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Myocardial atrophy and chronic mechanical unloading of the failing human heart: implications for cardiac assist device-induced myocardial recovery.
- Source :
-
Journal of the American College of Cardiology [J Am Coll Cardiol] 2014 Oct 14; Vol. 64 (15), pp. 1602-12. - Publication Year :
- 2014
-
Abstract
- Background: In animal models of heterotopic transplantation, mechanical unloading of the normal, nonhypertrophic heart results in atrophy. Primarily on the basis of these animal data, the notion that chronic left ventricular assist device (LVAD)-induced unloading will result in atrophy has dominated the clinical heart failure field, and anti-atrophic drugs have been used to enhance the cardiac recovery potential observed in some LVAD patients. However, whether unloading-induced atrophy in experimental normal heart models applies to failing and hypertrophic myocardium in heart failure patients unloaded by continuous-flow LVADs has not been studied.<br />Objectives: The study examined whether mechanical unloading by continuous-flow LVAD leads to myocardial atrophy.<br />Methods: We prospectively examined myocardial tissue and hemodynamic and echocardiographic data from 44 LVAD patients and 18 untransplanted normal donors.<br />Results: Cardiomyocyte size (cross-sectional area) decreased after LVAD unloading from 1,238 ± 81 μm(2) to 1,011 ± 68 μm(2) (p = 0.001), but not beyond that of normal donor hearts (682 ± 56 μm(2)). Electron microscopy ultrastructural evaluation, cardiomyocyte glycogen content, and echocardiographic assessment of myocardial mass and left ventricular function also did not suggest myocardial atrophy. Consistent with these findings, t-tubule morphology, cytoplasmic penetration, and distance from the ryanodine receptor were not indicative of ongoing atrophic remodeling during LVAD unloading. Molecular analysis revealed no up-regulation of proatrophic genes and proteins of the ubiquitin proteasome system.<br />Conclusions: Structural, ultrastructural, microstructural, metabolic, molecular, and clinical functional data indicated that prolonged continuous-flow LVAD unloading does not induce hypertrophy regression to the point of atrophy and degeneration. These findings may be useful in designing future investigations that combine LVAD unloading and pharmaceutical therapies as a bridge to recovery of the failing heart.<br /> (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Atrophy genetics
Atrophy metabolism
Atrophy pathology
Blotting, Western
Cardiomyopathies etiology
Cardiomyopathies genetics
Echocardiography
Female
Follow-Up Studies
Heart Failure complications
Heart Failure therapy
Heart Ventricles diagnostic imaging
Heart Ventricles physiopathology
Heart Ventricles ultrastructure
Humans
Male
Microscopy, Confocal
Microscopy, Electron
Middle Aged
Myocardial Contraction
Prognosis
Prospective Studies
RNA genetics
Real-Time Polymerase Chain Reaction
Ubiquitin biosynthesis
Ubiquitin genetics
Up-Regulation
Ventricular Remodeling
Cardiomyopathies pathology
Heart Failure physiopathology
Heart-Assist Devices
Myocardium ultrastructure
Recovery of Function physiology
Ventricular Function, Left physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-3597
- Volume :
- 64
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Journal of the American College of Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 25301465
- Full Text :
- https://doi.org/10.1016/j.jacc.2014.05.073