expression of KV1.5 in atrial specific ultra-rapid delayed rectifier outward potassium current IKUR density, resulting in shorted actual potential duration, and eventually contribute to atrial fibrillation susceptibility. Sorting Nexin-17 facilitated the endocytic sorting of KV1.5 from the plasma membrane to early endosomes following the 4.1 ezrin radixin moesin called Firm domain. The authors concluded that Sorting Nexin-17 mediates susceptibility to atrial fibrillation through this mechanism, and thus may be a potent target for the development of new drugs for atrial fibrillation. That's it for this month, we hope that you'll find the journal the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology March 2019 Issue25.03.2019 (00:15:22)
Dr Paul Wang: Welcome to the monthly podcast "On the Beat" for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in Chief, with some of the key highlights from this month's issue. In our first manuscript, Marie Bayer Elming and associates, examined whether the right ventricular ejection fraction can identify patients with non-ischemic systolic heart failure, more likely to benefit from ICD implantation. The Danish study, to assess the efficacy of ICDs in patients with non-ischemic systolic heart failure, on mortality, the Danish study, randomized patients with non-ischemic systolic heart failure to ICD our control. In 239 patients with interpretable cardiovascular magnetic resonance images, the right ventricular volume and ejection fraction was measured. Right ventricular ejection fraction was an independent predictor of all-cause mortality, with a hazard ration 1.34 per 10% absolute decrease in our right ventricular ejection fraction. P=0.02. There is statistically significant interaction between right ventricular ejection fraction and the effect of ICD implantation. P=0.001. ICD implantation significantly reduced all-cause mortality in patients with right ventricular systolic dysfunction. Hazard ratio 0.41, but not in patients without right ventricular systolic dysfunction. Thus, in this post-hoc analysis of the Danish trial, ICD therapy was associated with survival benefit in patients with bi-ventricular heart failure. In our next paper, Dawn Pedrotty and Volodymyr Kuzmenko and associates, have proposed a concept of using a stretchable, flexible, bio patch, with conductive properties, to attempt to restore conduction across regions in which activation is disrupted. They use carbon nanotube patches, composed of nanofibrillated cellulose, in single wall carbon nanotube ink, 3-D printed in conductive patterns onto bacterial nanocellulose. Electro anatomic mapping was performed on normal epicardium and repeated over surgically disruptive epicardium, and finally with the patch applied passively. The patch resulted in restored conduction based on mapping. In our next paper, Ayman Hussein and colleagues developed a fully automated platform to collect patient reported outcomes in a prospective cohort of atrial fibrillation ablation. Two thousand one hundred and seventy-five patients were eligible to receive 10,903 patient reported outcome assessment invitations. More follow up assessments were obtained with automated patient reported outcomes in routine follow-up, compared with routine follow up alone, P > 0.001, which allowed for longer duration of follow up, 378 vs 217 days. By automated patient reported outcomes, a large number of disease specific variables were collected and showed improvement in quality of life. Baseline median AF symptom severity score of 12 and ranged between 2 and 3 on subsequent assessments, P > 0.0001. This improvement was also true for each of the atrial fibrillation symptom severity score components. In patient reported outcomes, there was a significant reduction in atrial fibrillation burden, such as frequency and duration episodes and associated healthcare utilization including emergency visits and hospitalizations after the ablation procedures. In our next paper, Nicolas Johner, Dipen Shah, and associates, examined the role of post pacing intervals shorter than tachycardia cycling during entrainment mapping. The author studied 24 non-cavotricuspid isthmus dependent macro oriented atrial flutters in 19 consecutive patients. High density electro anatomic activation maps were acquired with a 64-electrode basket catheter of 102 entrainment mapping sites. Post pacing interval difference less than 30 was observed at 72 sites on complete maps of 24 atypical atrial flutters compared to sites with the difference in post pacing intervals 0 to 30, with 45 sites difference in the post pacing interval less than 0 at 27 were more commonly located within isthmuses less than 15mm wide and more frequently located in within 5mm of the leading wave front. It also exhibited slower local conduction, lower voltages in more frequently fractioned electrograms. The authors concluded that in atrial flutter, sites with differences with the post pacing interval are markers of limited width critical isthmuses with slower conduction velocity, while sites with difference in post pacing interval 0 to 30ms are often not in close proximity to the reentrance circuit. Virtual electrode simultaneous down and up stream, antidromic capture of a confined isthmus of slow conduction can explain a difference in the post pacing interval less than 0. In the next paper, José Manuel Alfonso-Almazán, and associates studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. The author studied 34 pigs undergoing in vivo catheter based ablation using continuous contact force and lesion index monitoring during 60 second radiofrequency delivery with an open, irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 watts, 50 watts, or 60 watts and acute, chronic arterial damage was quantified by multi photon microscopy in ex vivo samples. Adjacent microlesion were quantified in parallel samples. The remaining 8 pigs, these