The Association Between Late Gadolinium Enhancement by Cardiac Magnetic Resonance and Ventricular Arrhythmia in Patients With Mitral Valve Prolapse: A Systematic Review and Meta-Analysis.

INTRODUCTION: Malignant ventricular arrhythmia (VA) and sudden cardiac death (SCD) have been reported in patients with mitral valve prolapse (MVP); however, effective risk stratification methods are still lacking. Myocardial fibrosis is thought to play an important role in the development of VA; however, observational studies have produced contradictory findings regarding the relationship between VA and late gadolinium enhancement (LGE) in MVP patients. The aim of this meta-analysis and systematic review of observational studies was to investigate the association between left ventricular LGE and VA in patients with MVP. METHODS: We searched the PubMed, Embase, and Web of Science databases from 1993 to 2023 to identify case-control, cross-sectional, and cohort studies that compared the incidence of VA in patients with MVP who had left ventricular LGE and those without left ventricular LGE. RESULTS: A total of 1464 subjects with MVP from 12 observational studies met the eligibility criteria. Among them, VA episodes were reported in 221 individuals (15.1%). Meta-analysis demonstrated that the presence of left ventricular LGE was significantly associated with an increased risk of VA (pooled risk ratio 2.96, 95% CI: 2.26-3.88, p for heterogeneity = 0.07, I2 = 40%). However, a meta-regression analysis of the prevalence of mitral regurgitation (MR) showed that the severity of MR did not significantly affect the association between the occurrence of LGE and VA (p = 0.079). CONCLUSION: The detection of LGE could be helpful for stratifying the risk of VA in patients with MVP.

Molecular autopsy in Chinese sudden cardiac death in the young.

Inherited cardiovascular conditions are significant causes of sudden cardiac death in the young (SCDY), making their investigation using molecular autopsy and prevention a public health priority. However, the molecular autopsy data in Chinese population is lacking. The 5-year result (2017-2021) of molecular autopsy services provided for victims of SCDY (age 1-40 years) was reviewed. The outcome of family cascade genetic screening and clinical evaluation was reviewed. A literature review of case series reporting results of molecular autopsy on SCDY in 2016-2023 was conducted. Among the 41 decedents, 11 were found to carry 13 sudden cardiac death (SCD)-causative genetic variants. Likely pathogenic (LP) variants were identified in the DSP, TPM1, TTN, and SCN5A genes. Cascade genetic testing identified four family members with LP variants. One family member with familial TPM1 variant was found to have hypertrophic cardiomyopathy upon clinical evaluation. This study provided insight into the genetic profile of molecular autopsy in a Chinese cohort of SCDY. The detection of important SCD-causative variants through molecular autopsy has facilitated family cascade screening by targeted genetic testing and clinical evaluation of at-risk family members. A literature review of the current landscape of molecular autopsy in the investigation of SCDY was conducted.

Subcutaneous versus transvenous implantable cardioverter defibrillator in hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Background: A subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to a transvenous implantable cardio defibrillator (TV-ICD). An S-ICD reduces the risk of transvenous lead placement. However, further research is required to determine how S-ICDs affect patients with hypertrophic cardiomyopathy (HCM). In this study, we investigated the comparative efficacy and safety of S-ICDs versus TV-ICDs in HCM. Methods: On December 6th, 2023, we performed a comprehensive search of the PubMed, Embase, Scopus, and Cochrane databases to identify randomized clinical trials (RCTs) and observational studies comparing S-ICDs with TV-ICDs in HCM patients published from 2004 until 2023. No language restrictions were applied. The primary outcome was appropriate shocks (AS), with inappropriate shocks (IAS), and device-related complications considered as secondary outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random effects model. The ROBINS-I tool was used to assess the risk of bias of the studies. Results: The search yielded 1,114 records. Seven studies comprising 4,347 HCM patients were included, of whom 3,325 (76.0%) had TV-ICDs, and 1,022 (22.6%) had S-ICDs. There were 2,564 males (58.9%). The age range was from 39.1 to 49.4 years. Compared with the TV-ICD group, the S-ICD cohort had a significantly lower incidence of device-related complications (OR 0.52; 95% CI: 0.30-0.89; P=0.02; I2=4%). Contrastingly, there were no statistically significant differences in the occurrences of AS (OR 0.49; 95% CI: 0.22-1.08; P=0.08; I2=75%) and IAS (OR 1.03; 95% CI: 0.57-1.84; P=0.93; I2=65%) between the two device modalities. In the analysis of the overall risk of bias in the studies, we found 42% of them with several, 28% with moderate, and 14% with low risk of bias. Conclusions: In HCM patients, S-ICDs were associated with a lower incidence of device-associated problems than TV-ICDs. AS and IAS incidence rates were similar between groups. These findings may assist clinicians in determining the most suitable device for treating patients with HCM.

Advances and Challenges in the Management of Brugada Syndrome: A Comprehensive Review.

Brugada syndrome (BrS) is an inherited arrhythmogenic disorder marked by distinctive ST-segment elevations on electrocardiograms (ECG) and an increased risk of sudden cardiac death. Characterized by mutations primarily in the SCN5A gene, BrS disrupts cardiac ion channel function, leading to abnormal electrical activity and arrhythmias. Although BrS primarily affects young, healthy males, it poses significant diagnostic challenges due to its often concealed or intermittent ECG manifestations and clinical presentation that can mimic other cardiac disorders. Current management strategies focus on symptom control and prevention of sudden death, with implantable cardioverter-defibrillators (ICD) serving as the primary intervention for high-risk patients. However, the complications associated with ICDs and the lack of effective pharmacological options necessitate a cautious and personalized approach. Recent advancements in catheter ablation have shown promise, particularly for managing ventricular fibrillation (VF) storms and reducing ICD shocks. Additionally, pharmacological treatments such as quinidine have been effective in specific cases, though their use is limited by availability and side effects. This review highlights significant gaps in the BrS literature, particularly in terms of long-term management and novel therapeutic approaches. The importance of genetic screening and tailored treatment strategies to better identify and manage at-risk individuals is emphasized. The review aims to enhance the understanding of BrS and improve patient outcomes, advocating for a multidisciplinary approach to this complex syndrome.

Shifting Paradigms in Hypertrophic Cardiomyopathy: The Role of Exercise in Disease Management.

Hypertrophic cardiomyopathy (HCM) is traditionally associated with exercise restriction due to potential risks, yet recent evidence and guidelines suggest a more permissive stance for low-risk individuals. The aim of this comprehensive review was to examine existing research on the impact of exercise on cardiovascular outcomes, safety, and quality of life in this population and to consider implications for clinical practice. Recent studies suggest that regular exercise and physical activity in low-risk individuals with HCM are associated with positive outcomes in functional capacity, haemodynamic response, and quality of life, with consistent safety. Various studies highlight the safety of moderate-intensity exercise, showing improvements in exercise capacity without adverse cardiac remodelling or significant arrhythmias. Psychological benefits, including reductions in anxiety and depression, were also reported following structured exercise programs. These findings support the integration of individualised exercise regimens in the management of low-risk individuals with HCM, potentially improving overall well-being and cardiovascular health. Adoption of the FITT principle, consideration of individual risk profiles, and shared decision-making are recommended. Future research is warranted to clarify the definition of 'low-risk' for exercise participation and investigate the influence of physical activity on disease progression in HCM. Innovation in therapeutic strategies and lifestyle interventions, alongside improved patient and provider education, will help advance the care and safety of individuals with HCM engaging in exercise.

[Cardiac channelopathies in the context of hereditary arrhythmia syndromes]. / Kardiale Kanalopathien im Kontext hereditärer Arrhythmiesyndrome.

