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CLINICAL STUDY: HEART FAILURE

Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading

An immunohistochemical analysis of the contractile myofilaments

Nicolaas de Jonge, MD^*,*, Dick F. van Wichen, BSc, Marguerite E. I. Schipper, MD, Jaap R. Lahpor, MD, PhD^*, Frits H. J. Gmelig-Meyling, PhD, Etienne O. Robles de Medina, MD, PhD, FACC^* and Roel A. de Weger, PhD

^* Heart Lung Center Utrecht, Utrecht, The NetherlandsDepartment of
Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

Manuscript received August 6, 2001; revised manuscript received December 10, 2001, accepted December 18, 2001.

^* Reprint requests and correspondence: Dr. Nicolaas de Jonge, Heart Failure and Heart Transplantation Unit (E03.406), University Medical Center Utrecht, P.O. Box 85.500, 3508 GA Utrecht, The Netherlands.
n.dejonge{at}azu.nl

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 hematoxylin-eosin 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 µm² to 319 ± 53 µm² (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.

Abbreviations and Acronyms   LVAD   DCM   dilated cardiomyopathy   HF   heart failure   HTx   heart transplantation   IHD   ischemic heart disease   LV   left ventricle or ventricular   LVAD   left ventricular assist device

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