PRE-DETERMINE Cohort Study

PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study

This is a prospective, multi-center cohort study of 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 (LVEF 35-50%). The primary objective of this study is to determine whether biologic markers and ECGs can be utilized to advance SCD risk prediction in patients with 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 coronary heart disease (CHD) patients with preserved left ventricular ejection fraction (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.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease; Sudden Cardiac Death; Left Ventricular Dysfunction

Detailed Description

The PRE-DETERMINE Study is a prospective, multi-center study of 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 (LVEF 35-50%). Patients were enrolled at 135 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 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 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.

• Study Type: Observational
• Enrollment (Actual): 5764

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Ontario
    • Mississauga, Ontario, Canada, L5B 2P7
      • Mississauga Clinical Research Centre
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00924
    • Transcatheter Medical, Inc. Centro Cardiovascular de Caguas y del Caribe
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Heart Institute
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Phoenix Heart, PLLC
    • Phoenix, Arizona, United States, 85032
      • Cardiovascular Consultants
  • California
    • Banning, California, United States, 92220
      • Beaver Medical Group/Clinical Care Research
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Health System
    • Denver, Colorado, United States, 80204
      • Colorado Heart and Vascular
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Cardiology Associates, P.A.
    • Gainesville, Florida, United States, 32610
      • University of Florida - Gainsville
    • Miami, Florida, United States, 33135
      • Reliable Clinical Research
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Orlando, Florida, United States, 32804
      • Florida Hospital
    • Orlando, Florida, United States, 32806
      • Orlando Regional Medical Center
    • Palm Beach Gardens, Florida, United States, 33410
      • Palm Beach Gardens Research Center
    • Sarasota, Florida, United States, 34233
      • Velella Research
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Research Institute, Inc.
    • West Palm Beach, Florida, United States, 33401
      • Cardiology Associates of Palm Beach - West Palm Beach
  • Georgia
    • Covington, Georgia, United States, 30014
      • Georgia Heart Specialist
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Heart Center, P.C.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago
    • Chicago, Illinois, United States, 60643
      • Advocate Medical Group
    • Chicago, Illinois, United States, 60657
      • Advocate Medical Group - Heart and Vascular of IL
    • Melrose Park, Illinois, United States, 60160
      • Consultants in Cardiovascular Medicine
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Community Heart and Vascular
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Iowa Heart Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Louisiana
    • Houma, Louisiana, United States, 70363
      • Leonard J. Chabert Medical Center
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
    • Lewiston, Maine, United States, 04240
      • Maine Research Associates - Lewiston
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Ayer, Massachusetts, United States, 01432
      • Primary Care Cardiology Research
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Fall River, Massachusetts, United States, 02720
      • NECCR Internal Medicine and Cardiology Associates, LLC
    • North Dartmouth, Massachusetts, United States, 02747
      • Hawthorn Medical Associates
    • Springfield, Massachusetts, United States, 01199
      • Baystate Cardiology
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital & Medical Center
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Medical Center - Macomb
    • Ypsilanti, Michigan, United States, 48197
      • Michigan Heart
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65201
      • University of Missouri Health Care
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier View Cardiology
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • The Cardiac Center of Creighton University
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Advanced Heartcare, LLC
    • Paterson, New Jersey, United States, 07503
      • St. Joseph Regional Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • New Mexico VA Healthcare Systems
  • New York
    • Albany, New York, United States, 12205
      • Albany Associates Cardiology
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Buffalo, New York, United States, 14203
      • Buffalo General Hospital/Kaleida Health
    • Jamaica, New York, United States, 11418
      • Jamaica Hospital Medical Center
    • Kingston, New York, United States, 12401
      • Mid-Valley Cardiology
    • Mineola, New York, United States, 11501
      • Winthrop-University Hospital
    • New York, New York, United States, 10001
      • Gotham Cardiovascular
    • New York, New York, United States, 10032
      • Columbia University Health Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Utica, New York, United States, 13501
      • St. Elizabeth Medical Center - Hotvedt
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Cardiology Associates
    • Elizabeth City, North Carolina, United States, 27909
      • Eastern Carolina Cardiovascular
    • Lenoir, North Carolina, United States, 28645
      • Northstate Clinical Research
    • Pinehurst, North Carolina, United States, 28374
      • Pinehurst Medical Clinic, Inc.
    • Sanford, North Carolina, United States, 27330
      • Sanford Cardiology
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest
  • Ohio
    • Akron, Ohio, United States, 44304
      • Northeast Ohio Cardiovascular Specialists
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Elyria, Ohio, United States, 44035
      • North Ohio Research, Ltd.
    • Fairfield, Ohio, United States, 45014
      • Mercy Medical Associates
    • Toledo, Ohio, United States, 43615
      • Northwest Ohio Cardiology Consultants/The Toledo Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Foundation for Cardiovascular Research
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma City VA Medical Center Veterans Research and Education Foundation
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Bethlehem, Pennsylvania, United States, 18018
      • St. Luke's Bethlehem
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Cardiology Associates
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
    • Charleston, South Carolina, United States, 29425
      • VA Medical Center - Charleston
    • Rock Hill, South Carolina, United States, 29732
      • Carolina Cardiology Associates
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Cardiovascular Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37917
      • Cardiovasular Research of Knoxville
    • Memphis, Tennessee, United States, 38104
      • Memphis VA Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • St. Luke's Episcopal Hospital
    • Houston, Texas, United States, 77074
      • Non-Invasive Cardiovascular PA
    • Waco, Texas, United States, 76712
      • Providence Health Center
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Cardiovascular Associates Virginia Beach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Participants have been recruited throughout multicenter sites participating in the PRE-DETERMINE Cohort Study. Patients with a history of coronary artery disease and documentation of either a prior myocardial infarction (MI) or mild to moderate left ventricular dysfunction (LVEF 35-50%) have been enrolled. The clinical study staff at each site, which was either a research nurse, fellow, or physician approached eligible patients to discuss their potential participation.