were used to validate safety and efficacy parameters. Acute collagen elastic alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in patients without [steam pop 00:06:56]. The main parameters associated with steam pops were median peak temperature greater than 42C, and impedance falls greater than 23 ohms. Unlike other parameters, lesion index values of 9.1 units were associated with the presence of adjacent myocardial lesions in both univariate and multivariate analyses. In the validation group, lesion index values using 40 watts over a range of contact forces correlated with the size of radiofrequency lesions. Lesion index values obtained during 40 watts radiofrequency application reliably monitor safe and effective lesion creation at the root of the great arteries. In our next paper, Eiichiro Oka and associates examine the prevalence and significance of the early repolarization electrocardiographic pattern and its mechanistic insight based on cardiac magnetic resonance findings in patients with acute myocarditis. The author studied 30 patients with the diagnosis of acute myocarditis. Nine had an early repolarization electrocardiographical pattern, which was defined as a terminal QRS notching or slurring with an amplitude of greater than zero-point millivolts in at least two inferior and/or lateral leads. The early repolarization group, while the remaining 21 cases had broad ST elevation or pathological QAs. The non-early repolarization group. The cardiac prepotency level was significantly higher in the non-early repolarization group than the early repolarization group. The ECD changes returned to baseline, along with a normalization of the cardiac biomarkers. Nine of the 21 non-early repolarization group patients, but none of the 9 early repolarization groups developed fulminant course of lethal ventricular arrhythmias. T2-weighted cardiac magnetic resonance imaging showed high intensity signals over the entire transmittal left vertical in the non-early repolarization group, where as they were localized to the left ventricle epicardium in early repolarization group. The early repolarization pattern in acute myocarditis was transient and reversible, and was not associated with a worse prognosis. Inflammation or swelling localized to the left ventricular epicardium, due to myocarditis, may provide a mechanistic insight into the early repolarization pattern. In our next paper, Beatrix Scholz and Jan Sebastian Schulte and associates analyzed whether the histone deacetylase class I and II inhibitor valproic acid is able to attenuate atrial remodeling in CREM-IbΔCx (TG) transgenic mice. A mouse model of extensive atrial remodeling with age dependent progression from spontaneous atrial ectopy to paroxysmal and finally long lasting atrial fibrillation. Valproic acid was administered for 7 or 25 weeks to transgenic and control mice. Valproic acid attenuated many components of atrial remodeling that were present in the transgenic mice. Valproic acid significantly reduced atrial dilation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocytes ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of atrial fibrillation by 4 to 8 weeks. Increased histone H4 acetylation in atria from valproic acid treated transgenic mice verified effective in in vivo histone deacetylase inhibition. Cardiomyocyte specific genetic inactivation of histone deacetylase HDAC 2 in transgenic mice attenuated the ultrastructural disorganization of myocytes compared to valproic acid. The author suggests that valproic acid, clinically available, well tolerated, and prescribed to many patients for years, has a therapeutic potential to delay the development of atrial remodeling in the onset of atrial fibrillation in patients at risk. In our next paper, Bence Hegyi and associates measure the major inward currents in their calcium channel and beta-adrenergic dependence under physiologic action potential clamp in rabbit ventricular myocytes in chronic pressure volume overload induced heart failure versus age matched controls. They found that CAM kinase II dependent up regulation of late sodium current in heart failure significantly contributes to the action potential prolongation in increased short-term variability of action potential repolarization, which may lead to increased arrhythmia propensity and is further exacerbated by adrenergic stress. In a research letter, Arnaud Bisson and associates examined mitral regurgitation in 838, or 10%, of 8675 patients with atrial fibrillation. A total 135, or 16%, had severe mitral regurgitation. During mean follow-up with 2.5 years, 688 ischemic stroke or thromboembolic events were recorded. mitral regurgitation was associated with a non-significant higher risk of these embolic events. After adjustment for anticoagulant and antiplatelet use, CHA2DS2-VASc and HAS-BLED scores, patients with mitral regurgitation tended to have a higher all cause or cardiovascular mortality but had similar risks of ischemic stroke or thromboembolic events, when compared to patients with no mitral regurgitation. Severe mitral regurgitation was also associated with similar risk for ischemic stroke and thromboembolic events when compared with other atrial fibrillation patients. However, our findings indicate that in patients with atrial fibrillation, neither mitral regurgitation nor severe mitral regurgitation, appears to independently be associated with a different risk of ischemic stroke or thromboembolic events. The perceived protective effect of mitral regurgitation against the risk of thromboembolic events is not relevant in atrial fibrillation when using a contemporary risk score scheme, the CHA2DS2-VASc score. In our final research paper, Jack Z. Li and associates noted that in 2017, an aggregate of four manufacturers of devices yielded 89.6% with the DF-4 ICD implants. While DF-4 and DF-1 leads generally have comparable performance, several