Mechanical dyssynchrony and response to cardiac resynchronization therapy in heart failure patients with right ventricular pacing: a pre-specified subgroup analysis of the BUDAPEST CRT Upgrade trial
Authors: Fabian A , Lakatos B K , Kosztin A , Tokodi M , Hatala R , Wranicz J K , Polgar B , Geller L , Zima E , Osztheimer I , Molnar L , Kutyifa V , Solomon S D , Kovacs A , Merkely B 
Published: October 2024

Abstract

Introduction
The BUDAPEST CRT Upgrade trial has established the strong clinical benefit of upgrading heart failure patients with a reduced left ventricular (LV) ejection fraction (HFrEF) and a high right ventricular pacing (RVP) burden to cardiac resynchronization therapy with defibrillator (CRT-D). Importantly, however, the CRT upgrade response is not homogeneous regarding LV reverse remodeling and associated clinical outcomes. The presence of mechanical dyssynchrony (MD) assessed by echocardiography has been linked to more CRT benefits; still, its change in response to CRT and added prognostic value in HFrEF patients with high RVP are scarcely investigated.

Purpose
Accordingly, we aimed to assess the prevalence, clinical characteristics, CRT response rate, and prognostic value of RVP-induced MD in the BUDAPEST CRT Upgrade cohort.

Methods
The multicentre, randomized, controlled trial enrolled 360 HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD) and significant RVP (≥ 20%) who were randomly assigned to receive CRT-D upgrade or ICD in a 3:2 ratio. Protocol echocardiography was performed at baseline and at 12-month follow-up visits and was evaluated at a central core lab. Beyond LV end-diastolic (EDV) and end-systolic volumes (ESV), longitudinal strain-derived septal deformation patterns by speckle tracking were assessed to determine the presence of RVP-induced MD. The endpoints were volumetric non-response (defined by a relative decrease in LV ESV &lt;15%) and the composite of volumetric non-response or HF hospitalization.

Results
The echocardiographic assessment was feasible in 325 patients at baseline; 133 (41%) patients presented with MD. Females were more likely to present with MD (female vs. male, 65% vs. 38%, p=0.003). MD patients had higher LV EDV (MD vs. no-MD, 248±78 vs. 219±78 mL, p=0.001) and LV ESV (190±67 vs. 165±64 mL, p&lt;0.001) at baseline. In the CRT-D group, 126 (75%) patients were volumetric responders, and 41 (25%) were non-responders at 12 months. CRT patients with baseline MD were less likely to experience volumetric non-response (OR 0.35 [95% CI 0.15-0.82], p=0.015) or the composite endpoint (OR 0.37 [95% CI 0.17-0.77], p=0.008). Out of 57 CRT patients with baseline MD who had follow-up assessment available, 52 (91%) patients had a favorable change: the MD pattern disappeared. Patients with MD resolution at 12 months were less likely to experience volumetric non-response or the composite endpoint (OR 0.39 [95% CI 0.17-0.93], p=0.034; OR 0.38 [95% CI 0.16-0.86], p=0.021, respectively). CRT patients with resolved MD were less likely of ischemic etiology and had 100% posterior or lateral LV lead location.

Conclusions
The presence of RVP-induced MD and its resolution is associated with better clinical response in HFrEF patients undergoing CRT-D upgrade. MD assessment can refine patient selection algorithms of CRT.Figure 1