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BACKGROUND Cardiac resynchronization therapy (CRT) using bi-ventricular pacing (BVP) is effective in patients with heart failure, left bundle branch block (LBBB), and reduced left ventricular function. Left bundle branch area pacing (LBBAP) has been reported as an alternative option for CRT. OBJECTIVE The purpose of this study was to assess the feasibility and outcomes of LBBAP in patients who failed conventional BVP because of coronary venous (CV) lead complications or who were nonresponders to BVP. METHODS At 16 international centers, LBBAP was attempted in patients with conventional CRT indication who failed BVP because of CV lead complications or lack of therapeutic response to BVP. Heart failure hospitalization (HFH) and death, echocardiographic outcomes, procedural data, pacing parameters, and lead complications including CV lead failure are reported. RESULTS LBBAP was successfully performed in 200 patients (CV lead failures 156; nonresponders 44) (age 68 +/- 11 years; female 35%; LBBB 55%; right ventricular pacing 23%; ischemic cardiomyopathy 28%; nonischemic cardiomyopathy 63%; left ventricular ejection fraction [LVEF]

Cardiac resynchronization therapy (CRT) using biventricular pacing has limited efficacy in patients with heart failure (HF) and right bundle branch block (RBBB). Left bundle branch area pacing (LBBAP) is a novel physiologic pacing option. OBJECTIVE The aim of the study was to assess the feasibility and outcomes of LBBAP in HF patients with RBBB and reduced left ventricular systolic function, and indication for CRT or ventricular pacing. METHODS LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) = 5% increase in ejection fraction) to LBBAP were assessed. RESULTS LBBAP was attempted in 121 patients and successful in 107 (88%). Patient characteristics included age 74 +/- 12 years, female 25%, ischemic cardiomyopathy 49%, and ejection fraction 35% +/- 9%. QRS axis at baseline was normal in 24%, left axis 63%, right axis 13%. LBBAP threshold and R-wave amplitudes were 0.8 +/- 0.3 V@ 0.5 ms and 10 +/- 9 mV at implant and remained stable during mean follow-up of 13 +/- 8 months. LBBAP resulted in narrowing of QRS duration (156 +/- 20 ms to 150 +/- 24 ms (P = .01) with R-wave peak times in V-6 of 85 +/- 16 ms. LVEF improved from 35% +/- 9% to 43% +/- 12% (P,.01). Clinical and echocardiographic response was observed in 60% and 61% of patients, respectively. Female sex and reduction in QRS duration with LBBAP were predictive of echocardiographic response and super-response. CONCLUSION LBBAP is a feasible alternative to deliver CRT or physiologic ventricular pacing in patients with RBBB, HF, and LV dysfunction.

Background: Pulmonary vein isolation (PVI) has evolved to be an integral part of ablative therapy for atrial fibrillation (AF), however, recurrence rates of AF remain high even after complete wide area circumferential PVI. In recent years adjunct posterior wall isolation (PWI) has been performed in patients with more persistent forms of AF but the benefits remain unclear. Aim: The objective of this meta-analysis was to evaluate the efficacy of adjunct posterior wall isolation in reducing recurrence rate of AF using cryoballoon ablation (CBA). Methods: We searched PubMed, Google Scholar, Clinicaltrials.gov and Cochrane CENTRAL. We included studies comparing PVI to PVI + PWI in patients with persistent AF undergoing CBA. After data extraction and quality assessment of the studies, we assessed recurrence rates of atrial tachy-arrhythmias (AF, atrial flutter, and atrial tachycardia) as well as total ablation time and procedural adverse events. Risk ratio (RR), mean difference (MD) and 95% confidence interval (CI) were calculated using Review Manager. Results: Concomitant PWI demonstrated significant decrease in recurrence risk of AF (RR 0.48; 95% CI 0.36-0.64; p < 0.00001) as well as all atrial arrhythmias (RR 0.57; 95% CI 0.47-0.70; p < 0.0001). There was no significant difference in adverse events between both groups (RR 1.05; 95% CI 0.43-2.56; p = 0.91), whereas total ablation time was significantly increased in PVI + PWI group (MD 22.67, 95% CI, 7.61-37.73, p = 0.003). Conclusion: Adjunct PWI when compared to PVI alone decreases recurrence rates of atrial tachy-arrhythmias after CBA of persistent AF.

Objectives The aim of this study was to assess the feasibility and outcomes of left bundle branch area pacing (LBBAP) in patients eligible for cardiac resynchronization therapy (CRT) in an international, multicenter, collaborative study. Background CRT using biventricular pacing is effective in patients with heart failure and left bundle branch block (LBBB). LBBAP has been reported as an alternative option for CRT. Methods LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) Results LBBAP was attempted in 325 patients, and CRT was successfully achieved in 277 (85%) (mean age 71 ± 12 years, 35% women, ischemic cardiomyopathy in 44%). QRS configuration at baseline was LBBB in 39% and non-LBBB in 46%. Procedure and fluoroscopy duration were 105 ± 54 and 19 ± 15 min, respectively. LBBAP threshold and R-wave amplitudes were 0.6 ± 0.3 V at 0.5 ms and 10.6 ± 6 mV at implantation and remained stable during mean follow-up of 6 ± 5 months. LBBAP resulted in significant QRS narrowing from 152 ± 32 to 137 ± 22 ms (p Conclusions LBBAP is feasible and safe and provides an alternative option for CRT. LBBAP provides remarkably low and stable pacing thresholds and was associated with improved clinical and echocardiographic outcomes.

Although conventional biventricular pacing has been shown to benefit patients with heart failure and conduction system disease, there are limitations to its therapeutic success, resulting in widely variable clinical response. Limitations of conventional biventricular pacing evolve around myocardial scar, fibrosis, and inability to effectively stimulate diseased tissue. Several observational and acute hemodynamic studies have demonstrated improved electrical resynchronization and echocardiographic response with conduction system pacing. This article provides a systematic review of conduction system pacing as a physiologic alternative to conventional CRT, which is currently undergoing rigorous investigation.

We report seven patients who underwent bail out cryoballoon ablation of ventricular arrhythmias refractory to conventional endocardial radiofrequency ablation. Ablated arrhythmia substrates included right ventricular moderator band (n=2), left ventricular (LV) papillary muscle (n=2), left fascicular (n=1) and deep LV myocardial (n=2). Cryoballoon ablation was successful in 5/7 patients. Advantages of cryoballon ablation include adhesive stability on endocavitary structures and creation deep homogeneous myocardial lesionds. Newer balloon technologies designed to improve myocardial contact that incorporate high density mapping on the balloon surface may expand utility of this technology for ablation of ventricular arrhythmias.

The usage of flavored electronic nicotine delivery systems (ENDS) is popular, specifically in the teen and young adult age-groups. The possible cardiac toxicity of the flavoring aspect of ENDS is largely unknown. Vaping, a form of electronic nicotine delivery, uses “e-liquid” to generate “e-vapor,” an aerosolized mixture of nicotine and/or flavors. We report our investigation into the cardiotoxic effects of flavored e-liquids. E-vapors containing flavoring aldehydes such as vanillin and cinnamaldehyde, as indicated by mass spectrometry, were more toxic in HL-1 cardiomyocytes than fruit-flavored e-vapor. Exposure of human induced pluripotent stem cell-derived cardiomyocytes to cinnamaldehyde or vanillin-flavored e-vapor affected the beating frequency and prolonged the field potential duration of these cells more than fruit-flavored e-vapor. In addition, vanillin aldehyde-flavored e-vapor reduced the human ether-à-go-go-related gene (hERG)-encoded potassium current in transfected human embryonic kidney cells. In mice, inhalation exposure to vanillin aldehyde-flavored e-vapor for 10 wk caused increased sympathetic predominance in heart rate variability measurements. In vivo inducible ventricular tachycardia was significantly longer, and in optical mapping, the magnitude of ventricular action potential duration alternans was significantly larger in the vanillin aldehyde-flavored e-vapor-exposed mice than in controls. We conclude that the widely popular flavored ENDS are not harm free, and they have a potential for cardiac harm. More studies are needed to further assess their cardiac safety profile and long-term health effects. NEW & NOTEWORTHY The use of electronic nicotine delivery systems (ENDS) is not harm free. It is not known whether ENDS negatively affect cardiac electrophysiological function. Our study in cell lines and in mice shows that ENDS can compromise cardiac electrophysiology, leading to action potential instability and inducible ventricular arrhythmias. Further investigations are necessary to assess the long-term cardiac safety profile of ENDS products in humans and to better understand how individual components of ENDS affect cardiac toxicity.

In chronic systolic heart failure and conduction system disease, cardiac resynchronization therapy (CRT) is the only known non-pharmacologic heart failure therapy that improves cardiac function, functional capacity, and survival while decreasing cardiac workload and hospitalization rates. While conventional bi-ventricular pacing has been shown to benefit patients with heart failure and conduction system disease, there are limitations to its therapeutic success, resulting in widely variable clinical response. Limitations of conventional CRT evolve around myocardial scar, fibrosis, and inability to effectively simulate diseased tissue. Studies have shown endocardial stimulation in closer proximity to the specialized conduction system is more effective when compared with epicardial stimulation. Several observational and acute haemodynamic studies have demonstrated improved electrical resynchronization and echocardiographic response with conduction system pacing (CSP). Our objective is to provide a systematic review of the evolution of CRT, and an introduction to CSP as an intriguing, though experimental physiologic alternative to conventional CRT.

BACKGROUND Cardiac resynchronization therapy (CRT) based on the conventional biventricular pacing (BiV-CRT) technique sometimes results in broad QRS complex and suboptimal response. OBJECTIVE We aimed to assess the feasibility and outcomes of CRT based on left bundle branch area pacing (LBBAP, in lieu of the right ventricular lead) combined with coronary venous left ventricular pacing in an international multicenter study. METHODS LBBAP-optimized CRT (LOT-CRT) was attempted in nonconsecutive patients with CRT indications. Addition of the LBBA (or coronary venous) lead was at the discretion of the implanting physician, who was guided by suboptimal paced QRS complex, and/or on clinical grounds. RESULTS LOT-CRT was successful in 91 of 112 patients (81%). The baseline characteristics were as follows: mean age 70 +/- 11 years, female 22 (20%), left ventricular ejection fraction 28.7% +/- 9.8%, left ventricular end-diastolic diameter 62 +/- 9 mm, N-terminal pro-B-type natriuretic peptide level 5821 +/- 8193 pg/mL, left bundle branch block 47 (42%), nonspecific intraventricular conduction delay 25 (22%), right ventricular pacing 26 (23%), and right bundle branch block 14 (12%). The procedure characteristics were as follows: mean fluoroscopy time 27.3 +/- 22 minutes, LBBAP capture threshold 0.8 +/- 0.5 V @ 0.5 ms, and R-wave amplitude 10 mV. LOT-CRT resulted in significantly greater narrowing of QRS complex from 182 +/- 25 ms at baseline to 144 +/- 22 ms (P < .0001) than did BiV-CRT (170 +/- 30 ms; P < .0001) and LBBAP (162 +/- 23 ms; P < .0001). At follow-up of >= 3 months, the ejection fraction improved to 37% +/- 12%, left ventricular end-diastolic diameter decreased to 59 +/- 9 mm, N-terminal pro-B-type natriuretic peptide level decreased to 2514 +/- 3537 pg/mL, pacing parameters were stable, and clinical improvement was noted in 76% of patients (New York Heart Association class 2.9 vs 1.9). CONCLUSION LOT-CRT is feasible and safe and provides greater electrical resynchronization as compared with BiV-CRT and could be an alternative, especially when only suboptimal electrical re synchronization is obtained with BiV-CRT. Randomized controlled trials comparing LOT-CRT and BiV-CRT are needed.