concerns over reduced versatility of the DF-4 have been raised. First, to downgrade an ICD with a DF-4 lead to a pacemaker, a generator change, a new right ventricular pace sense lead must be implanted. The DF-4 pin is incompatible with the IS-1 port and there is no straightforward way to bridge this gap. In contrast, the DF-1 IS-1 lead requires only capping of the DF-1 pin. Second, if an ICD with DF-4 lead has either a distal coil or a right ventricular pacing malfunction, a new lead must be implanted. Third, if a ICD with DF-4 lead has a high defibrillation threshold, management requires either a new DF-1 IS-1 lead with an adapter for a subcutaneous array, or an adapter that inserts into the DF-4 port and receives both the DF-4 lead and the DF-1 pin of the subcutaneous lead. Physicians should have the foresight to select DF-1 leads at the time of initial implant in selected circumstances, such as high possibility for elevated defibrillation threshold requiring a subcutaneous lead or array. That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See ya next time. This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology February 2019 Issue19.02.2019 (00:09:29)
Dr Paul Wong: Welcome to the monthly podcast on the beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wong, Editor-in Chief with some of the key highlights from this month's issue. This month's issue is dedicated to a new exciting topic, His bundle pacing. His bundle pacing is designed to achieve a more physiological human dynamic response than right ventricular pacing alone, which may be needed in patients with AV conduction abnormalities. In our first paper, Marek Jastrzebski and associates examined whether program stimulation may be used to distinguish nonselective His bundle capture from right ventricular myocardial capture. Premature beats were introduced at 10 millisecond steps during intrinsic rhythm, and also after a drive train of 600 milli seconds. The longest coupling interval that resulted in an abrupt change in the QRS morphology was considered equal to the effective refractory period of the His bundle or right ventricular myocardium. Program His bundle pacing was performed from 50 different sites in 32 patients. In 34 out of 36 cases of nonselective His bundle pacing, the right ventricular myocardial effective refractory period was shorter than the His bundle effective a refractory period. 271 milliseconds versus 353 milliseconds, P less than 0.0001. Program His bundle pacing using a drive train typically resulted in an abrupt change of the QRS morphology. From nonselective His bundle to right ventricular myocardial QRS 34 out of 36 cases, or to selective His bundle QRS in two out of 36 cases. Program His bundle pacing deliver during native conduction resulted in obtaining selective His bundle QRS in 20 out of 34 patients, and right ventricular myocardial QRS in 14 out of 34 of the nonselective His bundle cases. In right ventricular myocardial only pacing cases, so-called false nonselective His bundle pacing, and equals 14. Such responses were not observed. The QRS morphology remained stable. Therefore His bundle pacing correctly diagnosed, using programs stimulation, all nonselective His bundle cases in all right ventricular myocardial pacing cases. In our next paper Aditya Saini and associates sought to determine whether the device electric cam can be used to differentiate between selective, nonselective His bundle pacing, and right ventricular septal capture. In 148 consecutive patients, His bundle pacing was performed. The near field ventricular electrogram morphology, the near field ventricular electrogram time to peak and the far field ventricular electrogram QRS duration were recorded while pacing the His bundle was simultaneous 12 lead ECG rhythm strips. The mean baseline QRS duration was 108 milliseconds, with QRS duration greater than 120 milliseconds in 57 or 39% of patients, including 27 with right bundle branch block, 18 with left bundle branch block, and 12 with an IVCD. Selective His bundle pacing was noted in 54 or 36% of patients. A positive near field ventricular electrogram time to peak, and a near field ventricular electrogram time to peak of greater than 40 milliseconds were highly sensitive, 94% and 93% respectively, and specific 90% and 94% for selective His bundle pacing, irrespective of baseline QRS duration. All three parameters including positive near field ventricular electrogram time to peak, the near field ventricular electrogram time to peak greater than 40 milliseconds, and far field ventricular electrogram QRS duration less than 120 milliseconds had high predictive negative predictive value, 97%, 95%, and 92%. Therefore, a novel device-based algorithm for a selective His bundle pacing was proposed. Electrogram transitions correlated with ECG transitions during threshold testing, and can accurately predict and differentiate between selective His bundle pacing, nonselective His bundle pacing, and right ventricular septal pacing with a cumulative positive predictive value of 91% and 100% in patients with a baseline QRS duration of less than 120 milliseconds. In the next paper, Pugazhendhi Vijayaraman and associates examined whether Cardiac Resynchronization Therapy could be optimized by sequential His bundle pacing followed by left ventricular pacing, which the authors called His optimize CRT or hot CRT. Hot CRT was successfully achieved in 25 of 27 patients. The QRS duration and baseline was 183 milliseconds, and significantly narrowed to 162 milliseconds with biventricular pacing, to 151 milli seconds during His bundle pacing, and further to 120 milliseconds during hot CRT pacing, P less than 0.0001. During a mean follow-up of 14 months, left ventricular ejection fraction improved from 24 to 38%, P less than 0.0001, and New York Heart Association Functional Class changed from 3.3 to 2.04. 