ABSTRACTOver a 5.5 year period, 1264 consecutive patients with acute myocardial infarction as confirmed by enzyme levels were prospectively identified. Of these, 25 (2%) suffered ventricular septal rupture (pulmonary/systemic flow range 1.5 to 6) 7 + 7 days after onset of myocardial infarction. Death occurred in 14 patients (56%) and was more common after inferior than anterior myocardial infarction (11 of 15 [73%] vs three of 10 [30%], p < .05). Among 133 variables analyzed, survivors and nonsurvivors were similar with respect to all premorbid clinical characteristics, infarct size as assessed by peak creatine kinase values, shunt size, two-dimensional echocardiographic and hemodynamic indexes of left ventricular function, and extent of coronary disease. Compared with survivors, the nonsurvivors had greater impairment of right ventricular function as determined by a higher two-dimensional echocardiographically derived right ventricular wall motion index (RVWMI) (0.55 + 0.87 vs 1.70 + 0.45, p < .001), greater elevation of right ventricular end-diastolic pressure (11 + 6 vs 17 ± 6, p < .02), and greater mean right atrial pressure (10 ± 6 vs 16 3, p < .01). Of interest, two of the three patients who presented with anterior myocardial infarction and who died had inferiorly extended infarcts and all had abnormal RVWMIs (2 1.0). As expected, cardiogenic shock shortly after onset of ventricular septal rupture was associated with a 91% mortality, but was more common after inferior than anterior myocardial infarction (60% vs 20%, p < .05). The mean effective cardiac index was also higher in survivors than nonsurvivors (2.1 ± 0.5 vs 1.2 ± 0.5, p < .001). Finally, multivariate analysis indicated that all nonsurvivors could be identified based on: (1) an effective cardiac index of 1.75 liters/min/m2 or less, (2) the presence of extensive right ventricular and septal dysfunction on the two-dimensional echocardiogram, (3) a mean right atrial pressure of 12 mm Hg or more, and (4) early onset of ventricular septal rupture. Thus, our data demonstrate that: (1) mortality is higher when ventricular septal rupture complicates inferior than when it complicates anterior myocardial infarction, (2) survivors can be distinguished from nonsurvivors and the prediction of outcome is highly accurate, and (3) combined right ventricular and septal dysfunction has a substantial impact on prognosis.