Transcatheter Edge-to-Edge Repair for Mitral Regurgitation: Distinct Interventional Paradigms for Primary and Secondary MR

Background/Objectives: Transcatheter edge-to-edge repair (TEER) has become an established therapeutic option for selected patients with mitral regurgitation (MR). However, primary (degenerative) and secondary (functional) MR represent distinct disease entities, characterized by different pathophysiological mechanisms, clinical trajectories, and determinants of benefit. This review aims to provide an interventional cardiology-oriented synthesis of TEER, emphasizing the fundamental differences between primary and secondary MR and their implications for patient selection, procedural strategy, and outcome interpretation. Methods: A targeted literature search was performed in PubMed and Embase to identify pivotal randomized trials, registries, guideline documents, and high-quality reviews addressing TEER in MR. The available evidence was synthesized narratively, with a focus on mechanistic insights, TEER-specific imaging and procedural endpoints, and clinically relevant outcomes. Results: In primary MR, TEER functions as a valve-centered therapy, with procedural success primarily determined by anatomical suitability and the balance between durable MR reduction and avoidance of elevated transmitral gradients. In secondary MR, TEER should be considered an adjunctive intervention within a comprehensive heart failure strategy, with benefit dependent on patient phenotype, myocardial substrate, optimization of background therapy, and appropriate timing. Emerging phenotypes, such as atrial functional MR, further challenge traditional classification and highlight the need for mechanism-based selection. Across MR subtypes, residual MR and transmitral gradients emerge as key post-procedural endpoints with differential prognostic implications. Conclusions: TEER represents a phenotype-specific intervention rather than a uniform solution for MR. Recognizing the distinct interventional paradigms of primary and secondary MR is essential to optimizing patient selection, procedural decision-making, and clinical outcomes.