Description

Inclusion Criteria:

1. Evidence of Coronary Artery Disease (CAD) a or documented prior Myocardial Infarction.
2. LVEF >35% by any current standard evaluation technique (e.g.,) echocardiogram, MUGA, angiography). 2.1. Patients who have an LVEF between 30-35% and NYHA Class I heart failure who do not have history of ventricular tachyarrhythmias,or inducible ventricular tachycardia during electrophysiological (EP) testing can be enrolled.
3. If documented prior MI is not present, evidence of mild-moderate systolic Left Ventricular Dysfunction with an EF >35- ≤50% as measured by any current standard screening technique (e.g.,echocardiogram, MUGA, angiography) must be present.

4. Patients aged 18 years or above

   1. CAD will be defined as evidence of one of the following two (2) criteria:

      • Significant stenosis of a major epicardial vessel (>50% proximal or 70% distal) by coronary angiography
      • Prior revascularization (percutaneous coronary intervention or coronary artery bypass surgery)

   2. 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 Ischemia
        • ECG changes indicative of new ischemia (new ST-T changes or new LBBB)
        • Development of pathological Q waves
        • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality

      • If no report from the MI hospitalization is available, prior MI can be met by either of the following:

        • Development of pathological Q waves
        • Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischaemic cause

Exclusion Criteria:

1. 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).
2. Unexplained syncope
3. Current or planned implantable cardiac defibrillator (ICD)
4. Any condition other than cardiac disease that, in the investigator's judgment, would seriously limit life expectancy (poor survival)
5. Metastatic cancer
6. Marked valvular heart disease requiring surgical intervention
7. Current or planned cardiac, renal or liver transplant
8. Current alcohol or drug abuse
9. Unwilling or unable to provide informed consent
10. LVEF <35% with Class II-IV CHF or LVEF <30%
11. Participation in a clinical trial where the active treatment arm is testing an agent and/or intervention with known antiarrhythmic properties

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sudden and/or arrhythmic cardiac death or resuscitated ventricular fibrillation.	A definite sudden cardiac death (SCD) is defined as a death or fatal cardiac arrest occurring within 1 hour of symptom onset or the presence of autopsy consistent with SCD (e.g. acute coronary thrombosis). Probable SCD is defined as an unwitnessed death or death during sleep where the participant was observed to be symptom-free within the preceding 24 hours. Arrhythmic death is defined as the abrupt spontaneous collapse of circulation without antecedent circulatory or neurologic impairment. Deaths classified as non-arrhythmic are not included in the primary endpoint regardless of timing. Resuscitated ventricular fibrillation is defined as out-of-hospital cardiac arrests with documented VF and/or use of external electrical defibrillation for resuscitation.	Median follow-up estimated to be 10.7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICD Shock	ICD therapies for ventricular arrhythmias over 200 BPMs will be added to the endpoint.	Median follow-up estimated to be 10.7 years
ICD Implantation		Median follow-up estimated to be 10.7 years
Total Cardiac Mortality		Median follow-up estimated to be 10.7 years
Total Mortality		Median follow-up estimated to be 10.7 years
Non-Sudden or Arrhythmic Causes of Mortality	Competing causes of mortality in competing risk analyses.	Median follow-up estimated to be 10.7 years

