Association between measures of cardiac remodeling after ARNI and outcomes in HFrEF
Reverse Cardiac Remodeling and Outcome After Initiation of Sacubitril/Valsartan
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 , 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 .
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).
- Event rates from month 6 to 12 were lower in patients with above-average reduction for NT-proBNP and LVESVi, intermediate for those with above-average reduction for at least 1 measure and events were highest in those with at/below-average reduction of NT-proBNP and LVESVi.
- After adjustment for demographics, outcomes were significantly higher for patients at/below-average linear slopes for both measures compared to patients above-average linear slopes for both measures (OD 2.03, 95%CI:1.25-3.30, P<0.001).
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.