Myocardial changes in patients with end-stage heart failure during continuous flow left ventricular assist device support

Abstract

With respect to the clinical outcome, cf-LVADs provide sufficient ventricular unloading and circulatory support. The post-operative mortality and morbidity in our centre are comparable with other recent experiences with this device. Based on these data, Heart Mate II (HM II) LVAD therapy can be considered as a successful life-saving therapy. Hitherto, there is a price to pay in terms of risk of serious adverse events during support. Perhaps the greatest challenge that remains of concern is in neurological outcomes with current LVADs, a morbidity that has not improved, despite the advent of newer devices. With regard to the histology, long-term cf-LVAD support is associated with lengthening of cardiomyocytes, without alterations in diameter size. Remarkably, myocardial fibrosis increased as well as circulating pro-fibrotic markers, suggesting insufficient remodeling of the extracellular matrix (ECM) collagen composition. Also, our data showed different microRNA (miR) expression profiles amongst pf-LVAD and cf-LVADs, thereby strengthening the concept that type of unloading type could influence different cellular and molecular processes, which might affect clinical outcomes. It seems that pf-LVADs might have some advantages over continuous-flow devices (morphologically spoken), which may be further translated to more favorable outcomes in terms of BTR. This thesis demonstrated that cf-LVAD support seems to provide adequate volume unloading in end-stage HF patients, as demonstrated by the severe decrease in BNP and Growth Differentiation Factor (GDF)-15. In our patient cohort, most patients showed partial reverse remodeling during cf-LVAD support (indicated by the improvement in NYHA class), but only few demonstrated profound reverse remodeling with subsequent explantation of the device. This then raises the question of what constitutes myocardial recovery. Moreover, histological analysis of paired myocardial tissue showed lengthening of cardiomyocytes and an increase in fibrosis during cf-LVAD support. These data indicate that clinical improvement during cf-LVAD support cannot be translated by biological improvement, since the unloaded heart is by no means a normal heart. Intuitively, one can speculate that harmful changes within the myocardium, including atrophy and increased fibrosis, are likely to be extremely important in terms of allowing the heart to recover. The quest for seeking the answers to myocardial recovery extends well beyond simple curiosity about the biology of HF. As controversy remains on the long-term effects of perfusion with reduced pulsatility, speed modulation of the pump might be beneficial to restore in part vascular pulsatility. When considering that cf-LVADs provide comparable or improved survival rates, quality of life and adverse event rates compared to pf-LVAD, combined with improved device reliability, ease of implantation and ease of surgery, there is no discussion of returning to the pf-LVAD mode. However, ongoing work into incorporated pulsatility in any form of mechanical support system, may in the end result in improved myocardial recovery.