21 out of the 25 patients, or 84% were clinical responders, while 23 of 25, 92% showed echocardiographic response. In our next paper, Parikshit Sharma and associates compared permanent His bundle pacing using three-dimensional electro anatomic mapping in low fluoroscopy in 10 patients, and compared the outcomes with conventional fluoroscopy guided His bundle pacing implants in 20 patients. His bundle pacing was successful in nine out of 10 patients using electro anatomic mapping, and 100% successful in the conventional patients. The mean His bundled fluoroscopy time was lower in electro anatomic mapping group, 0.2 minutes compared to eight minutes in the conventional group, P equals 0.002. The His bundle capture threshold was lower in the electro anatomic mapping group, 0.7 at one millisecond compared to the conventional group, 1.15 at one millisecond, P equals 0.04. There were no procedure related complications or lead dislodgements in either group. In our next paper, Michael Orlov and associates describe a new technique in which pacing leads for permanent His bundle pacing were connected to electro anatomical mapping in 28 patients. The selective and nonselective His bundle capture sites were tagged. The His bundle cloud was 360 millimeters squared, and the lead was successfully deployed in 25 patients in the threshold of the His bundle pacing, and implant was 1.5 volts at 1.5 milli seconds. In our final paper, Haran Burri and associates provide practical recommendations for programming pacemakers with His bundle pacing in order to deliver optimal therapy and ensure patient's safety. The authors discuss the important role of electrocardiographic analysis of His bundle capture. They also advise that ventricular capture management should be programmed inactive because of the absence of an evoked potential. The authors discuss the option of placing the His bundle electrode in the left and trigger a report of a cardiac resynchronization therapy pacemaker. The readers will find this overview of programming His bundle pacing very informative. In this issue, we also have a very special year-end review, which highlights many of the top discoveries in our field. You will not want to miss it. Okay. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association, 2019.
Circulation: Arrhythmia and Electrophysiology january 2019 Issue15.01.2019 (00:11:26)
Dr Paul Wang: Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. Koji Miyamoto and associates conducted the AD-Balloon Study, which investigates the ideal number of free cycles during second-generation cryoballoon pulmonary vein isolation. In a prospective, multicenter, randomized clinical trial, the authors compared in 110 patients the addition of a three minute freeze after pulmonary vein isolation had been achieved to pulmonary vein isolation alone. Delayed-enhancement magnetic resonance imaging was also performed one to two months after the pulmonary vein isolation to assess the ablation lesions. The freedom from atrial arrhythmias at one year was similar. Log rank test, P equals 0.78 in the two groups, 87.3% in the extra three-minute freeze group, and 89.1% in the pulmonary vein isolation group. There was no significant difference in the frequency of gaps on the pulmonary vein isolation lines in the delayed-enhancement magnetic resonance imaging. The authors conclude that an insurance freeze after achieving pulmonary vein isolation may be unnecessary and time consuming. In our next study, Robert Sheldon and associates examined the genetic basis of vasovagal syncope. They studied 160 subjects in 9 kindreds comprising 82 fainters and 78 controls. Common genetic variants were genotype for 12 genes for vascular signaling, potassium channels, the serotonin 5-HT1A receptor, the serotonin transporter and catecholamine-O-methyltransferase or COMT. They found that in 9 of 12 variants, there was no significant association between genotype and phenotype. However, the serotonin 5-HT1A receptor, HTR1-A G alleles were associated with syncope in males but not in females. P equals 0.005. The men with serotonin 5-HT1 receptor C alleles had a 9% likelihood of syncope while Gg males had a 77% likelihood of syncope. The SL6A4 promoter L alleles were associated with decreased syncope in males but increase in females. P equals 0.059. The Ll males had a 25% syncope likelihood and Ss males had a 47% syncope likelihood. The COMT A alleles were associated with decreased syncope in males but increased in females. P equals 0.017. The Gg males had a 50% syncope likelihood and A males had a 15% syncope likelihood. The Gg females had 52% syncope likelihood and the Aa females had a 73% syncope likelihood. The authors concluded that there is a sex-dependent effect of alleles of serotonin signaling in vasovagal syncope, supporting the serotonin hypothesis of the physiology of vasovagal syncope. In the next study, Michael Barkagan and associates sought to examine whether the standard criteria for mitral line block with endocardial and epicardial activation mapping may not distinguish from slow conduction or conduction via epicardial bridging connections. In 56 patients, the authors creates a posterior mitral line using radiofrequency ablation. Mitral block determined by pacing with conduction block defined as trans-isthmus time of 100 milliseconds or greater in reversal of coronary sinus activation during pacing from the left atrial appendage was achieved in 51 out of 56 or 91% of patients. In 11 of 51 or 22% of patients, high-resolution activation mapping, using Rhythmia, of the endocardium and epicardium via the coronary sinus demonstrated residual endocardial in 27% or residual epicardial in 73% connections. Epicardial bridging connections were distant from the line, 2.4 plus or minus 1.6 centimeters, inserting laterally at the proximal-mid coronary sinus and septally at the left atrial ridge. Patients with residual conduction were prone to complex circuits involving the epicardium in 7 of 11 patients. Mitral line block was achieved in 75% by targeting these insertion sites. The trans-isthmus time had limited predictive value for distinguishing block from pseudoblock. The authors concluded the connections are a frequent cause of complex circuits, and their insertion sites can be targeted for ablation. In our next paper, Santiago Rivera and associates examined the causes of QRS variability in Papillary muscle arrhythmias usually attributed to anisotropy. In 33 patients with papillary muscle arrhythmias prospectively undergoing cardiac resonance imaging, papillary muscle connections away from the papillary muscle base were identified. Arrhythmogenic papillary muscles, N equals 35, exhibited a higher number of papillary muscle connections, 72 versus 18, P equals 0.01. Patients with inconsistent QRS precordial transition and inconsistent QRS access exhibited a 100% prevalence of papillary muscle connections. Those with consistent precordial transition and consistent QRS access showed 40% and 26% prevalence of papillary muscle connections respectively. Inconsistent QRS precordial transition and inconsistent QRS access predicted the presence of papillary muscle connections with 59% or 28% sensitivity and 100% specificity respectively. Those papillary muscles exhibiting clinical recurrence after ablation presented a higher prevalence of papillary muscle connections, 91% versus 60%, P=0.04. In our next paper, Jason Coult and associates examined the quantitative measures of the electrocardiogram waveform during ventricular fibrillation to assess myocardial physiology and predict cardiac arrest outcomes. They collected five second ventricular fibrillation ECG segments with and without chest compressions prior to 2,755 defibrillation shocks from 1,151 out of hospital cardiac arrest patients. 24 individual measures and 3 combination measures were optimized to predict functionally intact survival using 460 training cases. Measures predicted functionally intact survival in 691 independent test cases with an area under the receiver operating curve (AUC) ranging from 0.56 to 0.75 without chest compressions and 0.53 to 0.75 with compressions, P less than 0.001. Of all measures evaluated, the support vector machine model ranked highest both without chest compressions, AUC equals 0.75, and with compressions, AUC equals 0.75. The authors concluded the waveform measures predict functionally intact survival when calculated during chest compressions, but prognostic performance is generally reduced compared to analysis without compressions. Support vector machine models exhibited similar performance with and without compressions while also achieving the highest area under the curve. In our last paper, Hailey Jansen, Martin Mackasey and associates examined the effective natriuretic peptides in the specific natriuretic peptide receptor NPR-C on angiotensin II-mediated atrial fibrillation. The authors examined wild-type and NPR-C knockout mice to investigate the effects of angiotensin II administered three milligrams per kilo per day for three weeks on atrial fibrillation susceptibility and atrial function. In wild-type mice, angiotensin II increased susceptibility to atrial fibrillation and associated with a prolonged P wave duration, increased atrial refractory period, and slowed atrial conduction. These effects were exacerbated in angiotensin II-treated NPR-C knockout mice. Angiotensin II prolonged action potential duration and reduced action potential upstroke velocity. Angiotensin II also increased fibrosis in the atria in wild-type mice while angiotensin II-treated NPR-C knockout mice exhibited substantially higher atrial fibrosis. Co-treating wild-type mice with angiotensin II and the NPR-C agonist cANF, those dependently reduced atrial fibrillation inducibility by preventing some of the angiotensin II-induced changes in atrial myocyte electrophysiology and preventing atrial fibrosis. The authors suggested that the NPR-C receptor may represent a new target for the prevention of angiotensin II-induced atrial fibrillation via protective effects on atrial, electrical and structural remodeling. That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time! This program is copyright American Heart Association 2019.
Circulation: Arrhythmia and Electrophysiology December 2018 Issue18.12.2018 (00:14:14)
Dr Paul Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights for this month's issue. In our first paper, Pasquale Vergara and Associates develop a predictive risk score to assess the outcome of ventricular tachycardia ablation creating what they call the IVT score. The authors examined 16 demographics, clinical, and procedural related variables in 1,251 patients. They used a technique called survival tree analysis, which uses a recursive partitioning algorithm to find relationships among variables. They then compared the survival time and time to VT recurrence in groups derived from survival tree analysis using a log rank test. A random forest analysis was then run to extract a variable importance index and internally validate the survival tree models. They found that the left ventricular ejection fraction, ICD, or CRT device, previous ablation were the best predictors of ventricular tachycardia recurrence. While left ventricular ejection fraction, previous ablation, electrical storm was identified as best predictors of mortality. They identified a high-risk group in which 65% of patients survived and 52.1% were free from VT occurrence. A medium risk group in which 84% survived and 72% were free of VT, and a low risk group in which 97% of patients survived and 88% were free of VT recurrence. In our next paper, Alwin Zweerink and Associates examined the relationship between cure restoration and left ventricular dimension as predictors of outcomes after cardiac re-synchronization therapy. The present study