Unmasking Risk in Mitral Regurgitation: Prognostic Value of Exercise Stress Echocardiography-A Systematic Review

Background: Risk stratification of patients with mitral regurgitation (MR), including both primary (degenerative) and secondary (functional) forms, remains challenging, particularly in asymptomatic or minimally symptomatic stages, as clinical assessment and resting echocardiography may underestimate disease severity and functional impairment. Exercise stress echocardiography (ESE) enables dynamic evaluation of regurgitation severity, ventricular performance, and cardiopulmonary response, potentially improving prognostic assessment. Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and EMBASE were searched from inception to March 2026. Studies including adult patients with primary or secondary MR undergoing exercise-based stress echocardiography and reporting clinical outcomes were selected. Studies using exclusively pharmacological stress were excluded. Data were qualitatively synthesized, and continuous variables were summarized as weighted medians and interquartile ranges. In addition, emerging and non-conventional prognostic markers, including anatomical indices such as the modified Haller index (MHI), were explored to provide a more comprehensive risk stratification framework. Results: Nineteen studies were included, encompassing a heterogeneous population in terms of MR etiology, severity, and clinical presentation. During follow-up, a substantial proportion of patients experienced adverse events, including heart failure, mitral valve intervention, or death. Exercise-derived parameters consistently showed strong prognostic value. In particular, exercise-induced worsening of MR severity (increase in effective regurgitant orifice area and regurgitant volume), absence of contractile reserve, elevated filling pressures (E/e'), and exercise-induced pulmonary hypertension were associated with worse outcomes. Reduced functional capacity and impaired right ventricular-pulmonary arterial coupling provided additional prognostic information. Emerging markers, including chest wall configuration assessed by MHI, appeared to further refine risk stratification in selected patient subsets. In contrast, resting parameters were less consistently predictive. Conclusions: ESE provides incremental prognostic information in patients with MR by identifying dynamic abnormalities not evident at rest. Its integration into clinical evaluation, together with novel anatomical and functional markers, may improve risk stratification and support earlier identification of high-risk patients who could benefit from timely intervention. Further studies are needed to standardize methodologies and define clinically relevant thresholds.