The cardiotoxicity of epirubicin (EPI) was evaluated clinically, radiologically, with ECG, and with multiple ECG-gated radionuclide determination of the left ventricular ejection fraction (LVEF) during rest in 135 patients with advanced breast cancer. The EPI doses were 60 mg/m2 on days 1 and 8 every 4 weeks or 45 mg/m2 plus vindesine 3 mg/m2 on the same schedule. The median cumulative dose of EPI was 500 mg/m2 (range, 47 to 1,563). Eight of the 135 patients developed congestive heart failure (CHF). Of 67 patients treated with EPI less than 500 mg/m2, none developed CHF. Among 48 patients treated with doses between 500 and 1,000 mg/m2, one had CHF (2%; 95% confidence limits, 0.1 to 11.1). Among 20 patients who received EPI from 1,000 to 1,563 mg/m2, seven developed CHF (35%; 95% confidence limits, 15.4 to 59.2). Four patients died due to cardiotoxicity. The risk of EPI cardiotoxicity at the present schedule is considerable at doses above 1,000 mg/m2. At doses between 500 and 1,000 mg/m2 the risk of CHF decreases, and at doses below 500 mg/m2, it is negligible. For all patients, the prevalence of CHF was 6% and the sensitivity of LVEF high (95%), mainly due to the low incidence of CHF. Among the 20 patients who received EPI at more than 1,000 mg/m2, the prevalence of CHF was 35% and the sensitivity only 64%. The specificity was maximally 62%. Our results suggest that LVEF is of no value as a predictor for CHF.
Physical work capacity was evaluated by a multistage bicycle exercise test in 29 patients, 22 men and seven women aged 35-61 years (mean 49) with alcoholic liver cirrhosis and in a sex- and age-matched control group. The maximal work load was reduced in the patient group, mean 122 vs. 186 watts in men (P less than 0.001), and 60 vs. 119 watts in women (P less than 0.005). Resting heart rate was higher in patients (91 vs. 78 beats X min-1, P less than 0.005), and the maximal heart rate was lower (159 vs. 170 beats X min-1, P less than 0.001) compared with controls. Thirteen of 29 (45%) patients compared with 5 of 29 (17%) control subjects had an increase in left ventricular ejection fraction of less than or equal to 5% during exercise (P less than 0.05). The present results suggest that an impaired capacity of the cardiac function to respond adequately to physical stress may at times contribute to the reduced physical work capacity seen in patients with alcoholic liver cirrhosis.
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