Recent epidemiology of sudden cardiac death.

We accessed the US CDC online database Wonder, which provides nationwide statistics on causes of death between the years 2018-2022. The crude mortality rate for sudden cardiac death (SCD) increased in parallel with age in both sexes, reaching the highest value in subjects aged 85 years or older. In all age groups, the crude death rate was always significantly higher in men than in women. Despite the cumulative number of officially recorded SCDs may be higher between the ages of 60 and 69 years, the risk of dying from SCD appears to increase with population age, peaking after the age of 85.

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.

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.

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.

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.

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.

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.

Can Hyperthermia Unveil Brugada Pattern?

Brugada syndrome (BrS) is characterized by ST segment elevations in the right precordial leads, V1 - V3, with additional findings of ventricular arrhythmias and family history (FH) of sudden cardiac death (SCD) at a young age. Here, we describe a case of hyperthermia, unveiling the Brugada electrocardiography (EKG) pattern and the resolution of EKG findings with appropriate hyperthermia management. It is important to distinguish the Brugada EKG pattern from other causes of ST elevations and treat appropriately to prevent patients from developing ventricular fibrillation and SCD. It is key to identify environmental triggers in patients presenting with Brugada EKG pattern and closely monitor for ventricular fibrillation. Educating patients on prompt fever treatment with antipyretics and avoiding medications like sodium channel blockers during the febrile event is paramount to counter patients going into ventricular fibrillation. It is also crucial for close follow-up of these patients, offering them genetic testing for BrS and screening families of patients with BrS.

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.

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.

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.

Vitamin D deficiency as a risk factor for sudden cardiac arrest: A multicenter case-control study.

BACKGROUND AND AIMS: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. METHODS AND RESULTS: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20). CONCLUSION: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR.

Human Genetics of Cardiac Arrhythmias.

Inherited forms of cardiac arrhythmias mostly are rare diseases (prevalence <1:2000) and considered to be either "primary electrical heart disorders" due to the absence of structural heart abnormalities or "cardiac ion channel disorders" due to the myocellular structures involved. Precise knowledge of the electrocardiographic features of these diseases and their genetic classification will enable early disease recognition and prevention of cardiac events including sudden cardiac death.The genetic background of these diseases is complex and heterogeneous. In addition to the predominant "private character" of a mutation in each family, locus heterogeneity involving many ion channel genes for the same familial arrhythmia syndrome is typical. Founder pathogenic variants or mutational hot spots are uncommon. Moreover, phenotypes may vary and overlap even within the same family and mutation carriers. For the majority of arrhythmias, the clinical phenotype of an ion channel mutation is restricted to cardiac tissue, and therefore, the disease is nonsyndromic.Recent and innovative methods of parallel DNA analysis (so-called next-generation sequencing, NGS) will enhance further mutation and other variant detection as well as arrhythmia gene identification.

Prediction of Sudden Cardiac Death With Ultra-Short-Term Heart Rate Fluctuations.

BACKGROUND: Conventional measures of heart rate variability (HRV) have shown only modest associations with sudden cardiac death (SCD). Detrended fluctuation analysis (DFA), with novel methodological developments to evaluate the short-term scaling exponent, is a potentially superior method compared to conventional HRV tools. OBJECTIVES: In this study, the authors studied the analysis of the association between DFA and SCD. METHODS: The investigators studied the predictive value of ultra-short-term heart rate fluctuations (1-minute electrocardiogram samples) with DFA at rest and during different stages of physical exertion for incident SCD among 2,794 participants undergoing clinical exercise testing in the prospective FINCAVAS (Finnish Cardiovascular Study). The novel key DFA measure, the short-scale scaling exponent computed with second-order detrending (DFA2 α1), was the main exposure variable. SCDs were defined by American Heart Association/European Society of Cardiology criteria using death certificates with written accounts of the events. RESULTS: During a median follow-up of 8.3 years (Q1-Q3: 6.4-10.5), 83 SCDs occurred. DFA2 α1 measured at rest (but not in exercise) associated highly significantly with the risk of SCD, with 1-SD lower values associating with a 2.4-fold (Q1-Q3: 2.0-3.0) risk (P < 0.001). The results persisted when adjusting for other major risk factors for SCD, including age, cardiovascular morbidities, cardiorespiratory fitness, heart rate reduction, and left ventricular ejection fraction. Associations between conventional HRV parameters (measured at any stage of exercise or at rest) and SCD were substantially weaker and statistically nonsignificant after adjusting for other risk factors. CONCLUSIONS: Ultra-short-term DFA2 α1, when measured at rest, is a powerful and independent predictor of SCD. The association between DFA2 α1 and SCD is modified by physical exertion.

The Electromechanical Window for Arrhythmia-Risk Assessment.

The electromechanical window (EMW) is calculated by subtracting the repolarization duration from a mechanical reference representing contraction duration in the same heartbeat (e.g., aortic-valve closure during echocardiography with simultaneous ECG). Here, we review the current knowledge on the role of the EMW as an independent parameter for ventricular arrhythmia-risk stratification. We (1) provide a standardized approach to echocardiographic EMW assessment, (2) define relevant cut-off values for both abnormal EMW negativity and positivity, (3) discuss pathophysiologic underpinnings of EMW negativity, and (4) outline the potential future role of cardiac electromechanical relations in patients with proarrhythmic conditions.