Background-Observational studies have suggested that a parental history of sudden death increases one's risk of dying suddenly. This study tested the hypothesis that a family history of sudden cardiac death (SCD) is a risk factor for SCD caused by an acute coronary event. Methods and Results-A retrospective case-control study included (1) consecutive victims of SCD (nϭ138) whose deaths were verified to be due to an acute coronary event without a history of prior myocardial infarction at medicolegal autopsy, (2) consecutive patients surviving an acute myocardial infarction (AMI; nϭ254), and (3) healthy control subjects (nϭ470). Family history of AMI and SCD among the first-degree relatives was ascertained in each study group.

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).

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Background: Despite recent progress in profiling of risk for sudden cardiac death (SCD) and prevention and intervention of cardiac diseases, SCD remains a major cause of death. Among women, the incidence of SCD is significant, but lower than in men, particularly in the premenopausal and early postmenopausal years. Possibly, as a consequence of the difference in population burden, the mechanisms and risk markers of SCD are not as well defined for women. The aim of this study was to determine the autopsy findings and causes of death among women in a large SCD population. Additionally, we sought to classify prior ECG characteristics in male and female subjects with SCD. Methods: The Fingesture study has systematically collected clinical and autopsy data from subjects with SCD in Northern Finland between 1998 and 2017. The cohort consists of 5869 subjects with SCD. Previously recorded ECGs were available and analyzed in 1101 subjects (18.8% of total population; and in 25.3% of women). Results: Female subjects with SCD were significantly older than men: 70.1±13.1 years versus 63.5±11.8 years (mean ± standard deviation, P <0.001). The most frequently identified cause of death was ischemic heart disease in both sexes: 71.7% among women versus 75.7% among men, P =0.005. In contrast, women were more likely to have nonischemic cause of SCD than men (28.3% versus 24.3%, P =0.005). The prevalence of primary myocardial fibrosis was higher among women (5.2%, n=64) than in men (2.6%, n=120; P <0.001). Female subjects with SCD were more likely to have normal prior ECG tracings (22.2% versus 15.3% in men, P <0.001). A normal ECG was even more common among nonischemic female subjects with SCD (27.8% versus 16.2% in men, P =0.009). However, ECG markers of left ventricular hypertrophy, with or without repolarization abnormalities, were more common among women (8.2%; 17.9%) than in men (4.9%; 10.6%, P =0.036; P <0.001, respectively). Conclusions: Women were considerably older at the time of SCD and more commonly had nonischemic causes. Women were also more likely to have a prior normal ECG than men, but an increased marker for SCD risk based on ECG criteria for left ventricular hypertrophy with repolarization abnormalities was more commonly observed in women.

BackgroundTissues that depend on aerobic energy metabolism suffer most in diseases caused by mutations in mitochondrial DNA (mtDNA). Cardiac abnormalities have been described in many cases, but their frequency and clinical spectrum among patients with mtDNA mutations is unknown.MethodsThirty-nine patients with the 3243A>G mtDNA mutation were examined, methods used included clinical evaluation, electrocardiogram, Holter recording and echocardiography. Autopsy reports on 17 deceased subjects were also reviewed. The degree of 3243A>G mutation heteroplasmy was determined using an Apa I restriction fragment analysis. Better hearing level (BEHL0.5–4 kHz) was used as a measure of the clinical severity of disease.ResultsLeft ventricular hypertrophy (LVH) was diagnosed in 19 patients (56%) by echocardiography and in six controls (15%) giving an odds ratio of 7.5 (95% confidence interval; 1.74–67). The dimensions of the left ventricle suggested a concentric hypertrophy. Left ventricular systolic or diastolic dysfunction was observed in 11 patients. Holter recording revealed frequent ventricular extrasystoles (>10/h) in five patients. Patients with LVH differed significantly from those without LVH in BEHL0.5–4 kHz, whereas the contribution of age or the degree of the mutant heteroplasmy in skeletal muscle to the risk of LVH was less remarkable.ConclusionsStructural and functional abnormalities of the heart were common in patients with 3243A>G. The risk of LVH was related to the clinical severity of the phenotype, and to a lesser degree to age, suggesting that patients presenting with any symptoms from the mutation should also be evaluated for cardiac abnormalities.

Background— Electrocardiographic early repolarization (ER) pattern has been previously associated with arrhythmic mortality and with an increased risk of ventricular fibrillation. We hypothesized that there is an association between ER and sudden cardiac death (SCD) during an acute coronary event. Methods and Results— The present study included 432 consecutive victims of SCD because of acute coronary event and 532 survivors of such an event, in whom 12-lead ECGs recorded before and unrelated to the event could be evaluated. SCDs were verified by medicolegal autopsy to be because of acute coronary event. ER was defined as an elevation of the QRS-ST junction in at least 2 inferior or lateral leads, manifested as QRS notching or slurring. The prevalence of ER pattern ≥0.1 mV was more common in cases (62/432; 14.4%) than controls (42/532; 7.9%) ( P =0.001). The victims of SCD were younger, were more commonly men and smokers, had lower body mass index, had elevated heart rate, had prolonged QRS complex, and had lower prevalence of history of prior cardiovascular disease than controls. After adjustments for baseline differences, the odds ratio for J waves without ST-segment elevation in the SCD group was 2.15 (95% CI, 1.20–3.85; P =0.01). Conclusions— Higher prevalence of ER in a standard 12-lead ECG in victims of SCD than in survivors of an acute coronary event suggests that the presence of ER increases the vulnerability to fatal arrhythmia during acute myocardial ischemia and provides a plausible mechanistic link between this ECG pattern and higher arrhythmic mortality of middle-aged/elderly subjects.

The use of psychotropic drugs, especially combined use of antipsychotic and antidepressant drugs, is strongly associated with an increased risk of SCD at the time of an acute coronary event.

A large proportion of subjects with PMF at autopsy had variants in genes associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy without autopsy findings of those diseases, suggesting that PMF can be an alternative phenotypic expression of structural disease-associated genetic variants or that risk-associated fibrosis was expressing before the primary disease. These findings have clinical implications for postmortem genetic testing and family risk profiling.