Randomized controlled trials in valvular heart disease: the evolving role of multimodality imaging

Valvular heart disease represents a significant global health burden, with an estimated prevalence of 2.5% in high-income countries and projected increases due to population ageing. Randomized controlled trials in valvular heart disease have undergone substantial evolution, shifting from mortality-focused endpoints toward comprehensive assessments integrating imaging parameters and patient-centered outcomes. Cardiovascular imaging modalities, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance, have become pivotal in trial design, patient selection, and endpoint definition. Recent landmark trials in aortic stenosis, including EARLY-TAVR and EVOLVED, have challenged traditional symptom-based intervention thresholds by incorporating imaging biomarkers of subclinical myocardial dysfunction and cardiac damage staging. In aortic regurgitation, the paucity of randomized controlled trials evidence contrasts with emerging transcatheter technologies, highlighting critical knowledge gaps. Mitral regurgitation trials have demonstrated the importance of patient phenotyping, with divergent outcomes between COAPT and MITRA-FR emphasizing the role of imaging in optimal patient selection. The recent TRILUMINATE and TRISCEND trials have transformed tricuspid regurgitation management through transcatheter interventions, prioritizing quality-of-life improvements alongside traditional clinical endpoints. Future directions include standardization of imaging protocols across modalities, development of artificial intelligence-enhanced analysis, and integration of multiparametric biomarkers for personalized risk stratification. The paradigm shift toward imaging-guided, patient-centered trial design represents a fundamental reimagining of therapeutic success in valvular heart disease, moving beyond procedural outcomes toward comprehensive assessment of clinical benefit and improved patient care.