Multiple factors influence brain natriuretic peptide (BNP) release in patients with heart failure. We hypothesized that extensive myocardial scarring could result in an attenuated BNP response. A total of 115 patients with New York Heart Association class III chronic heart failure and ischemic cardiomyopathy were evaluated for ischemia, hibernation, and myocardial scarring by dipyridamole-rubidium-positron emission tomographic scanning with fluorine-18, 2-fluoro-2-deoxyyglucose. Plasma BNP levels were determined within 2 weeks of the study. Left ventricular dimension and function were evaluated by echocardiography. Patients were categorized as having <33% myocardial scar (n=67) or>or=33% myocardial scar (n=48). BNP measurements were correlated with amount of myocardial scarring. Compared with patients with less scar, those with >or=33% scar had lower BNP levels (mean 317+/-364 vs 635+/-852 pg/ml, median 212 vs 357, p=0.016). Using multiple regression analysis, presence of scarring was associated with decreased BNP response (p=0.022). Further, patients with <33% scar in whom a higher BNP level was noted had more ischemia (51% vs 27%, p=0.01) and greater myocardial hibernation (22+/-14% vs 12+/-7%, p=0.02) compared with patients with >or=33% scar. In conclusion, in patients with chronic heart failure, a decreased BNP response indicated extensive myocardial scarring.