Benefits of Neurohormonal Therapy in Patients With Continuous-Flow Left Ventricular Assist Devices

Abstract

Left ventricular assist devices (LVADs) have dramatically improved short-term outcomes among patients with advanced heart failure. While neurohormonal blockade (NHB) is the cornerstone of treatment for patients with heart failure with reduced ejection fraction, its effect after LVAD placement has not been established. We reviewed medical records of 307 patients who underwent primary LVAD implantation from January 2006 to September 2015 at two institutions in the United States. Patients were followed for at least 2 years post-LVAD implantation or until explantation, heart transplantation, or death. Cox regression analysis stratifying on center was used to assess associations with mortality. Neurohormonal blockade use was treated as a time-dependent predictor. Stepwise selection indicated treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) (hazard ratio [HR] = 0.53 [0.30–0.95], p = 0.03), age at the time of implantation (HR = 1.28 [1.05–1.56] per decade, p = 0.02), length of stay postimplantation (HR = 1.16 [1.11–1.21] per week, p < 0.01) and INTERMACS profile of 1 or 2 (HR = 1.86 [1.17–2.97], p < 0.01) were independent predictors of mortality. In this large, retrospective study, treatment with ACEIs or ARBs was an independent factor associated with decreased mortality post-LVAD placement.

Implications of Heart Rate in Patients with Left Ventricular Assist Devices

“…Given the promising impact of beta-blocker therapy in improving hemodynamics and facilitating reverse remodeling in LVAD patients, appropriate HR modulation might reduce potential energy and improve diastolic filling. 7) Furthermore, higher HR decreases diastolic filling, 6) which is required to maintain preload also in LVAD patients. Applying the benefits of chronotropic modulation of beta-blockade in HFrEF patients, a lower HR might be beneficial in reverse remodeling also in LVAD patients.…”

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

“…The validity of the assumed beneficial effect of blocking the RAAS with ARBs and ACE inhibitors is enhanced by the 24-month reported survival rate of the study of 73%, which is in agreement with the survival rate of the INTERMACS report. 76,77 The role of RAAS modulation in achieving myocardial recovery may be substantial. ACEi have been found to decrease AngII levels and cross-linked collagen in myocardial tissue.…”

“…75 Moreover, in a noninvasive study, conducted by Yousefzai et al, ACE inhibitors and ARBs were the only regimens that significantly reduced the risk of mortality in LVAD patients almost by half (47%). 76 The study population consisted of 307 LVAD patients from two large centers in the United States and the follow-up period lasted 24 months. The validity of the assumed beneficial effect of blocking the RAAS with ARBs and ACE inhibitors is enhanced by the 24-month reported survival rate of the study of 73%, which is in agreement with the survival rate of the INTERMACS report.…”

“…The validity of the assumed beneficial effect of blocking the RAAS with ARBs and ACE inhibitors is enhanced by the 24-month reported survival rate of the study of 73%, which is in agreement with the survival rate of the INTERMACS report. 76,77…”

Sacubitril/valsartan in patients post‐left ventricular assist device implant: a single‐centre case series

“…This was accompanied by an overall decline in the mean total daily doses of non‐potassium‐sparing diuretics, aldosterone antagonists and other oral vasodilators from baseline after sacubitril/valsartan initiation and optimization ( Table 1 ): (i) furosemide oral equivalents decreased from 220.0 ± 167.9 mg to 120.0 ± 94.3 mg, (ii) spironolactone equivalents decreased from 26.3 ± 9.2 mg to 20.6 ± 15.1 mg, and (iii) all oral vasodilators were tapered as to be expected to 0 mg. Beta‐blockers and digoxin doses had a slight but non‐statistically significant reduction. Neuro‐hormonal blockade with ACEI/ARB use is associated with a lower mortality risk post‐CF‐LVAD [hazard ratio ((HR) 0.50, P = 0.01], 7 and a reduced risk of major gastrointestinal bleeding (GIB) in a dose‐dependent manner (HR 0.43, P = 0.04) and from arteriovenous malformation (HR 0.37, P = 0.017) 8 . In our study cohort, one patient had GIB in the setting of supra‐therapeutic international normalized ratio.…”