Elsevier

JACC: Heart Failure

Volume 9, Issue 2, February 2021, Pages 137-145
JACC: Heart Failure

Focus Issue: Mechanistic Insights and Drug Therapy
Original Research
Reverse Cardiac Remodeling Following Initiation of Sacubitril/Valsartan in Patients With Heart Failure With and Without Diabetes

https://doi.org/10.1016/j.jchf.2020.09.014Get rights and content
Under a Creative Commons license
open access

Abstract

Objective

This study sought to determine whether patients with heart failure and reduced ejection fraction (HFrEF) with type 2 diabetes mellitus (T2DM) have similar reverse cardiac remodeling with sacubitril/valsartan as patients without T2DM.

Background

Sacubitril/valsartan promotes reverse cardiac remodeling and improves outcomes in patients with HFrEF. Patients with HFrEF with T2DM have worse prognosis than those without T2DM.

Methods

In this post hoc analysis of PROVE-HF (Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure), we examined changes in N-terminal pro–b-type natriuretic peptide (NT-proBNP), measures of cardiac remodeling, and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) scores from baseline to 12 months following initiation of sacubitril/valsartan between patients with HFrEF with and without T2DM. Using latent growth curve modeling, we evaluated the longitudinal association between changes in NT-proBNP, left ventricular ejection fraction, and KCCQ-OS.

Results

Among 794 patients enrolled, 361 (45.5%) had T2DM. NT-proBNP concentrations were modestly higher at baseline among patients with T2DM but were reduced after initiation of sacubitril/valsartan. Cross-sectional improvement was observed in left ventricular ejection fraction (T2DM: 28.3% at baseline and 37% at 12 months vs. non-T2DM: 28.1% at baseline and 38.3% at 12 months) and KCCQ-OS (T2DM: 71 at baseline and 83 at 12 months vs. non-T2DM: 76 at baseline and 88 at 12 months). Similar changes were also observed for other echocardiographic measures. In longitudinal analyses, the average NT-proBNP change was similar in patients with T2DM (–5.6% vs. –7.1% per 90-day interval; p = 0.64), whereas improvements in KCCQ-OS scores were slightly smaller (2.1 vs. 3.46 per 90-day interval; p = 0.07).

Conclusions

Sacubitril/valsartan favorably affects natriuretic peptide levels, reverse cardiac remodeling, and health status in patients with HFrEF with and without T2DM. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183)

Key Words

cardiac remodeling
diabetes
heart failure
NT-proBNP
sacubitril/valsartan

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
ARB
angiotensin receptor blocker
ARNI
angiotensin receptor blocker/neprilysin inhibitor
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
ICD
implantable cardioverter-defibrillator
KCCQ
Kansas City Cardiomyopathy Questionnaire
LV
left ventricular
LVEDVI
LV end-diastolic volume index
LVEF
left ventricular ejection fraction
LVESVI
LV end-systolic volume index
NT-proBNP
N-terminal pro–B-type natriuretic peptide
SGLT-2
sodium glucose co-transporter-2
T2DM
type 2 diabetes mellitus

Cited by (0)

Barry Greenberg, MD, served as Guest Editor for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.