Noninvasive methods for the early detection of doxorubicin-induced cardiomyopathy

Ninety-eight female patients (mean age 54 years) who underwent doxorubicin therapy because of metastatic breast cancer were submitted to radionuclide angiography at rest. Left ventricular ejection fractions (LVEFs) were found to decrease significantly with the increasing cumulative doxorubicin dosage. Patients with prior local radiotherapy showed lower LVEFs at the same dosage level than nonirradiated patients, but the difference was not statistically significant. In a further study, 52 patients (mean age 56 years) were followed up regularly for their history and systolic time intervals prior to each doxorubicin treatment course. Before starting treatment, LVEF values were normal in all cases. Fifteen of these patients complained of dyspnea at some time during the treatment period before the critical cumulative dosage level of 550 mg/m2 was reached. Nine of these 15 patients showed an increase of the PEPI:LVETI ratio (greater than or equal to 0.40) and 12 patients a decrease of the LVEF values at rest at the same time. The rest of the patients did not complain of cardiac symptoms and did not show any significant alterations in systolic-time-interval measurements until the borderline dosage level (550 mg/m2) was attained. To evaluate myocardial function with greater accuracy, these 15 patients were submitted to right-heart catheterization and radionuclide angiography at rest and during exercise. As a result, doxorubicin treatment had to be discontinued in three of these patients because of heart failure of stage III or IV and treatment with methyl digoxin and nifedipine was started. In these three patients cardiotonic medication could produce more or less complete cardiac recompensation. We conclude from our findings that signs of stage-III heart failure in radionuclide angiography performed while the patient is at rest and exercising should be regarded as the upper limit of the therapeutic risk, where further doxorubicin treatment is contraindicated. Cardiotonic medication during cytostatic courses should be avoided, however, because the true functional condition of the myocardium could be masked during a potentially cardiotoxic therapy.