P3806Very long-term and late response to CRT: is left ventricular ejection fraction a powerful indicator of sustained and late response?

Background Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in selected symptomatic patients with reduced left ventricular ejection fraction (LVEF) and wide QRS complex. While many patients demonstrate a response to CRT within the first year of follow-up, sustained or late response to CRT is highly relevant but poorly characterized. Purpose To characterize the patient population that demonstrates improvements of LVEF late after CRT implantation, irrespective of the primary response, and to identify factors associated with beneficial long-term outcome. Methods All patients undergoing CRT implantation at our institution between Nov 2000 and Jan 2015 with at least two follow-up echocardiographic studies were included. Primary follow-up (FU1) was performed within one year after CRT implantation (median 6.1 months [IQR: 3.5–10.7]). The most recent echocardiography at a median follow-up time of 3.9 years [27.3–70.4] was considered as long-term follow-up (FU2). LVEF-based response to CRT was stratified into 4 categories: non-response (ΔLVEF +15%). Primary study endpoint was the composite of all-cause death, heart transplantation or implantation of a ventricular assist device. Results Out of 362 patients (median age 65.9 years, 23% female, 41% with ischemic cardiomyopathy), 99 (27.3%) demonstrated LVEF improvements beyond their primary response to CRT (blue bars in figure). At baseline, late responders demonstrated lower LVEF (23.4% [19.0–30.0] vs. 27.0 [22.0–32.0], p=0.005) and an increased prevalence of non-ischemic cardiomyopathy (67.8% vs. 55.9%, p=0.042) compared to the remaining patients. Reduction in LVEDV(I) at FU1 correlated positively with late response (ΔLVEDV −28.5 ml [−71.8; −3.25] vs. 18.0 [−46.0; 3.0], p=0.033). Importantly, late responders were seen amongst all types of primary response, including patients demonstrating a negative response with substantially worsened LVEF at first follow-up after CRT implantation. Finally, patients with late response demonstrated significantly better survival compared to patients with late progression of heart failure or continued non-progression (median survival 7.8 [7.1–8.5] vs. 7.0 [6.6–7.5] years, aHR 0.54 [0.33–0.88] p=0.013 on multivariate cox regression analysis). Conclusions A significant proportion of patients achieves LVEF improvements beyond the initial phase after CRT implantation indicating a substantial limitation in categorizing patients into “responders” and “non-responders” based on the initial response to CRT. Further prospective studies are required to validate these findings and optimize treatment strategies for CRT patients.