PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study

The PRE-DETERMINE Study is a prospective, multi-center study of 5,764 patients with a history of coronary artery disease (CAD) and documentation of either a prior myocardial infarction (MI) or mild to moderate left ventricular dysfunction (LVD) with left ventricular ejection fraction (LVEF) 35-50%. Patients were enrolled at 136 sites where information on baseline demographics, clinical characteristics, pertinent past medical history, lifestyle habits, cardiac test results, and medications were collected via electronic data capture. Electrocardiograms (ECG) along with a blood sample was also collected at baseline, sent to central laboratories, and stored for future analyses. Contrast-enhanced magnetic resonance imaging (CE-MRI) scans were collected on a subset of patients and analyzed. Enrollment closed in November 2013 and patients are now being followed centrally by the Clinical Coordinating Center via mail/phone to document interim non-fatal arrhythmic events and cause-specific mortality. Questionnaires that inquire about intervening implantable cardiac defibrillator (ICD) implantations, ICD therapies, cardiac arrest, and other pertinent cardiovascular endpoints are mailed to participants every six months, and follow-up telephone calls are made to non-responders. Study endpoints are being confirmed through review of medical records, interviews with next-of-kin, and autopsy reports, if available.The primary objective of PRE-DETERMINE is to determine whether biologic markers and ECGs can be utilized to advance sudden cardiac death (SCD) risk prediction in patients with coronary heart disease (CHD) and LVEF >30-35%. The overarching goal of the study is to identify a series of markers that alone or in combination specifically predict risk of arrhythmic death as compared to other causes of mortality among this at risk population of CHD patients with preserved LVEF> 30-35%. If biologic or ECG markers are identified that can specifically predict risk of ventricular arrhythmias, then these markers may serve as relatively inexpensive methods to identify those at risk. The public health impact of identifying markers could be quite substantial, leading to more efficient utilization of ICDs and advances in our understanding of mechanisms underlying SCD.Among the 95% of participants that provided a blood sample at baseline, genome wide genotyping using the Illumina Global Screening Array (GSA) has been performed. A total of 4,335 participants with European ancestry gave consent that allows genetic research and deposition of data into dbGaP.
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Inclusion Criteria:
Evidence of Coronary Artery Disease (CAD) or documented prior Myocardial Infarction (MI)LVEF >35% by any current standard evaluation technique (e.g., ECG, MUGA, angiography). Patients who have an LVEF between 30-35% and New York Heart Association (NYHA) Class I heart failure do not have history of ventricular tachyarrhythmias or inducible ventricular tachycardia during electrophysiological (EP) testing can be enrolled.If documented prior MI is not present, evidence of mild-moderate systolic LVD with a LVEF >35 - ≤50% as measured by any current standard screening technique (e.g., ECG, MUGA, angiography) must be present.Patients aged 18 years or abovea. CAD will be defined as evidence of one of the following two criteria:Significant stenosis of a major epicardial vessel (>50% proximal or 70% distal) by coronary angiographyPrior revascularization (percutaneous coronary intervention or coronary artery bypass surgery)b. MI can be documented in the following ways:From the MI hospitalization: Detection of a rise and fall of cardiac biomarkers > 99th percentile of lab (e.g., CPK elevation or Troponin at least > two times the upper limit of normal) together with myocardial ischemia with at least one of the following:Symptoms of IschemiaECG changes indicative of new ischemia (new ST-T changes or new LBBB)Development of pathological Q wavesImaging evidence of new loss of viable myocardium or new regional wall motion abnormalityIf no report from the MI hospitalization is available, prior MI can be met by either of the following:Development of pathological Q wavesImaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic causeExclusion Criteria:History of cardiac arrest or spontaneous or inducible sustained VT (15 beats or more at a rate of 120 BPM or greater; the occurrence of cardiac arrest or spontaneous VT in the setting of an acute MI is not considered an exclusion)Unexplained syncope
Current or planned implantable cardiac defibrillator (ICD)
Any condition other than cardiac disease that, in the investigator's judgment, would seriously limit life expectancy (poor survival)
Metastatic cancer
Marked valvular heart disease requiring surgical intervention
Current or planned cardiac, renal or liver transplant
Current alcohol or drug abuse
Unwilling or unable to provide informed consent
LVEF <35% with Class II-IV congestive heart failure (CHF) or LVEF <30%
Participation in a clinical trial where the active treatment arm is testing an agent and/or intervention with known antiarrhythmic properties]]>
Enrollment began (July 2007)Enrollment ended (November 2013)Participant follow-up and endpoint data collection for cardiovascular disease events and death remain ongoingPlease reference clinicaltrials.gov and PRE-DETERMINE for additional details.]]>