Right ventricular strain predicts outcome in patients receiving sacubitril/valsartan: A sub-analysis of DISCOVER-ARNI

Aims: Angiotensin receptor/neprilysin inhibitors (ARNI) have emerged as a pivotal medical treatment considerably improving the clinical outcome of patients with heart failure and reduced ejection fraction (HFrEF). Identifying individuals who stand to benefit the most from ARNI could markedly enhance patient management strategies. The aim of this sub-analysis of DISCOVER-ARNI register was to evaluate the prospective prognostic significance of speckle tracking echocardiography (STE) parameters in patients undergoing ARNI therapy. Methods and results: DISCOVER-ARNI multicentre Italian register retrospectively enrolled 341 patients with HFrEF referred for treatment with ARNI. These patients underwent clinical, biohumuoral, and echocardiographic assessment at baseline. Subsequently, among those with available right ventricular STE data, a prospective long-term follow-up was conducted by telephone interview or on-site visits. The primary endpoint encompassed a composite of outcomes, including all-cause or cardiovascular mortality, heart failure hospitalization, heart transplantation, and left ventricular assist device (LVAD) implantation. Overall, 136 HFrEF patients were included in this sub-analysis (mean age 65 ± 10 years, 82% male). The mean follow-up was 40 ± 18 months, during which 32 patients reached the primary endpoint (14 deaths of which 10 due to cardiovascular reasons, 22 hospitalization, 3 heart transplantation, 1 LVAD implantation). Baseline assessment revealed that patients with events had higher LV volumes and EF (LV end-diastolic volume 212 ± 65 vs.174 ± 57 mL, P = 0.002; LV end-systolic volume 156 ± 52 vs. 122 ± 49 mL, P = 0.001; LV EF = 26 ± 5 vs. 29 ± 5 mL, P = 0.006, respectively), lower but preserved tricuspid annular plane systolic excursion (TAPSE, 17 ± 3 vs.19 ± 3, P = 0.008), and higher systolic pulmonary artery pressures (38 ± 11 vs. 31 ± 8 mmHg, P = 0.001) compared to those who did not experience events. LV, left atrial (LA), and free wall right ventricular longitudinal strain (fwRVLS) were reduced in patients with events (−7 ± 2 vs. −8 ± 2%, P = 0.002; 11 ± 3 vs. 15 ± 7%, P = 0.001 and −15 ± 5 vs. −22 ± 5%, P = 0.007, respectively). Employing Cox proportional hazard model including LVEF, TAPSE, RVFAC, LV strain, LA strain, and fwRVLS, the latest emerged as the sole independent predictor of the combined endpoint (hazard ratio = 1.15 [1.05;1.26], P = 0.002). Receiver operating characteristic (ROC) curves determined that fwRVLS = −20% was the optimal cut-off for predicting the combined endpoint (area under curve [AUC] = 0.70). This threshold was used for constructing Kaplan–Meier survival curves, demonstrating effective risk stratification of fwRVLS over long-term follow-up for the primary endpoint. Conclusions: fwRVLS by STE holds promise as a valuable parameter to assess response to ARNI therapy in terms of overall survival, heart failure hospitalizations, heart transplantation, or LVAD implantation.