Impact of guideline-directed medical therapy on outcomes of mitral transcatheter edge-to-edge repair

Abstract Background 0ptimization of guideline-directed medical therapy (GDMT) is a cornerstone of heart failure (HF) management but often remains incomplete, especially in patients with significant mitral regurgitation (MR). Hemodynamic improvement following mitral transcatheter edge-to-edge repair (M-TEER) may enable initiation or up-titration of therapy. This study evaluated the impact of GDMT optimization—before and after M-TEER—on outcomes and identified predictors of successful optimization in a cohort including both primary and secondary MR. Purpose To assess the relationship between GDMT optimization and clinical outcomes after M-TEER, and to identify predictors of achieving pharmacologic optimization in a real-world mixed-etiology population. Methods we retrospectively analyzed 76 consecutive patients who underwent M-TEER between 2021 and 2024. The cohort included both functional and primary MR and patients with reduced, mildly reduced, and preserved LVEF. Patients were stratified as: (1) GDMT optimized at baseline and maintained post-procedure;(2) optimized only after M-TEER; (3) never optimized. GDMT was defined according to ESC Heart Failure Guidelines as the use of ARNI (or ACEi/ARB), β-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors. For HFmrEF/HFpEF, optimal SGLT2 inhibitor and diuretic therapy were also considered. The primary endpoint was the composite of all-cause mortality or HF hospitalization. Predictors of outcomes and of GDMT optimization were analyzed using Cox and logistic regression models. Results at baseline, 34% of patients were optimized; among those unoptimized, 44% achieved optimization after M-TEER, while 31% remained non-optimized. Procedural success was similar across groups (residual MR ≤1+ in 46%). At 12 months, optimized patients—either at baseline or after M-TEER—had fewer composite events (log-rank p=0.011). Lack of optimization was associated with increased event risk (HR 2.38, 95% CI 1.19–4.73; p=0.013). Although multivariable adjustment attenuated significance, the trend toward improved outcomes persisted for both mortality and HF hospitalization. Indexed stroke volume (SVi) was the only independent predictor of GDMT optimization (OR 1.26, 95% CI 1.07–1.48; p=0.006). Conclusions In this single-center, mixed-etiology cohort, a favorable trend was observed between GDMT optimization—before or after M-TEER—and improved clinical outcomes, independent of procedural success. M-TEER appears to act as a therapeutic enabler, allowing previously non-optimized patients to achieve comprehensive medical therapy. Despite the limited sample size and single-center design, these findings support a synergistic interaction between M-TEER and GDMT, warranting confirmation in larger multicenter prospective studies.