Determinants of ventricular arrhythmias in sickle cell anemia: toward better prevention of sudden cardiac death.

Sudden death is 1 of the leading causes of death in adults with sickle cell anemia (SCA) but its etiology remains mostly unknown. Ventricular arrhythmia (VA) carries an increased risk of sudden death; however, its prevalence and determinants in SCA are poorly studied. This study aimed to identify the prevalence and predictors of VA in patients with SCA. From 2019 to 2022, 100 patients with SCA were referred to the physiology department to specifically analyze cardiac function and prospectively included in the DREPACOEUR registry. They underwent a 24-hour electrocardiogram monitoring (24h-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary end point was the occurrence of VA, defined as sustained or nonsustained ventricular tachycardia (VT), >500 premature ventricular contractions (PVCs) on 24h-Holter, or a recent history of VT ablation. The mean patient age was 46 ± 13 years, and 48% of the patients were male. Overall, VA was observed in 22 (22%) patients. Male sex (81% vs 34%; P = .02), impaired global longitudinal strain (GLS): -16% ± 1.9% vs -18.3% ± 2.7%; P = .02), and decreased platelet count (226 ± 96 giga per liter [G/L] vs 316 ± 130 G/L) were independently associated with VA. GLS correlated with PVC load every 24 hours (r = 0.39; P < .001) and a cutoff of -17.5% could predict VA with a sensitivity of 82% and a specificity of 63%. VAs are common in patients with SCA, especially in men. This pilot study uncovered GLS as a valuable parameter for improving rhythmic risk stratification.

The Cardio-Kidney Patient: Epidemiology, Clinical Characteristics and Therapy.

Patients with chronic kidney disease (CKD) are at high risk to develop cardiovascular disease with its manifestations coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. In addition, the presence of CKD has a major impact on the prognosis of patients with cardiovascular disease, leading to an increased morbidity and mortality if both comorbidities are present. Therapeutic options including medical therapy and interventional treatment are often limited in patients with advanced CKD, and in most cardiovascular outcome trials, patients with advanced CKD have been excluded. Thus, in many patients, treatment strategies for cardiovascular disease need to be extrapolated from trials conducted in patients without CKD. The current article summarizes the epidemiology, clinical presentation, and treatment options for the most prevalent manifestations of cardiovascular disease in CKD and discusses the currently available treatment options to reduce morbidity and mortality in this high-risk population.

Childhood-onset hypertrophic cardiomyopathy caused by thin-filament sarcomeric variants.

Up to 20% of children with sarcomeric hypertrophic cardiomyopathy (HCM) have disease-causing variants in genes coding for thin-filament proteins. However, data on genotype-phenotype correlations for thin-filament disease are limited. This study describes the natural history and outcomes of children with thin-filament-associated HCM and compares it to thick-filament-associated disease.Longitudinal data were collected from 40 children under 18 years with a disease-causing variant in a thin-filament protein from a single quaternary referral centre. Twenty-one (female n=6, 35.5%) were diagnosed with HCM at a median age of 13.0 years (IQR 8.3-14.0). Over a median follow-up of 5.0 years (IQR 4.0-8.5), three (14.3%) experienced one or more major adverse cardiac events (MACE) (two patients had an out-of-hospital arrest and eight appropriate implantable cardiac defibrillator (ICD) therapies in three patients). One gene carrier died suddenly at age 9 years. Compared with those with thick-filament disease, children with thin-filament variants more commonly experienced non-sustained ventricular tachycardia [NSVT; n=6 (28.6%) vs n=14 (10.8%), p=0.024] or underwent ICD insertion (thin, n=13 (61.9%) vs thick, n=50 (38.5%), p=0.040). However, there was no difference in the incidence of MACE (thin 2.47/100 pt years (95% CI 0.80 to 7.66) vs thick 3.63/100 pt years (95% CI 2.25 to 5.84)) or an arrhythmic event (thin 1.65/100 pt years (95% CI 0.41 to 6.58) vs thick 2.55/100 pt years (95% CI 1.45 to 4.48), p value 0.43).This study suggests that adverse events in thin-filament disease are predominantly arrhythmic and may occur in the absence of hypertrophy, but overall short-term outcomes do not differ significantly from thick-filament disease.

Dynamic electrocardiogram changes are a novel risk marker for sudden cardiac death.

