ARNI Pre-Operative Use and Vasoplegic Syndrome in Patients Undergoing Heart Transplantation or Left Ventricular Assist Device Surgery

Abstract

Background: Vasoplegic syndrome after orthotopic heart transplantation (OHT) or left ventricular assist device (LVAD) implantation is a rare but highly lethal syndrome with complex etiologies. The objective of this study was to assess if the preoperative use of sacubitril-valsartan combination is associated with an increased vasoplegic syndrome (VS) frequency after OHT or LVAD implantation and its relationship with 30-day mortality. Methods: A retrospective review of perioperative data, between January 2016 and December 2017, from 73 consecutive OHT and LVAD surgery adult patients at our institution was performed. VS was defined as normal cardiac output with persistent low systemic resistance requiring a norepinephrine intravenous perfusion > 0.5 µg/kg/min and the absence of sepsis or hemorrhagic shock within 48 h after surgery. Patients were all followed-up for adverse events and all-cause mortality at 30 days. Results: In our cohort of 73 patients (median age 51.7 years, 65% male patients), 25 (34%) patients developed VS. Twenty-two (30.1%) patients were on ARNI at the time of surgery, 31 (42.5%) were on other RAS blockers, 12 (16.4%) were on norepinephrine and 8 (11%) had no pre-operative drug. The pre-operative use of any vasoactive agent, was not significantly associated with VS (OR = 1.36; IC95% [0.78; 2.35]; p = 0.38). The pre-operative use of an ARNI compared to all other groups was not significantly associated with VS (OR = 2.0; IC95% [0.71; 5.62]; p = 0.19). The pre-operative use of an ARNI compared to other RAS blockers was also not significantly associated with VS (OR = 1.25; IC95% [0.37; 4.26]; p = 0.72). At 30 days, 18 (24.7%) patients had died. The pre-operative treatment with ARNI, or other RAS inhibitors was associated with a significantly lower rate of death compared to the absence of treatment (HR = 0.11; IC95% [0.02; 0.55]; p = 0.009 for ARNI and HR = 0.20; IC95% [0.06; 0.69]; p = 0.011 for other RASi). Conclusions: Preoperative use of sacubitril-valsartan was not significantly associated with development of vasoplegic syndrome in patients undergoing OHT or LVAD surgery. Furthermore, our data suggests a significant 30-day survival benefit with efficient renin-angiotensin blockade before surgery.

Predictors and Impact of Prolonged Vasoplegia After Continuous-Flow Left Ventricular Assist Device Implantation

“…Moreover, although we had no information on the use of angiotensin receptor-neprilysin inhibitors in this patient cohort, others have not found an association between preoperative angiotensin receptor-neprilysin inhibitor use and postoperative vasoplegia after CF-LVAD implantation. 25 …”

Severe Refractory Vasoplegic Shock Syndrome after OPCABG Successfully Treated with Hydroxycobalamin: A Case Report and Review of the Literature

“…To our knowledge, to date, this is the first case reporting the possible association of sacubitril/valsartan and VSS in OPCABG. Previous data regarding the use of sacubitril/valsartan and VSS after cardiac surgery are controversial [ 11 ], although some case reports have described profound vasoplegia after CPB [ 12 ]. Haider et al [ 11 ] reported the preoperative use of sacubitril-valsartan in patients undergoing heart transplantation or left ventricular assist device (LVAD) surgery and found that the angiotensin receptor neprilysin inhibitor was not significantly associated with the development of vasoplegic syndrome.…”

“…Previous data regarding the use of sacubitril/valsartan and VSS after cardiac surgery are controversial [ 11 ], although some case reports have described profound vasoplegia after CPB [ 12 ]. Haider et al [ 11 ] reported the preoperative use of sacubitril-valsartan in patients undergoing heart transplantation or left ventricular assist device (LVAD) surgery and found that the angiotensin receptor neprilysin inhibitor was not significantly associated with the development of vasoplegic syndrome. Similar results were also described by Domínguez et al, in their multicentric study, in which the incidence of vasoplegic syndrome associated with the preoperative use of sacubitril-valsartan in a cohort of 96 patients undergoing heart transplant was 15.6% [ 13 ].…”

Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure

“…A different strategy might be the pre-operative use of sacubitril–valsartan (ARNI: angiotensin receptor antagonist and neprilysin inhibitor) to reduce post-operative mortality in patients undergoing LVAD implantation. Heder et al reported an association with better survival outcomes after cardiac surgery (LVAD or HTx) [ 85 ]. According to Kaplan and Meier’s analysis, the lowest rate of death was observed in ARNI (13.6%), then ACEi, ARB (19.4%), and, lastly, the no-vasoactive group, with the worst 30-day survival rate (62.5%; p = 0.043).…”