Project 2

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Project 2: Functional energetics and imaging for phenotypic characterization of patients at risk for sudden cardiac death

Project Director: Robert G. Weiss, M.D.
Project Co-Director: João A.C. Lima, M.D.

Co-Investigators: Henry Halperin M.D., Paul A. Bottomley, Ph.D, Gary Gerstenblith, M.D., David A. Bluemke, M.D., Ph.D., Steven P. Schulman M.D., Ronald D. Berger M.D.,Ph.D., Shenghan Lai, M.D., Ph.D., Raimond L. Winslow, Ph.D., Nael F. Osman, Ph.D., Matthias Stuber, Ph.D., Ronald Ouwerkerk, Ph.D., Albert C. Lardo, Ph.D, Edward P. Shapiro, M.D.
Associate: Katherine C. Wu, M.D.

Patients with post-MI ventricular dysfunction have a lower mortality when treated prophylactically with implantable cardioverter defibrillators (ICD) [1-3]. However, these ICDs turn out to be required only in a presently-unpredictable subset of the patients at risk.

Project 2 is developing and exploiting multiple new, noninvasive imaging and spectroscopic techniques to identify individuals who are at greatest risk for SCD following a myocardial infarction (MI). Investigators will evaluate information on individual variation in ventricular geometry and function, and the presence and extent of myocardial scarring and ionic and metabolic abnormalities in patients following infarction. Included in this prospective clinical study are patients recruited from the Reynolds ICD Registry of Project 3. In these patients who have recently experienced acute MI and reduced left ventricular ejection fraction, imaging work will be performed before and after ICD implantation. Appropriate ICD firings will be used as the surrogate marker for SCD. All these phenotypic markers will be correlated with the genomic, proteomic, and other biomarker data from other projects with the Hopkins Reynolds Center network.

The results will not only enable us to predict which post-MI patients require an ICD or alternative therapies, but also promise to shed light on the functional, structural, and metabolic factors that predispose to lethal arrhythmias. Such insights will be important biologically, and will also have enormous public health and economic impact by laying the groundwork for tailored therapy.

View examples of imaging techniques used by Project 2 investigators at the Reynolds Resource page Images in Cardiovascular Medicine.

References

Moss AJ, Hall J, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JL, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med.1996;335:1933-1940.
Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med. 1999;341:1882-1890.
Moss AJ, Zareba W, Hall J, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Eng J Med. 2002;346:877-883.