Impact of mechanical unloading on microvasculature and associated central remodeling features of the failing human heart.
OBJECTIVE
This study investigates alterations in myocardial microvasculature, fibrosis, and hypertrophy before and after mechanical unloading of the failing human heart.


BACKGROUND
Recent studies demonstrated the pathophysiologic importance and significant mechanistic links among 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.


METHODS
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.


RESULTS
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). We also identified, in agreement with these findings, ultrastructural and immunohistochemical 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.


CONCLUSIONS
The 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 might guide future studies of unloading-induced reverse remodeling of the failing human heart.
Drakos
Stavros G
SG
Cardiovascular Department and Utah Artificial Heart Program, Intermountain Medical Center, Salt Lake City, Utah, USA. stavros.drakos@u2m2.utah.edu
Kfoury
Abdallah G
AG
Hammond
Elizabeth H
EH
Reid
Bruce B
BB
Revelo
Monica P
MP
Rasmusson
Brad Y
BY
Whitehead
Kevin J
KJ
Salama
Mohamed E
ME
Selzman
Craig H
CH
Stehlik
Josef
J
Clayson
Stephen E
SE
Bristow
Michael R
MR
Renlund
Dale G
DG
Li
Dean Y
DY
D000293:Adolescent; D000328:Adult; D002309:Cardiology / Q000379:methods; D006332:Cardiomegaly / Q000473:pathology; D004727:Endothelium / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000628:therapy*; D006352:Heart Ventricles / Q000473:pathology; D006353:Heart-Assist Devices; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008833:Microcirculation; D008854:Microscopy, Electron / Q000379:methods; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D013314:Stress, Mechanical; D020257:Ventricular Remodeling