BACKGROUND AND AIMS: Electrocardiogram (ECG) abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD), but the potential importance of dynamic ECG remodelling has not been investigated. In this study, the nature and prevalence of dynamic ECG remodelling were studied among individuals who eventually suffered SCD. METHODS: The study population was drawn from two prospective community-based SCD studies in Oregon (2002, discovery cohort) and California, USA (2015, validation cohort). For this present sub-study, 231 discovery cases (2015-17) and 203 validation cases (2015-21) with ≥2 archived pre-SCD ECGs were ascertained and were matched to 234 discovery and 203 validation controls based on age, sex, and duration between the ECGs. Dynamic ECG remodelling was measured as progression of a previously validated cumulative six-variable ECG electrical risk score. RESULTS: Oregon SCD cases displayed greater electrical risk score increase over time vs. controls [+1.06 (95% confidence interval +0.89 to +1.24) vs. -0.05 (-0.21 to +0.11); P < .001]. These findings were successfully replicated in California [+0.87 (+0.7 to +1.04) vs. -0.11 (-0.27 to 0.05); P < .001]. In multivariable models, abnormal dynamic ECG remodelling improved SCD prediction over baseline ECG, demographics, and clinical SCD risk factors in both Oregon [area under the receiver operating characteristic curve 0.770 (95% confidence interval 0.727-0.812) increased to area under the receiver operating characteristic curve 0.869 (95% confidence interval 0.837-0.902)] and California cohorts. CONCLUSIONS: Dynamic ECG remodelling improved SCD risk prediction beyond clinical factors combined with the static ECG, with successful validation in a geographically distinct population. These findings introduce a novel concept of SCD dynamic risk and warrant further detailed investigation.

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Declining Risk of Sudden Cardiac Death in Heart Failure: Fact or Myth?

The notion that the risk of sudden cardiac death (SCD) in patients with heart failure (HF) is declining seems to be gaining traction. Numerous editorials and commentaries have suggested that SCD, specifically arrhythmic SCD, is no longer a significant risk for patients with HF on guideline-directed medical therapy. In this review, we question whether the risk of SCD has indeed declined in HF trials and in the real world. We also explore whether, despite relative risk reductions, the residual SCD risk after guideline-directed medical therapy still suggests a need for implantable cardioverter defibrillator therapy. Among our arguments is that SCD has not decreased in HF trials, nor in the real world. Moreover, we argue that data from HF trials, which have not adhered to guideline-directed device therapy, do not obviate or justify delays to implantable cardioverter defibrillator therapy. In this context, we underline the challenges of translating the findings of HF randomized, controlled trials of guideline-directed medical therapy to the real world. We also make the case for HF trials that adhere to current guideline-directed device therapy so that we can better understand the role of implantable cardioverter defibrillators in chronic HF.

Asymptomatic Patients With Brugada ECG Pattern: Long-Term Prognosis From a Large Prospective Study.

BACKGROUND: Brugada syndrome poses significant challenges in terms of risk stratification and management, particularly for asymptomatic patients who comprise the majority of individuals exhibiting Brugada ECG pattern (BrECG). The aim of this study was to evaluate the long-term prognosis of a large cohort of asymptomatic patients with BrECG. METHODS: Asymptomatic patients with BrECG (1149) were consecutively collected from 2 Italian centers and followed-up at least annually for 2 to 22 years. For the 539 asymptomatic patients (men, 433 [80%]; mean age, 46±13 years) with spontaneous type 1 documented on baseline ECG (87%) or 12-lead 24-hour Holter monitoring (13%), an electrophysiologic study (EPS) was proposed; for the 610 patients with drug-induced-only type 1 (men, 420 [69%]; mean age, 44±14 years), multiple ECGs and 12-lead Holter were advised in order to detect the occurrence of a spontaneous type-1 BrECG. Arrhythmic events were defined as sudden death or documented ventricular fibrillation or tachycardia. RESULTS: Median follow-up was 6 (4-9) years. Seventeen (1.5%) arrhythmic events occurred in the overall asymptomatic population (corresponding to an event-rate of 0.2% per year), including 16 of 539 (0.4% per year) in patients with spontaneous type-1 BrECG and 1 of 610 in those with drug-induced type-1 BrECG (0.03% per year; P<0.001). EPS was performed in 339 (63%) patients with spontaneous type-1 BrECG. Patients with spontaneous type-1 BrECG and positive EPS had significantly higher event rates than patients with negative EPS (7 of 103 [0.7% per year] versus 4 of 236 [0.2% per year]; P=0.025). Among 200 patients who declined EPS, 5 events (0.4% per year) occurred. There was 1 device-related death. CONCLUSIONS: The entire population of asymptomatic patients with BrECG exhibits a relatively low event rate per year, which is important in view of the long life expectancy of these young patients. The presence of spontaneous type-1 BrECG associated with positive EPS identifies a subgroup at higher risk. Asymptomatic patients with drug-induced-only BrECG have a minimal arrhythmic risk, but ongoing follow-up with 12-lead Holter monitoring is recommended to detect the appearance of spontaneous type-1 BrECG pattern.

