Molecular normalization of dystrophin in the failing left and right ventricle of patients treated with either pulsatile or continuous flow-type ventricular assist devices

Matteo Vatta, Sonny J. Stetson, Shinawe Jimenez, Mark L. Entman, George P. Noon, Neil E. Bowles, Jeffrey A. Towbin, Guillermo Torre

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Objectives We investigated the integrity of dystrophin in left ventricle (LV) and right ventricle (RV) of patients with end-stage heart failure due to ischemic cardiomyopathy (IHD) or dilated cardiomyopathy (DCM), and compared the efficacy of pulsatile or continuous flow assist devices on dystrophin reverse remodeling. Background Recently we demonstrated that the amino (N)-terminus of dystrophin is preferentially disrupted in failing LV myocardium irrespective the underlying etiology, and that this defect is reversed by mechanical unloading using left ventricular assist device (LVAD) therapy. Methods Myocardial samples were obtained from seven normal controls, seven failing hearts (either DCM or IHD), and 14 failing-heart patients who underwent placement of either pulsatile (7 patients) or continuous flow (7 patients) LVADs for progressive refractory HF. The expression and integrity of dystrophin in these samples were determined by immunohistochemistry using antibodies against the N-terminal and carboxyl (C)-terminal domains. Results Immunohistochemical staining identified disruption of the N-terminal dystrophin in both LVs and RVs of all seven failing-heart patients, whereas the C-terminus was normal. Furthermore, this disruption was reversed in 12 of the 14 patients after LVAD therapy using either pulsatile or continuous devices; the degree of the reverse remodeling was similar in both ventricles, although greater recovery was noted in patients treated with pulsatile flow devices. Conclusions Integrity of the N-terminus of dystrophin is a useful indicator of both LV and RV function. In addition to improving LV hemodynamics, LVAD therapy results in amelioration of the myocardial structure of the right cardiac chamber.

Original languageEnglish (US)
Pages (from-to)811-817
Number of pages7
JournalJournal of the American College of Cardiology
Volume43
Issue number5
DOIs
StatePublished - Mar 3 2004

Keywords

  • Amino
  • Becker muscular dystrophy
  • BMD
  • DAPC
  • DMD
  • Duchenné muscular dystrophy
  • Dystrophin-associated protein complex
  • Heart failure
  • HF
  • IHD
  • Ischemic cardiomyopathy
  • Left ventricle/ventricular
  • Left ventricular assist device
  • LV
  • LVAD
  • N
  • RV

ASJC Scopus subject areas

  • Nursing(all)

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