Prospective Observational Study of Implantable Cardioverter‐Defibrillators in Primary Prevention of Sudden Cardiac Death: Study Design and Cohort Description

Abstract

BackgroundPrimary‐prevention implantable cardioverter‐defibrillators (ICDs) reduce total mortality in patients with severe left ventricular systolic function. However, only a minority of patients benefit from these devices. We designed the Prospective Observational Study of Implantable Cardioverter‐Defibrillators (PROSE‐ICD) to identify risk factors and enhance our understanding of the biological mechanisms that predispose to arrhythmic death in patients undergoing ICD implantation for primary prevention of sudden death.Methods and ResultsThis is a multicenter prospective cohort study with a target enrollment of 1200 patients. The primary end point is ICD shocks for adjudicated ventricular tachyarrhythmias. The secondary end point is total mortality. All patients undergo a comprehensive evaluation including history and physical examination, signal‐averaged electrocardiograms, and blood sampling for genomic, proteomic, and metabolomic analyses. Patients are evaluated every 6 months and after every known ICD shock for additional electrocardiographic and blood sampling. As of December 2011, a total of 1177 patients have been enrolled with more nonwhite and female patients compared to previous randomized trials. A total of 143 patients have reached the primary end point, whereas a total of 260 patients died over an average follow‐up of 59 months. The PROSE‐ICD study represents a real‐world cohort of individuals with systolic heart failure receiving primary‐prevention ICDs.ConclusionsExtensive electrophysiological and structural phenotyping as well as the availability of serial DNA and serum samples will be important resources for evaluating novel metrics for risk stratification and identifying patients at risk for arrhythmic sudden death.Clinical Trial RegistrationURL: http://clinicaltrials.gov/ Unique Identifier: NCT00733590.

Protein Biomarkers Identify Patients Unlikely to Benefit From Primary Prevention Implantable Cardioverter Defibrillators

“…Details of the design and baseline characteristics of study participants have been described elsewhere; study participants underwent ICD implantation based on current guidelines. 9,10 The study enrolled 1,189 participants. All centers obtained approval from their respective institutional review boards and all patients provided written informed consent.…”

“…9 All patients underwent a baseline comprehensive history and cardiovascular examination along with a digitally-recorded resting 12-lead electrocardiogram (ECG), a five minute three lead ECG, an echocardiogram and fasting blood collection. Study participants were evaluated twice a year.…”

“…Detailed information from ICDs and patient outcomes were adjudicated as previously described 9 . For sensitivity analysis, we also examined the association of biomarkers with all-cause mortality after censoring participants at their first appropriate ICD shock.…”

A feasibility study of arrhythmia risk prediction in patients with myocardial infarction and preserved ejection fraction

“…Arrhythmia risk prediction in patients with MI and preserved ejection fraction programmed electrical stimulation, similar to the protocol used in the standard clinical protocols, 22 was simulated; the same protocol was used in the original VARP study. 11 Specifically, each patient-derived ventricular model was subjected to pacing from multiple locations in an attempt to elicit reentrant arrhythmias, thus assessing the potential of the diseaseremodelled ventricles to cause degeneration of electrical signal propagation into arrhythmic activity following premature beats that originate at different locations in the heart.…”

Early detection of sudden cardiac death using Poincaré plots and recurrence plot-based features from HRV signals

“…When the electrical system of the heart becomes irregular, SCD will occur. One of the signs of SCD is ventricular fibrillation (VF) [16]. Arrhythmias like VF occur because for various reasons such as diabetes, alcohol, and smoking [17,18].…”