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The limited literature and increasing interest in studies on cardiac electrophysiology, explicitly focusing on cardiac ion channelopathies and sudden cardiac death in diverse populations, has prompted a comprehensive examination of existing research. Our review specifically targets Hispanic/Latino and Indigenous populations, which are often underrepresented in healthcare studies. This review encompasses investigations into genetic variants, epidemiology, etiologies, and clinical risk factors associated with arrhythmias in these demographic groups. The review explores the Hispanic paradox, a phenomenon linking healthcare outcomes to socioeconomic factors within Hispanic communities in the United States. Furthermore, it discusses studies exemplifying this observation in the context of arrhythmias and ion channelopathies in Hispanic populations. Current research also sheds light on disparities in overall healthcare quality in Indigenous populations. The available yet limited literature underscores the pressing need for more extensive and comprehensive research on cardiac ion channelopathies in Hispanic/Latino and Indigenous populations. Specifically, additional studies are essential to fully characterize pathogenic genetic variants, identify population-specific risk factors, and address health disparities to enhance the detection, prevention, and management of arrhythmias and sudden cardiac death in these demographic groups., (© 2024 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Introduction: Electrocardiographic characteristics in COVID-19-related mortality have not yet been reported, particularly in racial/ethnic minorities., Methods and Results: We reviewed demographics, laboratory and cardiac tests, medications, and cardiac rhythm proximate to death or initiation of comfort care for patients hospitalized with a positive SARS-CoV-2 reverse-transcriptase polymerase chain reaction in three New York City hospitals between March 1 and April 3, 2020 who died. We described clinical characteristics and compared factors contributing toward arrhythmic versus nonarrhythmic death. Of 1258 patients screened, 133 died and were enrolled. Of these, 55.6% (74/133) were male, 69.9% (93/133) were racial/ethnic minorities, and 88.0% (117/133) had cardiovascular disease. The last cardiac rhythm recorded was VT or fibrillation in 5.3% (7/133), pulseless electrical activity in 7.5% (10/133), unspecified bradycardia in 0.8% (1/133), and asystole in 26.3% (35/133). Most 74.4% (99/133) died receiving comfort measures only. The most common abnormalities on admission electrocardiogram included abnormal QRS axis (25.8%), atrial fibrillation/flutter (14.3%), atrial ectopy (12.0%), and right bundle branch block (11.9%). During hospitalization, an additional 17.6% developed atrial ectopy, 14.7% ventricular ectopy, 10.1% atrial fibrillation/flutter, and 7.8% a right ventricular abnormality. Arrhythmic death was confirmed or suspected in 8.3% (11/133) associated with age, coronary artery disease, asthma, vasopressor use, longer admission corrected QT interval, and left bundle branch block (LBBB)., Conclusions: Conduction, rhythm, and electrocardiographic abnormalities were common during COVID-19-related hospitalization. Arrhythmic death was associated with age, coronary artery disease, asthma, longer admission corrected QT interval, LBBB, ventricular ectopy, and usage of vasopressors. Most died receiving comfort measures., (© 2020 Wiley Periodicals LLC.)

Introduction: Coronavirus disease 2019 (COVID-19) is a worldwide pandemic, and cardiovascular complications and arrhythmias in these patients are common. Cardiac monitoring is recommended for at risk patients; however, the availability of telemetry capable hospital beds is limited. We sought to evaluate a patch-based mobile telemetry system for inpatient cardiac monitoring during the pandemic., Methods: A prospective cohort study was performed of inpatients hospitalized during the pandemic who had mobile telemetry devices placed; patients were studied up until the time of discharge or death. The primary outcome was a composite of management changes based on data obtained from the system and detection of new arrhythmias. Other clinical outcomes and performance characteristics of the mobile telemetry system were studied., Results: Eighty-two patients underwent mobile telemetry device placement, of which 31 (37.8%) met the primary outcome, which consisted of 24 (29.3%) with new arrhythmias detected and 18 (22.2%) with management changes. Twenty-one patients (25.6%) died during the study, but none from primary arrhythmias. In analyses, age and heart failure were associated with the primary outcome. Monitoring occurred for an average of 5.3 ± 3.4 days, with 432 total patient-days of monitoring performed; of these, QT-interval measurements were feasible in 400 (92.6%)., Conclusion: A mobile telemetry system was successfully implemented for inpatient use during the COVID-19 pandemic and was shown to be useful to inform patient management, detect occult arrhythmias, and monitor the QT-interval. Patients with advanced age and structural heart disease may be more likely to benefit from this system., (© 2020 Wiley Periodicals LLC.)

Introduction: Sudden cardiac death is a substantial cause of mortality in patients with cardiomyopathy, but evidence supporting implantable cardioverter-defibrillator (ICD) implantation is less robust in nonischemic cardiomyopathy (NICM) than in ischemic cardiomyopathy. Improved risk stratification is needed. We assessed whether absolute quantification of stress myocardial blood flow (sMBF) measured by positron emission tomography (PET) predicts ventricular arrhythmias (VA) and/or death in patients with NICM., Methods: In this pilot study, we prospectively followed patients with NICM (left ventricular ejection fraction ≤ 35%) and an ICD who underwent cardiac PET stress imaging with sMBF quantification. NICM was defined as the absence of angiographic obstructive coronary stenosis, significant relative perfusion defects on imaging, coronary revascularization, or acute coronary syndrome. Endpoints were appropriate device therapy for VA and all-cause mortality. Subgroup analysis was performed in patients who had no prior history of VA (ie, the primary prevention population)., Results: We followed 37 patients (60 ± 14 years, 46% male) for 41 ± 23 months. The median sMBF was 1.56 mL/g/min (interquartile range: 1.00-1.82). Lower sMBF predicted VA, both in the whole population (hazard ratio [HR] for each 0.1 mL/g/min increase: 0.84, P = .015) and in the primary prevention subset (n = 27; HR for each 0.1 mL/g/min increase: 0.81, P = .049). Patients with sMBF below the median had significantly more VA than those above the median, both in the whole population (P = .004) and in the primary prevention subset (P = .046). Estimated 3-year VA rates in the whole population were 67% among low-flow patients vs 13% among high-flow patients, and 39% vs 8%, respectively, among primary-prevention patients. sMBF did not predict all-cause mortality., Conclusions: In patients with NICM, lower sMBF predicts VA. This relationship may be useful for risk stratification for ventricular arrhythmia and decision making regarding ICD implantation., (© 2020 Wiley Periodicals, Inc.)

Background: Vest Prevention of Early Sudden Death Trial did not demonstrate a significant reduction in arrhythmic death with the wearable cardioverter-defibrillator (WCD), but compliance with the device may have substantially affected the results. ThePletcher influence of WCD compliance on outcomes has not yet been fully evaluated., Methods: Using linear and pooled logistic models, we performed as-treated analyses omitting person-time in the hospital and adjusted for correlates of WCD compliance. To assess the impact of early stopping of WCD, we performed a per-protocol Kaplan-Meier analysis, censoring after the last day the WCD was worn. Interactions of potential effect modifiers with treatment assignment and WCD compliance on outcomes were investigated. Finally, we used linear models to identify predictors of WCD compliance., Results: A per-protocol analysis demonstrated a significant reduction in total (P < .001) and arrhythmic (P = .001) mortality. Better WCD compliance was independently predicted by cardiac arrest during index myocardial infarction (MI), higher Cr, diabetes, prior heart failure, EF ≤ 25%, Polish enrolling center and number of WCD alarms, while worse compliance was predicted by being divorced, Asian race, higher body mass index, prior percutaneous coronary intervention, or any WCD shock. Neither excluding time in hospital from the as-treated analysis nor adjustment for factors affecting WCD compliance materially changed the results. No variable demonstrated a significant interaction in either the intention-to-treat or as-treated analysis., Conclusion: Robust sensitivity analyses of as-treated and per-protocol analyses suggest that the WCD is protective in compliant patients with ejection fraction less than or equal to 35% during the first 3 months post-MI., (© 2020 Wiley Periodicals, Inc.)