The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, abnormal results on exercise stress testing are predictive of heart failure outcomes. Our goal was to determine whether an abnormal exercise response is associated with adverse outcomes in pediatric patients with HCM. METHODS: In an international cohort study including 20 centers, phenotype-positive patients with primary HCM who were <18 years of age at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response and new or worsened ST- or T-wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of abnormal exercise test results with transplant and SCD event-free survival. RESULTS: Of 724 eligible patients, 630 underwent at least 1 exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8 years (interquartile range, 4.7 years); 78% were male and 39% were receiving beta-blockers. A total of 175 (28%) had abnormal test results. Patients with abnormal test results had more severe septal hypertrophy, higher left atrial diameter z scores, higher resting left ventricular outflow tract gradient, and higher frequency of myectomy compared with participants with normal test results (P<0.05). Compared with normal test results, abnormal test results were independently associated with lower 5-year transplant-free survival (97% versus 88%, respectively; P=0.005). Patients with exercise-induced ischemia were most likely to experience all-cause death or transplant (hazard ratio, 4.86 [95% CI, 1.69-13.99]), followed by those with an abnormal blood pressure response (hazard ratio, 3.19 [95% CI, 1.32-7.71]). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (hazard ratio, 3.32 [95% CI, 1.27-8.70]). Exercise-induced ectopy was not associated with survival. CONCLUSIONS: Exercise abnormalities are common in childhood HCM. An abnormal exercise test result was independently associated with lower transplant-free survival, especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.

Arrhythmia and Survival Outcomes Among Black Patients and White Patients With a Primary Prevention Defibrillator.

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.

Arrhythmia and Death Following Percutaneous Revascularization in Ischemic Left Ventricular Dysfunction: Prespecified Analyses From the REVIVED-BCIS2 Trial.

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82-1.30]; P=0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01920048.

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

Regional disparities and risk factors of mortality among patients at high risk of sudden cardiac death in emerging countries: a nonrandomized controlled trial.

BACKGROUND: Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. METHODS: Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. RESULTS: We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531-0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116-0.343, p < 0.0001) lower SCD risk. CONCLUSIONS: There was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02099721.

Regional variation in cause of death in patients with type 2 diabetes: Insights from EXSCEL.

AIMS: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD). METHODS AND RESULTS: The international EXSCEL trial included 14,752 participants with T2D (73% with established CVD). We identified the proportion of deaths over 5-year follow-up attributed to cardiovascular and non-cardiovascular causes, and associated risk factors. During median 3.2-year follow-up, 1,091 (7.4%) participants died. Adjudicated causes of death were 723 cardiovascular (66.3% of deaths), including 252 unknown, and 368 non-cardiovascular (33.7%). Most deaths occurred in North America (N = 356/9.6% across region) and Eastern Europe (N = 326/8.1%), with fewest in Asia/Pacific (N = 68/4.4%). The highest proportional cause-specific deaths by region were sudden cardiac in Asia/Pacific (23/34% of regional deaths) and North America (86/24%); unknown in Eastern Europe (90/28%) and Western Europe (39/21%); and non-malignant non-cardiovascular in Latin America (48/31%). Cox proportional hazards model for adjudicated causes of death showed prognostic risk factors (hazard ratio [95% CI]) for cardiovascular and non-cardiovascular deaths, respectively: heart failure 2.04 (1.72-2.42) and 1.86 (1.46-2.39); peripheral artery disease 1.83 (1.54-2.18) and 1.78 (1.40-2.26); and current smoking status 1.61 (1.29-2.01) and 1.77 (1.31-2.40). CONCLUSIONS: In a contemporary T2D trial population, with and without established CVD, leading causes of death varied by geographic region. Underlying mechanisms leading to variability in cause of death across geographic regions and its impact on clinical trial endpoints warrant future research.

