Slide 7 of 16

5. Forty-six (46) reports had sufficient detail regarding the severity of valvular regurgitation to permit classification as either a case or non-case, according to the FDA "research" case definition. Of these 46 classifiable spontaneous reports, 38 (83%), met the "research" definition of a case. Among these reports, the aortic valve was most frequently affected, followed closely by dysfunction at the mitral valve. The severity of regurgitation met the case definition at both the aortic and mitral valves in 47% (18/38). Data on symptomatology was available for 33 reports. Patients had symptoms of congestive heart failure or dyspnea (shortness of breath) in 61% (20/33). 24% (8/33) of patients were asymptomatic but new heart murmurs had been noted on physical examination. In 15% (5/33), no symptoms or signs were reported, and echocardiography was performed for screening purposes. Valve replacement surgery occurred in 32% (12/38). Two patients died: one following surgery and the other as sudden death. One other death was reported in a patient treated with fenfluramine as monotherapy following valve replacement surgery.