Background: Micra transcatheter pacemaker system (TPS) usually achieves low implant pacing threshold (IPT). However, IPT may increase in some patients during follow-up., Aim: To apply implant parameters in predicting long-term occurrence of very high pacing threshold (VHPT) in patients with Micra-TPS., Methods: A cohort of 110 consecutive patients implanted with a Micra-TPS from 2014 to 2018 was evaluated at discharge and at 1, 12, 24, 36, and 48 months follow-up. VHPT was defined as greater than 2 V/0.24 ms. VHPT predictors were identified., Results: Micra-TPS was implanted successfully in 108 patients (98.2%). During a mean follow-up of 24 ± 16 months, 18 patients (16.7%) died of causes nonpacemaker-related, and 4 (3.8%) developed VHPT. Patients with VHPT had higher IPT and lower implant impedance than patients with non-VHPT: 1 ± 0.31 vs 0.55 ± 0.29 V/0.24 ms (P = .003) and 580 ± 59 vs 837 ± 232 Ω (P = .03), respectively. IPT and impedance had excellent discriminative power to predict VHPT (area under the curve: 0.85 ± 0.07 and 0.91 ± 0.05, respectively). Negative predictive value (NPV) of IPT ≤ 0.5 V/0.24 ms was 100%; positive predictive value (PPV) was 8% throughout follow-up. Implant impedance ≤ 600 Ω had NPV of 99% throughout follow-up, whereas PPV varied: 16%, 21%, 16%, and 28% at 1, 12, 24, and 36 months, respectively. Sequential combination of IPT greater than 0.5 V/0.24 ms and impedance ≤ 600 Ω improved PPV to 25%, 35%, 27%, and 44%, respectively, whereas NPV remained 99% throughout follow-up., Conclusion: Despite favorable long-term electrical performance of Micra-TPS, a small percent of patients developed VHPT during follow-up. A sequential combination of IPT and impedance could allow the implanter to identify patients who will develop VHPT during long-term follow-up., (© 2020 Wiley Periodicals, Inc.)

Introduction: Wearable cardioverter-defibrillator (WCD) is recommended for patients with implantable cardioverter-defibrillator (ICD) removal. This study aimed to investigate the potential cost-effectiveness of WCD for patients with ICD explant in a high-income city of China., Methods and Results: A 5-year decision-analytic model was developed to simulate outcomes of three strategies during the period between ICD explant and reimplantation: discharge-to-home without WCD (home group), discharge-to-home with WCD (WCD group), and stay-in-hospital (hospital group). Outcome measures were mortality rates (during the period between ICD explant and reimplantation), direct medical costs, quality-adjusted life years (QALYs), and incremental cost per QALY saved (ICER). Model inputs were derived from literature and public data. Base-case analysis was performed at four cost levels of WCD. Robustness of model results was examined by sensitivity analyses. In base-case analysis, the 8-week mortality rates of WCD, hospital, and home groups were 7.3%, 8.1%, and 9.4%, respectively. WCD group gained the highest QALYs (3.0990 QALYs), followed by hospital group (3.0553 QALYs) and home group (3.0132 QALYs). The WCD group was the cost-effective option with ICERs less than willingness-to-pay (WTP) threshold (57 315 USD/QALY) at WCD daily cost ≤USD48. In probabilistic sensitivity analysis, the WCD group at daily cost of USD24, USD48, USD72, and USD96 were cost-effective in 100%, 94.16%, 22.08%, and 0.16% of 10 000 Monte Carlo simulations, respectively., Conclusions: Use of WCD during the period between ICD explant and reimplantation is likely to save life and gain higher QALYs. Cost-effectiveness of WCD is highly subject to the daily cost of WCD in China., (© 2019 Wiley Periodicals, Inc.)

Introduction: The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing arrhythmia burden following transendocardial stem cell therapy vs placebo in patients with chronic ischemic heart disease (CIHD)., Methods and Results: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. No restriction of stem cell type was specified. The outcomes included sustained supraventricular or ventricular arrhythmias (VAs), sudden cardiac death (SCD), and resuscitated sudden cardiac arrest (SCA). Effect sizes were reported as odds ratio (OR) and 95% CI. Poisson regression was used to account for zero-events data. Twelve randomized trials that included 736 patients (384 in the cell therapy group and 352 in the placebo group) were analyzed. Six different cell types were used. Follow-up ranged from 6 to 12 months. There was a significant decrease in risk of SCD in the cell therapy group, (FE OR, 0.19 [0.04, 0.93]; P = .04). In subgroup analysis, there was a significantly lower risk of SCD or resuscitated SCA in the cell therapy group limited to studies that did not use skeletal myoblasts, (FE OR, 0.23 [0.06, 0.83]; P = .03). There was no significant difference in the incidence of sustained VA between groups (FE OR, 0.91 [0.47, 1.77]; P = .8), even after stratifying by cell type. There was no difference in supraventricular arrhythmias between groups., Conclusion: Nonskeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of SCD or resuscitated SCA compared to control, with no proarrhythmic effects., (© 2019 Wiley Periodicals, Inc.)

Introduction: QTc-interval prolongation is associated with ventricular arrhythmias and mortality in a general population. Bazett's correction formula (QTcB) is routinely used despite its overcorrection at high heart rates. Recently, we proposed a patient-specific QT correcting algorithm (QTcA) resulting in improved rate correction and predictive value in a general population. We hypothesize risk stratification at the Emergency Department (ED) could be improved using QTcA., Methods and Results: A retrospective case-control study including a randomized age- and sex-matched control population was performed at a tertiary care ED. A total of 1930 patients were included in the analysis (63.0% males, age 71.5 ± 15.6 years). Patient characteristics, history, and test results at the time of the electrocardiogram were collected. QTc was dichotomized as prolonged (>450 millisecond for men, >470 millisecond for women) or severely prolonged (>500 millisecond). Implementation of QTcA would reduce the number of patients considered to have a prolonged QTc by 65.2%, for severely prolonged QTc 79.6%. Multivariate regression was performed for in-hospital mortality, cardiovascular endpoints, and hospital admission. Neither a prolonged QTcB (HR 1.04; 95% CI, 0.64-1.69) nor QTcA (HR 0.76; 95% CI, 0.42-1.38) was an independent predictor of in-hospital mortality. A severely prolonged QTcA (OR, 2.54; 95% CI, 1.04-6.23) was an independent predictor of cardiovascular events. Both a prolonged QTcA (OR, 1.52; 95% CI, 1.06-2.18) and a prolonged QTcB (OR, 1.37; 95% CI, 1.05-1.79) were associated with higher hospitalization rates., Conclusions: QTcA reduced the number of patients considered at risk. Neither QTcB nor QTcA were predictors of in-hospital mortality. A severely prolonged QTcA was associated with cardiovascular events., (© 2019 Wiley Periodicals, Inc.)

Introduction: While cardiac sarcoidosis (CS) carries a risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD), risk stratification of patients with CS and preserved left ventricular/right ventricular (LV/RV) systolic function remains challenging. We sought to evaluate the role of electrophysiologic testing and programmed electrical stimulation of the ventricle (EPS) in patients with suspected CS with preserved ventricular function., Methods: One hundred twenty consecutive patients with biopsy-proven extracardiac sarcoidosis and preserved LV/RV systolic function underwent EPS. All patients had either probable CS defined by an abnormal cardiac positron emission tomography or cardiac magnetic resonance imaging, or possible CS with normal advanced imaging but abnormal echocardiogram (ECG), SAECG, Holter, or clinical factors. Patients were followed for 4.5 ± 2.6 years for SCD and VAs., Results: Seven of 120 patients (6%) had inducible ventricular tachycardia (VT) with EPS and received an implantable cardioverter defibrillator (ICD). Three patients (43%) with positive EPS later had ICD therapies for VAs. Kaplan-Meier analysis stratified by EPS demonstrated a significant difference in freedom from VAs and SCD (P = 0.009), though this finding was driven entirely by patients within the cohort with probable CS (P = 0.018, n = 69). One patient with possible CS and negative EPS had unrecognized progression of the disease and unexplained death with evidence of CS at autopsy., Conclusions: EPS is useful in the risk stratification of patients with probable CS with preserved LV and RV function. A positive EPS was associated with VAs. While a negative EPS appeared to confer low risk, close follow-up is needed as EPS cannot predict fatal VAs related to new cardiac involvement or disease progression., (© 2019 Wiley Periodicals, Inc.)

Introduction: Clinical trials did not provide conclusive evidence concerning the benefit of prophylactic implantable cardioverter-defibrillators (ICDs) in patients with severe nonischemic cardiomyopathy (NICM). We aimed to compare incidence of appropriate sustained ventricular arrhythmia (SVA) and device therapy in ischemic cardiomyopathy (ICM) vs NICM ICD and/or cardiac resynchronization therapy (CRT-D) patients., Methods and Results: We analyzed remote-monitoring data from devices of the Home Monitoring Expert Alliance network. SVA recordings were adjudicated by three independent electrophysiologists. Our cohort included 1,946 patients who received either an ICD (55%) or a CRT-D (45%) for primary prevention of sudden cardiac death. Median (interquartile range) age was 70 (62-77) years, 81% were male, and 52% were in the ICM group. Patients were remotely monitored for a maximum follow-up of 5 years. The 5-year product-limit estimate of SVA incidence in patients with an ICD was 47.3% (95% confidence interval [CI], 41.0%-53.9%) in the ICM group and 44.7% (36.9%-53.3%) in the NICM group. In patients with a CRT-D, SVA incidence was 45.7% (37.3%-55.0%) in ICM patients and 49.2% (40.4%-58.7%) in NICM patients. The adjusted hazard ratio for SVA in the ICM vs NICM group was 0.96 (95% CI: 0.70-1.30, P = .77) in ICD patients and 0.85 (95% CI: 0.61-1.18, P = .34) in CRT-D patients. SVAs triggered appropriate device therapies with similar incidence in all groups., Conclusion: In a large cohort of remotely monitored ICD and CRT-D recipients, SVA incidence did not significantly differ in ICM and NICM patients., (© 2019 Wiley Periodicals, Inc.)

Introduction: To assess a potential relationship between sex and outcome in recipients of an implantable cardioverter-defibrillator (ICD)., Methods and Results: All 1471 ICD recipients between 2000 and 2015 were sex-related analyzed with the following outcome parameters: overall survival (OS), the occurrence of inappropriate and appropriate antitachycardia pacing (ATP), and shock therapy. We followed 1206 (82%) male and 265 (18%) female ICD recipients during 4.1 ± 3.6 and 4.3 ± 3.8 years, respectively, (P = .369). Kaplan-Meier analysis revealed that there was no significant difference in OS between female and male patients (P = .132). After adjustment for relevant confounding factors in a multivariate model, sex remained a nonsignificant predictor of overall mortality (hazard ratio [male] = 1.11; P = .493). Negative binomial regression analysis revealed that women received less appropriate ATP therapy (rate ratio [RR] = 0.37; P = .043), whereas rates of appropriate shock therapy (RR = 1.95; P = .369) did not differ between women and men. No significant differences were observed in the occurrence of inappropriate ATP (RR = 1.22; P = .715) and inappropriate shock therapy (RR = 0.64; P = .121)., Conclusion: Female and male patients equally benefit from ICD therapy in terms of OS. Women are less likely to receive appropriate ATP therapy, whereas appropriate shock and inappropriate ATP and shock therapy are independent of sex., (© 2019 The Authors Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals, Inc.)

Background: Remote monitoring of implantable cardioverter-defibrillators has been associated with reduced rates of all-cause rehospitalizations and mortality among device recipients, but long-term economic benefits have not been studied., Methods and Results: An economic model was developed using the PREDICT RM database comparing outcomes with and without remote monitoring. The database included patients ages 65 to 89 who received a Boston Scientific device from 2006 to 2010. Parametric survival equations were derived for rehospitalization and mortality to predict outcomes over a maximum time horizon of 25 years. The analysis assessed rehospitalization, mortality, and the cost-effectiveness (expressed as the incremental cost per quality-adjusted life year) of remote monitoring versus no remote monitoring. Remote monitoring was associated with reduced mortality; average life expectancy and average quality-adjusted life years increased by 0.77 years and 0.64, respectively (6.85 life years and 5.65 quality-adjusted life years). When expressed per patient-year, remote monitoring patients had fewer subsequent rehospitalizations (by 0.08 per patient-year) and lower hospitalization costs (by $554 per patient year). With longer life expectancies, remote monitoring patients experienced an average of 0.64 additional subsequent rehospitalizations with increased average lifetime hospitalization costs of $2784. Total costs of outpatient and physician claims were higher with remote monitoring ($47 515 vs $42 792), but average per patient-year costs were lower ($6232 vs $6244). The base-case incremental cost-effectiveness ratio was $10 752 per quality-adjusted life year, making remote monitoring high-value care., Conclusion: Remote monitoring is a cost-effective approach for the lifetime management of patients with implantable cardioverter-defibrillators., (© 2019 The Authors Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals, Inc.)

Introduction: Dual-coil leads (DC-leads) were the standard of choice since the first nonthoracotomy implantable cardioverter/defibrillator (ICD). We used contemporary data to determine if DC-leads offer any advantage over single-coil leads (SC-leads), in terms of defibrillation efficacy, safety, clinical outcome, and complication rates., Methods and Results: In the Shockless IMPLant Evaluation study, 2500 patients received a first implanted ICD and were randomized to implantation with or without defibrillation testing. Two thousand and four hundred seventy-five patients received SC-coil or DC-coil leads (SC-leads in 1025/2475 patients; 41.4%). In patients who underwent defibrillation testing (n = 1204), patients with both lead types were equally likely to achieve an adequate defibrillation safety margin (88.8% vs 91.2%; P = 0.16). There was no overall effect of lead type on the primary study endpoint of "failed appropriate shock or arrhythmic death" (adjusted HR 1.18; 95% CI, 0.86-1.62; P = 0.300), and on all-cause mortality (SC-leads: 5.34%/year; DC-leads: 5.48%/year; adjusted HR 1.16; 95% CI, 0.94-1.43; P = 0.168). However, among patients without prior heart failure (HF), and SC-leads had a significantly higher risk of failed appropriate shock or arrhythmic death (adjusted HR 7.02; 95% CI, 2.41-20.5). There were no differences in complication rates., Conclusion: In this nonrandomized evaluation, there was no overall difference in defibrillation efficacy, safety, outcome, and complication rates between SC-leads and DC-leads. However, DC-leads were associated with a reduction in the composite of failed appropriate shock or arrhythmic death in the subgroup of non-HF patients. Considering riskier future lead extraction with DC-leads, SC-leads appears to be preferable in the majority of patients., (© 2019 Wiley Periodicals, Inc.)

Subcutaneous implantable cardioverter defibrillators (S-ICDs) provide reliable defibrillation and have enhanced supraventricular tachycardia discrimination and fewer infection rates compared with traditional transvenous systems. However, inappropriate shocks remain a frequent problem. Herein, we review the various mechanisms of these inappropriate therapies, some of which are unique to S-ICDs, and propose an algorithm for preventing recurrences. Proper screening of preimplants is essential to help minimize inappropriate therapies, but patients with hypertrophic cardiomyopathy, Brugada syndrome, and arrhythmogenic right ventricular cardiomyopathy are at particular risk and may require additional measures., (© 2018 Wiley Periodicals, Inc.)

Introduction: Amiodarone reduces recurrent ventricular tachyarrhythmias (VTA) but may worsen cardiovascular outcomes in heart failure (HF) patients. Cardiac resynchronization therapy (CRT) may also be antiarrhythmic. When patients with prior sustained VTA are upgraded to CRT defibrillators (CRT-D) from conventional implantable cardioverter-defibrillators (ICDs), should concomitant amiodarone be continued or is CRT's antiarrhythmic potential sufficient?, Methods and Results: We identified 67 patients from a prospective CRT registry with spontaneous sustained VTA, New York Heart Association (NYHA) II-IV HF, and left bundle-branch block (LBBB) who were upgraded to CRT defibrillators from conventional ICDs. We compared changes in QRS duration and left ventricular ejection fraction (LVEF) pre- and post-CRT, time to death, transplant or ventricular assist device (VAD), and time to recurrent VTA therapies between 37 patients continuing amiodarone therapy and 30 amiodarone-naïve patients. Amiodarone-treated patients had worse renal function and a higher prevalence of prior VTA storm compared with amiodarone-naïve patients. After CRT, amiodarone-treated patients demonstrated less QRS narrowing (8 vs 20 ms; P = 0.021) and less LVEF improvement (-2.7 vs +5.2%; P = 0.006). Over 29 months, 31 (47%) patients died and 13 (20%) received transplant or VAD. Risk of death, transplant, or VAD was greater in amiodarone-treated than -naïve patients (corrected hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.12-4.11; P = 0.022). Appropriate CRT-D therapies occurred in 37 (55%) patients; amiodarone use was not associated time to first therapy (HR, 1.13; 95% CI, 0.59-2.16; P = 0.72)., Conclusion: In patients with sustained VTA and LBBB upgraded from conventional ICDs to CRT defibrillators, concomitant amiodarone use is associated with less QRS narrowing, less LVEF improvement, greater risk of death, transplant, or VAD, and similar risk of recurrent VTA., (© 2018 Wiley Periodicals, Inc.)

Background: Recently, certain forms of early repolarization (ER) on electrocardiograms (ECGs) have been considered a possible marker of increased sudden cardiac death risk. The frequency, characteristics, and clinical follow-up with which these forms of ER are present in epilepsy patients, and whether or not abnormal ER contributes to sudden unexplained death in epilepsy patients (SUDEP) is unknown., Methods and Results: The amplitude of J peak and ST-segment morphology after ER on 12-lead ECGs were assessed in 354 epilepsy patients (age, 33 ± 16 years; 54% men) and 140 age- and sex-matched control subjects (age, 31 ± 12 years; 50% men). Abnormal ER prevalence (J-wave amplitude ≥0.1 mV) was greater in epilepsy patients (19.8%) compared with controls (8.6%; P = 0.002) in inferior ECG leads but not in lateral leads ( P = 0.40). ER with a horizontal or descending ST segment was also more prevalent in epilepsy patients ( P < 0.001). After introducing antiepileptic drugs in 36 epilepsy patients, there were no significant ER changes. Similarly, in 64 epilepsy patients with seizure suppression, ER comparison before and after seizure control revealed no significant changes. Male gender was the only significant predictor of abnormal ER in epilepsy patients ( P = 0.03). During a median follow-up of 7 years, SUDEP occurred in two patients, one with abnormal ER., Conclusions: Abnormal ER may be more prevalent in epilepsy patients than in controls and is not altered by antiepileptic drugs or achievement of epilepsy suppression. The relation of abnormal ER to SUDEP remains in need of further study., (© 2018 Wiley Periodicals, Inc.)