evaluates the effect of normalization of the cure restoration to left ventricular dimension on the prediction of survival after CRT implantation. They study 250 heart failure patients with left ventricular ejection fraction less than or equal to 35% in cure restoration greater than or equal to 120 milliseconds, and they normalize the cure restoration based on the left ventricular dimension. The left ventricular and diastolic volumes obtained using cardiac magnetic resonance imaging. Before CRT implantation were used for cure restoration normalization. During a follow up period of 3.9 years, 79 patients or 32% reached the primary end point, which combined death, left ventricular assist device, or heart transplantation. Using univariable cox regression they found that although the unadjusted cure restoration was unrelated to CRT outcome, P=0.116, the normalized cure restoration was a strong predictor of survival. Hazard ratio 0.81 per 0.1 milliseconds per milliliter, P=0.008. Women demonstrated higher normalized cure restorations than men, 0.2 milliseconds per milliliter, versus 0.55 millisecond per milliliter, P=0.003, and showed better survival after CRT. Hazard ratio 0.52 with P=0.018. In our next study, Markus Linhart and Associates examined the impact of catheter ablation gaps on outcomes after first pulmonary vein isolation. Using delayed gadolinium enhancement cardiac magnetic resonance imaging three months after radio frequency ablation, they found that in 94 patients, 62% with paroxysmal atrial fibrillation, that there was a mean number of 5.4 gaps per patients. Atrial fibrillation recurrence within the first year of ablation was observed in 21 patients with paroxysmal AF, 36%, and 19 patients with persistent atrial fibrillation, 53%. In the unit variate analysis, CHA2DS2 -VASc score, afib type and relative gap length were predictors of recurrence. In multi-variant analysis, only relative gap length was significantly associated with recurrence. Hazard ratio 1.16 per each 10% of the gap. In our next paper, Antonius van Stipdonk, Iris ter Horst, Marielle Kloosterman, Alexander Maass, Kevin Vernooy and Associates examined the value of cueres area compared to that of cure restoration and morphology as predictors of clinical echocardiographical outcomes following cardiac resynchronization therapy. The authors found that in 1,492 cardiac resynchronization therapy patients during a mean follow up of 3.4 years, 32% of patients reached the combined prior endpoint of all-cause mortality, cardiac transplantation, and left ventricular assist device implantation. The authors found that cure restoration identified patients that did not experience the primary endpoint better than QRS morphology in cure restoration area under the curve 0.61 versus 0.55 and 0.51, P value less than 0.001. They also found that QRS area identifies patients with echocardiograph remodeling in response to CRT better than the QRS morphology and duration, area under the curve 0.69 versus 0.58 and 0.58, P Our next paper is a research letter in which Brian Hansen, Ning Li and Associates report the first in-vivo use in a canine model of near infrared optical mapping. In-vivo optical action potential showed a sharp upstroke that corresponded with atrial activation at a neighboring electrode. Imaging during in-vivo atrial fibrillation episodes showed re-entrant activation around the sinoatrial region minimizing the effect of motion artifact in validation in structurally remodeled hearts would be the next steps for this promising technology. Also, in a research letter, James Hummel and Associates studied whether infrared thermography over a six-centimeter segment can be effectively used to guide atrial fibrillation ablation. Thermography continuously sampled 7,680 points over a full 360 degree and refreshed every second. Ablation was guided by 3D mapping and performed using a 3.5-millimeter irrigated tip. Power was reduced to 25-watts on the left atrial posterior wall and could be further reduced to 20-watts in areas where there was excessive esophageal temperature rise. Esophageal temperature cutoff for radio frequency power delivery was initially 46 degrees and progressively raised to 50 degrees throughout the study at the discretion of the operators. All patients underwent upper endoscopy on post-ablation day one to three by a gastroenterologist blinded to temperature data. Thirty-four patients were studied, 94% of patients had luminal esophageal temperatures above 40 degrees during ablation of the posterior wall. Thermal events with Tmex greater than 40 degrees occurred commonly averaging 6.5 seconds during a procedure. On average, 231 seconds of ablation were performed with Tmex greater than 40 degrees centigrade. However, the excursions above threshold cutoff Tmex greater than 50 degrees centigrade lasted only 1.5 seconds per patient. In total, 38% of patients, 13 out of 34 had at least one energy delivery discontinued for exceeding threshold. This occurred eight out of 17 times or 47% when the cutoff was 46 degrees centigrade and five out of 15, or 33% at 50 degrees centigrade. On endoscopy one patient, 3% had thermal injury related to malpositioning of the infrared thermal probe below the region of ablation. Another patient had three lesions spanning 16 centimeters likely related to mechanical trauma with probe placement. The authors concluded that esophageal injury does not seem to occur with esophageal temperatures less than 50 degrees centigrade using thermography. In a review paper in this issue, Bruce Lerman and Associates discussed adenosine as a potent but underutilized tool that is useful in clarifying in clinical diagnoses of arrhythmias. Adenosine mediates its electrophysiological effect through binding to the cell surface adenosine receptor A1R, a G-protein receptor. In the sinoatrial node, activation of IKADO by adenosine results in negative chronotrophy, a