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Northwestern University; Quintiles, Inc.; Abbott Medical Devices; Roche Diagnostics
• Investigators: Principal Investigator: Christine M Albert, M.D., M.P.H., Brigham and Women's Hospital

Publications and helpful links

General Publications

• Chatterjee NA, Moorthy MV, Pester J, Schaecter A, Panicker GK, Narula D, Lee DC, Goldberger JJ, Kadish A, Cook NR, Albert CM; PRE-DETERMINE Study Group. Sudden Death in Patients With Coronary Heart Disease Without Severe Systolic Dysfunction. JAMA Cardiol. 2018 Jul 1;3(7):591-600. doi: 10.1001/jamacardio.2018.1049. Erratum In: JAMA Cardiol. 2018 Sep 1;3(9):898.
• Silverman MG, Yeri A, Moorthy MV, Camacho Garcia F, Chatterjee NA, Glinge CSA, Tfelt-Hansen J, Salvador AM, Pico AR, Shah R, Albert CM, Das S. Circulating miRNAs and Risk of Sudden Death in Patients With Coronary Heart Disease. JACC Clin Electrophysiol. 2020 Jan;6(1):70-79. doi: 10.1016/j.jacep.2019.08.011. Epub 2019 Oct 30.
• Lee DC, Albert CM, Narula D, Kadish AH, Panicker GK, Wu E, Schaechter A, Pester J, Chatterjee NA, Cook NR, Goldberger JJ. Estimating Myocardial Infarction Size With a Simple Electrocardiographic Marker Score. J Am Heart Assoc. 2020 Feb 4;9(3):e014205. doi: 10.1161/JAHA.119.014205. Epub 2020 Jan 24.
• Chatterjee NA, Tikkanen JT, Panicker GK, Narula D, Lee DC, Kentta T, Junttila JM, Cook NR, Kadish A, Goldberger JJ, Huikuri HV, Albert CM; PREDETERMINE Investigators. Simple electrocardiographic measures improve sudden arrhythmic death prediction in coronary disease. Eur Heart J. 2020 Jun 1;41(21):1988-1999. doi: 10.1093/eurheartj/ehaa177.
• Panicker GK, Narula DD, Albert CM, Lee DC, Kothari S, Goldberger JJ, Cook N, Schaechter A, Kim E, Moorthy MV, Pester J, Chatterjee NA, Kadish AH, Karnad DR. Validation of electrocardiographic criteria for identifying left ventricular dysfunction in patients with previous myocardial infarction. Ann Noninvasive Electrocardiol. 2021 Mar;26(2):e12812. doi: 10.1111/anec.12812. Epub 2020 Oct 30.
• Venkateswaran RV, Moorthy MV, Chatterjee NA, Pester J, Kadish AH, Lee DC, Cook NR, Albert CM. Diabetes and Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction. JACC Clin Electrophysiol. 2021 Dec;7(12):1604-1614. doi: 10.1016/j.jacep.2021.05.014. Epub 2021 Jul 28.
• Adabag S, Patton KK, Buxton AE, Rector TS, Ensrud KE, Vakil K, Levy WC, Poole JE. Association of Implantable Cardioverter Defibrillators With Survival in Patients With and Without Improved Ejection Fraction: Secondary Analysis of the Sudden Cardiac Death in Heart Failure Trial. JAMA Cardiol. 2017 Jul 1;2(7):767-774. doi: 10.1001/jamacardio.2017.1413.

Helpful Links

• U.S. FDA Resources
• Coronary Artery Disease
• Cardiac Arrest
• Pacemakers and Implantable Defibrillators
• Heart Disease

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Anticipated): November 1, 2026
• Study Completion (Anticipated): November 1, 2026

Study Registration Dates

• First Submitted: April 29, 2010
• First Submitted That Met QC Criteria: April 29, 2010
• First Posted (Estimate): May 3, 2010

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Percutaneous Coronary Intervention; Myocardial Infarction; Sudden Cardiac Death; Implantable Cardiac Defibrillator
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Death, Sudden; Heart Arrest; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Death; Ventricular Dysfunction; Death, Sudden, Cardiac; Ventricular Dysfunction, Left
• Other Study ID Numbers: 2007P000840; R01HL091069 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO