Background Cardiac resynchronisation therapy (CRT) fails to improve echocardiographic parameters and outcome in 20–40% of heart failure (HF) patients with reduced ejection fraction (EF) referred to as CRT non-responders (CRT-NR). The aim of this study was to compare the outcomes of CRT-NR patients who received a CRT defibrillator (CRT-D) device with patients after primary implantable cardioverter-defibrillator (ICD) implantation for impaired left ventricular (LV) function. Methods CRT-NR status was defined as no or less than 10% improvement in LV EF 12 months post implantation. CRT-NR patients and those after primary ICD implantation for LV EF<35% were identified in our database between 2010 and 2019. CRT-NR patients were further categorized as progressors (decrease in LV EF ≥5%) or non-progressors (LV EF change between +9 to −5%). Primary endpoint was all-cause mortality or the need for heart transplantation during follow-up. Statistical significance was assessed by Log-rank test of Kaplan-Meier survival analysis. Results 151 CRT-NR patients and 219 patients after primary ICD implantation were identified with a mean ± SEM follow-up of 43.7±2.5 and 47.3±2.2 months, respectively. Baseline (preoperative) LV EFs were higher (p<0.05) for the overall CRT-NR group (EF = 27.4±0.4%) than for the ICD group (EF = 25.2±0.3%) Further, both CRT-NR subgroups of progressors (n=49; EF = 28.6±0.7%) and non-progressors (n=102; EF = 26.9±0.5%) had also significantly higher baseline LV EF as compared to ICD patients (p<0.05). No statistical significance was found between the two CRT-NR subgroups. Event free median survival for the overall CRT-NR group (55.6 months) was significantly worse than for the ICD group (79.6; p<0.05). This difference was driven by progressor patients who had a significantly worse event free survival (37.8 months, p<0.05) than ICD patients, while vent free survival in non-progressors (60.8 months) was comparable to ICD patients (p=0.18). Conclusion Progressor subgroup of CRT-NR have worse outcome as compared to non-progressors and also to those after primary prevention ICD implantation. The poor prognosis of these patients should have implications for timely decision regarding all therapeutic measures currently available for the management of heart failure. 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, Developement and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme
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.
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