Combination Between Biomarkers and Echocardiographic Data for Prediction of Left Ventricular Reverse Remodelling in Cardiac Resynchronization Therapy

Purpose: Although biomarkers of myocardial fibrosis and inflammation have been proposed as potential modulators of response to cardiac resynchronization therapy (CRT), their clinical utility and interaction with echocardiographic parameters remain incompletely understood. This study aims to assess the dynamic changes in these biomarkers, their relationship with echocardiographic variables, and their association with structural response to CRT. Methods: We retrospectively evaluated 86 consecutive patients referred for CRT with symptomatic heart failure, left ventricular (LV) ejection fraction ≤ 35%, QRS width ≥ 130 ms and LBBB morphology. We measured sST-2, Gal-3, NTpro-BNP and eGFR at baseline and after 1 year of CRT. An echocardiographic reduction of LV end-systolic volume ≥ 15% was used to define a patient as a responder to CRT. Results: The mean baseline and follow-up values of Gal-3 (responders: 24.1 [16.8;32] ng/mL, non-responders: 30 [20;39.3] ng/mL, p = 0.03) and sST2 (responders: 28.5 [20;36] ng/mL, non-responders: 34.5 [25;37.7] ng/mL, p = 0.03) were lower in responders than non-responders. Responders showed a significant reduction between baseline and follow-up values of ΔGal-3 (−12.1% vs. −2.5%, p = 0.04), ΔsST2 (−30.8% vs. 2.2%, p < 0.001), ΔNT-proBNP (−16.4% vs. 5.2, p = 0.04) and ΔeGFR (6.7 ± 24.3% vs. -6.3 ± 27.9%, p = 0.03). At the multivariate analyses, baseline Gal-3 [cut-off: 38.5 ng/mL, AUC: 0.63, p = 0.03, (OR 7.13 [1.12;45.41], p = 0.03), together with TAPSE > 17.5 mm (OR 10.86 [3.15;37.44], p < 0.001) significantly correlated with the structural response to CRT in several prediction models. Among echocardiographic parameters, TAPSE remained the strongest predictive factor of positive response to CRT at the univariate and multivariate analyses. Conclusions: In patients with heart failure and reduced ejection fraction undergoing CRT, Gal-3 and TAPSE are significantly associated with a positive structural response to CRT.