The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Relationship of Myocardial Fibrosis with the Potential of Mechanical Unloading to Induce Favorable Cardiac Structural and Functional Response


      Previous studies of fibrosis changes after mechanical unloading in LVAD patients yielded conflicting results. Those pulsatile era LVAD studies were small-scale and rarely correlated their findings with post-LVAD cardiac functional response.


      We prospectively evaluated 142 dilated cardiomyopathy patients who required durable LVAD and 14 normal donors (ND). Tissue was obtained from the LV apex at LVAD implant and transplant and evaluated as previously validated (infarct related scars excluded). “Responders” were classified by serial post-LVAD echocardiography as: relative increase in LVEF >50%, a final resulting LVEF >40%, and a final LVEDD <60 mm.


      The pre-LVAD degree of interstitial fibrosis varied significantly and revealed that advanced heart failure (HF) patients had fibrosis levels both within and above the fibrosis range of the normal donor hearts (Low Fibrosis Group: n=53, High Fibrosis Group: n=89, Figure A). The percentage of Responders was similar between the Low and High Fibrosis groups (23% vs. 19%, p=ns, respectively). Responders from the High Fibrosis Group had a significant reduction in total collagen after LVAD unloading (from 31% to 18%, p=0.01, Figure B), whereas no post LVAD collagen changes were identified in the Non Responders of the High Fibrosis Group (Figure C) and in the Low Fibrosis Group regardless of response.


      In this large-scale human tissue study, advanced HF patients appear to have significant variation in the degree of interstitial fibrosis despite being clinically similarly ill. Increased pre-LVAD interstitial fibrosis does not appear to preclude patients from developing post-LVAD favorable functional and structural response. This unexpected result is consistent with the finding that Responders who had increased fibrosis pre-LVAD decreased collagen content post-unloading. Future investigations are warranted to elucidate the mechanisms driving these phenomena.
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