Genetic arrhythmia disorders are rare diseases; however, they are a common cause of sudden cardiac death in children, adolescents, and young adults. In principle, a distinction can be made between channelopathies and cardiomyopathies in the context of genetic diseases. This paper focuses on the channelopathies long and short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). Early diagnosis of these diseases is essential, as drug therapy, behavioral measures, and if necessary, implantation of a cardioverter defibrillator can significantly improve the prognosis and quality of life of patients. This paper highlights the pathophysiological and genetic basis of these channelopathies, describes their clinical manifestations, and comments on the principles of diagnosis, risk stratification and therapy.

Distinct Substrates of Idiopathic Ventricular Fibrillation Revealed by Arrhythmia Characteristics on Implantable Cardioverter-Defibrillator.

BACKGROUND: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts. OBJECTIVE: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates. METHODS: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates. RESULTS: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF. CONCLUSIONS: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications.

Mitral Annulus Disjunction in consecutive patients undergoing Cardiac Magnetic Resonance: where is the boundary between normality and disease?

BACKGROUND: The presence of mitral annulus disjunction (MAD) has been considered a high-risk feature for sudden cardiac death based on selected study populations. We aimed to assess the prevalence of MAD in consecutive patients undergoing clinically-indicated Cardiac Magnetic Resonance (CMR), its association with ventricular arrhythmias, Mitral Valve Prolapse (MVP), and other CMR features. METHODS: This single-center retrospective study included consecutive patients referred to CMR at our Institution between June 2021 and November 2021. The MAD was defined as a ≥1mm displacement between the left atrial wall-mitral valve leaflet junction and the left ventricular wall during end-systole. The MAD extent was defined as the maximum longitudinal displacement. Associates of MAD were evaluated at uni- and multi-variariable regression analysis. A study endpoint including (aborted) sudden cardiac death, unexplained syncope, and sustained ventricular tachycardia was evaluated at 12-month follow-up. RESULTS: Four-hundred-forty-one patients (55±18 years, 61% males) were included, and 29 (7%) had MVP. The prevalence of MAD ≥1mm, 4mm, and 6mm were 214 (49%), 63 (14%), and 15 (3%), respectively. Patients with MVP showed a higher prevalence of MAD greater than 1mm (90% vs. 46%; p<0.001), 4mm (48% vs. 12%; p<0.001), and 6mm (10% vs. 3%; p=0.03), and a greater MAD extent (4.2mm, 3.0-5.7mm vs. 2.8mm, 1.9-4.0mm; p<0.001) than patients without MVP. The MVP was the only morpho-functional abnormality associated with MAD at multivariable analysis (p<0.001). A high burden of ventricular ectopic beats at baseline Holter-ECG was associated with MAD ≥4mm and MAD extent (p<0.05). The presence of MAD ≥1mm (0.9% vs. 1.8%; p=0.46), MAD ≥4mm (1.6% vs. 1.3%; p=0.87), or MVP (3.5% vs. 1.2%; p=0.32) were not associated with the study endpoint, whereas patients with MAD ≥6mm showed a trend towards a higher likelihood of the study endpoint (6.7% vs. 1.2%; p=0.07). CONCLUSIONS: A MAD of limited entity was common in consecutive patients undergoing CMR. Patients with MVP showed higher prevalence and greater extent of MAD. Extended MAD was rarer and showed association with ventricular arrhythmias at baseline. The mid-term prognosis of MAD seems benign, however prospective studies are warranted to search for potential "malignant MAD extents" to improve patients' risk stratification.

The role of coronary CT angiography in athletes.

The sudden death of a young or high-level athlete or adolescent during recreational sports is one of the events with the greatest impact on public opinion in modern society. Sudden cardiac death (SCD) is the principal medical cause of death in athletes and can be the first and last clinical presentation of underlying disease. To prevent such episodes, pre-participation screening has been introduced in many countries to guarantee cardiovascular safety during sports and has become a common target among medical sports/governing organizations. Different cardiac conditions may cause SCD, with incidence depending on definition, evaluation methods, and studied populations, and a prevalence and etiology changing according to the age of athletes, with CAD most frequent in master athletes, while coronary anomalies and non-ischemic causes prevalent in young. To detect silent underlying causes early would be of considerable clinical value. This review summarizes the pre-participation screening in athletes, the specialist agonistic suitability visit performed in Italy, the anatomical characteristics of malignant coronary anomalies, and finally, the role of coronary CT angiography in such arena. In particular, the anatomical conditions suggesting potential disqualification from sport, the post-treatment follow-up to reintegrate young athletes, the diagnostic workflow to rule-out CAD in master athletes, and their clinical management are analyzed.

Ventriculo-arterial (VA) coupling and fQRS as new selection criteria for primary prevention ICD placement.

For decades, left ventricular ejection fraction (LVEF < 35%) has been a mainstay for identifying heart failure (HF) patients most likely to benefit from an implantable cardioverter defibrillator (ICD). However, LVEF is a poor predictor of sudden cardiac death (SCD) and ignores 50% of HF patients with mildly reduced and preserved LVEF. The current international guidelines for primary prophylaxis ICD therapy are inadequate. Instead of LVEF, which is not a good measure of LV contractility or hemodynamic characterization, we hypothesize ventriculo-arterial (VA) coupling combined with fragmented QRS (fQRS) will improve risk stratification and patient suitability for an ICD. Quantifying cardiac and aortic mechanics, and predicting active arrhythmogenic substrate, from varying fQRS morphologies, may help to stratify ischemic and non-ischemic patients with different functional capacities and predisposition for lethal arrhythmias. We propose HF patients with a low physiological reserve may not benefit from ICD therapy, whereas those patients with higher reserves and extensive arrhythmogenic substrate may benefit. Our hypothesis combining VA coupling with fQRS changes has the potential to widen HF patient participation (low and high LVEF) and advance personalized medicine for HF patients at high risk of SCD.

Mitral Annulus Disjunction: A Comprehensive Cardiovascular Magnetic Resonance Phenotype and Clinical Outcomes Study.

BACKGROUND: Clinical importance of mitral annulus disjunction (MAD) is not well established. PURPOSE: Characterize a population of MAD all-comers diagnosed by cardiac magnetic resonance imaging (MRI). STUDY TYPE: Retrospective. POPULATION: MAD confirmed in 222 patients, age of 49.2 ± 19.3 years, 126 (56.8%) males. FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T/steady-state free precession and inversion recovery. ASSESSMENT: Clinical history, outcomes, imaging, and arrhythmia data. MAD defined as a separation ≥2 mm between left ventricular myocardium and mitral annulus. Presence and pattern of late gadolinium enhancement (LGE) were analyzed. LGE in the papillary muscles and adjacent to MAD were identified as MAD related. Ventricular arrhythmias (VA) were grouped into non-sustained ventricular arrhythmias (NSVA) or sustained. Cardiovascular death assessed. STATISTICAL TESTS: Differences between baseline characteristics were compared. Univariate regression was used to investigate possible associations between ventricular arrhythmia and cardiovascular death with characteristics associated with the severity of MAD. A multivariable logistic regression included significant variables from the univariate analysis and was performed for MAD-related and global LGE. RESULTS: MAD extent 5.0 ± 2.6 mm. MV annulus expanded during systole for MAD ≥6 mm. Systolic expansion associated with prolapse, billowing, and curling. LGE present in 82 patients (36.9%). Twenty-three patients (10.4%) showed MAD-related LGE by three different observers. No association of LGE with MAD extent (P = 0.545) noted. Follow-up 4.1 ± 2.4 years. No sustained VA observed. In univariable analysis, NSVA was more prevalent in patients with MAD ≥6 mm (33.3% vs. 9.9%), but this was attenuated on multivariate analysis (P = 0.054). The presence of NSVA was associated with global LGE but not MAD-related LGE in isolation (P = 0.750). Three patients died of cardiovascular causes (1.4%) and none had MAD-related LGE. None died of sudden cardiac arrest. CONCLUSION: In patients referred for cardiac MRI, mitral valve dysfunction was associated with MAD severity. Scar was not related to the extent of MAD, but associated with NSVA. The risk of sustained arrhythmias and cardiovascular death was low in this population. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Heritability of sudden cardiac death in Thoroughbred racehorses.

BACKGROUND: Sudden cardiac death (SCD) is an important cause of exercise-associated fatalities in Thoroughbred racehorses. Equine deaths share similarities with fatalities in human athletes that result from inherited cardiac disease. Whilst genetic causes have been postulated in horses, these have not been confirmed and heritability of SCD has not previously been estimated in Thoroughbred racehorses. OBJECTIVES: To determine the heritability of SCD in a sample population of Thoroughbred racehorses. STUDY DESIGN: Retrospective case-control study. METHODS: Steward and post-mortem reports of Thoroughbred racehorses in Australia between 2007 and 2020 were reviewed to identify horses with SCD. Control horses were randomly selected from races in which SCD occurred or from races on the date of the case fatality. A five-generation integrated pedigree chart was collected for each horse. Estimates of heritability were obtained using an animal model in the ASReml-R program with variance components estimated assuming SCD was normally distributed, and on the logit transformed scale. Inbreeding coefficients were calculated and the risk of producing SCD-affected progeny was calculated for stallions that sired ≥5 individuals in the case-control population. RESULTS: Ninety-three horses with SCD and 465 control horses were identified. Heritability on the underlying scale was 0.15 ± 0.09 (logit animal) and 0.24 ± 0.12 (normal animal). Inbreeding coefficients were not significantly different between groups. Of the 16 first generation sires that appeared ≥5 times in the case-control data set, two sires more frequently produced affected progeny (OR 7.95-10.41). MAIN LIMITATIONS: Challenges in definitively confirming SCD may lead to misclassification of some cases. Some control horses may have not been exposed to environmental influences of SCD. Case numbers are low and the studied population may not represent the entire Thoroughbred genetic pool. CONCLUSION: The heritability of SCD in this population was relatively low. However, individual stallions appear more likely to produce affected progeny. Further studies are required to understand the genetic and environmental influences that contribute to disease expression.

Predictors of ventricular tachyarrhythmia in patients with a wearable cardioverter defibrillator: an international multicenter registry.

BACKGROUND AND AIMS: Wearable cardioverter defibrillator (WCD) can protect patients from sudden cardiac death due to ventricular tachyarrhythmias and serve as a bridge to decision of definite defibrillator implantation. The aim of this analysis from an international, multicenter WCD registry was to identify predictors of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) in this population. METHODS: One thousand six hundred seventy-five patients with WCD were included in a multicenter registry from 9 European centers, with a median follow-up of 440 days (IQR 120-893). The primary study end point was the occurrence of sustained VT/VF. RESULTS: Sustained VT was detected by WCD in 5.4% and VF in 0.9% of all patients. Of the 30.3% of patients receiving ICD implantation during follow-up, sustained VT was recorded in 9.3% and VF in 2.6%. Non-ischemic cardiomyopathy (HR 0.5, p < 0.001), and medication with angiotensin-converting enzyme inhibitors (HR 0.7, p = 0.027) and aldosterone antagonists (HR 0.7, p = 0.005) were associated with a significantly lower risk of VT/VF. CONCLUSIONS: Patients who received WCD due to a transient increased risk of sudden cardiac death have a comparatively lower risk of VT/VF in the presence of non-ischemic cardiomyopathy. Of note, optimal medical treatment for heart failure not only results in an improvement in left ventricular ejection fraction but also in a reduction in the risk for VT/VF.

Short-term exposures to temperature and risk of sudden cardiac death in women: A case-crossover analysis in the Nurses' Health Study.