Late life-threatening arrhythmia in patients with Brugada syndrome: Results from long-term follow-up in a large Japanese cohort.

INTRODUCTION: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS. METHODS: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined. RESULTS: During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. CONCLUSION: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

Prior history of atrial fibrillation and arrhythmic outcomes: Data from the WEARIT-II prospective registry.

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.

Evaluation of patients with implantable cardioverter-defibrillator in a Latin American tertiary center.

INTRODUCTION: Despite advancements in implantable cardioverter-defibrillator (ICD) technology, sudden cardiac death (SCD) remains a persistent public health concern. Chagas disease (ChD), prevalent in Brazil, is associated with increased ventricular tachycardia (VT) and ventricular fibrillation (VF) events and SCD compared to other cardiomyopathies. METHODS: This retrospective observational study included patients who received ICDs between October 2007 and December 2018. The study aims to assess whether mortality and VT/VF events decreased in patients who received ICDs during different time periods (2007-2010, 2011-2014, and 2015-2018). Additionally, it seeks to compare the prognosis of ChD patients with non-ChD patients. Time periods were chosen based on the establishment of the Arrhythmia Service in 2011. The primary outcome was overall mortality, assessed across the entire sample and the three periods. Secondary outcomes included VT/VF events and the combined outcome of death or VT/VF. RESULTS: Of the 885 patients included, 31% had ChD. Among them, 28% died, 14% had VT/VF events, and 37% experienced death and/or VT/VF. Analysis revealed that period 3 (2015-2018) was associated with better death-free survival (p = .007). ChD was the only variable associated with a higher rate of VT/VF events (p < .001) and the combined outcome (p = .009). CONCLUSION: Mortality and combined outcome rates decreased gradually for ICD patients during the periods 2011-2014 and 2015-2018 compared to the initial period (2007-2010). ChD was associated with higher VT/VF events in ICD patients, only in the first two periods.

Association of temporal change in body mass index with sudden cardiac arrest in diabetes mellitus.

BACKGROUND: Underweight imposes significant burden on cardiovascular outcomes in patients with diabetes mellitus. However, less is known about the impact of serial change in body weight status measured as body mass index (BMI) on the risk of sudden cardiac arrest (SCA). This study investigated the association between SCA and temporal change in BMI among patients with diabetes mellitus. METHODS: Based on Korean National Health Insurance Service database, participants with diabetes mellitus who underwent health examination between 2009 and 2012 and had prior health examination data (four years ago, 2005-2008) were retrospectively analyzed. BMI was measured at baseline (2005-2008) and 4-year follow-up health examination (2009-2012). Patients were classified in four groups according to the body weight status and its temporal change: sustained non-underweight, sustained underweight, previous underweight, and newly developed underweight. Primary outcome was defined as occurrence of SCA. RESULTS: A total of 1,355,746 patients with diabetes mellitus were included for analysis, and SCA occurred in 12,554 cases. SCA was most common in newly developed underweight (incidence rate = 4.45 per 1,000 person-years), followed by sustained underweight (incidence rate = 3.90), previous underweight (incidence rate = 3.03), and sustained non-underweight (incidence rate = 1.34). Adjustment of covariates resulted highest risk of SCA in sustained underweight (adjusted hazard ratio = 2.60, 95% confidence interval [2.25-3.00], sustained non-underweight as a reference), followed by newly developed underweight (2.42, [2.15-2.74]), and previous underweight (2.12, [1.77-2.53]). CONCLUSIONS: In diabetes mellitus, sustained underweight as well as decrease in body weight during 4-year follow-up imposes substantial risk on SCA. Recovery from underweight over time had relatively lower, but yet increased risk of SCA. Both underweight and dynamic decrease in BMI can be associated with increased risk of SCA.

Association of triglyceride glucose index and triglyceride glucose-body mass index with sudden cardiac arrest in the general population.

