Effect of angiotensin receptor neprilysin inhibitors on left atrial remodeling and prognosis in heart failure

Aims: The angiotensin receptor–neprilysin inhibitor (ARNI), sacubitril/valsartan, confers additional protective effects compared with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) in terms of reversed left ventricular (LV) remodelling and improves the prognosis of patients with heart failure (HF). However, few studies have examined the effects of ARNI on the left atrium. Accordingly, this study compared the effects of ARNI and ACEI/ARB on left atrial (LA) remodelling in heart failure with reduced ejection fraction (HFrEF). Methods and results: This was a single-centre retrospective study of patients with HFrEF hospitalized at the First Affiliated Hospital of Dalian Medical University between 26 February 2016 and 8 July 2020. Patients were classified into ARNI and ACEI/ARB groups and further subgroups based on the left atrial volume index (LAVI): mildly abnormal (29 mL/m² ≤ LAVI < 34 mL/m²), moderately abnormal (34 mL/m² ≤ LAVI < 40 mL/m²), and severely abnormal (LAVI ≥ 40 mL/m²). The primary endpoint was changes in LA parameters by echocardiography. The secondary endpoint was all-cause mortality. A total of 336 patients (mean age: 64.11 ± 12.86, 30.06% female) were included. Except those lost to follow-up, 274 HFrEF patients remained, with 144 cases in the ARNI group and 130 cases in the ACEI/ARB group. Greater reductions from baseline were seen with ARNI in LA diameter (LAD) (P = 0.013, t-test), superior and LA superior–inferior diameter (LASID) (P < 0.0001), LA transverse diameter (LATD) (P < 0.0001), LA volume (LAV) (P < 0.0001), LAVI (P < 0.0001), and LA sphericity index (LASI) (P < 0.0001). Over a mean follow-up of 19.40 months, 97 patients (67.3%) in the ARNI group and 29 patients (22.3%) in the ACEI/ARB group showed LA reverse remodelling (LARR). Kaplan–Meier analysis showed significantly lower overall mortality in the ARNI group compared with the ACEI/ARB group (P = 0.048, log-rank test). The mildly abnormal LAVI group of ARNI patients showed a reduction in mortality compared with ACEI/ARB patients (P = 0.044). However, no significant difference was observed for the moderately abnormal (P = 0.571) or severely abnormal LAVI groups (P = 0.609), suggesting that early initiation of ARNI was associated with a better prognosis. Conclusions: In this proof-of-concept study, ARNI use showed greater effects on LARR and was associated with a better prognosis compared with ACEI/ARB use in HFrEF. Early initiation of ARNI in the HF disease process may produce greater benefit, but this needs to be confirmed in future studies.