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Objectives: We aimed to evaluate the relationship between echocardiographic response to cardiac resynchronization therapy (CRT) and the risk of subsequent ventricular tachyarrhythmias (VTAs). Background: Current data regarding the effect of CRT on the risk of VTA are limited and conflicting. Methods: The risk of a first appropriate implantable cardioverter-defibrillator (ICD) therapy for VTA (including ventricular tachycardia, ventricular fibrillation, and ventricular flutter) was compared between high- and low-echocardiographic responders to CRT defibrillator (CRT-D) therapy (defined as ≥ 25% and <25% reductions, respectively, in left ventricular end-systolic volume [LVESV] at 1 year compared with baseline) and ICD-only patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy). Results: The cumulative probability of a first VTA at 2 years after assessment of echocardiographic response was highest among low responders to CRT-D (28%), intermediate among ICD-only patients (21%), and lowest among high responders to CRT-D (12%), with p < 0.001 for the overall difference during follow-up. Multivariate analysis showed that high responders to CRT-D experienced a significant 55% reduction in the risk of VTA compared with ICD-only patients (p < 0.001), whereas the risk of VTA was not significantly different between low responders and ICD-only patients (hazard ratio [HR]: 1.26; p = 0.21). Consistently, assessment of response to CRT-D as a continuous measure showed that incremental 10% reductions in left ventricular end-systolic volume were associated with corresponding reductions in the risk of subsequent VTA (HR: 0.80; p < 0.001), VTA/death (HR: 0.79; p < 0.001), ventricular tachycardia (HR: 0.80; p < 0.001), and ventricular fibrillation/ventricular flutter (HR: 0.75; p = 0.044). Conclusions: In patients with left ventricular dysfunction enrolled in the MADIT-CRT trial, reverse remodeling was associated with a significant reduction in the risk of subsequent life-threatening VTAs. (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271). [ABSTRACT FROM AUTHOR]

The clinical course and risk factors associated with beta(2)-agonist therapy for asthma have not been investigated previously in patients with the long-QT syndrome (LQTS). The risk of a first LQTS-related cardiac event due to beta(2)-agonist therapy was examined in 3,287 patients enrolled in the International LQTS Registry with QTc > or = 450 ms. The Cox proportional hazards model was used to assess the independent contribution of clinical factors for first cardiac events (syncope, aborted cardiac arrest, or sudden death) from birth through age 40. Time-dependent beta(2)-agonist therapy for asthma was associated with an increased risk for cardiac events (hazard ratio [HR] = 2.00, 95% confidence interval 1.26 to 3.15, p = 0.003) after adjustment for relevant covariates including time-dependent beta-blocker use, gender, QTc, and history of asthma. This risk was augmented within the first year after the initiation of beta(2)-agonist therapy (HR = 3.53, p = 0.006). The combined use of beta(2)-agonist therapy and anti-inflammatory steroids was associated with an elevated risk for cardiac events (HR = 3.66, p <0.01); beta-blocker therapy was associated with a reduction in cardiac events in those using beta(2) agonists (HR = 0.14, p = 0.05). In conclusion, beta(2)-agonist therapy was associated with an increased risk for cardiac events in patients with asthma with LQTS, and this risk was diminished in patients receiving beta blockers. [ABSTRACT FROM AUTHOR]

Determines the outcome of patients with acute myocardial infarction (AMI) receiving thrombolytic therapy with electrocardiographic criteria of left ventricular hypertrophy (LVH). Reliability of LVH as a risk factor for increased long-term mortality in survivors of AMI after reperfusion therapy; Demonstration of an improved short-term outcome in AMI patients.

Introduction: The implantable cardioverter defibrillator reduces mortality among patients with heart failure (HF) due to ischemic heart disease. Clinical trial data have called into question the benefit of an ICD in patients with HF due to nonischemic cardiomyopathy (NICM). We developed a risk stratification score for ventricular tachyarrhythmia (VTA) among patients with NICM receiving a primary prevention ICD., Methods: The study population comprised 1515 patients with NICM who were enrolled in the landmark MADIT trials. Fine and Gray analysis was used to develop a model to predict the occurrence of VTAs and ICD therapies while accounting for the competing risk of non-arrhythmic mortality. External validation was carried out in the RAID Trial population., Results: Four risk factors associated with increased risk for VTA were identified: male sex, left ventricular ejection fraction ≤25%, no indication for cardiac resynchronization therapy with a defibrillator (CRT-D), and Black race. A score was generated based on this model, and patients were stratified into low (N = 390), intermediate (N = 728), and high-risk (N = 387) groups. The 5-year cumulative incidences of VTA were 15%, 24%, and 42%, respectively. Application of score groups for the secondary endpoints of Fast VT or VF and Appropriate ICD Shock revealed similar findings. Recurrent event analysis yielded consistent results. The AUC in the validation cohort for the endpoint of Appropriate ICD Shock was 69.3., Conclusions: Our study shows that patients with NICM can be risk stratified using demographic and clinical variables and may be used when evaluating such patients for a primary prevention ICD., (© 2024 Wiley Periodicals LLC.)

Background and Aims: Long QT syndrome (LQTS) and coronary artery disease (CAD) are both associated with increased risk of ventricular tachyarrhythmia . However, there are limited data on the incremental risk conferred by CAD in adult patients with congenital LQTS. We aimed to investigate the risk associated with CAD and life threatening events (LTEs) in patients with LQTS after age 40 years., Methods: The risk of LTEs (comprising aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shock) from age 40 through 75 years was examined in 1,020 subjects from the Rochester LQTS registry, categorized to CAD ( n  = 137) or no-CAD ( n  = 883) subgroups., Results: Survival analysis showed that patients with CAD had a significantly higher cumulative event rate of LTEs from 40 to 75 years (35%) compared with those without CAD (7%; p  < 0.001 for the overall difference during follow-up). Consistently, multivariate analysis showed that the presence of CAD was associated with a 2.5-fold (HR = 2.47; p  = 0.02) increased risk of LTEs after age 40 years. Subgroup analyses showed that CAD vs. no CAD was associated with a pronounced >4-fold ( p  = 0.008) increased risk of LTEs among LQTS patients with a lower-range QTc (<500 ms). The increased risk of LTEs associated with CAD was not significantly different among the 3 main LQTS genotypes. Patient treatment was suboptimal, with only 63% on β-blockers and 44% on non-selective β-blockers., Conclusions: Our findings suggest that CAD is associated with a higher risk of LTEs in LQTS patients, with the risk being more pronounced in those with QTc <500 ms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Barsheshet, Goldenberg, Bjelic, Buturlin, Erez, Goldenberg, Chen, Polonsky, McNitt, Aktas, Zareba and Golovchiner.)

Purpose of Review: Members of a technical panel representing Australia, Canada, New Zealand, the UK, and the US collaborated to develop surveys designed to provide military leaders with information to guide decisions early in the COVID-19 pandemic. The goal of this paper is to provide an overview of this collaboration and a review of findings from the resulting body of work., Recent Findings: While surveys pointed to relatively favorable mental health and perceptions of leadership among military personnel early in the pandemic, these observations did not reflect the experiences of personnel deployed in COVID-19 response operations, nor were these observations reflective of later stages of the pandemic. Establishing and leveraging networks that enable the rapid development of employee surveys and sharing of results can serve as a pathway for empowering military leaders in times of crisis. Organizational support and leadership decisions are especially critical for maintaining well-being among personnel during crises., (© 2024. His Majesty the King in Right of Canada as represented by the Minister of National Defence. Parts of this work were authored by US Federal Government authors and are not under copyright protection in the US; foreign copyright protection may apply.)

Current guidelines advocate for the use of prophylactic implantable cardioverter defibrillators (ICDs) for all patients with symptomatic heart failure (HF) with low ejection fraction (EF). As many patients will never use their device and some are prone to device-related complications, scoring systems for delineating subgroups with differential ICD survival benefits are crucial to maximize ICD benefit and mitigate complications. This review summarizes the main scores, including MADIT trial-based Risk Stratification Score (MRSS) and Seattle Heart Failure Model (SHFM), which are based on randomized trials with a control group (HF medication only) and validated on large cohorts of 'real-world' HF patients. Recent studies using cardiac MRI (CMR) to predict ventricular arrhythmia (VA) are mentioned as well. The review shows that most scores could not delineate sustained VA incidence, but rather mortality without prior appropriate ICD therapies. Multiple scores could identify high-risk subgroups with extremely high probability of early mortality after ICD implant. On the other hand, low-risk subgroups were defined, in whom a high ratio of appropriate ICD therapy versus death without prior appropriate ICD therapy was found, suggesting significant ICD survival benefit. Moreover, MRSS and SHFM proved actual ICD survival benefit in low- and medium-risk subgroups when compared with control patients, and no benefit in high-risk subgroups, consisting of 16-20% of all ICD candidates. CMR reliably identified areas of myocardial scar and 'channels', significantly associated with VA. We conclude that as for today, multiple scoring models could delineate patient subgroups that would benefit differently from prophylactic ICD. Due to their modest-moderate predictability, these scores are still not ready to be implemented into clinical guidelines, but could aid decision regarding prophylactic ICD in borderline cases, as elderly patients and those with multiple co-morbidities. CMR is a promising technique which might help delineate patients with a low- versus high-risk for future VA, beyond EF alone. Lastly, genetic analysis could identify specific mutations in a non-negligible percent of patients, and a few of these mutations were found to predict an increased arrhythmic risk.

Background: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown., Methods: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis., Results: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup., Conclusions: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02549664., Competing Interests: Dr Lampert reports honoraria and research support from Medtronic, Abbott-St. Jude, and Boston Scientific, as well as serving on the Advisory Board for Medtronic. Dr Day received consulting and grant funding from Lexicon Pharmaceuticals, grant funding from Bristol Myers Squibb, and DMC from Cytokinetics. L. Salberg consulted for Biomarin. Dr Tome Esteban consulted for BMS and Cytokinetics. Dr Abrams served on the Scientific Advisory Board for Thryv Therapeutics and consulted for Rocket Pharmaceuticals. Dr Aziz served on the Medtronic Advisory Committee. Dr Behr consulted for Boston Scientific. Dr Berul received research funding from Medtronic. Dr Cerrone provided teaching and CME activities for Abbott and Medtronic. Dr Erickson received funding from Integer. Dr Estes reports consulting for Boston Scientific and Medtronic. Dr Ethridge reports funding from Spauling Research (ECG reading) and UpToDate. Dr James was a consultant for Pfizer and Lexeo Therapeutics and received research funding from Lexeo Therapeutics and StrideBio. Dr Law was a consultant for Medtronic and St. Jude and a speaker for Boston Scientific. Dr Olshansky, AstraZeneca DSMB (Data Safety Monitoring Board). Dr Noseworthy and Mayo Clinic have filed patents related to the application of artificial intelligence to the ECG for diagnosis and risk stratification and have licensed several A-ECG algorithms to Anumana. Dr Noseworthy and Mayo Clinic have a relationship with AliveCor related to the measurement of the QT interval on the Kardia device. Dr Shah was a consultant for Medtronic and Tenaya. Dr Ware received research support and/or consultancy fees from MyoKardia, Bristol Myers Squibb, Foresite Labs, Pfizer, and Health Lumen. Dr Ware is supported by Medical Research Council (UK), British Heart Foundation (RE/18/4/34215), and the NIHR Imperial College Biomedical Research Centre. Dr Ackerman has served as a consultant for Abbott, BioMarin Pharmaceuticals, Boston Scientific, Bristol Myers Squibb, Daiichi-Sankyo, Illumina, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. Dr Ackerman and Mayo Clinic are involved in an equity/royalty relationship with AliveCor, Anumana, ARMGO Pharma, Pfizer, and Thryv Therapeutics. The other authors report no conflicts.

Background: Some studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in heart failure patients with an implantable cardioverter-defibrillator (ICD)., Objectives: This study sought to assess whether digoxin use is associated with increased risk of VT/VF in patients with heart failure with reduced ejection fraction with a primary prevention ICD in landmark clinical trials., Methods: The study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in 4 landmark MADIT trials (Multicenter Automatic Defibrillator Implantation Trials). We employed propensity score quintile stratification for treatment with digoxin as well as additional multivariable adjustment to assess the risk of digoxin vs no-digoxin therapy for the endpoints of first and recurrent VT/VF and all-cause mortality. The proportional hazards regression models for arrhythmia-specific endpoints incorporated adjustments for the competing risk of death., Results: At baseline, 1,155 of 4,499 patients were on digoxin (26%). After propensity score quintile stratification, patients prescribed digoxin were shown to exhibit a statistically significant 48% increased risk of VT/VF (P < 0.001), 42% increased risk of the composite of VT/VF or death (P < 0.001), and a 37% increased risk of all-cause mortality (P = 0.006). Digoxin use was also associated with increased risk of appropriate ICD shocks (HR: 1.91; P < 0.001) and with increased burden of VT/VF events (HR: 1.46; P = 0.001)., Conclusions: Our findings suggests that digoxin use is associated with ventricular tachyarrhythmia and death in heart failure with reduced ejection fraction patients with an ICD., Competing Interests: Funding Support and Author Disclosures The MADIT-RISK study was supported by NIH grant HL077478. Dr Aktas has received research funding from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Heart failure patients with a history of atrial fibrillation (AF) and ventricular tachycardia/ventricular fibrillation (VT/VF) are known to have worse outcomes. However, there are limited data on the temporal relationship between development of these arrhythmias and the risk of subsequent congestive heart failure (CHF) exacerbation and death., Methods: The study cohort comprised 5511 patients implanted with an implantable cardioverter-defibrillator (ICD) in landmark clinical trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID) who were in sinus rhythm at enrollment. Multivariate cox analysis was performed to evaluate the time-dependent association between development of in-trial device detected AF and VT/VF with subsequent CHF exacerbation and death., Results: Multivariate analysis showed that AF occurrence and VT/VF occurrence were both associated with a similar magnitude of risk for subsequent CHF exacerbation (HR = 1.73 and 1.87 respectively, p < .001 for both). In contrast, only in-trial VT/VF was associated with a significant > two-fold increase in the risk of subsequent mortality (HR = 2.13, p < .001) whereas AF occurrence was not associated with a significant mortality increase after adjustment for in-trial VT/VF (HR = 1.36, p = .096)., Conclusion: Our findings from a large cohort of ICD recipients enrolled in landmark clinical trials show that device detected AF and VT/VF can be used to identify patients with increased risk for CHF exacerbation and mortality. These findings suggest a need for early intervention in CHF patients who develop device-detected atrial and ventricular tachyarrhythmias., (© 2024 Wiley Periodicals LLC.)

Introduction: Wearable cardioverter defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with atrial fibrillation (AF). However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood., Methods: In WEARIT-II, the cumulative probability of any sustained or nonsustained VT/VF (WCD-treated and nontreated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method by prior AF, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by prior AF using negative binomial regression., Results: WEARIT-II enrolled 2000 patients, 557 (28%) of whom had AF before enrollment. Cumulative probability of any sustained or nonsustained WCD-detected VT/VF during WCD use was significantly higher among patients with a history of AF than without AF (6% vs. 3%, p = .001). Similarly, the recurrent rate of any sustained or nonsustained VT/VF was significantly higher in patients with prior AF versus no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p = .001). Patients with prior AF also had a significantly higher burden of any WCD-detected atrial arrhythmias/SVT/inappropriate arrhythmias therapy (183.2 events per 100 patient-years vs. 74.8 events per 100 patient-years, p < .001)., Conclusion: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation., (© 2024 Wiley Periodicals LLC.)

The risk of sudden cardiac death (SCD) in patients with cancer receiving cancer therapies is not well defined. In this study we aimed to (1) evaluate the risk of SCD during the first 6 months of cancer treatment and (2) identify risk factors (RFs) for SCD in patients who underwent active cancer treatment. The study population comprised 8,356 patients who received any cancer treatment at the University of Rochester Medical Center from 2011 to 2020. The primary end point was the occurrence of SCD within 6 months of cancer treatment. SCD was defined by using the modified Hinkle-Thaler classification. The mean age at the time of cancer treatment was 64 ± 14 years and 49% were women. All-cause mortality occurred in 834 patients (10%), of whom 51 (6%) were identified as SCD. The cumulative probability of SCD at 6 months was 0.6%. Age <74 years (0.042), history of congestive heart failure (0.058) and lung cancer (0.004) were identified as independent RFs for SCD in the multivariate Cox regression models. The cumulative probability of SCD at 6 months from cancer treatment initiation was significantly higher in patients with ≥2 RFs (1.6%) than in patients with 0 or 1 RF (0.5%) (log-rank p <0.001). In conclusion, our findings suggest that active cancer treatment is associated with SCD risk that is more pronounced in younger patients (< 74 years), patients with cancer and a history of heart failure, and those who underwent treatment for lung cancer. Future studies should address appropriate modalities for prevention and protection in this high-risk population., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Sex-specific risk management may improve outcomes in congenital long QT syndrome (LQTS). We recently developed a prediction score for cardiac events (CEs) and life-threatening events (LTEs) in postadolescent women with LQTS. In the present study, we aimed to develop personalized risk estimates for the burden of CEs and LTEs in male adolescents with potassium channel-mediated LQTS., Methods and Results: The prognostic model was derived from the LQTS Registry headquartered in Rochester, NY, comprising 611 LQT1 or LQT2 male adolescents from age 10 through 20 years, using the following variables: genotype/mutation location, QTc-specific thresholds, history of syncope, and β-blocker therapy. Anderson-Gill modeling was performed for the end point of CE burden (total number of syncope, aborted cardiac arrest, and appropriate defibrillator shocks). The applicability of the CE prediction model was tested for the end point of the first LTE (excluding syncope and adding sudden cardiac death) using Cox modeling. A total of 270 CEs occurred during follow-up. The genotype-phenotype risk prediction model identified low-, intermediate-, and high-risk groups, comprising 74%, 14%, and 12% of the study population, respectively. Compared with the low-risk group, high-risk male subjects experienced a pronounced 5.2-fold increased risk of recurrent CEs ( P <0.001), whereas intermediate-risk patients had a 2.1-fold ( P =0.004) increased risk . At age 20 years, the low-, intermediate-, and high-risk adolescent male patients had on average 0.3, 0.6, and 1.4 CEs per person, respectively. Corresponding 10-year adjusted probabilities for a first LTE were 2%, 6%, and 8%., Conclusions: Personalized genotype-phenotype risk estimates can be used to guide sex-specific management in male adolescents with potassium channel-mediated LQTS.

