The role of renin-angiotensin system in patients with left ventricular assist devices

Abstract

End-stage heart failure is a condition in which the up-regulation of the systemic and local renin-angiotensin-aldosterone system (RAAS) leads to end-organ damage and is largely irreversible despite optimal medication. Left ventricular assist devices (LVADs) can downregulate RAAS activation by unloading the left ventricle and increasing the cardiac output translating into a better end-organ perfusion improving survival. However, the absence of pulsatility brought about by continuous-flow devices may variably trigger RAAS activation depending on left ventricular (LV) intrinsic contractility, the design and speed of the pump device. Moreover, the concept of myocardial recovery is being tested in clinical trials and in this setting LVAD support combined with intense RAAS inhibition can promote recovery and ensure maintenance of LV function after explantation. Blood pressure control on LVAD recipients is key to avoiding complications as gastrointestinal bleeding, pump thrombosis and stroke. Furthermore, emerging data highlight the role of RAAS antagonists as prevention of arteriovenous malformations that lead to gastrointestinal bleeds. Future studies should focus on the role of angiotensin receptor inhibitors in preventing myocardial fibrosis in patients with LVADs and examine in greater details the target blood pressure for these patients.

Changes in renin‐angiotensin‐aldosterone system during cardiac remodeling after mitral valvuloplasty in dogs

“…In humans, there is continued tissue RAAS activation after various surgical interventions, 22 , 23 with some reports concluding that pharmacological blockade of RAAS after cardiovascular surgeries is prognostically beneficial. 9 , 16 , 17 , 24 , 25 , 26 Since the current study focused on the systemic instead of local components of RAAS, results of tissue RAAS evaluation could be different but were not evaluated. We do currently believe that no further recovery in the cardiovascular system is required for our dogs.…”

Ventricular assist device–promoted recovery and technical aspects of explant

“…Indeed, risk reduction for stroke, pump thrombosis, and gastrointestinal bleeding from arteriovenous malformation have been described by renin-angiotensin-aldosterone inhibition on LVAD. 23 Currently, the relevance of the individually suggested recovery mechanisms is not clear. An interplay of many mechanisms was suggested to cause both remodeling and its reversal with or without VAD support.…”

“…A detailed description has been subject of several reviews. 17 , 22 , 23 , 24 In addition to strictly cardiac effects, it has been shown that VAD support decreases inflammation-mediated myocardial injury by reducing the level of plasma cytokines and production of autoantibodies against cardiac proteins level. 24 Furthermore, it has been shown that VAD support itself can downregulate the pathologically upregulated renin–angiotensin–aldosterone and sympathetic nervous systems.…”

“… 24 Furthermore, it has been shown that VAD support itself can downregulate the pathologically upregulated renin–angiotensin–aldosterone and sympathetic nervous systems. 23 Continuing guideline-directed medical therapy (GDMT) for heart failure should therefore be complimentary to the specific effects of mechanical unloading. Indeed, risk reduction for stroke, pump thrombosis, and gastrointestinal bleeding from arteriovenous malformation have been described by renin–angiotensin–aldosterone inhibition on LVAD.…”

“…Indeed, risk reduction for stroke, pump thrombosis, and gastrointestinal bleeding from arteriovenous malformation have been described by renin–angiotensin–aldosterone inhibition on LVAD. 23

Figure 1 Mechanisms of ventricular assist device–promoted functional cardiac recovery. Modified after Miyagawa and colleaegues 17 and Gallo and colleagues.

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