Clinical trial NCT01114269: PRE-DETERMINE Cohort Study
Official title: PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Coronary Artery Disease
Left Ventricular Dysfunction
Sudden Cardiac Death
Keywords: Coronary Artery Disease
Sudden Cardiac Death
Myocardial Infarction
Percutaneous Coronary Intervention
Implantable Cardiac Defibrillator
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Abbott Medical Devices
name: Northwestern University
name: Roche Diagnostics GmbH
name: Quintiles, Inc.
First posted: 2010-05-03
Enrollment: 5764
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sudden and/or arrhythmic cardiac death or resuscitated ventricular fibrillation.
timeFrame: Median follow-up estimated to be 10.7 years
Secondary outcomes:
measure: ICD Shock
timeFrame: Median follow-up estimated to be 10.7 years
measure: ICD Implantation
timeFrame: Median follow-up estimated to be 10.7 years
measure: Total Cardiac Mortality
timeFrame: Median follow-up estimated to be 10.7 years
measure: Total Mortality
timeFrame: Median follow-up estimated to be 10.7 years
measure: Non-Sudden or Arrhythmic Causes of Mortality
timeFrame: Median follow-up estimated to be 10.7 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Heart Institute
state: Alaska
city: Glendale
country: United States
facility: Phoenix Heart, PLLC
state: Arizona
city: Phoenix
country: United States
facility: Cardiovascular Consultants
state: Arizona
city: Banning
country: United States
facility: Beaver Medical Group/Clinical Care Research
state: California
city: Colorado Springs
country: United States
facility: Memorial Health System
state: Colorado
city: Denver
country: United States
facility: Colorado Heart and Vascular
state: Colorado
city: Brandon
country: United States
facility: Bay Area Cardiology Associates, P.A.
state: Florida
city: Gainesville
country: United States
facility: University of Florida - Gainsville
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: Reliable Clinical Research
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Regional Medical Center
state: Florida
city: Palm Beach Gardens
country: United States
facility: Palm Beach Gardens Research Center
state: Florida
city: Sarasota
country: United States
facility: Velella Research
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute, Inc.
state: Florida
city: West Palm Beach
country: United States
facility: Cardiology Associates of Palm Beach - West Palm Beach
state: Florida
city: Covington
country: United States
facility: Georgia Heart Specialist
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Heart Center, P.C.
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Chicago
country: United States
facility: Advocate Medical Group
state: Illinois
city: Chicago
country: United States
facility: Advocate Medical Group - Heart and Vascular of IL
state: Illinois
city: Melrose Park
country: United States
facility: Consultants in Cardiovascular Medicine
state: Illinois
city: Anderson
country: United States
facility: Community Heart and Vascular
state: Indiana
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Houma
country: United States
facility: Leonard J. Chabert Medical Center
state: Louisiana
city: Auburn
country: United States
facility: Maine Research Associates
state: Maine
city: Lewiston
country: United States
facility: Maine Research Associates - Lewiston
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Ayer
country: United States
facility: Primary Care Cardiology Research
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Fall River
country: United States
facility: NECCR Internal Medicine and Cardiology Associates, LLC
state: Massachusetts
city: North Dartmouth
country: United States
facility: Hawthorn Medical Associates
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Cardiology
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital & Medical Center
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Medical Center - Macomb
state: Michigan
city: Ypsilanti
country: United States
facility: Michigan Heart
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Medical Center
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: Kalispell
country: United States
facility: Glacier View Cardiology
state: Montana
city: Omaha
country: United States
facility: The Cardiac Center of Creighton University
state: Nebraska
city: Bridgewater
country: United States
facility: Advanced Heartcare, LLC
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph Regional Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico VA Healthcare Systems
state: New Mexico
city: Albany
country: United States
facility: Albany Associates Cardiology
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Buffalo
country: United States
facility: Buffalo General Hospital/Kaleida Health
state: New York
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: Kingston
country: United States
facility: Mid-Valley Cardiology
state: New York
city: Mineola
country: United States
facility: Winthrop-University Hospital
state: New York
city: New York
country: United States
facility: Gotham Cardiovascular
state: New York
city: New York
country: United States
facility: Columbia University Health Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Utica
country: United States
facility: St. Elizabeth Medical Center - Hotvedt
state: New York
city: Asheville
country: United States
facility: Asheville Cardiology Associates
state: North Carolina
city: Elizabeth City
country: United States
facility: Eastern Carolina Cardiovascular
state: North Carolina
city: Lenoir
country: United States
facility: Northstate Clinical Research
state: North Carolina
city: Pinehurst
country: United States
facility: Pinehurst Medical Clinic, Inc.
state: North Carolina
city: Sanford
country: United States
facility: Sanford Cardiology
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest
state: North Carolina
city: Akron
country: United States
facility: Northeast Ohio Cardiovascular Specialists
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Elyria
country: United States
facility: North Ohio Research, Ltd.
state: Ohio
city: Fairfield
country: United States
facility: Mercy Medical Associates
state: Ohio
city: Toledo
country: United States
facility: Northwest Ohio Cardiology Consultants/The Toledo Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma City VA Medical Center Veterans Research and Education Foundation
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Cardiovascular Research
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Bethlehem
country: United States
facility: St. Luke's Bethlehem
state: Pennsylvania
city: Doylestown
country: United States
facility: Doylestown Cardiology Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health
state: South Carolina
city: Charleston
country: United States
facility: VA Medical Center - Charleston
state: South Carolina
city: Rock Hill
country: United States
facility: Carolina Cardiology Associates
state: South Carolina
city: Rapid City
country: United States
facility: Black Hills Cardiovascular Research
state: South Dakota
city: Knoxville
country: United States
facility: Cardiovasular Research of Knoxville
state: Tennessee
city: Memphis
country: United States
facility: Memphis VA Medical Center
state: Tennessee
city: Houston
country: United States
facility: St. Luke's Episcopal Hospital
state: Texas
city: Houston
country: United States
facility: Non-Invasive Cardiovascular PA
state: Texas
city: Waco
country: United States
facility: Providence Health Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Virginia Beach
country: United States
facility: Cardiovascular Associates Virginia Beach
state: Virginia
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Mississauga
country: Canada
facility: Mississauga Clinical Research Centre
state: Ontario
city: Rio Piedras
country: Puerto Rico
facility: Transcatheter Medical, Inc. Centro Cardiovascular de Caguas y del Caribe
Study officials:
affiliation: Brigham and Women's Hospital
name: Christine M Albert, M.D., M.P.H.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.