Background: Recent studies suggest that participation in recreational and even competitive sports is generally safe for patients with implantable cardioverter-defibrillators (ICDs). However, these studies included only patients with implanted transvenous ICD (TV-ICD). Nowadays, subcutaneous ICD (S-ICD) is a safe and effective alternative and is increasingly implanted in younger ICD candidates. Data on the safety of sport participation for patients with implanted S-ICD systems is urgently needed., Objectives: The goal of the study is to quantify the risks (or determine the safety) of sports participation for athletes with an S-ICD, which will guide shared decision making for athletes requiring an ICD and/or wishing to return to sports after implantation., Methods: The SPORT S-ICD (Sports for Patients with Subcutaneous Implantable Cardioverter Defibrillator) study is an international, multicenter, prospective, noninterventional, observational study, designed specifically to collect data on the safety of sports participation among patients with implanted S-ICD systems who regularly engage in sports activities., Results: A total of 450 patients will undergo baseline assessment including baseline characteristics, indication for S-ICD implantation, arrhythmic history, S-ICD data and programming, and data regarding sports activities. LATITUDE Home Monitoring information will be regularly transferred to the study coordinator for analysis., Conclusion: The results of the study will aid in shaping clinical decision making, and if the tested hypothesis will be proven, it will allow the safe continuation of sports for patients with an implanted S-ICD., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Data on the risk of ventricular tachycardia (VT), ventricular fibrillation (VF), and death by sex in patients with prior VT/VF are limited., Objectives: This study aimed to assess sex-related differences in implantable cardioverter-defibrillator (ICD)-treated VT/VF events and death in patients implanted for secondary prevention or primary prevention ICD indications who experienced VT/VF before enrollment in the RAID (Ranolazine Implantable Cardioverter-Defibrillator) trial., Methods: Sex-related differences in the first and recurrent VT/VF requiring antitachycardia pacing or ICD shock and death were evaluated in 714 patients., Results: There were 124 women (17%) and 590 men observed during a mean follow-up of 26.81 ± 14.52 months. Compared to men, women were at a significantly lower risk of VT/VF/death (HR: 0.67; P = 0.029), VT/VF (HR: 0.68; P = 0.049), VT/VF treated with antitachycardia pacing (HR: 0.59; P = 0.019), and VT/VF treated with ICD shock (HR: 0.54; P = 0.035). The risk of recurrent VT/VF was also significantly lower in women (HR: 0.35; P < 0.001). HR for death was similar to the other endpoints (HR: 0.61; P = 0.162). In comparison to men, women presented with faster VT rates (196 ± 32 beats/min vs 177 ± 30 beats/min, respectively; P = 0.002), and faster shock-requiring VT/VF rates (258 ± 56 beats/min vs 227 ± 57 beats/min, respectively; P = 0.30). There was a significant interaction for the risk of VT/VF by race (P = 0.013) with White women having significantly lower risk than White men (HR: 0.36; P < 0.001), whereas Black women had a similar risk to Black men (HR: 1.06; P = 0.851)., Conclusions: Women with a history of prior VT/VF experienced a lower risk recurrent VT/VF requiring ICD therapy when compared to men. Black Women had a risk similar to men, whereas the lower risk for VT/VF in women was observed primarily in White women. (Ranolazine Implantable Cardioverter-Defibrillator Trial; NCT01215253)., Competing Interests: Funding Support and Author Disclosures This study was supported by grants from the National Heart, Lung, and Blood Institute: Clinical Coordination Center (UO1 HL096607) and Data Coordination Center (UO1 HL096610. Study drug and additional financial support for drug distribution was provided by Gilead Sciences (grant IN-US-259-0125). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The current guidelines advocate prophylactic implantable cardioverter-defibrillator (ICD) for all patients with symptomatic heart failure (HF) with low left ventricular ejection fraction. Because many patients will never use their device, a score delineating subgroups with differential ICD benefit is crucial. We aimed to evaluate the MADIT-II-based Risk Stratification Score (MRSS) feasibility to delineate the ICD survival benefit in a nationwide registry of patients with HF with prophylactic ICDs. Accordingly, all Israeli patients with HF with prophylactic ICD/cardiac resynchronization therapy defibrillators were categorized into MRSS-based risk subgroups. The study end points included overall mortality, sustained ventricular arrhythmia (VA), and a competing risk of VA (potential preventable arrhythmic death, where ICD could benefit survival) versus nonarrhythmic death. Potential ICD survival benefit was estimated by the area between these cumulative incidence curves. In 2,177 patients with HF implanted prophylactic device, 189 patients (8.7%) had VA and 316 (14.5%) died during a median follow-up of 2.9 years. The MRSS risk subgroups were significantly associated with overall mortality (p <0.001) and weakly with VA (p = 0.3). The competing risk analysis of VA versus nonarrhythmic death revealed a significantly shorter duration (p <0.001) and smaller magnitude of ICD survival benefit with increased risk subgroups, yielding an estimated 76, 60, 38, and 0 life days gained from prophylactic ICD implant during a 5-year follow-up for the MRSS low-, intermediate-, high-, and very high-risk subgroups, respectively (p for trend <0.05). In conclusion, MRSS use in a nationwide registry of patients with ischemic and nonischemic cardiomyopathy, revealed subgroups with differing ICD survival benefit, suggesting it could help evaluate prophylactic ICD survival benefit., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There are conflicting data on the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risk of life-threatening ventricular tachyarrhythmia in heart failure patients., Objectives: The authors aimed to assess whether QRS morphology is associated with risk of ventricular arrhythmias in CRT recipients., Methods: The study population comprised 2,862 patients implanted with implantable cardioverter defibrillator (ICD)/CRT-D for primary prevention who were enrolled in 5 landmark primary prevention ICD trials (MADIT-II [Multicenter Automated Defibrillator Implantation Trial], MADIT-CRT [Multicenter Automated Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], MADIT-RIT [Multicenter Automated Defibrillator Implantation Trial-Reduction in Inappropriate Therapy], MADIT-RISK [Multicenter Automated Defibrillator Implantation Trial-RISK], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter Defibrillators]). Patients with QRS duration ≥130 ms were divided into 2 groups: those implanted with an ICD only vs CRT-D. The primary endpoint was fast ventricular tachycardia (VT)/ventricular fibrillation (VF) (defined as VT ≥200 beats/min or VF), accounting for the competing risk of death. Secondary endpoints included appropriate shocks, any sustained VT or VF, and the burden of fast VT/VF, assessed in a recurrent event analysis., Results: Among patients with left bundle branch block (n = 1,792), those with CRT-D (n = 1,112) experienced a significant 44% (P < 0.001) reduction in the risk of fast VT/VF compared with ICD-only patients (n = 680), a significantly lower burden of fast VT/VF (HR: 0.55; P = 0.001), with a reduced burden of appropriate shocks (HR: 0.44; P < 0.001). In contrast, among patients with non-left bundle branch block (NLBBB) (N = 1,070), CRT-D was not associated with reduction in fast VT/VF (HR: 1.33; P = 0.195). Furthermore, NLBBB patients with CRT-D experienced a statistically significant increase in the burden of fast VT/VF events compared with ICD-only patients (HR: 1.90; P = 0.013)., Conclusions: Our data suggest a potential proarrhythmic effect of CRT among patients with NLBBB. These data should be considered in patient selection for treatment with CRT., Competing Interests: Funding Support and Author Disclosures The MADIT studies were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center, Rochester, New York. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: This retrospective study investigated the impact of hemochromatosis on maternal and perinatal outcomes among delivery hospitalizations in the United States between 2010 and 2019, revealing notable trends and associations., Methods: Utilizing data from over 36 million delivery hospitalizations, we conducted a comprehensive analysis, focusing on maternal complications, perinatal outcomes, and healthcare utilization among women with hemochromatosis compared to those without., Results: Women with hemochromatosis exhibited a longer length of hospital stay (3.27 ± 0.20 days vs. 2.64 ± 0.04 days) and higher total hospital charges ($21,789.66 ± $1124.41 vs. $17,751.63 ± $97.71) compared to those without the condition. There was a significant increase in the prevalence of hemochromatosis among delivery hospitalizations over the studied period, from 1.91 per 100,000 hospitalizations to 8.65 cases per 100,000 hospitalizations. Hemochromatosis patients demonstrated a higher prevalence of hypertensive disorders of pregnancy (aOR: 1.50, 95 % CI: 1.03-2.19) and VTE(aOR: 20.35, 95 % CI: 5.05-82.05).There were no statistically significant differences in rates of peripartum hemorrhage, C-section, preterm birth, fetal growth restriction, large for gestational age infants, and fetal death between the two groups., Conclusions: Our findings underscore higher hypertensive disorders of pregnancy and VTE among women with hemochromatosis, despite unaffected perinatal outcomes. An increasing trend in hemochromatosis prevalence highlights the need for targeted interventions and cost-effective management strategies. Future research is needed to explore potential racial disparities and understand the rising incidence of hemochromatosis among pregnant women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Aim To compare the 1-year survival rate of patients with atrial fibrillation (AF) following left atrial appendage occluder (LAAO) implantation vs. treatment with novel oral anticoagulants (NOACs)., Methods: We have conducted an indirect, retrospective comparison between LAAO and NOAC registries. The LAAO registry is a national prospective cohort of 419 AF patients who underwent percutaneous LAAO between January 2008 and October 2015. The NOACs registry is a multicenter prospective cohort of 3138 AF patients treated with NOACs between November 2015 and August 2018. Baseline patient characteristics were retrospectively collected from coded diagnoses of hospitalization and outpatient clinic notes. Follow-up data was sorted from coded diagnoses and the national civil registry. Subjects were matched according to propensity score. Baseline characteristics were compared using Chi-Square and student's t -test. Survival analysis was performed using Kaplan-Meier survival curves, log-rank test, and multivariable Cox regression, adjusting for possible confounding variables., Results: This study included 114 subjects who underwent LAAO implantation and 342 subjects treated with NOACs. The mean age of participants was 77.9 ± 7.44 and 77.1 ± 11.2 years in the LAAO and NOAC groups, respectively ( p = 0.4). The LAAO group had 70 (61%) men compared to 202 (59%) men in the NOAC group ( p = 0.74). No significant differences were found in baseline comorbidities, renal function, or CHA 2 DS 2 -VASc score. One-year mortality was observed in 5 (4%) patients and 32 (9%) patients of the LAAO and NOAC groups, respectively. After adjusting for confounders, LAAO was significantly associated with a lower risk for 1-year mortality (HR 0.38, 95%CI 0.14-0.99). In patients with impaired renal function, this difference was even more prominent (HR 0.21 for creatinine clearance (CrCl) < 60 mL/min)., Conclusions: In a pooled analysis of two registries, we found a significantly lower risk for 1-year mortality in patients with AF who were implanted with LAAO than those treated with NOACs. This finding was more prominent in patients with impaired renal function. Future prospective direct studies should further investigate the efficacy and adverse effects of both treatment strategies.

