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.
Acute postinfarct ventricular septal defect (VSD) is associated with high mortality due to a combination of cardiogenic shock and a complex repair in recently infarcted fragile myocardium.1 Although the Impella heart pump is established as support for cardiogenic shock, it is relatively contraindicated in postinfarct VSD because of potential right-to-left shunt or stroke due to VSD tissue–related embolus. On autopsy, early repair is technically difficult due to tissue friability and as a result, 38% of surgically repaired patients have evidence of recurrent interventricular septal rupture.2 Delayed surgical repair (>7 days) is associated with superior survival—54% after 7 days versus 18% prior—but hemodynamic instability may prevent delay.3 Case reports have shown successful early left ventricular unloading with Impella patients with acute postinfarct VSD before surgical repair.4,5 We discuss our algorithm for pre-repair Impella support in which we stratify pre-repair support based on the Qp/Qs ratio. For VSD with Qp/Qs >2.5, we use a preoperative Impella heart pump and have not demonstrated reversal in the left-to-right shunt on echocardiography and/or stroke. Our findings are consistent with theoretical models of unloading as demonstrated by shifts in pressure–volume loops.6
Background
The clinical characteristics of mTOR (mammalian target of rapamycin) inhibitors use in heart transplant recipients and their outcomes have not been well described.
Methods and Results
We compared patients who received mTOR inhibitors within the first 2 years after heart transplantation to patients who did not by inquiring the United Network for Organ Sharing (UNOS) database between 2010 and 2018. The primary end point was all‐cause mortality with retransplantation as a competing event. Rejection, malignancy, hospitalization for infection, and renal transplantation were secondary end points. There were 1619 (9%) and 15 686 (81%) mTOR inhibitors+ and mTOR inhibitors− patients, respectively. Body mass index, induction, cardiac allograft vasculopathy, calculated panel reactive antibody, and fewer days in 1A status were independently associated with mTOR inhibitors+ status. Over a follow‐up of 10.4 years, there was no difference in all‐cause mortality after adjusting for donor and recipient characteristics (adjusted subdistribution hazard ratio, 1.03 [0.90–1.19];
P
=0.66). mTOR inhibitors+ were independently associated with increased risk for rejection (odds ratio [OR], 1.43 [1.11–1.83];
P
=0.005) and basal skin cancer (OR, 1.35 [1.19–1.51];
P
=0.012) but not for infection or renal transplantation.
Conclusions
mTOR inhibitors are used in <10% patients in the first 2 years after heart transplantation and are noninferior to contemporary immunosuppression regimens in terms of all‐cause mortality, infection, malignancy, or renal transplantation. They are associated with risk for rejection.
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