Septal ethanol ablation (SEA) is an alternative to surgical myectomy in patients who have drug-refractory obstructive hypertrophic cardiomyopathy. However, permanent atrioventricular conduction block is seen more frequently with SEA. To determine whether septal infarction risk area (SIRA) predicts outcome in patients who have obstructive hypertrophic cardiomyopathy and are undergoing SEA, we evaluated 51 patients (mean age 60 +/- 16, 53% women) who had a successful SEA at Toronto General Hospital (November 1998 to June 2003). Intracoronary myocardial contrast echocardiography that targeted the contact area between the septum and the anterior mitral leaflet was performed before ethanol injection. End-systolic myocardial contrast echocardiographic frames were color coded for better delineation of contrast borders, and myocardial contrast echocardiographic area was calculated by planimetry. Patients were assigned to 1 of 2 groups by median SIRA value (3.51 cm(2), range 0.4 to 7.8). The 2 groups did not differ significantly in age, medication before SEA, electrocardiographic characteristics, left ventricular function, left atrial diameter, volume of intracoronary ethanol injected, peak creatine kinase after ablation, and baseline and follow-up left ventricular outflow tract gradients at rest. Patients in the large SIRA group had greater hypertrophy and a larger septal artery than did patients in the small SIRA group. In the small SIRA group, 3 patients (11.5%) had pacemaker implantation; in the large SIRA group, 12 patients (48.0%) had complications after SEA (pacemaker in 5 patients, implantable defibrillator in 5 patients, death in 2 patients; p = 0.008). We conclude that patients who have hypertrophic cardiomyopathy with a small, well-localized SIRA benefit similarly from SEA as patients who have a larger SIRA but with significantly fewer serious complications.