Background and Aims: De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain., Methods: In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization., Results: Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06-0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16-0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)]., Conclusions: In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Both selective and nonselective beta-blockers are used to treat patients with heart failure (HF). However, the data on the association of beta-blocker type with risk of atrial arrhythmia and ventricular arrhythmia (VA) in HF patients with a primary prevention implantable cardioverter-defibrillator (ICD) are limited., Objectives: This study sought to evaluate the effect of metoprolol vs carvedilol on the risk of atrial tachyarrhythmia (ATA) and VA in HF patients with an ICD., Methods: This study pooled primary prevention ICD recipients from 5 landmark ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID). Fine and Gray multivariate regression models, stratified by study, were used to evaluate the risk of ATA, inappropriate ICD shocks, and fast VA (defined as ventricular tachycardia ≥200 beats/min or ventricular fibrillation) by beta-blocker type., Results: Among 4,194 patients, 2,920 (70%) were prescribed carvedilol and 1,274 (30%) metoprolol. The cumulative incidence of ATA at 3.5 years was 11% in patients treated with carvedilol vs 15% in patients taking metoprolol (P = 0.003). Multivariate analysis showed that carvedilol treatment was associated with a 35% reduction in the risk of ATA (HR: 0.65; 95% CI: 0.53-0.81; P < 0.001) when compared to metoprolol, and with a corresponding 35% reduction in the risk of inappropriate ICD shocks (HR: 0.65; 95% CI: 0.47-0.89; P = 0.008). Carvedilol vs metoprolol was also associated with a 16% reduction in the risk of fast VA. However, these findings did not reach statistical significance (HR: 0.84; 95% CI: 0.70-1.02; P = 0.085)., Conclusions: These findings suggests that HF patients with ICDs on carvedilol treatment experience a significantly lower risk of ATA and inappropriate ICD shocks when compared to treatment with metoprolol., Competing Interests: Funding Support and Author Disclosures Each of the MADIT trials were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center. The MADIT-RISK study was supported by the National Heart, Lung, and Blood Institute grant HL077478. The RAID trial was supported by National Heart, Lung, and Blood Institute grants UO1 HL096607 and UO1 HL096610 and by Gilead Sciences Inc grant IN-US-259-0125. Dr Goldenberg has received research grants from Boston Scientific, ZOLL Medical Corporation, Medtronic, Biosense-Webster, and Biotronik. Dr Kutyifa has received research grants from Boston Scientific, Biotronik, and ZOLL Medical Corporation, and Spire Inc; and has consulting agreements with ZOLL Medical Corporation and Biotronik. Dr Steinberg has received research grants from the National Institutes of Health, Medtronic, AliveCor, and Atricure. Dr Zareba has received research grants from Boston Scientific. Dr Aktas has received research grants from Boston Scientific, Abbott, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Lymphoma treatment may be associated with new-onset atrial fibrillation (AF), especially among patients treated with Bruton tyrosine kinase inhibitors (BTKi)., Objectives: The authors sought to assess the risk of new-onset AF, AF risk factors, and the impact of AF on mortality in patients with lymphoma and no history of AF., Methods: The University of Rochester Medical Center Lymphoma Database was used to identify patients. The primary outcome was any AF episode identified using the International Classification of Diseases-10th Revision codes. Multivariable Cox regression was used to assess the risk of AF through the use of a time-dependent covariate for treatment overall as well as separate time-varying measures of BTKi (mainly ibrutinib) and non-BTKi treatment. The relative risk of all-cause mortality was determined using Cox proportional hazards analysis., Results: Among 1,957 lymphoma patients, the rate of AF at 5-years following initiation of BTKi treatment was higher (25%) compared to those receiving non-BTKi therapy (8%), and those receiving no treatment (4%). Multivariable analysis showed that BTKi treatment was associated with pronounced increased risk for AF compared to no treatment (HR: 5.07 [95% CI: 2.88-8.90; P  < 0.001]). Non-BTKi treatment was associated with an increased risk of AF compared to no treatment (HR: 1.82 [95% CI: 1.14-2.89; P  = 0.012]). Risk factors for the development of AF included age ≥64 years, male sex, hypertension, and lymphoma treatment. New AF was associated with an increased risk for subsequent mortality (HR: 3.71 [95% CI: 2.59-5.31])., Conclusions: Patients undergoing lymphoma treatment, especially those with high-risk features, may benefit from AF surveillance., Competing Interests: Dr Zent has received research funding from Acerta/AstraZeneca and 10.13039/100013252TG Therapeutics. Dr Aktas has received research funding from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant., Methods: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life., Conclusion: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: Congenital Long QT Syndrome (LQTS) is a hereditary arrhythmic disorder. We aimed to assess the performance of current genetic variant annotation scores among LQTS patients and their predictive impact., Methods: We evaluated 2025 patients with unique mutations for LQT1-LQT3. A patient-specific score was calculated for each of four established genetic variant annotation algorithms: CADD, SIFT, REVEL, and PolyPhen-2. The scores were tested for the identification of LQTS and their predictive performance for cardiac events (CE) and life-threatening events (LTE) and then compared with the predictive performance of LQTS categorization based on mutation location/function. Score performance was tested using Harrell's C-index., Results: A total of 917 subjects were classified as LQT1, 838 as LQT2, and 270 as LQT3. The identification of a pathogenic variant occurred in 99% with CADD, 92% with SIFT, 100% with REVEL, and 86% with PolyPhen-2. However, none of the genetic scores correlated with the risk of CE (Harrell's C-index: CADD = 0.50, SIFT = 0.51, REVEL = 0.50, and PolyPhen-2 = 0.52) or LTE (Harrell's C-index: CADD = 0.50, SIFT = 0.53, REVEL = 0.54, and PolyPhen-2 = 0.52). In contrast, high-risk mutation categorization based on location/function was a powerful independent predictor of CE (HR = 1.88; p < .001) and LTE (HR = 1.89, p < .001)., Conclusion: In congenital LQTS patients, well-established algorithms (CADD, SIFT, REVEL, and PolyPhen-2) were able to identify the majority of the causal variants as pathogenic. However, the scores did not predict clinical outcomes. These results indicate that mutation location/functional assays are essential for accurate interpretation of the risk associated with LQTS mutations., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Introduction: The implantable cardioverter defibrillator (ICD) is effective for the prevention of sudden cardiac death (SCD) in patients with heart failure and a reduced ejection fraction (HFrEF). The benefit of the ICD in patients with advanced CKD, remains elusive. Moreover, the benefit of the ICD in patients with advanced chronic kidney disease (CKD) and HFrEF who are cardiac resynchronization therapy (CRT) recipients may be attenuated., Hypothesis: We hypothesized that patients with CKD who are CRT recipients may derive less benefit from the ICD due to the competing risk of dying prior to experiencing an arrhythmia., Methods: The study population included 1,015 patients receiving CRT with defibrillator (CRT-D) device for primary prevention of SCD who were enrolled in either (Multicenter Automated Defibrillator Implantation Trial) MADIT-CRT trial or the Ranolazine in High-Risk Patients with Implanted Cardioverter Defibrillator (RAID) trial. The cohort was divided into two groups based on the stage of CKD: those with Stage 1 to 3a KD, labeled as (S1-S3a)KD. The second group included patients with Stage 3b to stage 5 kidney disease, labeled as (S3b-S5)KD. The primary endpoint was any ventricular tachycardia (VT) or ventricular fibrillation (VF) (Any VT/VF)., Results: The cumulative incidence of Any VT/VF was 23.5% in patients with (S1-S3a)KD and 12.6% in those with (S3b-S5)KD ( p  < 0.001) The incidence of Death without Any VT/VF was 6.6% in patients with (S1-S3a)KD and 21.6% in patients with (S3b-S5)KD ( p  < 0.001). A Fine and Gray multivariate competing risk regression model showed that Patients with (S3b-S5)KD had a 43% less risk of experiencing Any VT/VF when compared to those with (S1-S3a)KD (HR = 0.56, 95% CI [0.33-0.94] p  = 0.03. After two years of follow up, there was almost a 5-fold increased risk of Death without Any VT/VF among patients with (S3b-S5)KD when compared to those with (S1-S3a)KD [HR = 4.63, 95% CI (2.46-8.72), p for interaction with time = 0.012]., Conclusion: Due to their lower incidence of arrhythmias and higher risk of dying prior to experiencing an arrhythmia, the benefit of the ICD may be attenuated in CRT recipients with advanced CKD. Future prospective trials should evaluate whether CRT without a defibrillator may be more appropriate for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Goldenberg, Kutyifa, Zareba, Huang, Rosero, Younis, Schuger, Gao, Mcnitt, Polonsky, Steinberg, Goldenberg and Aktas.)

