Baseline mechanical dyssynchrony is associated with better diastolic function in patients undergoing cardiac resynchronization therapy
Authors: Beela A , Manetti C , Lyon A , Prinzen F , Delhaas T , Herbots L , Lumens J 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovative program under the Marie Sklodowska -Curie grant agreement No. 860745.

Background
Outcome after cardiac resynchronization therapy has been shown to be worse in patients with diastolic dysfunction.

Aim
We aim at investigating the association between baseline mechanical dyssynchrony (Dyss) and diastolic function, both assessed using conventional 2D echocardiography in heart failure patients undergoing cardiac resynchronization therapy (CRT).

Methods
Datasets of 219 patients were retrospectively analyzed, including full echocardiographic diastolic function assessment before CRT implantation. Using the guideline approach (Nagueh et al 2016) for estimating left atrial pressure (LAP), patients were classified as elevated LAP (eLAP = 49%), normal LAP (nLAP = 40%), and undetermined LAP (uLAP = 11%). Patients with nLAP and uLAP together were referred to as non-elevated LAP (non-eLAP = 51%). Dyss was defined as the presence of apical rocking (ApRock) and /or septal flash (SF). All baseline characteristics, comorbidities, ECG data and left atrial (LA) strain components (reservoir, conduit, and pump strains) were collected and analyzed. The amount of CRT-induced LV reverse remodeling was assessed at 12±6 months after CRT and was defined as percentage decrease of LV end-systolic volume (LVESV) compared to baseline. Patients were followed up for a mean of 4.8 years (interquartile range (IQR): 2.7–6.0) for all-cause mortality.

Results
Compared to patients without Dyss, patients with Dyss were significantly more of female sex (39% vs. 14%), had less diabetes mellitus (21 vs. 34%), had lower serum creatinine (1.2±0.5 vs. 1.4±0.6 mg/dl) and less prevalence of ischemic cardiomyopathy, 43% vs. 68%). They used significantly more ACEi (91% vs. 76%). ECG data showed that they had less prevalence of AF (8 vs. 22%) and had wider QRS complex (158±18 vs. 152±18 msec), P-values &lt;0.05 for all comparisons. Baseline LV volumes and EF were not significantly different between patients with and without Dyss.
Patients with Dyss show less prevalence of eLAP compared to patients without Dyss (30% vs. 60%, P &lt;0.001, figure A). Additionally, they had better LA function on all LA strain indices (Figure B). In the multivariable analysis for predicting the association with eLAP, the presence of Dyss was independently associated with less eLAP after adjusting for most of the baseline variables (HR: 0.31, CI: 0.1–0.7, P &lt;0.01). At follow up, patients who had both Dyss and non-eLAP before CRT showed the largest amount of LV reverse remodeling compared to other patients. Similarly, the patients with Dyss and non-eLAP showed the best survival compared to other groups (figure C).

Conclusion
The presence of mechanical dyssynchrony is associated with better diastolic function and lower estimated LAP before CRT. Additionally, the combination of Dyss and non-eLAP before CRT was associated with the most CRT-induced LV reverse remodeling and best long-term survival.