The structural examination of myocardial samples from patients with end-stage heart failure supported by ventricular assist devices using electron microscopy and amino acid analysis reveals low degree of reverse remodeling.
BACKGROUND
Chronic heart failure is a multifactorial, progressive disease of many causes and is associated with complex ventricular remodeling. Deposition of extracellular matrix proteins and sarcomeric disarray of the myocytes occur in end-stage heart failure. Ventricular assist devices (VAD), implanted as bridge to transplantation, may reverse ventricular remodeling. Although successfully weaning patients from VAD support has been reported, it is not clear to what degree reversal of remodeling occurs in unloaded failing hearts. Because collagen deposition and ultrastructural disarray are hallmarks of myocardial remodeling, we analyzed the myocardial ultrastructure and collagen content of VAD-supported hearts before and after mechanical unloading.


METHODS
We used amino acid analysis to measure collagen content (4-hydroxyproline content) in 24 transplant candidates receiving VAD support. We used transmission electron microscopy to examine the ultrastructure in 6 patients receiving VAD support.


RESULTS
The 4-hydroxyproline content increased significantly at VAD implantation and was not altered by mechanical unloading. The ultrastructure showed signs of persisting cardiomyopathy.


CONCLUSIONS
Mechanical unloading does not alter the total collagen content of the supported, failing heart. Thus, structural reversal of the remodeling process associated with heart failure is not a general phenomenon in mechanically unloaded hearts.
Milting
Hendrik
H
Ruhr-Universität Bochum, Herz- und Diabeteszentrum NRW, Forschungslabor der Herzchirurgie, Bad Oeynhausen, Germany. hmilting@hdz-nrw.de
Jacob
Monika
M
Kassner
Astrid
A
Heimann
Peter
P
Mannherz
Hans Georg
HG
Becker
Gabriele
G
Meyer
Helmut E
HE
Böthig
Dietmar
D
Arusoglu
Latif
L
Morshuis
Michel
M
Körfer
Reiner
R
El Banayosy
Aly
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003094:Collagen / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000378:metabolism / Q000648:ultrastructure; D006353:Heart-Assist Devices; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism*; D008854:Microscopy, Electron; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure*; D020257:Ventricular Remodeling / Q000502:physiology*
D003094:Collagen; D006909:Hydroxyproline