Importance: Syncope is the most powerful predictor for subsequent life-threatening events (LTEs) in patients with congenital long QT syndrome (LQTS). Whether distinct syncope triggers are associated with differential subsequent risk of LTEs is unknown., Objective: To evaluate the association between adrenergic (AD)- and nonadrenergic (non-AD)-triggered syncopal events and the risk of subsequent LTEs in patients with LQT types 1 to 3 (LQT1-3)., Design, Setting, and Participants: This retrospective cohort study included data from 5 international LQTS registries (Rochester, New York; the Mayo Clinic, Rochester, Minnesota; Israel, the Netherlands, and Japan). The study population comprised 2938 patients with genetically confirmed LQT1, LQT2, or LQT3 stemming from a single LQTS-causative variant. Patients were enrolled from July 1979 to July 2021., Exposures: Syncope by AD and non-AD triggers., Main Outcomes and Measures: The primary end point was the first occurrence of an LTE. Multivariate Cox regression was used to determine the association of AD- or non-AD-triggered syncope on the risk of subsequent LTE by genotype. Separate analysis was performed in patients with β-blockers., Results: A total of 2938 patients were included (mean [SD] age at enrollment, 29 [7] years; 1645 [56%] female). In 1331 patients with LQT1, a first syncope occurred in 365 (27%) and was induced mostly with AD triggers (243 [67%]). Syncope preceded 43 subsequent LTEs (68%). Syncopal episodes associated with AD triggers were associated with the highest risk of subsequent LTE (hazard ratio [HR], 7.61; 95% CI, 4.18-14.20; P < .001), whereas the risk associated with syncopal events due to non-AD triggers was statistically nonsignificant (HR, 1.50; 95% CI, 0.21-4.77; P = .97). In 1106 patients with LQT2, a first syncope occurred in 283 (26%) and was associated with AD and non-AD triggers in 106 (37%) and 177 (63%), respectively. Syncope preceded 55 LTEs (56%). Both AD- and non-AD-triggered syncope were associated with a greater than 3-fold increased risk of subsequent LTE (HR, 3.07; 95% CI, 1.66-5.67; P ≤ .001 and HR, 3.45, 95% CI, 1.96-6.06; P ≤ .001, respectively). In contrast, in 501 patients with LQT3, LTE was preceded by a syncopal episode in 7 (12%). In patients with LQT1 and LQT2, treatment with β-blockers following a syncopal event was associated with a significant reduction in the risk of subsequent LTEs. The rate of breakthrough events during treatment with β-blockers was significantly higher among those treated with selective agents vs nonselective agents., Conclusion and Relevance: In this study, trigger-specific syncope in LQTS patients was associated with differential risk of subsequent LTE and response to β-blocker therapy.

