This study investigates alterations in myocardial microvasculature, fibrosis and hypertrophy before and after mechanical unloading of the failing human heart.
Recent studies demonstrated the pathophysiologic importance and significant mechanistic links between microvasculature, fibrosis and hypertrophy during the cardiac remodeling process. The effect of left ventricular assist device (LVAD) unloading on cardiac endothelium and microvasculature is unknown and its influence on fibrosis and hypertrophy regression to the point of atrophy is controversial.
Hemodynamic data and left ventricular tissue were collected from patients with chronic heart failure at LVAD implant and explant (n=15), and from normal donors (n=8). New advances in digital microscopy provided a unique opportunity for comprehensive whole-field, endocardium-to-epicardium evaluation for microvascular density, fibrosis, cardiomyocyte size and glycogen content. Ultrastructural assessment was done with electron microscopy.
Hemodynamic data revealed significant pressure unloading with LVAD. This was accompanied by a 33% increase in microvascular density (p=0.001) and a 36% decrease in microvascular lumen area (p=0.028). In agreement with these findings we also identified immunohistochemical ultrastructural evidence of endothelial cell activation. In addition, LVAD unloading significantly increased interstitial and total collagen content without any associated structural, ultrastructural or metabolic cardiomyocyte changes suggestive of hypertrophy regression to the point of atrophy and degeneration.
LVAD unloading resulted in increased microvascular density accompanied by increased fibrosis and no evidence of cardiomyocyte atrophy. These new insights into the effects of LVAD unloading on microvasculature and associated key remodeling features may guide future studies of unloading-induced reverse remodeling of the failing human heart.
Keywords: heart failure, remodeling, left ventricular assist device, unloading, microvasculature