Cardiac resynchronization therapy (CRT) is highly effective for patients with left bundle branch block (LBBB), heart failure and left ventricular (LV) systolic dysfunction. Chronic right ventricular (RV) apical pacing is associated with pacing-induced cardiomyopathy and can be associated with exertional intolerance. The goal of this study was to assess the acute hemodynamic effects of His-bundle Pacing (HBP) compared to RV apical pacing in absence of LV systolic dysfunction in patients with exertional intolerance. Our patient population consisted of 5 patients with preserved LV systolic function and complete AV block. All five patients suffered from exertional intolerance in spite of preserved LV systolic function. At the time of generator change, all patients underwent implantation of a HBP lead. The QRS duration decreased from 179±13 ms with RVP to 113±6 with HBP (p < 0.001). Compared to RVP, HBP was associated with significantly longer diastolic filling time and improved septal early diastolic myocardial relaxation velocity (E’). Four of five patients noted acutely improved exertional dyspnea. In patients with AV block, exertional intolerance and preserved LV systolic function who are treated with chronic RV apical pacing, HBP may improve acute diastolic function and symptoms of exertional intolerance when compared to RV apical pacing. Randomized controlled trials are warranted to explore the effects of conduction system pacing in this unique patient population.

[EN] BACKGROUND: The formation of recipient-to donor atrio-atrial connections (AAC) in patients after orthotopic heart transplantation (OHT) is poorly understood. We sought to investigate the mechanisms of atrial tachyarrhythmias after OHT, the role of AACs, and their relationship to the immunologic match. METHODS: In a large series of OHT patients, we performed a retrospective review of 42 patients who underwent catheter ablation for atrial arrhythmias. A realistic 3-dimensional computer model of human atria was used to study AAC conductivity. RESULTS: Patient age was 55 +/- 15 years (71% male). Biatrial anastomosis was present in 24/42 patients (57%). An AAC was found in 9/42 patients (21%, right-sided in 5 patients with biatrial anastomosis, left-sided in 4 patients). The AAC became apparent at the time of the electrophysiology study 10.1 +/- 7.6 years after OHT (range, 0.3-22.2 years). Donor-specific antibodies were present in no patient with AAC but were present in 69% of patients without AAC, P=0.002. In all patients with AAC, a recipient atrial tachycardia propagated via AAC to the donor atrium (4 patients presented with atrial fibrillation). Simulations showed AAC conduction requires an isthmus of >= 2 mm and is cycle length and location dependent. Patients without AAC (n=13) frequently presented with donor atrial arrhythmias, in 77% cavo-tricuspid isthmus flutter was ablated. The procedural success was high, although, 12 patients (29%) required reablation. CONCLUSIONS: AACs are found in 21% of OHT patients with atrial tachyarrhythmias and can manifest very early after OHT. Immune privilege characterized by the absence of donor-specific antibodies may facilitate AAC formation. Propagation across an AAC is width, cycle length, and location dependent. Patients with AAC present with focal atrial tachycardias or atrial fibrillation originating from the recipient atria; patients without most frequently present with cavo-tricuspid isthmus dependent atrial flutter. While multiple arrhythmias frequently require reablation, ablative therapy is highly effective., This study was supported in part by National Institutes of Health grants R21HL138064, and R01HL129136 to Dr Noujaim. This work was partially supported by the Direccion General de Politica Cientifica de la Generalitat Valenciana (PROMETEU2020/043).

Background: Cardiac resynchronization therapy (CRT) using biventricular pacing (BVP) has limited efficacy in patients with heart failure (HF) and right bundle branch block (RBBB). Left bundle branch area pacing (LBBAP) has been reported as an alternative option for BVP-CRT. The aim of the study was to assess the feasibility and outcomes of LBBAP in patients with RBBB and indication for CRT in an international, multicenter, collaborative study. Methods: LBBAP was attempted in patients with LVEF

Introduction: Right ventricular failure (RVF) and ventricular tachyarrhythmias (VA) are common causes of poor outcome and mortality in patients with left ventricular assist device (LVAD). VA can precipitate RVF and inotropic therapy can further exacerbate VA. The purpose of this observational study was to investigate the individual and combined impact of RVF and VA on mortality in the early postoperative period after LVAD. Methods: We performed a retrospective analysis of patients undergoing implantation of an LVAD between 2014 to 2017 (N=110). Telemetry tracings and device interrogations were reviewed. Early VA was defined as any ventricular tachycardia and ventricular fibrillation within the first month after LVAD associated with hemodynamic compromise that required device therapy, catheter ablation, and/or antiarrhythmic therapy. Kaplan-Meier statistics with the Mantel-Cox log-rank test was used to analyze survival. Results: We identified 110 LVAD patients, age 57±13 years, 80 males (73%), ischemic cardiomyopathy n=54 (49%), (HeartWare (n=44), HeartMate II (n=44), and HeartMate III (n=22)). Patients were categorized into group A - early VA and severe RVF (n=14); group B - early VA without RVF (n=16); group C - severe RVF without early VA (n=33); and group D - neither VA nor RVF (n=47). The 1-year survival of group A, B, C, and D was 50%, 69%, 73%, and 89%, respectively (p=0.001 comparing each group to the other groups, enclosed figure). The presence of early VA did not relate to RVF (p=0.7). Pre-operative VA was related to post-LVAD VA (RR 9.4, p=0.003). Conclusions: Patients without early VA or severe RVF demonstrated the best survival. Both, VA and severe RVF decreased survival. The presence of both, VA and RVF appears to potentiate mortality. Pre-operative VA is related to post-LVAD VA. These data raise the question if intra-operative ablative therapy in patients undergoing LVAD implantation could improve post-operative mortality, VA, and RVF.

