Heart Failure and Cardiomyopathy

Our faculty and colleagues in the Departments of Molecular Physiology and Biophysics, Pharmacology and Biology have developed an internationally renowned Program in Cardiomyopathy and Heart Failure. The participating scientists currently attract over $7,000,000 annually in NIH funding to support research in these areas. This support includes two Program Project Grants and two NIH Research Training Grants.

Components include extensive bench research focused on the contractile machinery, excitation-contraction coupling, myocardial relaxation and diastolic function, skeletal muscle myopathy, gene transfer and proteomics of cardiomyopathic and failing myocardium. Programmatic areas include:

  • hypertrophic and familial dilated cardiomyopathy, for which genetically engineered animals are used to simulate human disease;
  • animal preparations exhibiting acquired hypertrophy and the transition to failure; and
  • cardiomyopathic and failing human myocardium.

The latter work utilizes myocardial tissue from explanted hearts as well as biopsy tissue obtained in the operating room by our cardiac surgeons. These have allowed study of tissue from diverse patients including those who do not have end-stage disease such as those with diabetes, cardiomyopathy, and variably-compensated valvular heart disease. A new program focusing on the biology of reverse remodeling during resynchronization therapy for heart failure has recently been funded.

Clinical research emphasizes investigation of contractile reserve and diastolic function in cardiac hypertrophy and failure, valvular disease and diabetes, characterized with resting and stress echocardiography. A novel project examining mechanisms of cardiovascular maladaptation in relation to natriuretic hormone secretion in patients with congenital heart disease and acquired heart failure is well-established. Along with the new above program described above, magnetic resonance imaging will be employed to predict responses to resynchronization therapy in heart failure patients. Patients are also considered for participation in clinical trials, including both investigator-initiated local research and multi-center trials of novel treatments.

Dr. Martin LeWinter has had a longstanding interest in ventricular and myocardial function. Current areas of interest include mechanoenergetics of the myocardium in acquired heart failure and genetic models of cardiomyopathy. The goal is to use whole heart mechanoenergetic, skinned strip and in vitro motility and force analyses to provide a comprehensive understanding of abnormalities of the myofilament in disease.

A second area is diastolic left ventricular function, in particular the role of the giant cytoskeleton protein titin as a determinant of left ventricular stiffness and restoring forces. A third area is the effect of diabetes on myocardial function, both calcium handing and the myofilament. These studies utilize samples of human myocardium obtained in the operating room.