Abstract Objectives This study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk ...of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves. Background MS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI. Methods Seventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view. Results In 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre -procedural independent predictor of high-degree AV block (odds ratio OR: 1.35, 95% confidence interval CI: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post -procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively). Conclusions Short MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides unique pre-procedural information about the patient-specific propensity for the risk of AV block.
Summary Background An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring ...function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial. Methods We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II–III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov , number NCT00538356. Findings We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65·5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58·7%). At 1 year, 63 (18·9%) of 333 patients in the telemonitoring group versus 90 (27·2%) of 331 in the control group (p=0·013) had worsened composite score (odds ratio 0·63, 95% CI 0·43–0·90). Ten versus 27 patients died during follow-up. Interpretation Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice. Funding Biotronik SE & Co. KG.
Implantable cardioverter-defibrillators (ICDs) have become the mainstay of preventive measures for sudden cardiac death (SCD). However, there are limited data on rates of appropriate life-saving ICD ...shock therapies in contemporary real-life settings.
The purpose of the study was to evaluate the rate of appropriate life-saving ICD shock therapies in a contemporary registry.
The Israeli ICD Registry includes all implants and other ICD operative procedures nationwide. The present study comprises 2349 consecutive cases who were enrolled in the Registry and prospectively followed up for information regarding survival, hospitalizations, and ICD therapies since 2010.
Kaplan-Meier survival analysis showed that the rate of appropriate ICD shock therapy at 30-month follow-up was 2.6% among patients who received an ICD for primary prevention compared with 7.4% among those who received a device for secondary prevention (log-rank P < .001). Rates of appropriate ICD shocks among primary prevention patients were 1.1% at 1-year of follow-up and 2.6% at 30 months, whereas the corresponding rates in the secondary prevention group were 3.8% at 1 year and 7.4% at 30 months (log-rank P < .001). A total of 253 patients (4.8%) died during follow-up, 65% of noncardiac causes.
Rates of life-saving appropriate ICD shock therapies among patients implanted with a defibrillator for the primary prevention of SCD in a contemporary real-world setting are lower than reported previously. These findings suggest a need for improved risk stratification and patient selection in this population.
Transcatheter aortic valve implantation (TAVI) is a novel treatment for high risk or inoperable patients with symptomatic severe aortic stenosis. However, significant atrioventricular (AV) conduction ...system abnormalities requiring permanent pacemaker (PPM) implantation might complicate this procedure. We used best subsets logistic regression analysis to identify the independent predictors for the development of high-degree AV block (HDAVB) among 70 patients who underwent TAVI at 3 referral centers in Israel from 2008 to 2010. The mean age of the study patients was 83 ± 4.6 years. Of the 70 patients, 28 (40%) developed AV conduction abnormalities requiring PPM implantation within 14 days (median 2) of the procedure. The indications for PPM implantation were HDAVB (n = 25), new-onset left bundle branch block with PR prolongation (n = 2), and slow atrial fibrillation (n = 1). Best subsets logistic regression analysis showed that, among the 15 prespecified clinical, electrocardiographic, and echocardiographic candidate risk factors, only right bundle branch block at baseline (odds ratio 43; p = 0.002) and deep valve implantation (<6 mm from the lower edge of the noncoronary cusp to the ventricular end of the prosthesis, odds ratio 22; p <0.001) were independently associated with the development of periprocedural HDAVB. At 3 months of follow-up, HDAVB was still present in 40% of the patients who received PPM implantation for this indication. In conclusion, 40% of the patients who undergo CoreValve TAVI require PPM implantation after the procedure, with most cases (36%) associated with the development of postprocedural HDAVB. Baseline conduction abnormalities (right bundle branch block) and deep valve implantation (>6 mm) independently predicted the development of HDAVB and the need for PPM implantation after CoreValve TAVI.
Objectives The goal of this study was to establish a patient-specific human-induced pluripotent stem cells (hiPSCs) model of catecholaminergic polymorphic ventricular tachycardia (CPVT). Background ...CPVT is a familial arrhythmogenic syndrome characterized by abnormal calcium (Ca2+ ) handling, ventricular arrhythmias, and sudden cardiac death. Methods Dermal fibroblasts were obtained from a CPVT patient due to the M4109R heterozygous point RYR2 mutation and reprogrammed to generate the CPVT-hiPSCs. The patient-specific hiPSCs were coaxed to differentiate into the cardiac lineage and compared with healthy control hiPSCs-derived cardiomyocytes (hiPSCs-CMs). Results Intracellular electrophysiological recordings demonstrated the development of delayed afterdepolarizations in 69% of the CPVT-hiPSCs-CMs compared with 11% in healthy control cardiomyocytes. Adrenergic stimulation by isoproterenol (1 μM) or forskolin (5 μM) increased the frequency and magnitude of afterdepolarizations and also led to development of triggered activity in the CPVT-hiPSCs-CMs. In contrast, flecainide (10 μM) and thapsigargin (10 μM) eliminated all afterdepolarizations in these cells. The latter finding suggests an important role for internal Ca2+ stores in the pathogenesis of delayed afterdepolarizations. Laser-confocal Ca2+ imaging revealed significant whole-cell Ca2+ transient irregularities (frequent local and large-storage Ca2+ -release events, broad and double-humped transients, and triggered activity) in the CPVT cardiomyocytes that worsened with adrenergic stimulation and Ca2+ overload and improved with beta-blockers. Store-overload–induced Ca2+ release was also identified in the hiPSCs-CMs and the threshold for such events was significantly reduced in the CPVT cells. Conclusions This study highlights the potential of hiPSCs for studying inherited arrhythmogenic syndromes, in general, and CPVT specifically. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care, and aid in the development of new therapies.
Summary Background Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We ...aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing. Methods In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation SIMPLE), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov , number NCT00800384. Findings Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 7% per year) in the no-testing group than patients who did receive it (104 8% per year; HR 0·86, 95% CI 0·65–1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 2% of 1236 patients in the no-testing group vs 28 2% of 1242 patients in the testing group, p=0·25). Interpretation Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death. Funding Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office).
Cardiac resynchronization therapy (CRT) has become part of the standard of care for symptomatic patients with heart failure, reduced ejection fraction (HRrEF), and wide QRS, despite optimal medical ...therapy. Device technology, operator experience, and post-implant optimization on follow-up have significantly improved CRT response during the last decade. In parallel, conduction system pacing (CSP) has emerged as a new and potentially better tool for maintaining physiological ventricular activation in patients with antibradycardia pacing, as well as an alternative for dyssynchrony correction in HFrEF patients. The current review focuses on cardiac dyssynchrony pathophysiology and correction methods, clinical evidence on CRT and CSP as therapies for cardiac dyssynchrony, and the role of each according to clinical evidence and current guidelines for HFrEF treatment.
Atrial fibrillation (AF) is the most common arrhythmia in adults worldwide and represents an important burden for patients, physicians, and healthcare systems. AF is associated with substantial ...mortality and morbidity, due to the disease itself and its specific complications, such as the increased risk of stroke and thromboembolic events associated with AF. The temporal relation between AF episodes and stroke is nonetheless incompletely understood. The factors associated with an increased thromboembolic risk remain unclear, as well as the stroke risk stratification. Therefore, in this review, we intend to expose the mechanisms and physiopathology leading to intracardiac thrombus formation and stroke in AF patients, together with the evidence supporting the causal hypothesis. We also expose the risk factors associated with increased risk of stroke, the current different risk stratification tools as well as future prospects for improving this risk stratification.
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