Background: Sudden cardiac death (SCD) is a major source of mortality and is the first manifestation of heart disease for most cases. Thus, there is a definite need to identify risk factors for SCD that can be modified on the population level. Short-term exposures to temperature have been implicated as a potential risk factor. Our objective was to determine if short-term temperature exposures were associated with increased risk of SCD in a US-based time-stratified case-crossover study. Methods: A total of 465 cases of SCD were identified among participants of the prospective Nurses' Health Study (NHS). Control days were selected from all other matching days of the week within the same month as the case day. Average ambient temperature on the current day (Lag0) and preceding 27 days (Lags1-27) was determined at the residence level using 800-m resolution estimates. Conditional logistic distributed lag nonlinear models (DLNMs) were used to assess the relative risk (RR) of the full range of temperature exposures over the lag period. Results: Warmer exposures in the days before event and colder temperatures 21-28 days prior were associated with increased risks of SCD. These results were driven by associations in regions other than the Northeast and among married women. Conclusions: Both warm and cold ambient temperatures are suggestively associated with risks of SCD among middle-aged and older women living across the United States.

Out of hospital cardiac arrest, first steps to know and follow in Mexico to have cardioprotected territories. A point of view of a group of experts / Paro cardiaco extrahospitalario, primeros pasos que se deben conocer y hacer en México para tener espacios cardioprotegidos. Punto de vista de un grupo de expertos

Abstract Sudden cardiac death is a common occurrence. Out-of-hospital cardiac arrest is a global public health problem suffered by ≈3.8 million people annually. Progress has been made in the knowledge of this disease, its prevention, and treatment; however, most events occur in people without a previous diagnosis of heart disease. Due to its multifactorial and complex nature, it represents a challenge in public health, so it led us to work in a consensus to achieve the implementation of cardioprotected areas in Mexico as a priority mechanism to treat these events. Public access cardiopulmonary resuscitation (CPR) and early defibrillation require training of non-medical personnel, who are usually the first responders in the chain of survival. They should be able to establish a basic and efficient CPR and use of the automatic external defibrillator (AED) until the emergency services arrive at the scene of the incident. Some of the current problems in Mexico and alternative solutions for them are addressed in the present work.

Resumen La muerte súbita cardíaca (SCD) es un acontecimiento común. El paro cardiaco extrahospitalario (OHCA) es un problema de salud pública mundial que sufren ≈3.8 millones de personas al año. Se ha avanzado en el conocimiento de esta enfermedad, su prevención y tratamiento, sin embargo, la mayoría de los eventos se producen en personas sin diagnóstico previo de cardiopatía. Debido a su carácter multifactorial y complejo, representa un reto en salud pública, lo que obliga a trabajar en un consenso para lograr la implementación de "Espacios Cardio protegidos" en México, como mecanismo prioritario de atención a estos eventos. La reanimación cardiopulmonar básica (RCPB) y la desfibrilación temprana de acceso público requieren de entrenamiento al personal no médico, que suelen ser los primeros respondientes para iniciar la cadena de la supervivencia. Ellos deberían instaurar una RCPB eficiente y el uso del desfibrilador automático externo (AED) hasta que lleguen al lugar del incidente los servicios de emergencias. El presente trabajo menciona algunos de los problemas actuales en México y algunas opciones de solución para los mismos.

The NOS1AP gene rs10494366 common genetic variant does not modify the risk of sudden cardiac death in users of digoxin.