Introduction: Catheter ablation (CA) has emerged as the preferred modality of treatment for many cardiac arrhythmias. Anatomical sites of ablation are often located in close proximity to coronary arteries. However, the incidence of CA-related coronary injury has not been well studied. We sought to systematically evaluate all cases of CA-related coronary injuries., Methods and Results: A PubMed search was conducted from inception until May 1, 2017 using the keywords "coronary artery" and "ablation." We identified 2817 published articles of which 43 articles met our inclusion criteria representing 61 cases of coronary artery injury attributed to CA procedures from 1992 to 2017. Posteroseptal accessory pathway ablation was associated with the highest incidence of coronary injury (35.6% of cases), followed by cavotricuspid isthmus-dependent flutter (19.3%). The right coronary artery was the site of injury in over two-thirds of all reported cases. Coronary injury was detected intraprocedurally in about half of the cases (43.1%), whereas it was a delayed presentation in the other half. Coronary intervention was performed in a third of all cases (32.7%). There were a total of three deaths attributed to coronary artery injury., Conclusions: Most (91.8%) coronary injuries are a result of anatomic proximity to the site of ablation. Awareness of the relation between coronary artery course and anatomical site of ablation could prevent myocardial damage and improve procedural safety., (© 2018 Wiley Periodicals, Inc.)

Background: Implantable defibrillators (ICD) are an important therapy for arrhythmogenic right ventricular cardiomyopathy (ARVC) patients at high risk of sudden death. Given the high appropriate ICD therapy rate, some have argued that the mere act of implanting an ICD inflates the malignant arrhythmia rate in ARVC., Objective: To report the arrhythmic course of ARVC patients without ICDs at the fulfillment of the 2010 Task Force Criteria and explore predictors of malignant ventricular arrhythmias., Methods: We included 131 definite ARVC patients (age 32 ± 15 years, male 39%, proband 50%) either without ICDs (N  =  47) or receiving an ICD at least 6 months after the fulfillment of the diagnostic criteria. The primary outcome was a composite of cardiac arrest (both resuscitated successfully and unsuccessfully) and sustained ventricular tachyarrhythmias (cycle length< 600 milliseconds, at least 30 seconds or requiring an intervention for termination)., Results: At the fulfillment of the diagnostic criteria, ICDs were not recommended to 59 (45%) patients and declined by 22 (17%) patients. Forty (31%) patients were not recognized as having ARVC by the treating physicians. Over 8 (interquartile interval: 3-12) years, 38 (29%) patients had primary outcomes (8 cardiac arrests [3 died] and 30 sustained ventricular arrhythmias) while not having ICDs. The 1-year and 5-year event-free survival was 92% and 72%. Spontaneous sustained ventricular arrhythmias, cardiac syncope, men, proband, and inducibility in electrophysiology study were significantly associated with the primary outcome., Conclusion: In a contemporary cohort, a considerable risk of malignant arrhythmias existed in ARVC when ICDs were not implanted., (© 2018 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.)

Background: The definition of sudden death due to arrhythmia relies on the time interval between onset of symptoms and death. However, not all sudden deaths are due to arrhythmia. In patients with an implantable cardioverter defibrillator (ICD), postmortem device interrogation may help better distinguish the mode of death compared to a time-based definition alone., Objective: This study aims to assess the proportion of "sudden" cardiac deaths in patients with an ICD that have confirmed arrhythmia., Methods: We conducted a literature search for studies using postmortem ICD interrogation and a time-based classification of the mode of death. A modified QUADAS-2 checklist was used to assess risk of bias in individual studies. Outcome data were pooled where sufficient data were available., Results: Our search identified 22 studies undertaken between 1982 and 2015 with 23,600 participants. The pooled results (excluding studies with high risk of bias) suggest that ventricular arrhythmias are present at the time of death in 76% of "sudden" deaths (95% confidence interval [CI] 67-85; range 42-88)., Conclusion: Postmortem ICD interrogation identifies 24% of "sudden" deaths to be nonarrhythmic. Postmortem device interrogation should be considered in all cases of unexplained sudden cardiac death., (© 2018 Wiley Periodicals, Inc.)

Introduction: Little is known about the association between electrocardiographic abnormalities and exercise-related sudden cardiac death. Therefore, our aim was to identify possible electrocardiographic findings related to exercise-induced sudden cardiac death., Methods and Results: The FinGesture study includes 3,989 consecutive sudden cardiac deaths in northern Finland between 1998 and 2012, out of whom a total of 647 subjects had a previously recorded electrocardiography acquired from the archives of Oulu University Hospital. In 276 of these cases the death was witnessed, and the activity at the time of death was either rest or physical exercise (PE); in 40 (14%) cases sudden cardiac death was exercise-related and in 236 (86%) cases death took place at rest. Fragmented QRS complex in at least two consecutive leads within anterior leads (V1-V3) was more common in the exercise-group compared to rest-group (17 of 40, 43% vs. 51 of 236, 22%, P  =  0.005). Pathologic Q wave in anterior leads was more common in the PE group (9 of 40, 23% vs. 26 of 236, 11%; P  =  0.044). Median QRS duration was prolonged in the exercise-group compared to the rest-group (100 milliseconds vs. 94 milliseconds, P = 0.047). QTc interval, the prevalence of inverted T-waves, or other electrocardiographic abnormalities did not differ significantly between the two groups., Conclusions: As a conclusion, fragmented QRS complex in the anterior leads is associated with an increased risk of sudden cardiac death during PE., (© 2017 Wiley Periodicals, Inc.)

Background: Implantable cardioverter defibrillators (ICDs) improve survival in patients with heart failure due to ischemic cardiomyopathy, but their benefit in nonischemic cardiomyopathy (NICM) has been recently questioned. We performed a meta-analysis of randomized clinical trials to examine the effect of ICDs on total mortality and arrhythmic death in patients with NICM. We also examined the impact of age and cardiac resynchronization therapy (CRT) on the relative effect of ICD compared to control., Methods and Results: We searched the MEDLINE and EMBASE databases for randomized trials evaluating the effect of ICD versus control in patients with NICM. Hazard ratios (HR) with 95% confidence interval (CI) were calculated using a random effects model. Six trials involving 2,967 patients were included (ICD, n = 1,553; control, n = 1,414). Based on the pooled estimate across the six studies, the use of ICD was associated with a significant reduction in total mortality (HR = 0.78, 95% CI 0.66-0.92; P = 0.003), as well as arrhythmic death (HR = 0.46, 95% CI 0.29-0.71; P = 0.0005) compared to control. ICD decreased total mortality in younger patients compared to control (HR = 0.63, 95% CI 0.46-0.86; P = 0.004), but not in older patients (HR = 0.97, 95% CI 0.56-1.68; P = 0.92). In patients with CRT, ICD reduced total mortality compared to control (HR = 0.78, 95% CI 0.65-0.95; P = 0.02), but not in patients with CRT (HR = 0.71, 95% CI 0.40-1.26)., Conclusions: ICDs decrease total mortality and arrhythmic deaths in patients with NICM. The benefit of ICD appears to be dependent on age and concomitant use of CRT., (© 2017 Wiley Periodicals, Inc.)

Introduction: The subcutaneous implantable cardioverter defibrillator (ICD) has emerged as a viable therapeutic option for patients who are deemed high risk for sudden cardiac death. Previous studies have shown that 7-15% of patients are not candidates for the S-ICD based on their intrinsic QRS/T-wave morphology. Presently, it is not known if the S-ICD can be considered as supplementary therapy in patients who are ventricularly paced. We sought to determine the proportion of ventricularly paced patients who would qualify for an S-ICD., Methods and Results: We evaluated 100 patients with transvenous pacemakers/ICDs, including 25 biventricular devices to determine S-ICD candidacy during right ventricular (RV) pacing and biventricular pacing based on the recommended QRS:T-wave ratio screening template. Fifty-eight percent of patients qualified for an S-ICD based on their QRS morphology during ventricular pacing. More patients during biventricular pacing met criteria compared to during RV pacing alone (80% vs. 46%, P <0.01). Patients that were paced from the RV septum were more likely to qualify compared to those paced from the RV apex (67% vs. 37%, respectively, P <0.01)., Conclusion: While S-ICD implantation may be considered as supplemental therapy in select patients with preexisting transvenous devices, relatively fewer candidates who are paced from the RV apex qualify. QRS morphologies generated from biventricular pacing as well as from septal RV pacing are more likely to screen in based on the recommended S-ICD template., (© 2017 Wiley Periodicals, Inc.)

