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-hydroxyprohne content increased significantly at VAD implantation and was not altered by mechanical unloading. The ultrastructure showed signs of persisting. cardiomyopathy. Conclusion: 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.