Background: Studies of outcome differences by sex in out-of-hospital cardiac arrest (OHCA) have produced mixed results that may depend on age, a potential surrogate for menopausal status., Objective: We used quantitative measures of ventricular fibrillation (VF) waveforms - indicators of the myocardium's physiology - to assess whether survival differences according to sex and age group may be mediated via a biologic mechanism., Methods: We conducted a cohort study of VF-OHCA in a metropolitan EMS system. We used multivariable logistic regression to assess the association of survival to hospital discharge with sex and age group (<55, ≥55 years). We determined the proportion of outcome difference mediated by VF waveform measures: VitalityScore and amplitude spectrum area (AMSA)., Results: Among 1526 VF-OHCA patients, the average age was 62 years, and 29% were female. Overall, younger women were more likely to survive than younger men (survival 67% vs 54%, p = 0.02), while survival among older women and older men did not differ (40% vs 44%, p = 0.3). Adjusting for Utstein characteristics, women <55 compared to men <55 had greater odds of survival to hospital discharge (OR = 1.93, 95% CI 1.23-3.09), an association not observed between the ≥55 groups. Waveform measures were more favorable among women and mediated some of the beneficial association between female sex and survival among those <55 years: 47% for VitalityScore and 25% for AMSA., Conclusions: Women <55 years were more likely to survive than men <55 years following VF-OHCA. The biologic mechanism represented by VF waveform mediated some, though not all, of the outcome difference., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘TR and HK received modest support provided to the University of Washington by Philips, a major defibrillator manufacturer.’., (Copyright © 2023. Published by Elsevier B.V.)

Background: There are limited data regarding racial disparities in outcomes after left ventricular assist device (LVAD) implantation. The purpose of this study was to compare clinical characteristics and the burden of readmissions by race among patients with LVAD., Methods: The study population included 461 patients implanted with LVADs at the University of Rochester Medical Center, NY from May 2008 to March 2020. Patients were stratified by race as White patients (N = 396 [86%]) and Black patients (N = 65 [14%]). The Anderson-Gill recurrent regression analysis was used to assess the independent association between race and the total number of admissions after LVAD implant during an average follow-up of 2.45 ± 2.30 years., Results: Black patients displayed significant differences in baseline clinical characteristics compared to White patients, including a younger age, a lower frequency of ischemic etiology, and a higher baseline serum creatinine. Black patients had a significantly higher burden of readmissions after LVAD implantation as compared with White patients 10 versus 7 (average number of hospitalizations per patient at 5 years of follow-up, respectively) translated into a significant 39% increased risk of recurrent readmissions after multivariate adjustment (Hazard ratio 1.39, 95% CI; 1.07-1.82, p 0.013)., Conclusion: Black LVAD patients experience an increased burden of readmissions compared with White patients, after adjustment for baseline differences in demographics and clinical characteristics. Future studies should assess the underlying mechanisms for this increased risk including the effect of social determinants of health on the risk of readmissions in LVAD recipients., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Introduction: Use of sodium glucose cotransporter 2 inhibitors (SGLT2i) was associated with a reduction in atrial fibrillation hospitalizations. Therefore, we aim to evaluate the effects of SGLT2i on atrial tachy-arrhythmias (ATA) in patients with cardiac implantable electronic devices (CIEDs)., Methods: All 13 888 consecutive patients implanted with a CIED in two tertiary medical centers were enrolled. Treatment with SGLT2i was assessed as a time dependent variable. The primary endpoint was the total number of ATA. Secondary endpoints included total number of ventricular tachy-arrhythmias (VTA), ATA and VTA, and death. All events were independently adjudicated blinded to the treatment. Multivariable propensity score modeling was performed., Results: During a total follow-up of 24 442 patient years there were 62 725 ATA and 10 324 VTA events. Use of SGLT2i (N = 696) was independently associated with a significant 22% reduction in the risk of ATA (hazard ratio [HR] = 0.78 [95% confidence interval {CI} = 0.70-0.87]; p < .001); 22% reduction in the risk of ATA/VTA (HR = 0.78 [95% CI = 0.71-0.85]; p < .001); and with a 35% reduction in the risk of all-cause mortality (HR = 0.65 [95% CI = 0.45-0.92]; p = .015), but was not significantly associated with VTA risk (HR = 0.92 [95% CI = 0.80-1.06]; p = .26). SGLT2i were associated with a lower ATA burden in heart failure (HF) patients but not among diabetes patients (HF: HR = 0.68, 95% CI = 0.58-0.80, p < .001 vs. Diabetes: HR = 0.95, 95% CI = 0.86-1.05, p = .29; p < .001 for interaction between SGLT2i indication and ATA burden)., Conclusion: Our real world findings suggest that in CIED HF patients, those with SGLT2i had a pronounced reduction in ATA burden and all-cause mortality when compared with those not on SGLT2i., (© 2023 Wiley Periodicals LLC.)

Background: Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD)., Methods: The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM)., Results: Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; P <0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; P ≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; P <0.001 for both), and a higher risk of death (HR 1.92; P =0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation., Conclusions: Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients., Competing Interests: Disclosures Drs Younis, Ali, Ido Goldenberg, and Aktas, and S. McNitt and B. Polonsky, have nothing to declare. Drs Kutyifa, Wazni, Zareba, and Ilan Goldenberg report receiving grants from Boston Scientific.

