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 Towbin, Guillermo Torre-Amione

Research output: Contribution to journalArticle

66 Citations (Scopus)

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
Externally publishedYes

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Dystrophin
Heart-Assist Devices
Heart Ventricles
Dilated Cardiomyopathy
Cardiomyopathies
Equipment and Supplies
Pulsatile Flow
Myocardium
Therapeutics
Heart Failure
Hemodynamics
Immunohistochemistry
Staining and Labeling
Antibodies

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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Molecular normalization of dystrophin in the failing left and right ventricle of patients treated with either pulsatile or continuous flow-type ventricular assist devices. / Vatta, Matteo; Stetson, Sonny J.; Jimenez, Shinawe; Entman, Mark L.; Noon, George P.; Bowles, Neil E.; Towbin, Jeffrey; Torre-Amione, Guillermo.

In: Journal of the American College of Cardiology, Vol. 43, No. 5, 03.03.2004, p. 811-817.

Research output: Contribution to journalArticle

Vatta, Matteo ; Stetson, Sonny J. ; Jimenez, Shinawe ; Entman, Mark L. ; Noon, George P. ; Bowles, Neil E. ; Towbin, Jeffrey ; Torre-Amione, Guillermo. / Molecular normalization of dystrophin in the failing left and right ventricle of patients treated with either pulsatile or continuous flow-type ventricular assist devices. In: Journal of the American College of Cardiology. 2004 ; Vol. 43, No. 5. pp. 811-817.
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AU - Vatta, Matteo

AU - Stetson, Sonny J.

AU - Jimenez, Shinawe

AU - Entman, Mark L.

AU - Noon, George P.

AU - Bowles, Neil E.

AU - Towbin, Jeffrey

AU - Torre-Amione, Guillermo

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N2 - 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.

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