Impact of sacubitril/valsartan and gliflozins on cardiac resynchronization therapy response in ischemic and non-ischemic heart failure patients

Aims: Angiotensin receptor-neprilysin inhibitor (ARNi) and sodium-glucose co-transporter 2 inhibitor (SGLT2i) improve outcomes in heart failure with reduced ejection fraction (HFrEF) patients, however their effects in cardiac resynchronization therapy (CRT) recipients have been scarcely explored. This study investigated whether ARNi and SGLT2i 1) improve the rate of clinical and echocardiographic CRT response and 2) have different impact based on the ischemic or non-ischemic etiology. Methods: HFrEF patients referred for CRT implant were grouped in no treatment (group 1), only ARNi (group 2) and both ARNi and SGLT2i (group 3). Clinical and echocardiographic response were evaluated at 12 months. Results: A total of 178 patients were enrolled. At one-year follow-up, 74.4% patients in group 2 (p = 0.031) and 88.9% in group 3 (p = 0.014) were classified as clinical responders vs 54.5% in the no treatments group. In multivariable analysis, ARNi/SGLT2i use was an independent predictor of CRT response (OR 3.72; CI 95%, 1.40-10.98; p = 0.011), confirmed in both groups 2 and 3. At 12 months, the median Delta LVEF increase was 6% and 8.5% in groups 2 and 3 respectively, vs 4.5% in group 1 (p = 0.042 and p = 0.029) with significantly more echocardiographic responders in groups 2 and 3 (76% and 78% vs 50%, p = 0.003 and p = 0.036). Significantly more ischemic HFrEF patients than non-ischemic were considered clinical and echocardiographic responders in the treatment groups. Conclusions: ARNi alone or in combination with SGLT2i in CRT patients improves the clinical and echocardiographic response at 12 months. Ischemic patients seem to benefit more from these treatments.