AIMS: Common genetic variations in the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. In a previous study, we observed an association between the rs10494366 variant of this gene and an increased QT-interval shortening in digoxin users. As QT-interval shortening is a risk factor for sudden cardiac death (SCD), in this study, we investigated whether the association between digoxin use and risk of SCD differs in participants with different NOS1AP rs10494366 genotypes. METHODS: We included 11 377 individuals from the prospective population-based cohort of the Rotterdam Study. We used Cox proportional hazard regression analysis with digoxin as time-dependent exposure to estimate the associations between current digoxin use and the risk of SCD among different rs10494366 genotype groups in the adjusted models. We also studied whether such an association was dose-dependent, comparing high dosage (≥ 0.250 mg), moderate dosage (0.125 mg ≤ dose< 0.250 mg) and low dosage (< 0.125 mg) digoxin users with non-users. RESULTS: The median baseline age of the total study population was 62 (interquartile range [IQR] 58-71) years. The cumulative incidence of SCD was 4.1% (469 cases), and among them, 74 (15.7%) individuals were current digoxin users at the time of death, during a median follow-up of 11.5 (IQR 6.5-17) years. Current digoxin users had an increased risk of SCD (multivariable adjusted model hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 2.38-3.98), with no significant differences between the three genotype groups. The adjusted HRs were 4.03 [95% CI: 1.98-8.21] in the minor homozygous GG, 3.46 [95% CI: 2.37-5.04] in the heterozygous TG and 2.56 [95%CI: 1.70-3.86] in the homozygous TT genotype groups. Compared to low- and moderate-dose, high-dose digoxin users with GG genotype had the highest risk of SCD (HR: 5.61 [95% CI: 1.34-23.47]). CONCLUSIONS: Current use of digoxin is associated with a significantly increased risk of SCD. The NOS1AP gene rs10494366 variant did not modify the digoxin-associated risk of SCD in a population of European ancestry.

Sudden cardiac death due to ventricular arrhythmia in diabetes mellitus: A bench to bedside review.

Diabetes mellitus (DM) confers an increased risk of sudden cardiac death (SCD) independent of its associated cardiovascular comorbidities. DM induces adverse structural, electrophysiologic, and autonomic cardiac remodeling that can increase one's risk of ventricular arrhythmias and SCD. Although glycemic control and prevention of microvascular and macrovascular complications are cornerstones in the management of DM, they are not adequate for the prevention of SCD. In this narrative review, we describe the contribution of DM to the pathophysiologic mechanism of SCD beyond its role in atherosclerotic cardiovascular disease and heart failure. On the basis of this pathophysiologic framework, we outline potential preventive and therapeutic strategies to mitigate the risk of SCD in this population of high-risk patients.

Arrhythmic Mitral Valve Prolapse Phenotype: An Unsupervised Machine Learning Analysis Using a Multicenter Cardiac MRI Registry.

Purpose To use unsupervised machine learning to identify phenotypic clusters with increased risk of arrhythmic mitral valve prolapse (MVP). Materials and Methods This retrospective study included patients with MVP without hemodynamically significant mitral regurgitation or left ventricular (LV) dysfunction undergoing late gadolinium enhancement (LGE) cardiac MRI between October 2007 and June 2020 in 15 European tertiary centers. The study end point was a composite of sustained ventricular tachycardia, (aborted) sudden cardiac death, or unexplained syncope. Unsupervised data-driven hierarchical k-mean algorithm was utilized to identify phenotypic clusters. The association between clusters and the study end point was assessed by Cox proportional hazards model. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 female, 230 male) with two phenotypic clusters were identified. Patients in cluster 2 (199 of 474, 42%) had more severe mitral valve degeneration (ie, bileaflet MVP and leaflet displacement), left and right heart chamber remodeling, and myocardial fibrosis as assessed with LGE cardiac MRI than those in cluster 1. Demographic and clinical features (ie, symptoms, arrhythmias at Holter monitoring) had negligible contribution in differentiating the two clusters. Compared with cluster 1, the risk of developing the study end point over a median follow-up of 39 months was significantly higher in cluster 2 patients (hazard ratio: 3.79 [95% CI: 1.19, 12.12], P = .02) after adjustment for LGE extent. Conclusion Among patients with MVP without significant mitral regurgitation or LV dysfunction, unsupervised machine learning enabled the identification of two phenotypic clusters with distinct arrhythmic outcomes based primarily on cardiac MRI features. These results encourage the use of in-depth imaging-based phenotyping for implementing arrhythmic risk prediction in MVP. Keywords: MR Imaging, Cardiac, Cardiac MRI, Mitral Valve Prolapse, Cluster Analysis, Ventricular Arrhythmia, Sudden Cardiac Death, Unsupervised Machine Learning Supplemental material is available for this article. © RSNA, 2024.