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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

View larger version (74K): [in a new window]   Figure 1 Hematoxylin-eosin staining in left ventricular biopsies (original magnification x50) before and after left ventricular assist device (LVAD) support. (A) Before LVAD support, there were hypertrophic myocytes of varying nuclear sizes, with vacuolization and interstitial fibrosis. (B) After LVAD support, the myocytes showed less hypertrophy and vacuolization, together with a decrease in myocyte size and an increase in interstitial fibrosis.

View larger version (154K): [in a new window]   Figure 2 (A) Actin staining before left ventricular assist device (LVAD) support shows a severe distortion of the architecture and absence of cross-striation in nearly all myocytes (grade 1). (B) Actin after LVAD support demonstrates some improvement in the staining pattern, with partial restoration of cross-striation (grade 3). (C) Myosin before LVAD support displays a normal architecture (grade 5). (D) After LVAD support, some deterioration is observed (grade 3). (original magnification x250).

View larger version (117K): [in a new window]   Figure 3 Tropomyosin staining after left ventricular assist device (LVAD) support show the alternation of histochemical normal myocytes with abnormal ones in the same contractile fiber. (original magnification x150).

View larger version (17K): [in a new window]   Figure 4 Grading of the contractile proteins in myocytes before and after left ventricular assist device (LVAD) support. Myosin staining showed some deterioration (grade 4.6 before LVAD implantation vs. 3.6 after LVAD support; p = 0.058). In contrast, the contractile proteins of the thin filaments and titin showed improvement (grade 1.4 for actin before LVAD implantation vs. 2.7 after LVAD support; p = 0.004). Severe structural myocyte damage persisted, despite a period of LVAD support of 213 ± 135 days. HTx = heart transplantation; Trop = troponin.

View larger version (148K): [in a new window]   Figure 5 Human atrial cardiomyocytes show normal cross-striation (actin staining, grade 5; original magnification x250).