Long-term mortality benefit of adding an ICD to CRT in non-ischemic patients
Authors: Veres DR 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): This work was supported by the ÚNKP-20-3-I New National Excellence Program if the Ministry for Innovation and Technology in Hungary, the National Research, Development, and Innovation Office of Hungary (NKFIA; NVKP_16-1-2016-0017 National Heart Program), and the Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development thematic program of the Semmelweis University. This work was also supported by the Artificial Intelligence Research Filed Excellence Program of the National Research, Development and Innovation Office of the Ministry of Innovation and Technology in Hungary (TKP/ITM/NKFIH). The research was also financed by the Thematic Excellence Program (Tématerületi Kiválósági Program, 2020-4.1.1-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Bioimaging thematic program of the Semmelweis University."

OnBehalf
Heart failure study group

Background
Data is incomprehensive about the long-term mortality benefit of Cardiac Resynchronization Therapy with (CRT-D) or without (CRT-P) a defibrillator.

Purpose
To assess the long-term all-cause mortality benefit of CRT-D compared to CRT-P by ischemic aetiology.

Methods
Between 2000 and 2018, patients after a successful CRT implantation were registered. From 2524 patients, 1099 (44%) had CRT-P and 1366 (54%) CRT-D implantation. Those 59 (2%) patients, who had an ICD upgrade with a CRT-P device during the follow-up, were excluded from the current analysis. The primary composite endpoint was all-cause mortality, LVAD implantation or heart transplantation. Kaplan-Meier and multivariate Cox regression analyses were used to evaluate all-cause mortality in the total cohort and by ischemic aetiology.

Results
During the median follow-up time of 3,6 years, 1389 patients died from any cause, 697 patients (50%) with a CRT-P, 692 patients (50%) with a CRT-D device. Patients in the CRT-D cohort were younger (67 years vs. 70 years; p &lt; 0.001), had a less advanced functional class (NYHA III/IV., 52.2% vs. 61.4%; p &lt; 0.001), wider QRS [160ms (140/180) vs. 160ms (140/170); p = 0.03] and less females (18.9% vs. 33.3%; p &lt; 0.001) with an ischemic aetiology (57.7% vs. 40.2%; p &lt; 0.0001). CRT-D patients had a better renal function [eGFR, 60.5 (ml/min/1.73m2) vs. 57 (ml/min/1.73m2); p = 0.02], decreased ejection fraction (28% vs. 30%; p = 0.002), had more frequently ventricular arrhythmia (36% vs. 9.8%; p &lt; 0.001) and less frequently diabetes (77% vs. 87,2%; p &lt; 0.001). CRT-D patients took more amount of beta-blockers (90.2% vs. 87.3%; p = 0.03), MRA (72.2% vs. 61.6%; p &lt; 0.001) and amiodaron (32.2% vs. 20%; p &lt; 0.001). By multivariate analysis, aetiology, gender, functional class, renal function, and the presence of ICD were independent predictors of all-cause mortality in the total cohort. By multivariate analysis, patients with a CRT-D device showed a 25% decreased risk of long-term mortality compared to CRT-P alone (aHR 0.75; 95%CI 0.58-0.97; p = 0.03). When patients were dichotomized by their etiology, those with non-ischemic cardiomyopathy showed a long-term benefit from ICD even after adjusting for relevant clinical variables (aHR 0.45; 95%CI 0.28-0.72; p &lt; 0.01). In ischemic patients despite of having a clear mortality benefit of ICD during the mid-term follow-up, it is decreasing after 5 years and less pronounced after adjusting for clinical variables (aHR 0.92; 95%CI 0.67-1.27; p = 0.60).

Conclusions
However, during mid-term follow up, CRT-D had a clear mortality benefit in ischemic patients compared to CRT-P alone, after 5 years it became less pronounced. While in patients with non-ischemic cardiomyopathy, the benefit of adding an ICD to CRT lasts over 10 years.