manifestation of its modern effects on membrane hyperpolarization and a decrease in the rate of phase four depolarization. Adenosine also mediates its cellular effects in atrial and AV nodal cells predominantly through activation of IKADO. In atrial myocytes, this results in a shortening of action potential duration in decrease in refractoriness. By shortening the atrial refractory period without changing atrial conduction velocity, the wavelength of activation is shortened. A mechanism through which adenosine can facilitate induction of atrial fibrillation. Adenosine also exerts an antiadrenergic effect in atrial tissue, reducing cyclic AMP stimulated levels of L-type calcium current. Adenosine has a negative dromotropic effect on the AV node. The most potent effects of adenosine are expressed in N-cells. In these cells, as well as AN-cells, adenosine decreases excitability by reducing the plateau amplitude in abbreviating action potential duration. In addition, it reduces the rate of rise of the upstroke of N-cells. NH-cells are insensitive to adenosine. Adenosine terminates permanent form of junctional recipriatachycardia in the retrograde accessory pathway limb. The mechanism in which adenosine causes block in the retrograde decremental accessory pathway is thought to be by hyper-polarizing the pathways membrane potential. Adenosine has been helpful in illuminating differences in etiology of decremental conduction in three predominant antigrid decremental accessory pathways. Atrial ventricular pathways, atrial physicular pathways, and nodoventricular pathways. Adenosine can elicit dormant conduction defined as a restoration of excitability by adenosine in tissue rendered inexcitable by partial cellular damage secondary to ablation. There are three discrete clinical scenarios in which adenosine reveals dormant conduction - after pulmonary vein isolation, after achieving bi-directional cavo-tricuspid isthmus block, and following successful ablation of antegrade and retrograde accessory potential. Adenosine, through activation of IKADO hyperpolarizing these cells so that the sodium channels are reactivated, restoring excitability. Adenosine, though its inhibition of cyclic ANP mediated increases in the slow inward calcium current and its downstream inhibitory effects on SR-calcium release, INCX and ITI, terminates focal arrhythmias caused by triggered activity. The response to adenosine may indicate triggered activity where termination occurs versus insensitivity of localized re-entry to adenosine. That's it for this month, we hope that you will find The Journal to be the go-to place for everyone interested in the field. See you next time.
Circulation: Arrhythmia and Electrophysiology November 2018 issue20.11.2018 (00:00:00)
Dr Paul Wang: Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. In our first paper, Elizabeth Saarel and associates describe the analysis of athletes in the ICD sports registry. The authors found that over a median follow-up of 42 months of 129 young athletes, and a mean age of 16 years, there were 35 athletes, or 27%, that received a total of 38 shocks. Long QT syndrome and hypertrophic cardiomyopathy were the most common diagnoses. While shocks related to competition and practice were not uncommon, there were no serious adverse sequelae. Lead malfunction rates were similar to previously reported in an unselected pediatric ICD populations. There were no occurrences of death, arrest, injury related to arrhythmia during sports. There was one ventricular tachycardia ventricular fibrillation storm during competition. In our next paper, Kedar K. Aras and associates theorize that the tissue volume to wavelength volume ratio is important in determining ventricular fibrillation sustainability. They perform panoramic optical mapping of coronary perfused human left ventricular wedge preparations, which were subjected to acts of potential duration changes produced by IK,ATP agonist pinacidil and antagonist glybenclamide. They found that pinacidil and escalating concentrations progressively decreased the volume wavelength in ventricular fibrillation became sustained when the tissue volume to wavelength ratio was above the safety factor, K equals 4.4. In addition, ventricular fibrillation was only sustained when the ventricular volume exceeded the critical wavelength volume defined by the product of pacing cycle wave length in the longitudinal transverse and transmural directions. In our next paper Thomas Deneke and associates examine the ability of a novel infrared thermal probe to predict endoscopically detected thermal esophageal lesions post atrial fibrillation ablation. They studied six patients undergoing their first pulmonary vein isolation, using radio frequency point by point catheter ablation in the HEAT-AF study; 12 or 19% of patients had endoscopically detected thermal esophageal lesions. The peak esophageal temperature Tpeak was significantly higher, 56.3 degrees Celsius versus 45.7 degrees Celsius. P less than 0.0001 in patients with endoscopically detected thermal esophageal lesions compared to those without lesions. Logistical regression analysis demonstrated Tpeak was a statistically significant predictor, P equals 0.0008 pf endoscopically detected thermal esophageal lesions with an odds ratio of 1.52. In our next paper Dian Cheng and associates examine a novel algorithm incorporating right precordial and posterior leads to discriminate between left ventricular outflow tract and right ventricular outflow tract foci. The V3R to V7 index was prospectively tested in consecutive patients at four centers. In 94 patients of the validation cohort with 79% RVOT foci, a QS pattern in lead V3R exclusively recorded in right ventricular outflow tract foci, while an S wave in V3 was exclusively recorded in left ventricular outflow tract foci. The V3R to V7 index of LVOT origin was significantly great than that of