Author + information
- Received February 20, 2018
- Revision received April 3, 2018
- Accepted April 30, 2018
- Published online August 20, 2018.
- Wayne C. Levy, MDa,∗ (, )
- Anne S. Hellkamp, MSb,
- Daniel B. Mark, MD, MPHc,
- Jeanne E. Poole, MDa,
- Ramin Shadman, MDd,
- Todd F. Dardas, MDa,
- Jill Anderson, BSN, RNe,
- George Johnson, BSEEe,
- Daniel P. Fishbein, MDa,
- Kerry L. Lee, MDb,
- David T. Linkera and
- Gust H. Bardy, MDa,e
- aDivision of Cardiology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington
- bDepartment of Biostatistics, Duke Clinical Research Institute, Duke University, Durham, North Carolina
- cDivision of Cardiology, Duke University Medical Center, Durham, North Carolina
- dDivision of Cardiology, Department of Medicine, Southern California Permanente Medical Group, Los Angeles, California
- eSeattle Institute for Cardiac Research, Seattle, Washington
- ↵∗Address for correspondence:
Dr. Wayne C. Levy, Division of Cardiology, University of Washington, Box 3564222, 1959 Northeast Pacific Street, Seattle, Washington 98177.
Objectives The authors previously developed the Seattle Proportional Risk Model (SPRM) in systolic heart failure patients without implantable cardioverter-defibrillators (ICDs)to predict the proportion of deaths that were sudden. They subsequently validated the SPRM in 2 observational ICD data sets. The objectives in the present study were to determine whether this validated model could improve identification of clinically important variations in the expected magnitude of ICD survival benefit by using a pivotal randomized trial of primary prevention ICD therapy.
Background Recent data show that <50% of nominally eligible subjects receive guideline- recommended primary prevention ICDs.
Methods In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), a placebo-controlled ICD trial in 2,521 patients with an ejection fraction ≤35% and symptomatic heart failure, we tested the use of patient-level SPRM-predicted probability of sudden death (relative to that of non-sudden death) as a summary measurement of the potential for ICD benefit. A Cox proportional hazards model was used to estimate variations in the relationship between patient-level SPRM predictions and ICD benefit.
Results Relative to use of mortality predictions with the Seattle Heart Failure Model, the SPRM was much better at partitioning treatment benefit from ICD therapy (effect size was 2- to 3.6-fold larger for the ICD×SPRM interaction). ICD benefit varied significantly across SPRM-predicted risk quartiles: for all-cause mortality, a +10% increase with ICD therapy in the first quartile (highest risk of death, lowest proportion of sudden death) to a decrease of 66% in the fourth quartile (lowest risk of death, highest proportion of sudden death; p = 0.0013); for sudden death mortality, a 19% reduction in SPRM quartile 1 to 95% reduction in SPRM quartile 4 (p < 0.0001).
Conclusions In symptomatic systolic heart failure patients with a Class I recommendation for primary prevention ICD therapy, the SPRM offers a useful patient-centric tool for guiding shared decision making.
- heart failure
- non-sudden death
- proportional risk
- regression analysis
- risk prediction model
- sudden death
The SCD-HeFT was supported by U.S. National Institutes of Health/National Heart Lung Blood Institute grants UO1 HL55766, UO1 HL55297, and UO1 HL55496 and by Medtronic, Wyeth-Ayerst Laboratories, and Knoll Pharmaceuticals. Analysis was supported by a Medtronic investigator-initiated grant. Seattle Proportional Risk Model (SPRM) and Seattle Heart Failure Model (SHFM) copyrights are held by and licensing fees are paid to University of Washington CoMotion. Dr. Levy is a member of the GE Healthcare, Steering Committee; Novartis, Abbott, and EBR Systems clinical endpoint committee; and was local principal investigator for the research trial by Novartis. Dr. Mark has consulted for Medtronic; and has received research grants from Merck and Oxygen Therapeutics. Dr. Poole has received honoraria from Biotronik, Boston Scientific, Medtronic, Abbott, and Kestra Inc.; and has served on the advisory board of Boston Scientific; and has received research support from Kestra Inc. All other authors have reported that they have no relationships with industry relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received February 20, 2018.
- Revision received April 3, 2018.
- Accepted April 30, 2018.
- 2018 American College of Cardiology Foundation
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