NHLBI Workshop
Prediction and Prevention of Sudden Cardiac Death

Executive Summary

The National Heart, Lung, and Blood Institute (NHLBI), in partnership with the Heart Rhythm Society (HRS), convened a Workshop of experts in cardiac electrophysiology on September 29-30, 2009 at the Washington, D.C. headquarters of the HRS. The purpose of this Workshop was to explore emerging approaches for improved prediction and prevention of sudden cardiac death.  These approaches include novel non-invasive imaging modalities, strategies that emerge from mining data from existing large clinical studies and ICD cohorts, and those from fundamental science studies of arrhythmia mechanisms.  The purpose was to provide recommendations for the NHLBI and the scientific community for future research approaches to improve prediction and prevention of sudden cardiac death.  This Workshop is responsive to NHLBI Strategic Plan Goals 1 & 2 and the Division of Cardiovascular Diseases Strategic Plan Goal 2.3.a.

Discussion

Although the death rate for cardiovascular diseases has declined steadily since 1968, the abrupt and frequently fatal nature of arrhythmic cardiovascular collapse and its ability to strike seemingly healthy, active individuals makes this syndrome of “sudden cardiac death” (SCD) one of great interest to the public’s health and an area of research need.  Even the ability to estimate the number of patients affected--with an annual U.S. estimate of 180,000-450,000 cases—is hampered by lack of uniform definitions across studies and the difficulty of making a correct post-mortem classification. 

Prevention of SCD is hindered by multiple factors.  Foremost is the inability to identify predictive factors for the majority of patients at risk, many of whom have no prior evidence of cardiac disease. Second, even in higher risk patients, anti-arrhythmic strategies have largely been ineffective. Finally, guidelines for palliative therapies, such as implantable cardioverter-defibrillators (ICDs), are often not followed in part because physicians recognize that the majority of patients who receive these expensive invasive therapies never have cause to use them. 

The Workshop therefore convened experts in fundamental, clinical, and population-based electrophysiology research to provide recommendations for research goals that would help overcome these obstacles to prevention of SCD.

Recommendations (not prioritized):

1. Establish high throughput experimental strategies to rapidly determine the functional relevance of newly discovered genes associated with arrhythmias in humans.
2. Establish multi-scale integrative models, utilizing molecular, cellular, organ-level, animal and computational approaches, and apply these models to determine arrhythmia mechanisms.
3. Develop novel risk stratification strategies to improve outcomes in select populations:

• Patients with ICD indications based on current guidelines
• Other patients at risk, such as:

• Coronary artery disease with left ventricular ejection fraction (EF) > 35%
• Early phase post acute myocardial infarction
• Heart failure with preserved systolic function
• Left ventricular hypertrophy

4.  Facilitate study of well-phenotyped SCD and control populations, including understudied subgroups.

• Establish standardized definitions, including of SCD
• Improve understanding of presenting arrhythmias, i.e., ventricular fibrillation, pulseless electrical activity, asystole
• Create opportunities for collaborative analysis of shared data

5. Develop and validate a SCD risk score utilizing phenotypic, biologic and non-invasive markers
6. Establish strategies for SCD prevention that can be employed in the general population, targeting intermediate risk phenotypes

Publication Plans:

The Workshop report is planned for publication in a peer-reviewed journal.

Participating Divisions:

Division of Cardiovascular Sciences
Division of the Application of Research Discoveries

NHLBI Contacts:

Alice Mascette, M.D.
Division of Cardiovascular Science
mascetta@nhlbi.nih.gov, 301-435-0504

David Lathrop, Ph.D.
Division of Cardiovascular Science
lathropd@nhlbi.nih.gov, 301-435-0504

Zhi-Jie Zheng, M.D., Ph.D.
Division of the Application of Research Discoveries
Zhengz2@nhlbi.nih.gov, 301-496-1051

Working Group Members:

Chairs:
Glenn I. Fishman, M.D., New York University
Robert Bonow, M.D., Northwestern University

Members:
Christine Albert, M.D., Brigham & Women’s Hospital
Mark Anderson, M.D., University of Iowa
Alfred Buxton, M.D., Brown University
Peng-Sheng Chen, M.D., Indiana University
Sumeet Chugh, M.D., Cedars-Sinai Medical Center
John DiMarco, M.D., University of Virginia
Mark Estes, M.D., Tufts University
Dr. Xavier Jouven, INSERM, Paris, France
Raymond Kwong, M.D., Brigham & Women’s Hospital
Jeanne Nerbonne, Ph.D., Washington University
Brian O’Rourke, M.D., Johns Hopkins University
Richard Page, M.D., University of Washington
Dan Roden, M.D., Vanderbilt University
David Rosenbaum, M.D., Case Western University
Nona Sotoodehnia, M.D., University of Washington
Natalia Trayanova, Ph.D., Johns Hopkins University

Last updated: November 4, 2009