TTE establishes the baseline for pathoanatomy and pathophysiology from which comparison is made as the lesions progress over time. Doppler hemodynamics have been validated for patients with single-valve disease but have not necessarily been studied in patients with multivalve disease. Limitations exist for assessment of calculations, such as those for valve areas, because of differen- tial flows with multivalve disease.2 5 2. The complex nature of mixed valve disease makes it necessary to consider all available data to reach a final management decision. Although natural history data for many types of mixed valve disease are lacking, it is reasonable to assume that the onset of symptoms is a neg- ative prognostic occurrence, as it is for all other valve lesions. The difficulty may lie in attribut- ing such symptoms to the mixed valve disease at hand, especially if TTE demonstrates moder- ate but not severe mixed disease. Elevated BNP and elevated filling pressures at catheterization, either at rest or with exercise, support that car- diac disease is the cause of the patient s symp- toms and may help to further quantify lesion severity. CLINICAL STATEMENTS AND GUIDELINES 10.2. Timing of Intervention for Mixed VHD 10.2.1. Intervention for Mixed AS and AR Recommendations for Timing of Intervention for Mixed AS and AR Referenced studies that support the recommendations are summarized in Online Data Supplement 33. 