Physicians' Academy for Cardiovascular Education

ARNI-induced NT-proBNP changes associated with cardiac remodeling changes in HFrEF

Association of Change in N-Terminal Pro–B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction

Literature - Januzzi JL, Prescott MF, Butler J et al. - JAMA. 2019;322(11):1085-1095.

Introduction and methods

Cardiac remodeling during progression of heart failure with reduced ejection fraction (HFrEF) can lead to reduced left ventricular ejection fractions (LVEF) and increased left ventricular (LV) volumes [1-3]. Myocardial remodeling, associated with increased CV risk, is an important target of HF therapies [4]. Previous studies have revealed that a reduction in NT-proBNP concentration correlates with reverse LV remodeling [5,6]. Treatment with the angiotensin receptor/neprilysin inhibitor (ARNI) sacubitril/valsartan has been associated with decreased NT-proBNP concentrations [7]. However, the effect of sacubitril/valsartan on cardiac remodeling has remained unclear.

This study examined the correlation between sacubitril/valsartan induced NT-proBNP concentration changes and long-term changes in measures of cardiac volume and function in HFrEF patients.

The Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) trial was a phase 4, 12-month, open-label, single-group study of 654 patients with HFrEF started on sacubitril/valsartan, conducted in the US. NT-proBNP concentrations were measured in blood samples which were obtained at baseline, every 2 weeks until day 60 and at 3, 6, 9, and 12 months after the start of the study. Echocardiography measurements were performed at baseline, 6 months and 12 months. Measurements included LVEF, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), left atrial volume index (LAVI) and the ratio of early transmitral Doppler velocity/early diastolic annular velocity (E/e').

Primary endpoint was the correlation between changes in the concentration of NT-proBNP and cardiac remodeling, assessed by change in LVEDVI, LVESVI, LVEF, LAVI and E/e’ from baseline to 12 months.

Main results


In this study of HFrEF patients, initiation of sacubitril/valsartan led to reduced NT-proBNP concentrations and was associated with an increase in LVEF and decrease in LVEDVI, LVESVI, LAVI and E/e′ after 12 months. These improvements were also observed after 6 months, albeit less pronounced. These results may help in understanding the mechanisms that result in the effects of sacubitril/valsartan in patients with HFrEF.


Show references

Find this article online at JAMA

Share this page with your colleagues and friends: