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Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices.

ABSTRACT: Importance:Left ventricular assist devices (LVADs) improve outcomes in patients with advanced heart failure, but little is known about the role of neurohormonal blockade (NHB) in treating these patients. Objective:To analyze the association between NHB blockade and outcomes in patients with LVADs. Design, Setting, and Participants:This retrospective cohort analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) included patients from more than 170 centers across the United States and Canada with continuous flow LVADs from 2008 to 2016 who were alive with the device in place at 6 months after implant. The data were analyzed between February and November 2019. Exposures:Patients were stratified based on exposure to NHB and represented all permutations of the following drug classes: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, ?-blockers, and mineralocorticoid antagonists. Main Outcomes and Measures:The outcomes of interest were survival at 4 years and quality of life at 2 years based on Kansas City Cardiomyopathy Questionnaire scores and a 6-minute walk test. Results:A total of 12?144 patients in INTERMACS met inclusion criteria, of whom 2526 (20.8% ) were women, 8088 (66.6%) were white, 3024 (24.9%) were African American, and 753 (6.2%) were Hispanic; the mean (SD) age was 56.8 (12.9) years. Of these, 10?419 (85.8%) were receiving NHB. Those receiving any NHB medication at 6 months had a better survival rate at 4 years compared with patients not receiving NHB (56.0%; 95% CI, 54.5%-57.5% vs 43.9%; 95% CI, 40.5%-47.7%). After sensitivity analyses with an adjusted model, this trend persisted with patients receiving triple therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, ?-blocker, and mineralocorticoid antagonist having the lowest hazard of death compared with patients in the other groups (hazard ratio, 0.34; 95% CI, 0.28-0.41). Compared with patients not receiving NHB, use of NHB was associated with a higher Kansas City Cardiomyopathy Questionnaire score (66.6; bootstrapped 95% CI, 65.8-67.3 vs 63.0; bootstrapped 95% CI, 60.1-65.8; P?=?.02) and a 6-minute walk test (1103 ft; bootstrapped 95% CI, 1084-1123 ft vs 987 ft; bootstrapped 95% CI, 913-1060 ft; P?

SUBMITTER: McCullough M

PROVIDER: S-EPMC6865330 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices.

McCullough Megan M Caraballo Cesar C Ravindra Neal G NG Miller P Elliott PE Mezzacappa Catherine C Levin Andrew A Gruen Jadry J Rodwin Benjamin B Reinhardt Samuel S van Dijk David D Ali Ayyaz A Ahmad Tariq T Desai Nihar R NR

JAMA cardiology 20200201 2

<h4>Importance</h4>Left ventricular assist devices (LVADs) improve outcomes in patients with advanced heart failure, but little is known about the role of neurohormonal blockade (NHB) in treating these patients.<h4>Objective</h4>To analyze the association between NHB blockade and outcomes in patients with LVADs.<h4>Design, setting, and participants</h4>This retrospective cohort analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) included patients from m ...[more]

PMID: 31738366

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Project description:BackgroundContinuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation.MethodsTwelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30o and 60o. Heart rate and BP were monitored during cardiopulmonary exercise testing.ResultsCardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing.ConclusionsAmong patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.

Project description:BackgroundThe assessment of hemodynamics in patients supported with left ventricular assist devices (LVADs) is often challenging. Physical examination maneuvers correlate poorly with true hemodynamics. We assessed the value of novel transthoracic echocardiography (TTE)-derived variables to reliably predict hemodynamics in patients supported with LVAD.Methods and resultsA total of 102 Doppler-TTE images of the LVAD outflow cannula were obtained during simultaneous invasive right heart catheterization (RHC) in 30 patients supported with continuous-flow LVADs (22 HMII, 8 HVAD) either during routine RHC or during invasive ramp testing. Properties of the Doppler signal though the outflow cannula were measured at each ramp stage (RS), including the systolic slope (SS), diastolic slope (DS), and velocity time integral (VTI). Hemodynamic variables were concurrently recorded, including Doppler opening pressure (MAP), heart rate (HR), right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP), Fick cardiac output (CO) and systemic vascular resistance (SVR). Univariate and multivariate regression analyses were used to explore the dependence of PCWP, CO, and SVR on DS, SS, VTI, MAP, HR, and RS. Multivariate linear regression analysis revealed significant contributions of DS on PCWP (PCWPpred = 0.164DS + 4.959; R = 0.68). Receiver operating characteristic (ROC) curve analysis revealed that PCWPpred could predict an elevated PCWP ≥18 mm Hg with a sensitivity (Sn) of 94% and specificity (Sp) of 85% (area under the ROC curve 0.88). CO could be predicted by RS, VTI, and HR (COpred = 0.017VTI + 0.016HR + 0.12RS + 2.042; R = 0.61). COpred could predict CO ≤4.5 L/min with Sn 73% and Sp 79% (AUC 0.81). SVR could be predicted by MAP, VTI, and HR (SVRpred = 15.44MAP - 5.453VTI - 6.349HR + 856.15; R = 0.84) with Sn 84% and Sp 79% (AUC 0.91) to predict SVR ≥1200 dyn-s/cm5.ConclusionsDoppler-TTE variables derived from the LVAD outflow cannula can reliably predict PCWP, CO, and SVR in patients supported with LVADs and may mitigate the need for invasive testing.

Dataset Information

Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices.

Publications

Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices.

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