BACKGROUND: Insulin resistance (IR) significantly contributes to cardiovascular disease (CVD) development. Triglyceride glucose (TyG) index and triglyceride glucose-body mass index (TyG-BMI) are recognised as convenient proxies for IR. However, their relationship with sudden cardiac arrest (SCA) remains unclear. METHODS: This prospective cohort analysis included 355,242 UK Biobank participants with available TyG index and TyG-BMI data and no history of CVD. Cox proportional risk models assessed the association between the TyG index, TyG-BMI and SCA risk. Additionally, Accelerated Failure Time (AFT) models were employed to investigate the timing of SCA onset. The impact of dynamic increases in TyG index and TyG-BMI levels on SCA risk was examined using restricted cubic spline. RESULTS: Over a median follow-up period of 165.4 months (interquartile range 156.5-174 months), 1,622 cases of SCA were recorded. Multivariate Cox regression analysis revealed a 9% increase in SCA risk per standard deviation increase in TyG index (adjusted hazard ratio (aHR) = 1.09, 95% confidence interval (CI) 1.04-1.15) and an 14% increase per standard deviation increase in TyG-BMI (aHR 1.14, 95% CI 1.09-1.2). AFT models indicated earlier median times to SCA occurrence with increasing quintiles of TyG index and TyG-BMI compared to the lowest quintile (P for trend < 0.05). SCA risk was linearly (P = 0.54) and non-linearly (P = 0.007) correlated with gradual increases in TyG index and TyG-BMI levels, respectively. Sex-stratified analyses showed stronger associations in women. CONCLUSIONS: Higher TyG index and TyG-BMI levels are associated with an increased SCA risk and earlier onset, particularly in women.

Mitral annular disjunction and mitral valve prolapse extrapolating adult data to an adolescent cohort?

PURPOSE OF REVIEW: The aim of this study is to provide an update on mitral valve prolapse (MVP) and mitral annular disjunction (MAD) and who may be at risk for ventricular arrhythmias and sudden cardiac death. RECENT FINDINGS: MVP is generally considered a benign condition. However, a small subset of patients may be at risk for life-threatening ventricular arrhythmias. Among the risk factors identified in adults include patients with bileaflet mitral valves, myxomatous changes, myocardial fibrosis, and the presence of MAD. Advances in multimodal imaging have allowed for improved identification of fibrosis, anatomical valve derangements, and the amount of MAD. Recent guidelines have suggested that patients with MVP with or without MAD may be at risk for life-threatening arrhythmias if they have had prior ventricular arrhythmias, ventricular dysfunction, or unexplained syncope. Yet, extrapolation of adult data to a pediatric cohort with similar MVP and MAD at this juncture is challenging. There is, however, early evidence that some pediatric patients with significant myocardial fibrosis or abnormal tissue Doppler may be at risk for ventricular tachycardia. SUMMARY: Mitral valve prolapse and mitral annular disjunction at times coexist and at other times can be seen as isolated entities. While the incidence of arrhythmic MVP is quite rare, there is increasing evidence that certain select adults with MVP may be at risk for ventricular tachycardia and sudden cardiac death. Future multicenter studies are needed to better understand the natural history of arrhythmic mitral valve disease and how early disease manifestation in children may impact findings now being reported in young adults.

Assessment of Risk for Sudden Cardiac Death Among Adolescents and Young Adults After Receipt of COVID-19 Vaccine - Oregon, June 2021-December 2022.

COVID-19 vaccination has been associated with myocarditis in adolescents and young adults, and concerns have been raised about possible vaccine-related cardiac fatalities in this age group. In April 2021, cases of myocarditis after COVID-19 vaccination, particularly among young male vaccine recipients, were reported to the Vaccine Adverse Event Reporting System. To assess this possibility, investigators searched death certificates for Oregon residents aged 16-30 years who died during June 2021-December 2022 for cardiac or undetermined causes of death. For identified decedents, records in Oregon's immunization information system were reviewed for documentation of mRNA COVID-19 vaccination received ≤100 days before death. Among 1,292 identified deaths, COVID-19 was cited as the cause for 30. For 101 others, a cardiac cause of death could not be excluded; among these decedents, immunization information system records were available for 88, three of whom had received an mRNA COVID-19 vaccination within 100 days of death. Of 40 deaths that occurred among persons who had received an mRNA COVID-19 vaccine dose, three occurred ≤100 days after vaccination. Two of these deaths were attributed to chronic underlying conditions; the cause was undetermined for one. No death certificate attributed death to vaccination. These data do not support an association between receipt of mRNA COVID-19 vaccine and sudden cardiac death among previously healthy young persons. COVID-19 vaccination is recommended for all persons aged ≥6 months to prevent COVID-19 and complications, including death.