Heart Failure (HF) is a disease of epidemic proportion in the U.S. affecting over 5 million individuals. It is estimated that in the next year nearly 400,000 new cases will be diagnosed, 1 million individuals will be hospitalized and 300,000 deaths will occur because of HF. Approximately half of the deaths will be attributed to worsening pump function while the remainder will be attributable to sudden cardiac death. Biventricular (BIV) pacing has recently emerged as a new modality for the treatment of advanced HF Patients with ventricular conduction abnormalities who continue to suffer from severe HF symptoms (New York Heart Association Class III-IV) despite optimal pharmacologic therapy including angiotensin converting enzyme inhibitors, b-blockers, and potassium-sparing diuretics can extract benefits from BIV pacing in the form of improved maximum oxygen consumption, exercise tolerance, and quality of life, as well as reduced incidence of ventricular arrhythmias. New published reports also suggest a benefit from BIV pacing in improving the combined endpoint of death and hospitalization. Despite all this, little is known about the regional, cellular, and molecular mechanisms responsible for the benefits seen with BIV pacing. The present proposal aims at utilizing a rabbit model of HF to better understand the mechanisms of cardiac improvement with BIV pacing. Rabbits with coronary artery ligation will undergo right ventricular versus BIV pacing for 1 month. Results will be compared to sham-operated rabbits with right ventricular, BIV, and no pacing and to infarcted rabbits. The present project will 1) test the hypothesis that BIV pacing is superior to right ventricular pacing in improving echocardiographic, plasma neurohormonal, cellular and molecular markers of HF, 2) test the hypothesis that BIV pacing positively modulates electrical propagation and conduction velocity of impulses in HF, 3) and test the hypothesis that BIV pacing prevents adverse remodeling in the cellular electrophysiology of cardiac myocytes in HF.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZHL1-CSR-O (F2))
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Carlson, Drew E
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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Saba, Samir; Mehdi, Haider; Mathier, Michael A et al. (2010) Effect of right ventricular versus biventricular pacing on electrical remodeling in the normal heart. Circ Arrhythm Electrophysiol 3:79-87
Saba, Samir; Mathier, Michael A; Mehdi, Haider et al. (2008) Prevention of adverse electrical and mechanical remodeling with biventricular pacing in a rabbit model of myocardial infarction. Heart Rhythm 5:124-30
Saba, Samir; Mathier, Michael A; Mehdi, Haider et al. (2008) Dual-dye optical mapping after myocardial infarction: does the site of ventricular stimulation alter the properties of electrical propagation? J Cardiovasc Electrophysiol 19:197-202