Introduction: Catheter ablation has become the cornerstone for the treatment of drug-refractory paroxysmal atrial fibrillation. Two main forms of energy are used: cryoablation (CB) and radiofrequency (RF). Multiple studies have compared the effectiveness/safety curve between these two; among which is the FIRE AND ICE and the FREEZE AF trials which showed non-inferiority between these two technologies. Despite the remarkable success achieved at controlling arrythmias, complications as high as 16.3% have been reported in both technologies. Objectives: The main purpose of this meta-analysis is to compare the incidence of esophageal and myocardial injuries among patients undergoing radiofrequency ablation vs cryoablation for the treatment of atrial fibrillation or atrial flutter (AF). Methods/Results: We searched Pubmed/Embase, Medline and Cochrane from inception to April 2020 for studies that met our predetermined inclusion and exclusion criteria. All studies comparing RFA to CBA and reporting the incidence of life-threatening complications (esophageal injuries and perforation/tamponade) were included in our analysis. To limit confounding variables and significant heterogeneity between studies, we selected only randomized-control trials and propensity-matched observational studies. A total of 2748 patients were identified. Overall analyses show that RFA has significantly higher life-threatening complications than CBA (OR = 2.79, 95% CI: 1.41-5.52; p=0.003). Conclusion: The present systematic review and meta-analysis demonstrates that RFA has 3 times more life-threatening complications than CBA. As previous studies have already shown similar degree of freedom from AF between these two ablation technologies, CBA appears to be more advantageous overall.

The aim of this study was to assess the feasibility and outcomes of left bundle branch area pacing (LBBAP) in patients eligible for cardiac resynchronization therapy (CRT) in an international, multicenter, collaborative study.CRT using biventricular pacing is effective in patients with heart failure and left bundle branch block (LBBB). LBBAP has been reported as an alternative option for CRT.LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) 50% and indications for CRT or pacing. Procedural outcomes, left bundle branch capture, New York Heart Association functional class, heart failure hospitalization, echocardiographic data, and lead complications were recorded. Clinical (no heart failure hospitalization and improvement in New York Heart Association functional class) and echocardiographic responses (≥5% improvement in LVEF) were assessed.LBBAP was attempted in 325 patients, and CRT was successfully achieved in 277 (85%) (mean age 71 ± 12 years, 35% women, ischemic cardiomyopathy in 44%). QRS configuration at baseline was LBBB in 39% and non-LBBB in 46%. Procedure and fluoroscopy duration were 105 ± 54 and 19 ± 15 min, respectively. LBBAP threshold and R-wave amplitudes were 0.6 ± 0.3 V at 0.5 ms and 10.6 ± 6 mV at implantation and remained stable during mean follow-up of 6 ± 5 months. LBBAP resulted in significant QRS narrowing from 152 ± 32 to 137 ± 22 ms (p 0.01). LVEF improved from 33 ± 10% to 44 ± 11% (p 0.01). Clinical and echocardiographic responses were observed in 72% and 73% of patients, respectively. Baseline LBBB (odds ratio: 3.96; 95% confidence interval: 1.64 to 9.26; p 0.01) and left ventricular end-diastolic diameter (odds ratio: 0.62; 95% confidence interval: 0.49 to 0.79; p 0.01) were independent predictors of echocardiographic response.LBBAP is feasible and safe and provides an alternative option for CRT. LBBAP provides remarkably low and stable pacing thresholds and was associated with improved clinical and echocardiographic outcomes.

Background Cardiac resynchronization therapy (CRT) using biventricular pacing (BVP) is effective in patients with heart failure, bundle branch block (BBB), or right ventricular pacing. Permanent His-bundle pacing (HBP) has been reported as an alternative option for CRT. Objective The purpose of this study was to assess the feasibility and outcomes of HBP in CRT eligible or failed patients. Methods HBP was attempted as a rescue strategy in patients with failed left ventricular lead or nonresponse to BVP (group I), or as a primary strategy in patients with AV block, BBB, or high ventricular pacing burden as an alternative to BVP (group II) in patients with indications for CRT. Implant characteristics, New York Heart Association functional class, and echocardiographic data were assessed in follow-up. Results HBP was successful in 95 of 106 patients (90%): 30 in group I and 65 in group II. Mean age was 71 ± 12 years and 30% were female, with BBB in 45%, paced rhythm in 39%, and AV block in 16%. His capture and BBB correction thresholds were 1.4 ± 0.9 V and 2.0 ± 1.2 V at 1 ms, respectively. During mean follow-up of 14 months, both groups demonstrated significant narrowing of QRS from 157 ± 33 ms to 117 ± 18 ms (P = .0001), increase in left ventricular ejection fraction from 30% ± 10% to 43% ± 13% (P = .0001), and improvement in New York Heart Association functional class from 2.8 ± 0.5 to 1.8 ± 0.6 (P = .0001) with HBP. Lead-related complications occurred in 7 patients. Conclusion Permanent HBP is a promising alternative for CRT. HBP may be considered as a rescue strategy for failed BVP and may be a reasonable primary alternative to BVP for CRT.

Biventricular pacing has occasionally been associated with ventricular proarrhythmia, which at times can be refractory to conventional antiarrhythmic drug therapy and ablative intervention. Recently, permanent His-bundle pacing has emerged as a reasonable alternative to right ventricular and biventricular pacing. In addition, by maintaining the physiologic pattern of ventricular electrical activation, it is less likely to be arrhythmogenic. We report the use of permanent His-bundle pacing to manage ventricular proarrhythmia that developed after initiation of biventricular pacing and was unresponsive to antiarrhythmic and ablative therapy.

Background Atrial fibrillation (AF) prevalence increases significantly with age. Little is known about the effect of AF ablation on quality of life and healthcare utilization in the elderly. The objective of this study was to quantify the healthcare utilization and quality of life benefits of catheter ablation for AF, for patients ≥65 years compared to patients

Background: Cardiac resynchronization therapy (CRT) is an established therapy for patients with cardiomyopathy, left bundle branch block, and heart failure. His bundle pacing (HBP) may also improve clinical outcomes by narrowing QRS duration. The QRS narrowing by HBP may not always be optimal. The aim of the study was to determine if CRT could be optimized by sequential HBP followed by left ventricular (LV) pacing (His-Optimized CRT [HOT-CRT]) to maximize electrical resynchronization. Methods: We attempted permanent HBP in 27 patients (left bundle branch block 17, intraventricular conduction defect 5, and right ventricular pacing 5) referred for CRT in addition to LV lead. HBP was followed by LV pacing at a delay equal to His-ventricular interval. QRS duration at baseline, during HBP, biventricular pacing, and HOT-CRT was measured. Echocardiographic parameters and New York Heart Association functional class were assessed at baseline and during follow-up. Results: HOT-CRT was successful in 25 of 27 patients (age 72±15 years, men 23, ischemic 21). QRS duration at baseline was 183±27 ms and significantly narrowed to 162±17 ms with biventricular pacing ( P =0.003), to 151±24 ms during HBP ( P P P Conclusions: In this feasibility cohort, HOT-CRT resulted in improved electrical resynchronization. HOT-CRT may improve clinical and echocardiographic outcomes in advanced heart failure patients requiring CRT.

His-bundle pacing (HBP) is a physiological alternative to right ventricular pacing (RVP). The outcomes of HBP in patients with longstanding atrioventricular block (AVB) and RVP are unknown OBJECTIVE: The purpose of this study was to retrospectively assess the feasibility of HBP in patients with chronic RVP and longstanding AVB and to evaluate its efficacy in reversing the adverse remodeling induced by RVP.HBP was attempted in patients with longstanding AVB and chronic RVP and/or pacing-induced cardiomyopathy (PICM) in need for resynchronization therapy. The site of conduction block and feasibility of HBP was documented. Electrocardiographic and echocardiographic assessments at baseline and follow-up were recorded.HBP was successful in 79 of 85 patients (93%) with RVP for 77.6 ± 74.8 months (range 2-540 months). AV nodal block was present in 59 and infranodal block in 26. QRS duration increased from 123 ± 31 ms at baseline to 177 ± 17 ms (P.001) during RVP and decreased to 115 ± 20 ms with HBP (P.001). T-wave memory was observed in 53 of 79 patients with HBP and normalized in 2-12 weeks. HBP threshold was 1.47 ± 0.9 V @ 1 ms at implant and 1.9 ± 1.3 V @ 1 ms at last follow-up (25 ± 24 months). In 60 patients with PICM in whom left ventricular ejection fraction decreased from 54% ± 7.7% at baseline to 34.3% ± 9.6% (P .001), ejection fraction improved to 48.2% ± 9.8% (P .001) after HBP CONCLUSION: Despite a long duration of AVB and chronic RVP, HBP normalized QRS complexes and T waves with stable thresholds, suggesting that progression of distal conduction disease is uncommon in this population. Electrical and structural changes induced by chronic RVP were consistently reversed with HBP.

[EN] In clinical practice, reducing the burden of persistent atrial fibrillation by pharmacological means is challenging. We explored if blocking the background and the acetylcholine-activated inward rectifier potassium currents (I-K1 and I-KACh) could be antiarrhythmic in persistent atrial fibrillation. We thus tested the hypothesis that blocking I-K1 and I-KACh with chloroquine decreases the burden of persistent atrial fibrillation. We used patch clamp to determine the IC50 of I-K1 and I-KACh block by chloroquine and molecular modeling to simulate the interaction between chloroquine and Kir2.1 and Kir3.1, the molecular correlates of I-K1 and I-KACh. We then tested, as a proof of concept, if oral chloroquine administration to a patient with persistent atrial fibrillation can decrease the arrhythmia burden. We also simulated the effects of chloroquine in a 3D model of human atria with persistent atrial fibrillation. In patch clamp the IC50 of I-K1 block by chloroquine was similar to that of I-KACh. A 14-day regimen of oral chloroquine significantly decreased the burden of persistent atrial fibrillation in a patient. Mathematical simulations of persistent atrial fibrillation in a 3D model of human atria suggested that chloroquine prolonged the action potential duration, leading to failure of reentrant excitation, and the subsequent termination of the arrhythmia. The combined block of I-K1 and I-KACh can be a targeted therapeutic strategy for persistent atrial fibrillation., This work was supported in part by National Institutes of Health grants R21HL138064, R01HL129136, by the Direccion General de Politica Cientifica de la Generalitat Valenciana (PROMETEO 2016/088), and by the ACM SIGHPC/Intel Computational & Data Science fellowship.

Long-term right ventricular pacing has deleterious effects on the left ventricle (LV). The risk of pacemaker-induced cardiomyopathy (PICM) seems to be lower in patients with a normal LV ejection fraction (LVEF). Patients developing PICM respond favorably to a cardiac resynchronization therapy upgrade, suggesting that the dysfunction is partially reversible. Biventricular pacing has emerged as a treatment and/or prevention of PICM. Cumulative pacing greater than 40% of the time is considered the most important risk factor for PICM. No organizational guidelines exist for preventive biventricular pacing. The decision to pursue biventricular pacing should be individualized.

MRI Assessment of Ablation-Induced Scarring in Atrial FibrillationBackground There is limited knowledge on the extent and location of scarring that results from catheter ablation and its role in suppressing atrial fibrillation (AF). We examined the effect of atrial fibrosis and ablation-induced scarring on catheter ablation outcomes in AF. Methods We conducted a prospective multicenter study that enrolled 329 AF patients presenting for catheter ablation. Delayed enhancement magnetic resonance imaging (DE-MRI) of the left atrium was obtained preablation. Scarring was evaluated in 177 patients with a DE-MRI scan obtained 90 days postablation. We evaluated residual fibrosis, defined as preablation atrial fibrosis not covered by ablation scar. The primary outcome was freedom from recurrent atrial arrhythmia. Results In the analysis cohort of 177 patients, preablation fibrosis was 18.7 ± 8.7% of the atrial wall. Ablation aimed at pulmonary vein (PV) isolation was performed in 163 patients (92.1%). Ablation-induced scar averaged 10.6 ± 4.4% of the atrial wall. Scarring completely encircled all 4 PVs only in 12 patients (7.3%). Residual fibrosis was calculated at 15.8 ± 8.0%. At 325 days follow-up, 35% of patients experienced recurrent arrhythmia. Multivariable Cox proportional hazards models demonstrated that baseline atrial fibrosis (HR and 95% CIs) (1.09 [1.06–1.12], P < 0.001) and residual fibrosis (1.09 [1.05–1.13], P < 0.001) were associated with atrial arrhythmia recurrence, while PV encirclement and overall scar were not. Conclusions Catheter ablation of AF targeting PVs rarely achieves permanent encircling scar in the intended areas. Overall atrial fibrosis present at baseline and residual fibrosis uncovered by ablation scar are associated with recurrent arrhythmia.

Adipositas cordis is a rare cardiomyopathy characterized by diffuse fatty infiltration of the ventricular myocardium or interventricular septum. This occurs without myocardial cell destruction, unlike arrhythmogenic right ventricular cardiomyopathy. A 40-year-old obese woman was found to have a II/VI systolic murmur that worsened with standing. A transthoracic echocardiogram showed interventricular septal hypertrophy with a preserved left ventricular ejection fraction. Cardiac magnetic resonance imaging revealed a fatty mass in the interventricular septum. An endomyocardial biopsy revealed structurally normal myocytes with diffuse adipose cell infiltration and no evidence of malignant cells. Left and right cardiac catheterizations and stress echocardiography showed no abnormalities. This case shows the importance of considering a broad differential when approaching rare diseases. It also demonstrates the utility of noninvasive imaging and its impact on clinical decision making.

Objectives There is little information about arrhythmia burden in cancer survivors with chemotherapy-induced cardiomyopathy (CIC). We hypothesise that the rates and risk of arrhythmias will be similar in CIC when compared with other non-ischaemic cardiomyopathy (NICMO) aetiologies. Methods We retrospectively identified nine patients with CIC and an implantable defibrillator and 18 age and sex-matched control patients (nine patients with NICMO and nine patients with ischaemic cardiomyopathy (ICMO)). Rates and odds of arrhythmias were calculated by type of cardiomyopathy, adjusting for days since implantable cardioverter defibrillator implantation, history of atrial fibrillation and length of follow-up using logistic regression analysis. Results Compared with patients with NICMO, rates and adjusted odds were similar for patients with CIC for atrial arrhythmias (44.4% vs 33.3%; adjusted OR=1.89; 95% CI0.17 to 21.03; P=0.61), non-sustained ventricular tachycardia (NSVT) (44.4% vs 33.3%; OR=2.10; 95% CI 0.21 to 20.56; P=0.53), and the combined outcome of NSVT, sustained ventricular tachycardia and/or ventricular fibrillation (44.4% vs 44.4%; OR=2.70; 95% CI 0.25 to 29.48; P=0.42). Conversely, compared with patients with NICMO, patients with ICMO demonstrated higher rates and adjusted odds of the combined outcome (88.9% vs 44.4%; OR=28.60; 95% CI 1.26 to 648.2; P=0.04) and NSVT (77.8% vs 33.3%; OR=8.95; 95% CI 0.90 to 88.94; P=0.06). Conclusions While tentative based on sample size, rates of arrhythmias in patients with CIC appear to be similar to those experienced by patients with other forms of NICMO.

The DF-4 lead connector offers the advantage of a smaller, less complex header, requiring only a single set screw to connect all high and low voltage terminals. It reduces the possibility of lead/ connector failure at the cost of decreased flexibility to selectively replace or substitute individual components of the implantable cardioverter defibrillator (ICD) lead. New floating atrial bipole single-lead ICD systems offer the benefits of dual-chamber sensing, including atrial tachyarrhythmia detection and improved supra ventricular tachycardia (SVT) discrimination, avoiding the disadvantages of an additional atrial lead. They are not suitable for atrial pacing. Novel shock reduction strategies include sophisticated T-wave discrimination algorithms, advanced lead integrity monitoring, and enhanced lead noise discrimination; they are further enhanced by remote ICD monitoring. Remote monitoring of ICD devices has been associated with a reduction in office visits and hospitalizations, improved battery life, and reduction in inappropriate ICD shocks. The subcutaneous ICD is a new effective alternative for patients who lack vascular access or when it seems beneficial to avoid transvenous lead placement. Up to 75% of cardiac implantable electronic device patients will need a magnetic resonance imaging scan (MRI) at some point in their life. MRI conditional ICD and cardiac resynchronization therapy (CRT) devices are under clinical investigation.

Author(s): Arshad, Aysha; Johnson, Christopher K; Mittal, Suneet; Buch, Eric; Hamam, Ismail; Tran, Thanh; Shaw, Richard E; Musat, Dan; Preminger, Mark; Sichrovsky, Tina; Herweg, Bengt; Shivkumar, Kalyanam; Hummel, John; Steinberg, Jonathan S | Abstract: BackgroundThere are a variety of periprocedural anticoagulation strategies for atrial fibrillation (AF) ablation, including the use of dabigatran. It is unclear which strategy is superior.ObjectiveTo compare the safety and efficacy of anticoagulation with uninterrupted warfarin, dabigatran, and warfarin with heparin bridging in patients undergoing ablation of AF at four experienced centers.Methods and resultsIn this retrospective analysis, 882 patients (mean age: 61 ± 11 years) underwent ablation of AF using uninterrupted warfarin (n = 276), dabigatran (n = 374), or warfarin with heparin bridging (n = 232) for periprocedural anticoagulation. The rate of total complications was 23/276 (8.3%) in the uninterrupted warfarin group, 30/374 (8.0%) in the dabigatran group, and 29/232 (12.5%) in the bridged group (P = 0.15). Major complications were more frequent in the uninterrupted warfarin group 12/276 (4.3%) compared with 3/374 (0.8%) in dabigatran and 6/232 (2.6%) in the bridged group (P = 0.01). The most common major complication was the need for transfusion or occurrence of major bleeding. Minor complications did not differ among the three groups. On multivariate analysis, female gender (odds ratio [OR] 1.93, confidence interval [CI] 1.16-3.19, P = 0.011), bridging heparin (OR 2.13, CI 1.100-3.941, P = 0.016), use of triple antithrombotic therapy (OR 1.77, CI 1.05-2.98, P = 0.033), and prior myocardial infarction (OR 2.40, CI 1.01-5.67, P = 0.046) independently predicted total complications.ConclusionsWhen comparing the use of uninterrupted warfarin, dabigatran, and warfarin with heparin bridging in patients undergoing catheter ablation of AF, dabigatran was not associated with increased risk, major complications were more common in the uninterrupted warfarin group, and after adjustment, warfarin with bridging increased total complications.

Radiofrequency (RF) catheter ablation has proven efficacy for treating many types of supraventricular arrhythmias and has become an increasingly important clinical tool for treating atrial fibrillation (AF).1 Electrical isolation of the pulmonary veins (PVs) from the left atrium is the cornerstone for most AF ablation procedures and is considered the best interventional method to treat AF in the paroxysmal AF population.2 Efforts to improve the efficacy and safety of RF ablation (RFA) led to the development of the open irrigation 6-hole catheter, which was the first catheter approved for ablation of AF in 2009.3,4 The catheter design has now been improved with 56 irrigation holes to enhance cooling and reduce irrigation flow rate.5 The new porous tip provides uniform cooling over the entire tip rather than only localized cooling at the distal end, allowing more efficient heat dissipation and RF delivery. Park et al. reported on better procedural efficiency to reach complete pulmonary vein isolation (PVI), as compared to the 6-hole catheter, with a significant reduction in irrigation volume administered (approximately 500 mL less).5 Until now, safety data for the new catheter have largely been limited to unmonitored, single-center experiences.5–8 The primary objective of this paper is to report real world acute safety data from 2 prospective US observational registry studies using the porous tip catheter for the treatment of drug refractory, recurrent, symptomatic paroxysmal AF. It is believed that these registry results represent a wider range of techniques, operator experience, and patient profiles than past studies, and as such will be generalizable to a broader range of clinical practice. A secondary objective of this paper is to report on any differences in acute safety between patients age 65 and older and younger patients, as AF prevalence increases with age and adults age 65 years and older comprise an estimated 82% of all AF patients in the United States.9

Evaluation of: Curtis AB, Worley SJ, Adamson PB, et al; Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial Investigators. Biventricular pacing for atrioventricular block and systolic dysfunction. N. Engl. J. Med. 368(17), 1585-1593 (2013). Recent trials have shown the benefit of cardiac resynchronization (CRT) in mild or moderate heart failure with a left bundle branch block or intraventricular conduction delay. Randomized trials (including the BLOCK-HF study) have now shown that irrespective of baseline QRS duration, long-term left ventricular (LV) remodeling, dysfunction and heart failure are more common in patients with long-term conventional right ventricular (RV) than those with biventricular (BiV) pacing. The detrimental effects of long-term RV pacing may occur in patients with normal and abnormal LV ejection fractions (LVEF). LV dysfunction induced by RV pacing can be improved by upgrading to a BiV system. Possible new indications for CRT (currently under investigation), include heart failure due to diastolic dysfunction (normal LVEF) with left bundle branch block or intraventricular conduction delay in the absence of bradycardia, and conditions not necessarily associated with a wide QRS complex or bradycardia, such as hypertrophic cardiomyopathy and LV non-compaction. The widespread use of CRT will be limited by the greater complications of LV pacing, unfamiliarity with implantation techniques and cost. At first, CRT will be favored in young patients and those with a low LVEF where ventricular pacing is required >40% of the time.

We are reporting a patient with discrete intra-His conduction block and describe a refined technique of permanent His bundle pacing assuring reliable ventricular capture. Meticulous mapping of the site of block with lead placement distal to the site of block and non-selective His bundle pacing with local myocardial capture as an additional safety back up appears to be the technique of choice.

The diagnosis of myocardial infarction (MI) in the presence of left bundle branch block (LBBB) or during ventricular pacing (VP) is challenging because of inherent changes in the sequence of ventricular depolarization and repolarization associated with both conditions. Although LBBB and right ventricular (RV) pacing may both produce abnormalities in the ECG, it is often possible to diagnose an acute MI (AMI) or an old MI based on selected morphologic changes. Primary ST-segment changes scoring 3 points or greater according to the Sgarbossa criteria are highly predictive of an AMI in patients with LBBB or RV pacing. The modified Sgarbossa criteria are useful for the diagnosis of AMI in patients with LBBB; however, these criteria have not yet been studied in the setting of RV pacing. Although changes of the QRS complex are not particularly sensitive for the diagnosis of an old MI in the setting of LBBB or RV pacing, the qR complex and Cabrera sign are highly specific for the presence of an old infarct. Diagnosing AMI in the setting of biventricular (BiV) pacing is challenging. To date there is minimal evidence suggesting that the traditional electrocardiographic criteria for diagnosis of AMI in bundle branch block may be applicable to patients with BiV pacing and positive QRS complexes on their ECG in lead V1. This report is a careful review of the electrocardiographic criteria facilitating the diagnosis of acute and remote MI in patients with LBBB and/or VP.