Background: Multiple definitions of reverse ventricular remodeling (RVR) employing various changes in left ventricular end-systolic (LVESV) or diastolic volumes (LVEDVs) or left ventricular ejection fraction (LVEF) have been used in determining cardiac resynchronization therapy (CRT) response, making comparability across studies difficult. We compared different metrics to each other, and in combination, in terms of association with long-term outcomes., Methods: We collected clinical and echocardiographic data on 436 patients undergoing CRT. LVEF was assessed via a combined volumetric and visual assessment. Volumes were manually traced. Using a nested multivariate model of a priori determined predictors of long-term survival free of left ventricular assist device (LVAD) or heart transplant, multiple definitions of RVR were added to the model individually to determine which provided the best model fit., Results: Over a mean follow-up of 5.4 ± 2.3 years, there were 198 endpoints (10 LVADs, 15 heart transplants, and 173 deaths). When added to a nested model controlling for multiple potential confounders, all definitions of RVR were significantly associated with improved survival. Changes in LVEF and LVESV were superior to changes in LVEDV. A combination metric of an LVEF improvement ≥ 5% and LVESV reduction ≥ 10% was the best overall metric for model fit., Conclusions: Changes in LVESV and LVEF are better predictors of long-term outcome following CRT compared to changes in LVEDV. Adding an assessment of LVEF to reduction in LVESV ≥ 10% provided the best overall definition for RVR in predicting CRT outcomes., (© 2017 Wiley Periodicals, Inc.)

Long-term right ventricular (RV) apical pacing has been associated with an increased risk of death, heart failure, and atrial fibrillation (AF). Alternative sites for RV pacing have not proven to be superior to RV apical pacing. Cardiac resynchronization therapy (CRT) using a biventricular (BiV) lead system is indicated for patients with a low left ventricular ejection fraction and QRS prolongation, but there remains about a 25-30% nonresponse rate. CRT has been less effective for nonleft bundle branch block conduction delay and with normal/low normal left ventricular function. Over the past decade, there have been more data on the feasibility and advantages of pacing at the His Bundle (HB) region. We review the anatomy and physiology of the HB, the available data on permanent HB pacing, its current and potential future applications., (© 2016 Wiley Periodicals, Inc.)

Introduction: A fragmented QRS (fQRS) is reported to be associated with a poor prognosis or sudden cardiac death (SCD) in patients with Brugada syndrome or ischemic heart disease. However, no studies have clarified the impact of the presence of an fQRS on SCD or ventricular arrhythmic events in patients receiving cardiac resynchronization therapy (CRT). This study aimed to clarify this point in patients with nonischemic cardiomyopathy., Methods and Results: This study included 137 heart failure patients with nonischemic cardiomyopathy who received CRT (NYHA functional class: II/III/IV = 25/84/28). The 12-lead ECGs before and after CRT were analyzed. The presence of an fQRS was decided in accordance with the definition in previous papers. Before the CRT, an fQRS was observed in 67 patients (fQRS-pre; 49%). However, it was masked in 35 (52% of fQRS-pre) patients after the CRT. Inversely, in 70 patients in whom an fQRS was absent before the CRT, it appeared after the CRT in 15 (21%) patients. As a result, 47 patients (34%) had an fQRS after the CRT (fQRS-post), and it was less than that before the CRT (P = 0.014). During 18 months of follow-up, SCD or ventricular arrhythmic events were observed more frequently in patients with an fQRS-post than in those without (36.2% vs. 3.3%, P < 0.001). A Cox regression analysis revealed that an fQRS-post was significantly associated with those events (hazard ratio = 9.18; 95% confidence interval = 2.45-34.48, P = 0.001)., Conclusion: In patients with nonischemic cardiomyopathy who received CRT, an fQRS-post was independently associated with SCD or ventricular arrhythmic events., (© 2016 Wiley Periodicals, Inc.)

Introduction: Data are lacking on the relationship between improved left ventricular ejection fraction (LVEF) and the incidence of ventricular arrhythmia in patients with an implantable cardioverter-defibrillator (ICD) for secondary prevention. The aim of this study was to evaluate the incidence and predictors of improvement in left ventricular (LV) function and determine the impact of improved LVEF on the occurrence of appropriate ICD therapy in patients with reduced LVEF and ICD for secondary prevention., Methods: In this study, 93 patients who received ICDs for secondary prevention, had an LVEF of < 45%, and underwent echocardiographic follow-up assessment after receiving an ICD were enrolled., Results: The mean patient age was 56.9 ± 13.1 years, the median time of repeat LVEF assessment was 19.7 (10.4-29.7) months, and the mean LVEF was 30.6 ± 8.5%. Of the patients, 58 (62.4%) had nonischemic cardiomyopathy. LV function improved after ICD implantation in 24 (25.8%) of 93 patients. Multivariable logistic regression revealed a short duration from the time of diagnosis of heart failure to ICD implantation and the presence of ventricular fibrillation as significant predictors of improved LV function. The incidence of appropriate ICD therapy was lower in the patients with than in those without LV function improvement. The composite endpoint of all-cause mortality or heart transplant was lower in the patients with than in those without LV function improvement., Conclusion: Overall survival was better and the recurrence of ventricular arrhythmia was lower in the patients with improved LV function., (© 2016 Wiley Periodicals, Inc.)

The identification of patients at risk for sudden cardiac death (SCD) is fundamental for both acquired cardiovascular diseases (such as coronary artery diseases, CAD) and inherited arrhythmia syndromes (such as the long-QT syndrome, LQTS). Genetics may play a role in both situations, although the potential to exploit this information to reduce the burden of SCD varies among these two groups. Concerning acquired cardiovascular diseases, which affect most of the general population, preliminary data suggest an association between genetics and the risk of dying suddenly. The maximal utility, instead, is reached in inherited arrhythmia syndromes, where the discovery of monogenic diseases such as LQTS tracked the way for the first genotype-phenotype correlations. The aim of this review is to provide a general overview focusing on the current genetic knowledge and on the present and future applicability for prevention in these two populations at risk for SCD., (© 2016 Wiley Periodicals, Inc.)

Introduction: Improvements in risk stratification for sudden cardiac arrest (SCA) will require discovery of markers that extend beyond the LV ejection fraction (LVEF). The frontal QRS-T angle has been shown to predict risk of SCA but the value of this marker independent of the LVEF has not been investigated., Methods and Results: Cases of adult SCA with an archived electrocardiogram (12-lead ECG) available before the event, with a computable frontal QRS-T angle, were identified from the Oregon Sudden Unexpected Death Study (Oregon SUDS) ongoing in the Portland, Oregon metro area. A total of 666 SCA cases (mean age 67.2 years; 95% CI, 52.3-82.1 years; 68.6% males) were compared to 863 controls (mean age 66.6 years, 55.2-78.0 years; 68.1% males; 75.0% had CAD) from the same geographical region. The mean frontal QRS-T angle was wider in cases (74(o) ; 95% CI, 17(o) -131(o) ) compared to controls (51(o) ; 95% CI, 5(o) -97(o;) P< 0.0001). A frontal QRS-T angle of more than 90(o) remained associated with increased risk of SCD after adjusting for age, gender, heart rate, prolonged intraventricular conduction, electrocardiographic left ventricular hypertrophy (ECG LVH), baseline comorbidities, and left ventricular ejection fraction (LVEF) (OR 2.2; 95% CI, 1.60-3.09; P< 0.0001)., Conclusion: A wide QRS-T angle greater than 90(o) is associated with an increased risk of SCA independent of the left ventricular ejection fraction., (© 2016 Wiley Periodicals, Inc.)

Introduction: At the time of generator replacement, after ICD implantation for primary prevention, many patients may no longer meet implantation criteria. We investigated the occurrence of ICD therapy after generator replacement in patients initially implanted ICD for primary prevention., Methods: Patients from 3 hospitals undergoing ICD generator replacement, who were initially implanted for primary prevention, were retrospectively evaluated for occurrence of appropriate ICD therapy after generator replacement. Patients were categorized as to whether or not they had appropriate ICD therapy during their first battery life, and by their left ventricular ejection fraction (LVEF) before generator replacement., Results: Data from 168 patients were analyzed, with average follow-up after generator replacement of 41.2 ± 26.5 months. Seventy-six (45.2%) patients had ventricular arrhythmia episodes (>180 beats per minutes) and 63 (37.5%) received appropriate ICD therapy during the first battery life. Among 105 patients without ICD therapy before generator replacement, those with an LVEF ≤35% before ICD replacement had higher occurrence of ICD therapy after generator replacement than patients with an LVEF ≥36%. Patients who no longer met primary prevention ICD indications (no ICD therapy and LVEF ≥36% before generator replacement) showed a lower risk for ICD therapy after generator replacement (11.6% over 5-year follow-up)., Conclusions: In patients without ICD therapy before generator replacement, low LVEF (≤35%) contributed to future ICD therapy. In patients initially undergoing ICD implantation for primary prevention, history of ICD therapy during the first battery life and LVEF should be utilized for risk stratification at the time of generator replacement., (© 2016 Wiley Periodicals, Inc.)

