Physicians' Academy for Cardiovascular Education

Association between measures of cardiac remodeling after ARNI and outcomes in HFrEF

Reverse Cardiac Remodeling and Outcome After Initiation of Sacubitril/Valsartan

Literature - Januzzi JL Jr, Camacho, A, Piña IL et al. - Circ Heart Fail. 2020;. DOI:10.1161/CIRCHEARTFAILURE.119.006946

Introduction and methods

Treatment with sacubitril/valsartan has resulted in improved outcomes in HFrEF patients. Although therapies that improve prognosis in HFrEF usually result in reverse cardiac remodeling [1], mechanisms of benefit by sacubitril/valsartan remain elusive. The PROVE-HF trial demonstrated that treatment with sacubitril/valsartan resulted in significant reduction of NT-proBNP and that both magnitude and speed of NT-proBNP reduction were associated with reverse modeling [2].

This analysis of PROVE-HF examined whether achievement of an above-average rate of change in NT-proBNP at 3 months and LV end-systolic volume index (LVESVi), which is a key index of remodeling, at 6 months was associated with outcomes between 6 and 12 months.

Participants without events at 6 months and with echocardiograms at baseline and 6 months were included (n=638). Outcomes of interest were HF hospitalization and death. Patients were grouped based on extent of change in each measure (above vs. at/below 95% CI lower bound for the linear slope).

Main results


Achieving at/below reduction of measures of reverse cardiac remodeling with sacubitril/valsartan was associated with increased risk of outcomes in HFrEF patients compared to those patients who achieved above-average reduction of measures. These results indicate that more rapid and robust reduction of NT-proBNP and LVESVi might identify patients with reverse cardiac remodeling and thus more likely to benefit from therapy with sacubitril/valsartan.


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