Interplay of mechanical dyssynchrony and electrical substrate on long-term outcomes after cardiac resynchronisation therapy
C S L Chiu, W Gerrits, M J Cramer, A H Maass, M Guglielmo, C P Allaart, M A Vos, M Rienstra, F W Prinzen, K Vernooy, M Meine, P C WoutersAbstract
Aims
Contemporary cardiac resynchronisation therapy (CRT) patient selection relies on left bundle branch block (LBBB) morphology and QRS duration, although heterogeneity in LBBB definitions limits consistency. QRSarea, a quantitative marker of electrical substrate, and left ventricular mechanical dyssynchrony (LVMD) parameters have been proposed to refine patient selection. We evaluated the discriminative and prognostic value of five echocardiographic LVMD parameters for sustained CRT response and long-term event-free survival, stratified by LBBB definitions (ESC 2013, AHA/ACC/HRS, Strauss) and QRSarea.
Methods
From a prospective multicentre cohort of 240 CRT recipients, 224 had long-term follow-up (median 9.0 years [4.8–11.6]). Mean age was 66 ± 10 years, 64% were male, and 46% had ischaemic cardiomyopathy. LVMD was examined using apical rocking, septal flash, interventricular mechanical delay, systolic rebound stretch of the septum, and the systolic stretch index. Discriminative performance and optimal cut-off values of these LVMD parameters for sustained response were assessed using receiver operating characteristic analyses. Sustained response was defined as ≥15% left ventricular end-systolic volume reduction at both 6 and 12 months. The composite outcome of cardiovascular hospitalisation or all-cause mortality was evaluated using Kaplan–Meier analyses and Cox proportional hazards models, adjusted for LBBB or QRSarea.
Results
Higher QRSarea demonstrated stronger associations with sustained response (OR 4.10; P<0.001) and the composite outcome (HR 0.49; P<0.001) than all LBBB definitions. LVMD discriminated sustained response in the presence of concurrent electrical substrate (i.e., LBBB and/or high QRSarea; AUC 0.69-0.76 in high QRSarea), whereas in its absence, LVMD had limited value. LVMD parameters provided incremental prognostic value for event-free survival beyond all LBBB definitions, but not consistently when electrical substrate was defined using QRSarea.
Conclusion
Higher QRSarea demonstrated stronger associations with sustained response and long-term event-free survival than all LBBB definitions. LVMD discriminated sustained CRT response only in the presence of concurrent electrical substrate. For the composite outcome, LVMD provided incremental prognostic value beyond all contemporary LBBB definitions. Although independent incremental prognostic value beyond QRSarea could not be robustly confirmed, small to modest additional effects cannot be excluded.Graphical abstractFor image description, please refer to the figure legend and surrounding text.Kaplan-Meier curves for compositeFor image description, please refer to the figure legend and surrounding text.