Background: The benefit of implantable cardioverter-defibrillators (ICDs) in elderly patients is controversial., Objectives: The aims of this study were to evaluate the risk for ventricular tachyarrhythmia (VTA) and ICD shocks by age groups and to assess the competing risk for VTA and death without prior VTA., Methods: The study included 5,170 primary prevention ICD recipients enrolled in 5 landmark ICD trials (MADIT [Multicenter Automatic Defibrillator Implantation Trial] II, MADIT-Risk, MADIT-CRT [MADIT Cardiac Resynchronization Therapy], MADIT-RIT [MADIT Reduce Inappropriate Therapy], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillator]). Fine and Gray regression analysis was used to evaluate the risk for fast VTA (ventricular tachycardia ≥200 beats/min or ventricular fibrillation) vs death without prior fast VTA in 3 prespecified age groups: <65, 65 to <75, and ≥75 years., Results: The cumulative incidence of fast VTA at 3 years was similar for patients <65 years of age and those 65 to <75 years of age (17% vs 15%) and was lowest among patients ≥75 years of age (10%) (P < 0.001). Multivariate Fine and Gray analysis showed a 40% lower risk for fast VTA in patients ≥75 years of age (HR: 0.60; 95% CI: 0.46-0.78; P < 0.001) compared with patients <65 years of age. In patients ≥75 years of age, a risk reversal was observed whereby the risk for death without prior fast VTA exceeded the risk for developing fast VTA. A history of nonsustained ventricular tachycardia, male sex, and the presence of nonischemic cardiomyopathy were identified as predictors of fast VTA in patients ≥75 years of age., Conclusions: Patients ≥75 years of age have a significantly lower risk for VTA and ICD shocks compared with younger patients. Aging is associated with a higher risk for death compared with the risk for fast VTA, the reverse of what is seen in younger patients., Competing Interests: Funding Support and Author Disclosures Each of the MADIT trials was funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center. The MADIT-Risk study was supported by National Heart, Lung, and Blood Institute grant HL077478. The RAID trial was supported by National Heart, Lung, and Blood Institute grants UO1 HL096607 and UO1 HL096610 and by a grant from the Gilead Sciences (IN-US-259-0125). Dr Aktaş has received research grants from Boston Scientific and Medtronic. Dr Kutyifa has received research grants from Boston Scientific, Biotronik, and ZOLL. Dr Steinberg has received research grants from the National Institutes of Health, Medtronic, AliveCor, and Atricure. Dr Zareba has received research grants from Boston Scientific. Dr Rosero has received research grants from Medtronic and Biotronik. Dr Huang has received research grants from Medtronic, Biosense Webster, and Biotronik. Dr Goldenberg has received research grants from Boston Scientific, Zoll, Medtronic, Biosense Webster, and Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The predictive value of left ventricular (LV) global longitudinal strain (GLS) to predict outcomes in different left ventricular ejection fraction (LVEF) cohorts is not well known. We aimed to assess the role of LV GLS predicting outcomes in HF patients by LVEF., Methods: In the Multicenter Automatic Defibrillator Implantation Trial Cardiac Resynchronization Therapy (MADIT-CRT), we studied 1077 patients (59%) with 2D speckle tracking data available, 437 patients with LVEF > 30% and 640 with LVEF ≤ 30%. Baseline LV GLS was stratified in tertiles in both LVEF subgroups. The primary endpoint was ventricular tachycardia/fibrillation (VT/VF) or death; the secondary endpoint was heart failure (HF) or death., Results: In patients with LVEF ≤ 30%, a higher tertile GLS (T3, less contractility) was associated with a higher rate of VT/VF/death (P < 0.001), with similar association in patients with LVEF > 30% (P = 0.057). In patients with LVEF ≤ 30%, a higher tertile GLS was also associated with a higher rate of HF/death. In multivariable models, LV GLS predicted VT/VF or death in the LVEF ≤ 30% subgroup [T1 vs. T2/3 HR = 1.67 (1.16-2.38), P = 0.005], but not in those with LVEF > 30% [T1 vs. T2.3 HR = 1.32 (0.86-2.04), P = 0.21]. LV GLS predicted HF/death in the LVEF ≤ 30% subgroup [T1 vs T2/3 HR = 2.00 (1.30-3.13), P = 0.002], but not in in those with LVEF > 30%., Conclusions: In this MADIT-CRT sub-study, LV GLS identified patients at higher risk of VT/VF, HF/death risk independently of conventional clinical parameters in patients with LVEF ≤ 30%, but not in patients with LVEF > 30%., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background There are limited data on risk of arrhythmias among patients with lymphoproliferative disorders. We designed this study to determine the risk of atrial and ventricular arrhythmia during treatment of lymphoma in a real-world setting. Methods and Results The study population comprised 2064 patients included in the University of Rochester Medical Center Lymphoma Database from January 2013 to August 2019. Cardiac arrhythmias-atrial fibrillation/flutter, supraventricular tachycardia, ventricular arrhythmia, and bradyarrhythmia-were identified using International Classification of Diseases, Tenth Revision ( ICD-10 ) codes. Multivariate Cox regression analysis was used to assess the risk of arrhythmic events with treatments categorized as Bruton tyrosine kinase inhibitor (BTKi), mainly ibrutinib/non-BTKi treatment versus no treatment. Median age was 64 (54-72) years, and 42% were women. The overall rate of any arrhythmia at 5 years following the initiation of BTKi was (61%) compared with (18%) without treatment. Atrial fibrillation/flutter was the most common type of arrhythmia accounting for 41%. Multivariate analysis showed that BTKi treatment was associated with a 4.3-fold ( P <0.001) increased risk for arrhythmic event ( P <0.001) compared with no treatment, whereas non-BTKi treatment was associated with a 2-fold ( P <0.001) risk increase. Among subgroups, patients without a history of prior arrhythmia exhibited a pronounced increase in the risk for the development of arrhythmogenic cardiotoxicity (3.2-fold; P <0.001). Conclusions Our study identifies a high burden of arrhythmic events after initiation of treatment, which is most pronounced among patients treated with the BTKi ibrutinib. Patients undergoing treatments for lymphoma may benefit from prospective focused cardiovascular monitoring prior, during, and after treatment regardless of arrhythmia history.

Background: Percutaneous catheter ablation (CA) to achieve pulmonary vein isolation is an effective treatment for drug-refractory paroxysmal and persistent atrial fibrillation (AF). However, recurrence rates after a single AF ablation procedure remain elevated. Conventional management after CA ablation has mostly been based on clinical AF recurrence. However, continuous recordings with insertable cardiac monitors (ICMs) and patient-triggered mobile app transmissions post-CA can now be used to detect early recurrences of subclinical AF (SCAF). We hypothesize that early intervention following CA based on personalized ICM data can prevent the substrate progression that promotes the onset and maintenance of atrial arrhythmias., Methods: This is a randomized, double-blind (to SCAF data), single-tertiary center clinical trial in which 120 patients with drug-refractory paroxysmal or persistent AF are planned to undergo CA with an ICM. Randomization will be to an intervention arm (n = 60) consisting of ICM-guided early intervention based on SCAF and patient-triggered mobile app transmissions versus a control arm (n = 60) consisting of a standard intervention protocol based on clinical AF recurrence validated by the ICM. Primary endpoint is AF burden, which will be assessed from ICMs at 15 months post-AF ablation. Secondary endpoints include healthcare utilization, functional capacity, and quality of life., Conclusion: We believe that ICM-guided early intervention will provide a novel, personalized approach to post-AF ablation management that will result in a significant reduction in AF burden, healthcare utilization, and improvements in functional capacity and quality of life., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)