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BACKGROUND: Pulmonary hypertension in response to exercise is a marker of the hemodynamic severity of mitral stenosis (MS). However, the factors related to elevated pulmonary pressure with exercise are not well defined. The aim of this study was to assess the parameters associated with the pulmonary pressure response to exercise in patients with pure rheumatic MS. An additional aim was to determine the impact of exercise-induced pulmonary hypertension on clinical outcome. METHODS: One hundred thirty patients with MS (94% women; mean age, 45 ± 11 years) underwent exercise echocardiography. A range of echocardiographic parameters were obtained at rest and at peak exercise. Symptom-limited graded ramp bicycle exercise was performed in the supine position. The primary end point was mitral valve intervention, either percutaneous or surgical. RESULTS: In the overall population, systolic pulmonary artery pressure (SPAP) increased from 38.3 ± 13.4 mm Hg at rest to 65.8 ± 20.7 mm Hg during exercise. Increases in mean mitral gradient, right ventricular function, left atrial volume, and net atrioventricular compliance were independently associated with SPAP at peak exercise, after adjusting for changes in heart rate. During the follow-up period (median, 17 months; range, 1–45 months), 46 adverse clinical events were observed. By multivariate Cox proportional-hazards analysis adjusted for age and sex, SPAP achieved at peak exercise was an important predictor of adverse outcome (adjusted hazard ratio, 1.025; 95% CI, 1.010–1.040; P = .001). New York Heart Association functional class (adjusted hazard ratio, 2.459; 95% CI, 1.509–4.006; P < .001) and the interaction between valve area and net atrioventricular compliance (P = .001) were also significant predictors of adverse events. Time-dependent areas under the receiver operating characteristic curve for the model with SPAP during exercise were better than for the model with SPAP at rest, with a significant improvement from 3 years onward. CONCLUSIONS: In patients with MS, the pulmonary artery pressure response to exercise is determined by a combination of factors, including transmitral mean gradient at exercise, net atrioventricular compliance, left atrial volume, and right ventricular function. Pulmonary artery pressure at peak exercise is a predictor of clinical outcomes and adds incremental prognostic value beyond that provided by standard resting measurements, including valve area. (J Am Soc Echocardiogr 2020;33:550–8.)