The Effects of Diminished Pulsatility in Long-Term Continuous-Flow Left Ventricular Assist Device Recipients

Continuous flow left ventricular assist devices (CF-LVADs) are used as mechanical support to improve or replace the functions of the failing heart. However, little is known of the long-term effects of the non-physiological, low-pulsatile blood flow of CF-LVADs. To address some of the potential effects that CF-LVADs have on the cardiovascular system, we conducted a set of studies to examine the levels of inflammation in CF-LVAD recipients and compare them to those of healthy controls and to heart failure patients who were candidates for CF-LVAD support. We found that inflammatory markers were generally elevated in CF-LVAD recipients. Importantly, several of these inflammatory markers were significantly higher in the CF-LVAD group compared to both the heart failure and healthy control groups. In another study we conducted, we found that despite elevated levels of the inflammatory marker C-reactive protein (CRP), which tends to inhibit cGMP production, the levels of cGMP were significantly elevated in CF-LVAD recipients. We found that cGMP levels were significantly associated with gastrointestinal (GI) bleeding but not bleeding in general. This increase in cGMP may be related to a higher incidence of GI bleeding in CF-LVAD recipients as cGMP impairs platelet aggregation. Additionally, we observed that following CF-LVAD implantation, both exercise capacity and chronotropic responses continued to be impaired. The novel finding of the study is that high levels of inflammation were significantly associated with impaired exercise capacity. The mechanisms by which inflammation contributes to impaired exercise capacity in patients supported with CF-LVADs should be further investigated. In a longitudinal study, we documented increased levels of chemokines and cytokines at 3, 6, and 9 months post-CF-LVAD implantation compared to those of healthy controls, suggesting that the high levels of inflammation in CF-LVAD recipients may be the result of both the heart failure condition prior to implantation and the long-term device support. We conclude that since elevated levels of inflammation may be detrimental to CF-LVAD recipients, further studies should investigate the source of inflammation and the clinical outcomes of anti-inflammatory treatment in these patients.Ph