RVOT 1.05 versus 0.28 P, less than 0.001 with a V3R to V7 index of greater than equal to 0.85 predicting an LVOT origin with 87% sensitivity and 96% specificity. With the V3R to V7 index of 0.85 or greater RVOT origin could be excluded with 98.6% accuracy. In the next paper Jim Cheung and associates examine the in-hospital outcomes, cause, and thirty-day readmissions following catheter ablation of MI associated ventricular tachycardia. The authors use a nationwide readmissions database to evaluate 4109 admissions for catheter ablation of MI associated ventricular tachycardia occurring between 2010 and 2015. The index admission in-hospital mortality rate was 2.7% and the procedural complication rate after ventricular tachycardiablation was 11.5%. Pulmonary hypertension, lung disease, obesity and coagulopathy were independent predictors of mortality. Following discharge after VT ablation the thirty-day readmission rate was 19.2%. With the median time to readmission of 10.0 days, in an in-hospital mortality of 2.9%. Cardiac causes accounted for 74% of readmissions. With ventricular tachycardia accounting for 41% of admissions and congestive heart failure accounting for 14% of readmissions. Pulmonary hypertension, congestive heart failure, smoking, chronic pulmonary disease, and prolonged index hospitalization were significant independent predictors of thirty-day readmission. After adjustment thirty-day readmissions were associated with a 38.9% increase in cumulative hospitalization costs. In the next paper Tomofumi Nakamura and associates examine the relation of hemorrhagic and thromboembolic events with anticoagulations strategy in the setting of epicardial axis procedures for ventricular arrhythmia mapping and ablation. In 355 patients oral anticoagulants were stopped perioperatively in heparin administered prior to the procedure. The patients were divided to three groups per the anticoagulations strategy. Group 1, no heparin was administered before pericardial access, Group 2, heparin was administered in reverse before pericardial access, and Group 3 heparin was administered and not reversed. Significant pericardial bleeding defined is greater than 80 milliliter occurred in 46 cases or 13% and did not differ among the three groups. Unintentional cardiac puncture in left ventricular chest infraction less than [inaudible 00:07:32] 35% were independently associated with pericardial bleeding with an odd ratio of 16.4 or 2.28. Of 38 procedures with unintentional cardiac puncture there were no differences in pericardial bleeding for different anti-coagulant strategies. Thromboembolic events occur in 5 patients, 1 coronary embolism, 1 stroke, 2 deep vein thrombosis, and 1 fatal pulmonary embolism and 1 thrombus on a temporary ventricular assist device. In the next paper, Elisabeth Mouws and associates examine whether the combination of lines of conduction block with multiple wave fronts at the pulmonary vein area may result in increased arrhythmogenicity and susceptibility to atrial fibrillation. The author performed intra-operative high-density epicardial mapping of pulmonary vein area and is 450 sites with an intra-electrical distance of 2 milliliters which performed during sinus rhythm in 327 patients. With and without preoperative intra-fibrillation. Excitation of the pulmonary vein area occurred via multiple consecutive wave fronts in the vast majority, 81% of patients. In total 561 wave fronts were observed which propagated through the septal or paraseptal regions tore the pulmonary vein area in 82%. Substantial dissociation of consecutive wave fronts was observed with delta activation times of 10.6 milliseconds. No difference was observed in delta activation times of consecutive wave fronts during sinus rhythm between patients with and without atrial fibrillation. In excitation-based risk factor model including conduction delay of greater equal to 6 millimeters conduction block of greater than or equal to 6 millimeters and conduction delay conduction block of 16 millimeters or greater, wave fronts vie the posterior inferior and posterior superior in multiple opposing wave fronts demonstrated a 5-fold risk of atrial fibrillation when multiple risk factors were present. In our final paper Yoshitaka Kimura and associates examine the prognostics significance of PR interval prolongation on adverse cardiac events. They studied 176 patients with repaired tetralogy of flow with a median age of 17.4 years then they evaluated their correlation with right ventricular volume and function measured by cardiac magnetic resonance and the significance as a risk factor of adverse cardiac events were ventricular arrhythmias, atrial arrhythmias, heart failure, hospitalization, complete AV block, and all cause death. First degree AV block was noted 25 patients or 14% during a median follow-up of 10 years there was a progressive prolongation of PR interval 2.0 milliseconds per year. Importantly there were significant correlations between PR interval prolongation and right ventricular enlargement or right ventricular disfunction. In contrast, patients who underwent pulmonary valve replacement, N equal 23, significant shortening of PR interval was noted, 204 versus 176 milliseconds, P equals 0.007. Cox regression analysis showed that the first degree AV block was an independent risk factor for ventricular arrhythmias hazard ratio 5.479, in complete heart block, hazard ratio 27.67, and it had a tendency for heart failure hospitalization, hazard ratio 3.3. In addition PR interval prolongation greater than 2 millisecond per year was also a significant risk factor for ventricular arrhythmias regardless of the presence or absence of first degree AV block in enrollment. That's it for this month. We hope that you will find the journal to be the go to place for everyone interested in the field. See you next time.

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