Citations

Although the occurrence of sudden cardiac death (SCD) in a young person is a rare event, it is traumatic and often widely publicized. In recent years, SCD in this population has been increasingly seen as a public health and safety issue. This review presents current knowledge relevant to the epidemiology of SCD and to strategies for prevention, resuscitation, and identification of those at greatest risk. Areas of active research and controversy include the development of best practices in screening, risk stratification approaches and postmortem evaluation, and identification of modifiable barriers to providing better outcomes after resuscitation of young SCD patients. Institution of a national registry of SCD in the young will provide data that will help to answer these questions.

Background Hyper‐ and hypokalemia are clinically silent, common in patients with renal or cardiac disease, and are life threatening. A noninvasive, unobtrusive, blood‐free method for tracking potassium would be an important clinical advance. Methods and Results Two groups of hemodialysis patients (development group, n=26; validation group, n=19) underwent high‐resolution digital ECG recordings and had 2 to 3 blood tests during dialysis. Using advanced signal processing, we developed a personalized regression model for each patient to noninvasively calculate potassium values during the second and third dialysis sessions using only the processed single‐channel ECG . In addition, by analyzing the entire development group's first‐visit data, we created a global model for all patients that was validated against subsequent sessions in the development group and in a separate validation group. This global model sought to predict potassium, based on the T wave characteristics, with no blood tests required. For the personalized model, we successfully calculated potassium values with an absolute error of 0.36±0.34 mmol/L (or 10% of the measured blood potassium). For the global model, potassium prediction was also accurate, with an absolute error of 0.44±0.47 mmol/L for the training group (or 11% of the measured blood potassium) and 0.5±0.42 for the validation set (or 12% of the measured blood potassium). Conclusions The signal‐processed ECG derived from a single lead can be used to calculate potassium values with clinically meaningful resolution using a strategy that requires no blood tests. This enables a cost‐effective, noninvasive, unobtrusive strategy for potassium assessment that can be used during remote monitoring.

Dysrhythmias and Death in BiMVPIntroductionBileaflet mitral valve prolapse (BiMVP) is common among survivors of otherwise unexplained sudden cardiac death, but prognostic implications of BiMVP are unknown. This study evaluated whether patients with BiMVP are at higher risk for ventricular dysrhythmias, ICD placement, or death compared to controls with either single‐leaflet mitral valve prolapse (SiMVP) or no mitral valve prolapse (MVP).Methods and ResultsThis retrospective, matched cohort study included 18,786 patients who underwent echocardiography at Mayo Clinic between June 1990 and September 2014. The study included three cohorts: BiMVP, SiMVP, and controls without MVP. We assessed rates of ventricular dysrhythmias, ICD placement, and all‐cause mortality between groups. BiMVP was associated with higher rates of ventricular tachycardia compared to SiMVP and controls (adjusted HR 1.48 [1.14–1.92], P = 0.003 and 1.40 [1.04–1.88], P = 0.026, respectively); however, there were no statistically significant differences in rates of ventricular fibrillation/cardiac arrest or ICD placement between groups. BiMVP was associated with a lower rate of all‐cause mortality compared to SiMVP and controls (adjusted HR 0.86 [0.79–0.94], P = 0.0008, and 0.55 [0.50–0.60], P < 0.0001, respectively).ConclusionAlthough BiMVP is associated with ventricular tachycardia, it is not associated with an increased risk of cardiac arrest/ventricular fibrillation or ICD implantation and is, paradoxically, associated with a better survival compared to SiMVP or matched controls. The findings suggest that, despite its association with ventricular tachycardia, BiMVP in the absence of other risk factors does not seem to portend a poor prognosis at the population level.

Background— A portion of sudden cardiac deaths can be attributed to structural heart diseases, such as hypertrophic cardiomyopathy (HCM) or cardiac channelopathies such as long-QT syndrome (LQTS); however, the underlying molecular mechanisms are distinct. Here, we identify a novel CACNA1C missense mutation with mixed loss-of-function/gain-of-function responsible for a complex phenotype of LQTS, HCM, sudden cardiac death, and congenital heart defects. Methods and Results— Whole exome sequencing in combination with Ingenuity variant analysis was completed on 3 affected individuals and 1 unaffected individual from a large pedigree with concomitant LQTS, HCM, and congenital heart defects and identified a novel CACNA1C mutation, p.Arg518Cys, as the most likely candidate mutation. Mutational analysis of exon 12 of CACNA1C was completed on 5 additional patients with a similar phenotype of LQTS plus a personal or family history of HCM-like phenotypes and identified 2 additional pedigrees with mutations at the same position, p.Arg518Cys/His. Whole cell patch clamp technique was used to assess the electrophysiological effects of the identified mutations in Ca V 1.2 and revealed a complex phenotype, including loss of current density and inactivation in combination with increased window and late current. Conclusions— Through whole exome sequencing and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and congenital heart defects annotated as cardiac-only Timothy syndrome. Our electrophysiological studies, identification of mutations at the same amino acid position in multiple pedigrees, and cosegregation with disease in these pedigrees provide evidence that p.Arg518Cys/His is the pathogenic substrate for the observed phenotype.