Objective: To compare the clinical outcomes of a single- versus dual-chamber ICD for primary prevention of sudden cardiac death in a large, national ICD registry., Methods: Data were collected from the prospective Israeli ICD Registry. Baseline characteristics and clinical outcomes including mortality, admissions for heart failure (HF), and ICD therapy were compared between the two groups., Results: A total of 1,125 subjects, 37% with a single-chamber and 63% with a dual-chamber ICD, constructed the baseline cohort. Approximately 80% had ischemic heart disease (IHD). Mean follow-up was 22 months, mean ejection fraction was 30%, and mean QRS width was 103 milliseconds in both groups. During follow-up, there were no significant differences in the rate of mortality, admissions for HF, appropriate or inappropriate therapy, or in time to any of the clinical outcomes. Using multivariate analysis, single-chamber ICD was not associated with increased risk of death or admission for HF. In a subgroup of patients with IHD, single-chamber ICD was associated with a higher rate of inappropriate therapy., Conclusions: In this large retrospective population-based cohort, dual-chamber ICD showed no benefit in reducing the incidence of death or HF admissions, whereas in a subgroup of patients with IHD, single-chamber ICD was associated with increased inappropriate therapy. Further prospective studies are necessary to assess the benefit of dual-chamber ICD in reducing the rate of inappropriate therapy., (© 2016 Wiley Periodicals, Inc.)

Introduction: We aim to compare the acute and long-term success of defibrillation between non-apical and apical ICD lead position., Methods and Results: The position of the ventricular lead was recorded by the implanting physician for 2,475 of 2,500 subjects in the Shockless IMPLant Evaluation (SIMPLE) trial, and subjects were grouped accordingly as non-apical or apical. The success of intra-operative defibrillation testing and of subsequent clinical shocks were compared. Propensity scoring was used to adjust for the impact of differences in baseline variables between these groups. There were 541 leads that were implanted at a non-apical position (21.9%). Patients implanted with a non-apical lead had a higher rate of secondary prevention indication. Non-apical location resulted in a lower mean R-wave amplitude (14.0 vs. 15.2, P < 0.001), lower mean pacing impedance (662 ohm vs. 728 ohm, P < 0.001), and higher mean pacing threshold (0.70 V vs. 0.66 V, P = 0.01). Single-coil leads and cardiac resynchronization devices were used more often in non-apical implants. The success of intra-operative defibrillation was similar between propensity score matched groups (89%). Over a mean follow-up of 3 years, there were no significant differences in the yearly rates of appropriate shock (5.5% vs. 5.4%, P = 0.98), failed appropriate first shock (0.9% vs. 1.0%, P = 0.66), or the composite of failed shock or arrhythmic death (2.8% vs. 2.3% P = 0.35) according to lead location., Conclusion: We did not detect any reduction in the ICD efficacy at the time of implant or during follow-up in patients receiving a non-apical RV lead., (© 2016 Wiley Periodicals, Inc.)

Background: Despite growing attention to performance and quality measures, national standards for reporting of outcomes after all electrophysiology (EP) procedures have not yet been developed. We sought to characterize the incidence and timing of adverse events up to 30 days after EP procedures at a tertiary academic medical center., Methods and Results: We prospectively followed all patients undergoing EP procedures between January 2010 and September 2012. All were followed for 30 days postprocedure either in clinic or by telephone. Major complications were defined as events related to the procedure that led to prolongation of hospital stay or readmission, required additional procedural intervention, or resulted in death or significant injury. These were further categorized as intraprocedure, postprocedure, or postdischarge events. Seven EP physicians collectively adjudicated whether complications were directly related to the procedure. A total of 3,213 procedures were performed. Major complications occurred in 2.2% of patients; 49% of these events occurred after discharge. Death occurred in 0.6% of patients; 73% of these deaths were found to be secondary to worsening of the patient's underlying comorbid conditions and unrelated to the procedure., Conclusions: When considering national standards for reporting outcomes of all EP procedures, continued follow-up after discharge is important. In our cohort, half of major complications occurring within 30 days occurred after discharge. In addition, three-quarters of deaths within 30 days were not directly related to the procedure and caution should be used in using all-cause mortality as an outcome measure for EP procedures., (© 2015 Wiley Periodicals, Inc.)

Introduction: The subcutaneous ICD system (S-ICD) has been shown to be a safe and effective treatment for patients at risk for sudden cardiac death. This device reliably detects ventricular tachyarrhythmias with a low incidence of inappropriate shocks for supraventricular arrhythmias. However, T-wave oversensing (TWOS) is more common with the S-ICD compared with transvenous systems. We developed a novel discrimination algorithm to reduce TWOS without compromising tachyarrhythmia discrimination., Methods and Results: The algorithm was developed using a database of recorded episodes, including 244 appropriate therapies for ventricular arrhythmias and 133 episodes with an inappropriate detection due to TWOS, and using a computer model that simulates the S-ICD system. An independent set of data of 161 TWOS episodes, 137 ventricular and 328 supraventricular episodes, was used to validate the algorithm on actual device hardware. The S-ICD performance with the new algorithm was compared with the S-ICD without the new algorithm. Development results showed a decrease in inappropriate charge due to TWOS by 30.7 ± 18%. All ventricular arrhythmias were appropriately detected and the time to appropriate charge initiation was not increased. System validation showed that the new algorithm avoided an inappropriate charge due to TWOS by 39.8 ± 11.4%. No decrease in ventricular arrhythmia sensitivity and no significant change in supraventricular specificity were observed., Conclusions: A new algorithm that uses correlation of the existing complex to previous complexes reduced TWOS episodes by approximately 40%. The algorithm has potential for a clinically meaningful decrease in inappropriate shocks., (© 2015 Wiley Periodicals, Inc.)

Background: Myotonic dystrophy (MD) is the most common muscular dystrophy in adults and is associated with sudden death. Reported predictors of sudden death in this population include atrial tachyarrhythmias, a PR interval greater than 240 milliseconds, aberrant QRS conduction, and any degree of AV block., Objective: We sought to report on the arrhythmic outcome of a cohort of patients with a new diagnosis of genetically proven MD., Methods: We performed a retrospective review of 37 patients with genetically confirmed MD referred to our electrophysiology clinic for primary cardiac screening., Results: There were 25 patients with MD type 1 (MD1) and 12 patients with MD type 2 (MD2). Eight patients with MD1 (32%) had atrial fibrillation, compared to only one patient with MD2 (8.3%). Patients with MD1 were more likely to have evidence of conduction disease abnormalities (40% vs. 8.3%, P = ns) and had a higher all-cause mortality (16% vs. 0%) than those with MD2. Criteria for recommending ICD implantation were based on sudden death risk factors suggested by published literature. Eleven patients were offered an ICD, 2 refused and died within the next year. Of the 9 patients who received an ICD, 8 had MD1. Three patients received appropriate shocks, 2 for monomorphic VT, and one for polymorphic VT., Conclusion: The presence of AV conduction disturbance in MD patients is associated with a greater risk for ventricular arrhythmias. MD1 was more likely to be associated with cardiac arrhythmias than MD2. The incidence of ventricular arrhythmias among those who received a primary prevention ICD was 33% over 22 months, with 2 patients experiencing monomorphic VT and one experiencing polymorphic VT., (© 2014 Wiley Periodicals, Inc.)

Introduction: We reported impaired QT-rate dependence in early repolarization syndrome (ERS); however, contemporary data have shown peak incidence of sudden cardiac death (SCD) in ERS and Brugada syndrome (BrS) at mid-night and early morning. Taken together, we analyzed the nocturnal QT-rate dependence in both syndromes., Methods and Results: A total of 172 subjects were enrolled: 11 ERS, 11 BrS patients, 50 subjects with an uneventful ER pattern (ERP), and 100 non-J-wave control subjects. Ambulatory ECG-derived parameters (QT, QTc, and QT/RR slope) and day-night QT difference were analyzed and compared. Among the groups, there was no significant difference in the average QT or QTc; however, the 24-hour QT/RR slope was significantly smaller in ERS and BrS patients (0.103 ± 0.01 and 0.106 ± 0.01, respectively) than in the control group (0.156 ± 0.03, P < 0.001). Detailed analysis showed a lower day-night QT difference in ERS and BrS patients (19 ±18.7 and 24 ±14 milliseconds, respectively) than in the controls (40 ± 22 milliseconds, P = 0.007) with the lowest QT/RR slopes seen in the ERS and BrS groups from 0 to 3:00 am (QT/RR; 0.076 ± 0.02 vs. 0.092 ± 0.04 vs. 0.117 ± 0.04, for the ERS, BrS, and controls, respectively, P = 0.004) and from 3 to 6 am (QT/RR 0.074 ± 0.03 vs. 0.079 ± 0.02 vs. 0.118 ± 0.04, P < 0.001)., Conclusion: In a large population of age- and gender-matched groups, both ERS and BrS patients showed attenuated QT-rate dependence and impaired QT day-night modulation that may provide a baseline reentrant substrate. Importantly, QT/RR maladaptation was most evident at mid-night and early morning, which may explain the propensity of such patients to develop SCD during this critical period., (© 2014 Wiley Periodicals, Inc.)

