M. Janzen

Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry

Background—The Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) enrolls patients with apparently unexplained cardiac arrest and no evident cardiac disease to identify the pathogenesis of cardiac arrest through systematic clinical testing. Exercise testing, drug provocation, advanced cardiac imaging, and genetic testing may be useful when a cause is not apparent. Methods and Results—The first 200 survivors of unexplained cardiac arrest from 14 centers across Canada were evaluated to determine the results of investigation and follow-up (age, 48.6±14.7 years, 41% female). Patients were free of evidence of coronary artery disease, left ventricular dysfunction, or evident repolarization syndromes. Advanced testing determined a diagnosis in 34% of patients at baseline, with a diagnosis emerging during follow-up in 7% of patients. Of those who were diagnosed, 28 (35%) had an underlying structural condition and 53 (65%) had a primary electric disease. During a mean follow-up of 3.15±2.34 years, 23% of patients had either a shock or an appropriate antitachycardia pacing from their implantable cardioverter defibrillator, or both. The implantable cardioverter defibrillator appropriate intervention rate was 8.4% at 1 year and 18.1% at 3 years, with no clear difference between diagnosed and undiagnosed subjects, or between those diagnosed with a primary electric versus structural pathogenesis. Conclusions—Obtaining a diagnosis in previously unexplained cardiac arrest patients requires systematic clinical testing and regular follow-up to unmask the cause. Nearly half of apparently unexplained cardiac arrest patients ultimately received a diagnosis, allowing for improved treatment and family screening. A substantial proportion of patients received appropriate implantable cardioverter defibrillator therapy during medium-term follow-up. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.

Cardiac Abnormalities in First-Degree Relatives of Unexplained Cardiac Arrest Victims: A Report From the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry.

Background—Unexplained cardiac arrest (UCA) may be explained by inherited arrhythmia syndromes. The Cardiac Arrest Survivors With Preserved Ejection Fraction Registry prospectively assessed first-degree relatives of UCA or sudden unexplained death victims to screen for cardiac abnormalities. Methods and Results—Around 398 first-degree family members (186 UCA, 212 sudden unexplained death victims’ relatives; mean age, 44±17 years) underwent extensive cardiac workup, including ECG, signal averaged ECG, exercise testing, cardiac imaging, Holter-monitoring, and selective provocative drug testing with epinephrine or procainamide. Genetic testing was performed when a mutation was identified in the UCA survivor or when the diagnostic workup revealed a phenotype suggestive of a specific inherited arrhythmia syndrome. The diagnostic strength was classified as definite, probable, or possible based on previously published definitions. Cardiac abnormalities were detected in 120 of 398 patients (30.2%) with 67 of 398 having a definite or probable diagnosis (17%), including Long-QT syndrome (13%), catecholaminergic polymorphic ventricular tachycardia (4%), arrhythmogenic right ventricular cardiomyopathy (4%), and Brugada syndrome (3%). The detection yield was similar for family members of UCA and sudden unexplained death victims (31% versus 27%; P=0.59). Genetic testing was performed more often in family members of UCA patients (29% versus 20%; P=0.03). Disease-causing mutations were identified in 20 of 398 relatives (5%). The most common pathogenic mutations were RyR2 (2%), SCN5A (1%), and KNCQ1 (0.8%). Conclusions—Cardiac screening revealed abnormalities in 30% of first-degree relatives of UCA or sudden unexplained death victims, with a clear working diagnosis in 17%. Long-QT, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia were the most common diagnoses. Systematic cascade screening and genetic testing in asymptomatic individuals will lead to preventive lifestyle and medical interventions with potential to prevent sudden cardiac death. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.

Response to Letter Regarding Article, “Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry”

We would like to thank Professors Jaimez and Sanchez for their letter of response commenting on our recent summary of evaluation and outcome of our first 200 unexplained cardiac arrest probands.1 We would first like to point out that we excluded patients with a manifest diagnosis, so none of these patients had overt evidence of an ion channelopathy or cardiomyopathy that are typically both readily diagnosed and treated. This is reflected in our empirical strength of diagnosis framework, which is necessary when a classic diagnosis is not forthcoming.2 In addition, registries do not mandate care but rather capture it, and reflect the reality of practice with the vagaries of contextual clinical decision making. In response to the concerns about the incidence of shocks and the inefficacy of medical therapy, it is important to point out the difference between efficacy and effectiveness. Without …

The QT Interval in Anorexia Nervosa: A Meta-Analysis

Anorexia nervosa (AN) affects 1% of the population, with the highest mortality of any eating disorder, in part attributed to ventricular arrhythmia [(1)][1]. The QT interval on the electrocardiogram (ECG), corrected for heart rate (QTc interval), provides a simple and reliable measure of cardiac