The effectiveness of ARNI medication in patients, non-responder to cardiac resynchronization therapy

Abstract

Introduction Almost 30% of patients are non-responders to cardiac resynchronization therapy (CRT) with no improvement of heart failure (HF) symptoms and left ventricular ejection fraction (LVEF). Angiotensin Receptor Neprilysin Inhibitor (ARNI), a novel class of medication resulted in a significant improvement in HF with reduced ejection fraction (HFrEF) in recent trials. No data has been reported on the clinical effectiveness of ARNI in the specific HF patient cohort of CRT non-responders (CRT-NR). Objective Herein, we compared the efficacy of ARNI medication in a general HF patient population and in CRT-NR patients. Method CRT-NR patients on ARNI therapy initiated at least 6 months after CRT implantation in years 2019–2021 were enrolled. Criterium for CRT-NR was a no, or less than 10% improvement in LVEF measured with echocardiography 6 months post-implantation. HF patients on ARNI therapy from our HF Clinic were used as controls. Changes in LVEF, in NYHA functional class and in the level of NT-proBNP were compared before ARNI therapy initiation and 6 months thereafter in both groups. Results 70 patients (age: 66,03±9.06 years, 9 women) were enrolled in the CRT-NR and 135 patients (age 62,36±11.26 years; 31 women) in the control group. LVEF increased from 25,25±5.70% to 29,47±6.73% (p<0.001), NYHA class decreased from 2,74±0.55 to 2.03±0.68 (p<0.001) and NT-proBNP from 3884.21±2503.95 to 2676,16±1745.94 (p<0.001) in CRT-NR patients after a 6-month treatment with ARNI. Similar improvement was demonstrated in all parameters in the control group: LVEF increased from 26,64±6.47% to 29,91±6.64% (p<0,001), NYHA class decreased from 2,97±0.54 to 2,18±0.58% (p<0,001) and NT-proBNP from 5355,17±1731.71 to 2062,66±1919.07 (p<0,001). During a mean follow-up of 20,55±11,36 months mortality rates were 17,14% in the CRT-NR group, and 18,51% in the control group. Conclusion ARNI therapy resulted in significant improvement in functional class, LVEF and HF biomarker level in CRT-NR patients, similarly to what was observed in a general HF patient cohort with no CRT. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project no. TKP2021-EGA-18 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme.