Left ventricular assist device in end-stage heart failure: Persistence of structural myocyte damage after unloading - An immunohistochemical analysis of the contractile myofilaments

OBJECTIVES We sought to evaluate the contractile proteins in cardiomyocytes of patients with end-stage heart failure (HF) before and after mechanical support with a left ventricular assist device (LVAD). BACKGROUND Improvement of myocyte dysfunction has been suggested after LVAD support. METHODS Fourteen patients' myocardial biopsies taken at the time of LVAD implantation and after explantation, at the time of heart transplantation, were processed for routine hematoxylineosin staining and immunohistochemistry using monoclonal antibodies against actin, myosin, tropomyosin, troponin C and T and titin. A grading scale from 1 (abnormal staining of all myocytes, no cross-striation) to 5 (normal fiber anatomy and striation) was used. The cross-sectional area of cardiomyocytes was also measured. RESULTS The cardiomyocytes' cross-sectional area decreased after support, from 519 +/- 94 mum(2) to 319 +/- 53 mum(2) (p < 0.001). Actin, tropomyosin, troponin C, troponin T and titin at the time of LVAD implantation showed widespread distortion of architecture; their grades were 1.4 +/- 0.6, 2.3 +/- 1.0, 2.1 +/- 0.9, 2.1 +/- 1.2 and 2.0 +/- 0.6, respectively. In contrast, myosin morphology was preserved (4.6 +/- 0.7). After LVAD support, actin, tropomyosin, troponin C, troponin T and titin showed improvement (grades 2.7 +/- 1.3 [p = 0.004], 3.2 +/- 1.2 [p = 0.021], 3.3 +/- 0.9 [p = 0.004], 3.0 +/- 1.1 [p = 0.048] and 3.1 +/- 0.9 [p = 0.001], respectively), but no normalization. The myosin pattern deteriorated slightly (3.6 +/- 1.6 [p = 0.058]). CONCLUSIONS After LVAD support, during a period of 213 135 days in patients with end-stage HF, despite a decrease in the size of the cardiomyocytes, severe structural myocyte damage persisted. This does not support complete recovery of myocyte histologic features. (J Am Coll Cardiol 2002;39:963-9) (C) 2002 by the American College of Cardiology Foundation.