Link, Mark S.

Importance Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy–related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro–B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate ( P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. Trial Registration ClinicalTrials.gov Identifier: NCT01915615

ABSTRACT Background Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤ 1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3‐month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR = 1.28, p < 0.001) and HFpEF (HR = 1.21, p = 0.02), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re‐do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. Conclusions Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke, HF hospitalization and mortality rates were similar, suggesting earlier ablation may enhance rhythm control over other outcomes.

Background: Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective: To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3-month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results: After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR 1.25, p < 0.001) and HFpEF (HR 1.27, p = 0.01), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re-do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. Conclusions: Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke and mortality rates were similar, suggesting earlier ablation may enhance rhythm control without affecting long-term survival.

11pt, fleqn, a4paper, ]LegrandOrangeBook Background: Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective: To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3-month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results: After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR 1.25, p < 0.001) and HFpEF (HR 1.27, p = 0.01), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re-do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. CONCLUSIONS: Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke and mortality rates were similar, suggesting earlier ablation may enhance rhythm control without affecting long-term survival. Condensed Abstract Delayed atrial fibrillation (AF) ablation was associated with higher (AF) recurrence in both HFrEF and HFpEF. In HFrEF, delayed ablation led to increased use of re-do ablation, cardioversion and antiarrhythmic drugs (AADs). In HFpEF, only AAD use was significantly higher with delayed ablation. Stroke and mortality rates were similar between early and delayed ablation groups.

BACKGROUND: Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing of atrial fibrillation (AF) ablation relative to the diagnosis time. We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on clinical outcomes after AF ablation. METHODS: We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials through August 2024. Pairwise, prognostic, and reconstructed time-to-event data meta-analyses were conducted using R V. 4.3.1. Our primary end point was time to first AF recurrence, with secondary end points of all-cause mortality, tamponade, stroke, and heart failure. RESULTS: Our cohort included 23 studies with 43 711 patients. Shorter DAT was significantly associated with reduced AF recurrence across both paroxysmal and persistent AF subgroups ( P <0.01). There was a significant decrease in benefit for paroxysmal AF over time and a slight decrease in benefit for persistent AF over time. However, the benefit remained significant in both over time. DAT per year was significantly associated with a 10% increased risk of AF recurrence. Reconstructed Kaplan-Meier analysis showed that DAT >1 year was significantly associated with a 70% increased risk of AF recurrence in paroxysmal AF and 30% in persistent AF. DAT ≤1 year was significantly associated with decreased all-cause mortality ( P <0.01) and showed a trend toward an association with a lower incidence of stroke ( P =0.08). However, there was no significant difference in heart failure between DAT ≤1 year and DAT >1 year. CONCLUSIONS: Early ablation is more beneficial in paroxysmal AF, with a notable decrease in benefit over time, while in persistent AF, the benefit remains significant but slightly decreases over time. Shorter DAT was significantly associated with decreased all-cause mortality and showed a trend toward an association with a lower incidence of stroke. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/display_record.php? ; Unique identifier: CRD42024525542.

Introduction: Pulsed field ablation (PFA) is an adaptation of direct current ablation first used for catheter ablation in the 1980s. Expectations of a reduced risk profile led to the current resurgence in investment and interest in the technology as a potential alternative energy source for ablations to treat atrial fibrillation (AF). However, reports of adverse events, including new risks, are increasing. Research Question: How many adverse effects are reported with the use of newly available PFA systems? Aims: Quantify and describe the adverse events from PFA reported to date in the Food and Drug Administration’s (FDA) Manufacturer and User Facility Device Experience (MAUDE) database. Methods: We searched the U.S. FDA’s MAUDE database for all reports filed with the code “QZI”, which is the product code for PFA systems created with the first FDA approvals in February 2024. All reports from inception through April 2024 (a total of 3 months) were included in this review. Per manufacturer presentation in May 2024, approximately 1000 cases utilizing PFA had been captured in a post-market registry of the predominant commercially used technology, but the exact number of cases can not be determined from MAUDE data. Results: A total of 217 adverse events were reported over the first 3 months of US approval, with 91 of these considered patient injuries. These injuries included 10 cases of cardiac tamponade, 7 reports of postoperative arrhythmia, 6 instances of device-related tissue entrapment, 5 cases of hemolysis with impaired renal function, 5 cases of stroke or TIA, including both embolic and hemorrhagic, 3 cases of intraoperative heart block, 2 coronary spasms, and 2 cases of intraoperative ST elevation. (Figure) Of the 91 reported patient safety events, 46 required hospitalization, 13 cases required temporary pacing, 11 required pericardiocentesis, 4 required dialysis, 4 required cardiothoracic surgery, and 2 required cardioversion. Conclusions: A number of adverse events have been reported to the MAUDE database in the first 3 months of FDA approval of PFA. The cardiac electrophysiology community should remain vigilant to ensure that the benefit-risk profile remains acceptable for patient safety.

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.

Introduction: The ICD Sports Registry demonstrated that many athletes with ICDs can participate in competitive sports without death, failure to defibrillate, or physical injury. However, sudden cardiac arrest is more prevalent and has worse outcomes in Black compared to White individuals in the general population and among athletes. Outcomes of sports participation for Black athletes with ICDs have not been described. Aim: To describe the risk of arrhythmia and efficacy of ICDs in Black athletes. Methods: This is a post-hoc subgroup analysis of the ICD Sports Registry, which enrolled athletes with ICDs age 10 to 60, participating in organized, competitive sports, and followed them prospectively for four years. The endpoints and methods are reported previously. Results: Among the 440 athletes, 15 were Black and 410 white. Among the Black athletes, hypertrophic cardiomyopathy was the most common diagnosis (40%) and 87% were implanted for secondary prevention or syncope (vs 69% in White athletes). Most common sports were basketball (8), softball (4), and running (3), with 7 Black athletes competing on varsity/junior varsity/traveling teams. Among the Black athletes, there were no appropriate shocks during sports, among white athletes, 7% received an appropriate shock during sports. Among Black athletes, there was one appropriate shock event for ventricular tachycardia (7%), a VT storm in an athlete with idiopathic VF, non-sports-related. Among white athletes, 10% received appropriate shocks during non-sports activities. Two Black athletes (13%) received an inappropriate shock, one competition-related (sinus tachycardia) and the other for T wave oversensing at rest, vs 12% of white athletes. There were no sports-related deaths, arrests, or arrhythmia-related injuries in either group. Conclusions: Black athletes represented a small subset of the ICD Sports Registry. Reasons for this are unknown, but may include disparities in ICD implantation and/or in research recruitment/ participation. These Black athletes experienced both appropriate and inappropriate shocks as did white athletes. These data do not suggest a signal for harm for competitive sports participation for Black athletes with ICDs but larger studies are needed.

AbstractCardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Importance Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures Amount and intensity of physical activity. Main Outcomes and Measures The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient’s exercise category. Results Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.