Key result
Prolonged LVAD unloading linked to an ~18% decrease in cardiomyocyte size without reaching atrophy.
Why the study?
Whether unloading-induced atrophy observed in normal animal hearts applies to failing and hypertrophic myocardium in heart failure patients unloaded by continuous-flow LVADs had not been studied.
Does mechanical unloading by continuous-flow LVAD lead to myocardial atrophy in patients with heart failure?
Observational (n=62)
Does mechanical unloading by continuous-flow LVAD lead to myocardial atrophy in patients with heart failure?
Absolute Event Rate: 1011% vs 1238%
p-value: p=0.001
Prolonged continuous-flow LVAD unloading reverses hypertrophy but does not induce myocardial atrophy or degeneration in failing human hearts, challenging assumptions derived from normal animal models.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“University of Utah Health investigator Stavros George Drakos, MD, and colleagues analyzed human heart tissue and produced evidence refuting the widely held notion that prolonged off-loading of the failing heart induced by cardiac assist devices results in disuse atrophy that further deteriorates heart function. In contrast, there was significant heart recovery following the implantation of cardiac assist devices.”
May signal atrophy risk with prolonged unloading; leaves open effects on recovery and MCS duration in advanced HF.
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. OBJECTIVES: The study examined whether mechanical unloading by continuous-flow LVAD leads to myocardial atrophy. METHODS: We prospectively examined myocardial tissue and hemodynamic and echocardiographic data from 44 LVAD patients and 18 untransplanted normal donors. 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. 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.
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Diakos et al. (2014) conducted an observational in Heart failure (n=62). Continuous-flow LVAD unloading vs. Pre-LVAD baseline and untransplanted normal donors was evaluated on Cardiomyocyte size (cross-sectional area) (p=0.001). Prolonged mechanical unloading by continuous-flow LVAD decreased cardiomyocyte size (from 1,238 to 1,011 μm2; p=0.001) but did not induce hypertrophy regression to the point of atrophy.
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