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Background: Congestive heart failure (CHF) is among the most serious toxicities of doxorubicin, a potent cancer chemotherapeutic agent. Serial left ventricular ejection fraction (LVEF) monitoring during doxorubicin therapy for preventing CHF was proposed over 20 years ago. The current utility and cost-effectiveness of this approach in the present era are not known., Methods and Results: Clinical and follow-up data of 265 patients with cancer (age, 53 +/- 14 years; 76% women) undergoing doxorubicin chemotherapy with serial equilibrium radionuclide angiocardiography (ERNA) monitoring (> or =2 studies) were analyzed retrospectively. Patients with a normal baseline LVEF (> or =50%) and a 10% or greater point fall in LVEF to a final value of less than 50% during doxorubicin therapy were considered "at risk" for CHF (n = 41). Over 679 +/- 426 days of follow-up, 7 patients (2.6%) had CHF develop and 90 (34%) died (all cancer-related deaths, with none due to CHF). A comparison of "at-risk" (n = 41 [15%]) and "low-risk" (n = 224 [85%]) groups showed a higher incidence of CHF (12% vs 0.9%, P <.0001), lower baseline LVEF (58% +/- 8% vs 64% +/- 8%, P <.0001), lower value for the lowest LVEF (42% +/- 8% vs 57% +/- 7%, P <.0001), and higher rate of cancer-related deaths (59% vs 29%, P =.0003) in the former despite similar cumulative doxorubicin dose (304 +/- 124 mg/m(2) vs 284 +/- 110 mg/m(2), P = not significant). There were no differences in age, gender, cancer type, and co-morbidity. Cost analysis showed the overall cost of ERNA studies to be lower than the 1-year cost of caring for additional cases of CHF that would potentially be prevented by routine LVEF monitoring., Conclusions: An incipient fall in LVEF detected on serial ERNA during doxorubicin therapy provides an appropriate and cost-effective approach for predicting and preventing impending CHF. Use of this approach was associated with a low incidence of CHF (2.6%) and no CHF-related mortality in this study.