Desmin-free cardiomyocytes and myocardial dysfunction in end stage heart failure.

ABSTRACT

Our aim was to evaluate the desmin content in the myocardial tissue of patients with end-stage heart failure of ischaemic origin and to assess its role on cardiac function. We studied 18 explanted hearts from patients transplanted for end-stage heart failure due to ischaemic cardiomyopathy (ICM). Control myocardial tissue was obtained from the cardiac biopsies of six women with breast cancer taken prior to commencing chemotherapy with anthracyclines, four male donors for heart transplantation and two autoptic hearts from patients who died due to non-cardiac events. Myocardial tissue, obtained from the left ventricle (remote zone from infarcted area), was analyzed by light and confocal immunochemistry (desmin) microscopy. The desmin content of myocardial tissue was obtained by real-time PCR. Cardiac function was evaluated by echocardiographic and right heart catheterization data, obtained before heart transplantation. Confocal microscopy evaluation showed a significant decrease in the number of desmin-positive myocytes (P<0.01) in ICM hearts compared to controls. At real-time PCR evaluation, there was a reduction (P<0.01) in desmin content in the ICM patients compared to controls. A negative correlation was found between desmin-free cardiomyocytes and ejection fraction (EF) (r=-0.834; P<0.02) on echocardiogram. A negative relationship (r=-0.688) was also found between desmin-negative myocytes and capillary wedge pressure. In conclusion, the myocardial tissue of patients with end-stage heart failure of ischaemic origin, shows a decreased number in desmin-positive myocytes at immunochemistry evaluation compared to normal individuals. This deficiency in cytoskeletal intermediate filament content is associated with reduced cardiac function.