The review discusses the epidemiology and the possible underlying mechanisms of sudden cardiac death (SCD) in chronic kidney disease (CKD), and highlights the unmet clinical need for noninvasive risk stratification strategies in these patients. Although renal dysfunction shares common risk factors and often coexists with atherosclerotic cardiovascular disease, the presence of renal impairment increases the risk of arrhythmic complications to an extent that cannot be explained by the severity of the atherosclerotic process. Renal impairment is an independent risk factor for SCD from the early stages of CKD; the risk increases as renal function declines and reaches very high levels in patients with end-stage renal disease on dialysis. Autonomic imbalance, uremic cardiomyopathy, and electrolyte disturbances likely play a role in increasing the arrhythmic risk and can be potential targets for treatment. Cardioverter defibrillator treatment could be offered as lifesaving treatment in selected patients, although selection strategies for this treatment mode are presently problematic in dialyzed patients. The review also examines the current experience with risk stratification tools in renal patients and suggests that noninvasive electrophysiological testing during dialysis may be of clinical value as it provides the necessary standardized environment for reproducible measurements for risk stratification purposes., (© 2013 Wiley Periodicals, Inc.)

Background: Shock therapy delivery by implantable cardioverter-defibrillators (ICD) can be painful and may have adverse consequences. Reducing shock burden for patients with ICDs would be beneficial., Methods: PROVIDE was a prospective, randomized study of primary prevention ICD patients. Patients in the experimental group received a combination of programmed parameters with higher detection rates, longer detection intervals, empiric antitachycardia pacing (ATP), and optimized supraventricular tachycardia (SVT) discriminators, while those in the control group were programmed with conventional parameters. Shock therapy and arrhythmic syncope were compared., Results: Of 1,670 patients enrolled (846 in the experimental group, 824 in the control group) and monitored over a follow-up of 530 ± 241 days, 202 patients received shock therapy for any cause (82 in the experimental group and 120 in the control group). The median time to first shock was significantly prolonged (13.1 vs 7.8 months, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.47 to 0.82, P = 0.0005) and the 2-year shock rate significantly reduced (12.4% vs 19.4%, P < 0.001) in the experimental group compared to the control group. There was no increase in arrhythmic syncope (HR: 1.64, 95% CI: 0.69 to 3.90, P = 0.26), while the overall mortality was reduced (HR: 0.7, 95% CI: 0.50 to 0.98, P = 0.036) in the experimental group compared to the control group., Conclusion: A combination of programmed parameters utilizing higher detection rate, longer detection intervals, empiric ATP, and optimized SVT discriminators reduced ICD therapies without increasing arrhythmic syncope and was associated with reduction in all-cause mortality among ICD patients., (© 2014 Wiley Periodicals, Inc.)

Background: Current data on efficacy, safety and impact on clinical outcome of single- versus dual-coil implantable cardioverter-defibrillator (ICD) leads are limited and contradictory., Methods: Defibrillation threshold (DFT) at implantation and first shock efficacy were compared in patients implanted with single- versus dual-coil ICD leads in MADIT-CRT. The risk for atrial tachyarrhythmias and all-cause mortality were evaluated. Short- (< 30 days after the implantation) and long-term (throughout the entire study duration) complications were assessed., Results: Patients with dual-coil ICD leads had significantly lower DFTs compared to patients with single-coil ICD leads (17.6 ± 5.8 J vs 19.4 ± 6.1 J, P < 0.001). First shock efficacy was similar among patients with dual and single-coil ICD leads (89.6% vs 92.3%, P = 1.00). When comparing patients with dual versus single-coil ICD leads, there was no difference in the risk of atrial tachyarrhythmias (HR = 1.57, 95% CI: 0.81-3.02, P = 0.18), or in the risk of all-cause mortality (HR = 1.10, 95% CI: 0.58-2.07, P = 0.77). Patients implanted with single- or dual-coil ICD lead had similar short and long-term complication rates (short-term HR = 0.96, 95% CI: 0.56-1.65, P = 0.88, long-term procedure-related HR = 0.99, 95% CI: 0.62-1.59, P = 1.00, long-term ICD lead related: HR = 1.2, 95% CI: 0.5-2.9, P = 0.68) during the mean follow-up of 3.3 years., Conclusions: Patients with single-coil ICD leads have slightly higher DFTs compared to those with dual-coil leads, but the efficacy, safety, and clinical impact on atrial tachyarrhythmias, and mortality is similar. Implantation of single-coil ICD leads may be favorable in most patients., (© 2013 Wiley Periodicals, Inc.)

Objective: This study aimed to investigate whether adequate treatment of Cheyne-Stokes respiration (CSR) reduces the risk of arrhythmic events in patients with chronic heart failure (CHF)., Methods: A cohort of 403 registry patients with CHF (LVEF≤45%, NYHA-class≥2) and implanted cardioverter-defibrillator devices (ICD) was studied. They underwent overnight polygraphy, with 221 having mild or no CSR (apnea-hypopnea index [AHI]<15/h), and 182 having moderate to severe CSR (AHI>15/h). Latter ones were offered therapy with adaptive servoventilation (ASV), which 96 patients accepted and 86 rejected. During follow-up (21± 15 months) defibrillator therapies were recorded in addition to clinical and physiologic measures of heart failure severity., Results: Event-free survival from (a) appropriate cardioverter-defibrillator therapies and (b) appropriately monitored ventricular arrhythmias was shorter in the untreated CSR group compared to the treated CSR and the no CSR group. Stepwise Cox proportional hazard regression analysis showed untreated CSR (a: hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.46-2.72, P < 0.001; b: HR 2.19, 95%CI 1.42-3.37, P < 0.001), but not treated CSR (a: HR 1.06, 95%CI 0.74-1.50; P = 0.77; b: HR 1.21, 95%CI 0.75-1.93, P = 0.43) was an independent risk factor. The treated CSR group showed improvements in cardiac function and respiratory stability compared to the untreated CSR group., Conclusion: This study demonstrates a decrease of appropriate defibrillator therapies by ASV treated CSR in patients with CHF and ICD. A reduced exposure to hyperventilation, hypoxia, and improvement in indices of CHF severity and neurohumoral disarrangements are potential causative mechanisms., (© 2013 Wiley Periodicals, Inc.)

Introduction: The extent of left ventricular (LV) scar, characterized by late gadolinium enhancement cardiac MRI (LGE-CMR), has been shown to predict the occurrence of ventricular arrhythmias in implantable cardioverter defibrillator (ICD) recipients. However, the specificity of LGE-CMR for sudden cardiac death (SCD) versus non-SCD is unclear. The aim of this retrospective, observational study was to evaluate this relationship in a cohort of ICD recipients., Methods and Results: We included consecutive patients who had undergone LGE-CMR before ICD implantation over a 4-year period (2006-2009). Scar (defined as myocardium with a signal intensity ≥50% of the maximum in scar tissue) was characterized in terms of percent scar and number of transmural LV scar segments in a 17-segment model. The endpoints were appropriate ICD therapy and all-cause mortality. Sixty-four patients (average age 66 ± 11 years, 51 male, median LVEF 30%) were included. During 42 ± 13 months follow-up, appropriate ICD therapy occurred in 28 patients (44%), and 14 patients (22%) died. Number of transmural scar segments (P = 0.005) and percentage LV scar (P = 0.03) were both significantly associated with appropriate ICD therapy. However, neither number of transmural scar segments (P = 0.32) or percent LV scar (P = 0.59) was significantly associated with all-cause mortality., Conclusion: In this observational study, in medium-term follow-up, the extent of LV scar characterized by LGE-CMR was strongly associated with the occurrence of spontaneous ventricular arrhythmias but not all-cause mortality. We hypothesize that scar quantification by LGE-CMR may be more specific for SCD than non-SCD, and may prove a valuable tool for the selection of patients for ICD therapy., (© 2012 Wiley Periodicals, Inc.)

Introduction: Sudden cardiac death (SCD) is a large public health problem that warrants on-going evaluation in the general population. While single-year community-based studies have been performed there is a lack of studies that have extended evaluation to multiple years in the same community., Methods and Results: From the on-going Oregon Sudden Unexpected Death Study, we analyzed prospectively identified SCD cases in Multnomah County, Ore, (population ≈700,000) from February 1, 2002 to January 31, 2005. Detailed information ascertained from multiple sources (first responders, clinical records, and medical examiner) was analyzed. A total of 1,175 SCD cases were identified (61% male) with a mean age of 65 ± 18 years for men versus 70 ± 20 for women (P < 0.001). The overall incidence rate for the period was 58/100,000 residents/year. One-quarter (24.6%) was ≤ 55 years of age. The most common initial rhythm was ventricular tachycardia or fibrillation (39% of cases, survival 27%) followed by asystole (36%, survival 0.7%) and pulseless electrical activity (23%, survival 6%). Among subjects that underwent resuscitation, the rate of survival to hospital discharge was 12% and overall survival to hospital discharge irrespective of resuscitation was 8%. Of the 68 survivors, 16 (24%) received a secondary prevention ICD., Conclusion: We report annualized SCD incidence from a multiple-year, multiple-source community-based study, with higher than expected rates of women and subjects age ≤ 55 years. The low implantation rate of secondary prevention ICDs is likely to be multifactorial, but there are potential implications for recalibration of the projected need for ICD implantation; larger and more detailed studies are warranted., (© 2012 Wiley Periodicals, Inc.)

Introduction: Mutations of human ether-à-go-go-related gene (hERG), which encodes a cardiac K(+) channel responsible for the acceleration of the repolarizing phase of an action potential and the prevention of premature action potential regeneration, often cause severe arrhythmic disorders. We found a novel missense mutation of hERG that results in a G487R substitution in the S2-S3 loop of the channel subunit [hERG(G487R)] from a family and determined whether this mutant gene could induce an abnormality in channel function., Methods and Results: We made whole-cell voltage-clamp recordings from HEK-293T cells transfected with wild-type hERG [hERG(WT)], hERG(G487R), or both. We measured hERG channel-mediated current as the "tail" of a depolarization-elicited current. The current density of the tail current and its voltage- and time-dependences were not different among all the cell groups. The time-courses of deactivation, inactivation, and recovery from inactivation and their voltage-dependences were not different among all the cell groups. Furthermore, we performed immunocytochemical analysis using an anti-hERG subunit antibody. The ratio of the immunoreactivity of the plasma membrane to that of the cytoplasm was not different between cells transfected with hERG(WT), hERG(G487R), or both., Conclusion:  hERG(G487R) can produce functional channels with normal gating kinetics and cell-surface expression efficiency with or without the aid of hERG(WT). Therefore, neither the heterozygous nor homozygous inheritance of hERG(G487R) is thought to cause severe cardiac disorders. hERG(G487R) would be a candidate for a rare variant or polymorphism of hERG with an amino acid substitution in the unusual region of the channel subunit., (© 2012 Wiley Periodicals, Inc.)

Introduction: The relationship between QT interval and cardiovascular disease is controversial., Methods: All male residents aged 20-61 years and female residents aged 20-56 years were invited to the Tromsø Study in 1986-1987. A total of 15,558 participants free of heart disease were prospectively followed over 20 years for myocardial infarction and death. QT interval at baseline was measured on lead I of the electrocardiogram. Hazard ratios (HRs) with 95% confidence intervals (CIs) per standard deviation change in QT interval were calculated using a Cox regression model., Results: We identified 756 cases of myocardial infarction and 1,183 all-cause deaths. Prolonged QT interval was present in 792 (5%) participants. QT interval was not associated with increased risk of myocardial infarction (HR: 0.95, 95% CI: 0.84-1.07, after adjustment for potential confounders). Heart-rate-corrected QT interval was a significant predictor for all-cause death in men (HR: 1.15, 95% CI: 1.03-1.29), but not in women (HR: 1.04, 95% CI: 0.91-1.18), after adjustment for potential confounders., Conclusions: The findings suggest that the previously observed relationship between QT interval and increased risk of cardiovascular death is not mediated by increased risk of myocardial infarction. The clinical utility of the QT interval to identify individuals at high risk for coronary events is limited in a general population without prior heart disease., (© 2011 Wiley Periodicals, Inc.)

Introduction: Coronary revascularization (CR) may reduce arrhythmia risk and improve long-term outcome in patients with left ventricular dysfunction. This study was designed to evaluate the effect of elapsed time from CR on long-term mortality and arrhythmic risk among patients who receive an implantable cardioverter defibrillator (ICD)., Methods and Results: We evaluated the risk of 8-year mortality by elapsed time from CR to ICD implantation (categorized as: no CR; recent CR [<2 years]; or nonrecent CR [≥2 years], and assessed as a continuous measure) among 720 ICD recipients enrolled in the Multicenter Automatic Defibrillator Trial-II. At 8 years of follow-up, patients who did not undergo CR and those who underwent nonrecent CR had significantly higher mortality rates than patients who underwent recent CR (54%, 54%, and 36%, respectively; P < 0.001). Multivariate analysis demonstrated that no- and nonrecent CR were associated with respective 48% (P = 0.022) and 67% (P < 0.001) increases in mortality risk compared with recent CR. Assessment of time from CR as a continuous measure showed that every year elapsed from CR was associated with an adjusted 6% increase in 8-year mortality (P < 0.001), and in respective 6% (P < 0.001) and 6% (P = 0.003) increased risk for in-trial appropriate ICD therapy of ventricular tachyarrhythmias and appropriate ICD shocks., Conclusions: We observed a direct relationship between elapsed time from CR and long-term mortality following ICD implantation. The favorable long-term effect on outcome of recent CR may be related to a time-dependent effect of CR on ventricular arrhythmic burden and the need for appropriate ICD shocks., (© 2011 Wiley Periodicals, Inc.)

Athletes are thought the healthiest segment of the population. Yet, there is a general appearance that athletes are more prone to sudden cardiac death and arrhythmias than nonathletes. Bradycardias in athletes are nearly universal, but advanced heart block is usually pathologic. Athletes may be more prone to atrial fibrillation, but not likely to other types of supraventricular tachycardias. Sudden cardiac death in athletes is rare in the absence of heart disease, with the exception of commotio cordis. Treatment strategies for athletes are focused for the return to athletics. Guidelines for treatment will be derived from the 36th Bethesda Guidelines for athletes, and the European Society of Cardiology (ESC) guidelines for athletes., (© 2010 Wiley Periodicals, Inc.)

Background: The optimal timing of implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death after myocardial infarction (MI) remains unknown., Methods and Results: We developed a Markov model to investigate the optimal timing of ICD implantation after MI (no ICD, ICD at 60 days, 6 months, and 1 year) in patients who meet current guidelines. Estimates of arrhythmic death (baseline risk 6%, range 1-20% per year), nonarrhythmic death, and ICD efficacy were based upon MADIT-II and other contemporary post-MI clinical trials. We used both deterministic and stochastic modeling processes in our analysis. After 10 years follow-up, the baseline probability of survival was higher in those treated with ICD implantation versus not (42% vs 30%, P < 0.001). Survival was highest with ICD implantation at 60 days versus 6 months versus 1 year: 42.4%, 42.3%, and 42.0% (P = 0.0028). ICD implantation at 60 days provided a mean incremental survival of 0.28 months and 0.84 months per patient (compared with implantation at 6 months and 1 year). In sensitivity analyses, patients' competing risk for nonarrhythmic death was the primary determinant of benefit from ICD implantation. Overall, ICD implantation at 60 days resulted in the greatest life expectancy over a wide range of plausible nonarrhythmic and arrhythmic death rates., Conclusions: The benefits of early ICD implantation are modest when compared with delayed implantation at 6 months/1 year. Our results suggest that making sure a patient receives an ICD, when appropriate, may be more important than the timing of the implantation procedure.

Objective: The purpose of this large multicenter study was to evaluate the long-term reliability of an implantable cardioverter defibrillator (ICD) lead to determine the incidence of adverse events (AEs)., Background: A recent concern has been the performance of cardiac defibrillator leads. There have been conflicting reports regarding the rate of lead perforation and other AEs., Methods: Medical records from patients implanted from 6-1-2001 to 11-27-2007 with the St. Jude Medical Riata family of RV leads at 23 US (N = 12,969) and 5 German (N = 2,418) centers were reviewed for chronic lead-related AEs. These included perforation, dislodgment, conductor fracture and insulation damage. The mean follow-up period was 18.0 months. AEs were defined as those that required Riata lead revision, extraction, or replacement., Results: The incidence of lead AEs was <1% for each AE type. Perforation occurred in 0.38%, dislodgement in 0.93%, conductor fracture in 0.18%, and insulation damage in 0.21% of patients studied., Conclusions: During the follow-up of the 15,387 patients with Riata leads, the incidence of AEs which included perforation, dislodgement, conductor fraction and insulation damage was low and within the range of what is considered clinically acceptable.