Atrial fibrillation (AF) prevalence increases significantly with age. Little is known about the effect of AF ablation on quality of life and healthcare utilization in the elderly. The objective of this study was to quantify the healthcare utilization and quality of life benefits of catheter ablation for AF, for patients ≥65 years compared to patients65 years.Two multicenter U.S. registry studies enrolled patients with paroxysmal AF. Baseline characteristics and acute outcomes were collected for 736 patients receiving catheter ablation with the Navistar® ThermoCool® SF Catheter (Biosense Webster, Inc., Diamond Bar, CA, USA). Healthcare utilization and quality of life outcomes were collected through 1 year postablation for 508 patients.The rates of acute pulmonary vein isolation were high and similar between patients ≥65 years and65 years (97.5% vs 95.8%, P = 0.2130). Length of stay for the index procedure was similar between age groups with 82.2% of the older group and 83.2% of the younger group having one-day hospitalization. Disease-specific quality of life instrument scores improved significantly and similarly for older and younger patients at 1 year postablation, compared to baseline. AF-related hospitalizations and emergency department visits were similar or lower in older patients compared to younger patients, as reported at 1 year postablation.For older patients undergoing catheter ablation for paroxysmal AF, healthcare utilization parameters were lower or not significantly different than for younger patients, and quality of life outcomes were similarly improved. These findings support the use of catheter ablation as a treatment option in older patients with paroxysmal AF.

Biventricular pacing has occasionally been associated with ventricular proarrhythmia, which at times can be refractory to conventional antiarrhythmic drug therapy and ablative intervention. Recently, permanent His-bundle pacing has emerged as a reasonable alternative to right ventricular and biventricular pacing. In addition, by maintaining the physiologic pattern of ventricular electrical activation, it is less likely to be arrhythmogenic. We report the use of permanent His-bundle pacing to manage ventricular proarrhythmia that developed after initiation of biventricular pacing and was unresponsive to antiarrhythmic and ablative therapy.

Background: Ablation of ventricular tachycardia (VT) in patients with left ventricular assist devices (LVAD) is challenging and not well documented. This report describes our experience with endocardial VT ablation in six patients with an LVAD. Methods: We retrospectively reviewed the clinical records of LVAD patients who underwent an ablation procedure for refractory VT. Results: A total of eight ablation procedures were performed in six patients who, during the last 2 weeks before the ablation procedure, received a total of 101 appropriate shocks for VT. A closed aortic valve (n = 2) or aortic atheroma (n = 1) required a transseptal catheterization in three of six patients. The apical LVAD cannula served as a VT substrate in two of six patients. VT was eliminated in four patients and markedly reduced in two others. The latter two patients experienced a total of only four implantable cardioverter defibrillator (ICD) shocks during a follow-up of 130 and 493 days. Intravenous antiarrhythmic medications used in five of six patients before ablation were discontinued in all. The ablation procedures permitted hospital discharge in four of six patients. Five patients died during follow-up (228 ± 207 days after the procedure). The cause of death was unrelated to cardiac arrhythmias. One patient is still alive 1,205 days after the procedure. Conclusion: Ablation of VT in LVAD patients is feasible and can result in a markedly decreased VT burden with a reduction of ICD shocks. The subsequent discontinuation of intravenous antiarrhythmic medications may facilitate hospital discharge. (PACE 2012; 35:1377–1383)

Recent reports suggest that first-degree atrioventricular block is not benign. However, there is no evidence that shortening of the PR interval can improve outcome except for symptomatic patients with a very long PR interval ≥0.3 s. Because these patients require continual forced pacing, biventricular pacing should be used according to accepted guidelines for third-degree AV block. Functional atrial undersensing may occur in patients with conventional dual-chamber pacing and first-degree AV block because the sinus P-wave tends to be displaced into the post-ventricular atrial refractory period (PVARP) an arrangement that may cause a pacemaker syndrome. Prevention requires programming a shorter AV and PVARP that is feasible because retrograde conduction is rare in first-degree AV block patients. A relatively new pacing mode to minimize right ventricular stimulation has been designed by eliminating the traditional AV interval but with dual-chamber backup. This pacing mode permits the establishment of very long AV intervals that may cause pacemaker syndrome. About 50% of patients undergoing cardiac resynchronization therapy (CRT) have a PR interval ≥200 ms. The CRT patients with first-degree AV block are prone to develop electrical desynchronization more easily than those with a normal PR interval. The duration of desynchronization after exceeding the upper rate on exercise is also more pronounced. AV junctional ablation is rarely necessary in patients with first-degree AV block but should be considered for symptomatic functional atrial undersensing or when the disturbances caused by first-degree AV block during CRT cannot be managed by programming.

Three recent trials (Resynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE], MADIT-CRT, and Resynchronization-Defibrillation for Ambulatory Heart Failure [RAFT]) [1–3] have demonstrated the benefit of cardiac resynchronization therapy (CRT) in a relatively large number of New York Heart Association (NYHA) class II heart failure (HF) patients with a wide QRS complex, and a much smaller NYHA class I group of asymptomatic patients with severe left ventricular (LV) dysfunction also with a wide QRS complex. These trials generated a large number of substudies, meta-analyses and review articles about CRT in NYHA asymptomatic class I patients and class II HF patients and fostered the expansion of indications for CRT. The large number of publications about CRT has created or reactivated problems with the terminology of HF a situation compounded by the common misinterpretation of the NYHA classification [4]. The following descriptions from recent publications illustrate how confusing the terminology of HF has become. Descriptions such as “severe”, “chronic” and “refractory” used alone are excluded. 1. HF with mild symptoms. Also “…mildly symptomatic patients with heart failure”. This terminology is acceptable but the definition of mild symptoms is missing. Presumably it refers to functional class II NYHA, but not class I [4–6].

Background: We report three patients with St Jude ICDs (St. Jude Medical, Sylmar, CA, USA) where some aspect of the marker channel was missing. Methods and Results: Two cases were caused by the simultaneous occurrence of two distinct cardiac or device events that affected the proper delivery of markers by the telemetry system. Inability of the devices to sequentially process these events resulted in incomplete transmission of telemetry data to the programmers and caused missing markers in the telemetry recordings. In the third case, sensed atrial interference resulted in a short period of atrial asynchronous pacing, which prevented the delivery of a sensed atrial marker coincident with an atrial electrogram. This atrial electrogram by virtue of its timing would have otherwise been sensed outside the atrial refractory period. Conclusion: The perplexing recordings of the three patients should not be interpreted as representing true pacemaker malfunction.