Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention (PROSe-ICD)

PROSe-ICD is a multicenter prospective cohort study of patients who undergo ICD implantation for primary prevention of SCD, designed to compare patients who sustain SCD (as measured by an appropriate ICD firing for rapid ventricular tachycardia (VT) or rapid ventricular fibrillation (VF) to those who do not. The cohort for this observational study consists of patients with cardiomyopathy who have an ICD implanted for primary SCD prevention according to recent trials (MADIT II, SCD-HeFT, DEFINITE) and practice guidelines.

Patients are followed longitudinally for clinical, ECG, genomic and proteomic markers and for index events. The primary outcome variable is an appropriate adjudicated ICD firing for rapid ventricular tachycardia or fibrillation.

The study standardizes initial therapeutic ICD settings, reflecting the current standard of care rather than an intervention, because by definition the study cohort consists of patients without a history of malignant arrhythmia, in whom the ICD functions simply as a defibrillator rather than as a more complex device employing anti-tachycardia pacing or tiered therapy. In order to facilitate the identification of rhythms prompting ICD therapy, programming includes far field ventricular electrogram storage. For patients who have firings (appropriate or not), all subsequent clinical care (including drug and device prescriptions) will be managed independently by the clinical attending electrophysiologist/cardiologist according to the local standard of care, unaffected by the study protocol. For safety reasons, any clinically-significant data (such as symptomatic complaints or documented episodes of ventricular arrhythmia) obtained during the study will be promptly communicated to the clinical attending physician both by telephone and in writing.

After informed consent, patients undergo an initial history and examination conducted by an attending electrophysiologist. Thereafter, patients are generally seen by an ICD nurse every 3 months and are evaluated for the purposes of the study every six months. The physician and/or nurse will record the variables shown in Table D1 on paper forms or directly into REDCap, web-based entry form. At each routine clinic visit (Q 3 month intervals) the ICD will be interrogated and any episodes of ventricular tachycardia lasting >10 beats with a cycle length < 400 ms, ventricular fibrillation, or any anti-tachycardia pacing or ICD therapies will be recorded. If a ventricular arrhythmia is detected blood will be drawn and a digital ECG will be performed as described for the 6 month follow up visits. Further evaluation and treatment of the arrhythmia will be managed independently by the clinical attending physician, who will be notified of the arrhythmia by telephone, with written confirmation and documentation. At alternate visits (every 6 months) the patient will be evaluated by an attending electrophysiologist, a 60cc blood sample will be obtained, a 5-minute digital ECG, and any additional laboratory and diagnostic testing will be performed as clinically indicated.

Data on clinical events (admission for myocardial infarction/acute coronary syndrome (MI/ACS), admission for congestive heart failure (CHF), diagnostic angiography, revascularization, ICD device revision) will be collected by medical record review. Patients will be followed for a minimum of ten years or until death, cardiac transplantation or ventricular assist device implantation. A patient who experiences an appropriate ICD firing will have been considered to meet the primary endpoint of the study but will continue to be followed, particularly for the development of adverse events. Investigators will continue to follow and leverage this population as well as enroll additional patients who have ICDs in place and are undergoing elective pacemaker generator (PG) replacement for end-of-life indicators. The aims of this proposal are: