Continuous reduction of left ventricular pump function during mitoxantrone - Therapy in multiple sclerosis

Apart from genetic and environmental factors autoimmune mechanisms are believed to play a leading role in the pathogenesis of multiple sclerosis (MS). Among immunosuppressive regimens, low dose mitoxantrone therapy is considered a promising strategy to stop the progressive course of this disabling disease. In 30 consecutive patients (pts) with a mean age of 46.8 +/- 9.7 years, low dose mitoxantrone (12 mg/m(2)) infusion was administered in 3 months intervals. Because of potential cardiotoxic side effects resting ECG and echocardiography (M-mode, 2-D) were performed prior every course of mitoxantrone infusion. A total of 181 mitoxantrone infusions with a cumulative dose of 75.0 +/- 35.5 mg/m(2) was given without any complications. During treatment no patient experienced clinical signs of heart failure. Heart rate remained unaffected throughout the study period. Two-dimensional and M-mode echocardiography prior mitoxantrone infusions revealed neither local or overt global contraction abnormalities nor LV enlargement. However, the time course of fractional shortening respective ejection fraction in individual patients demonstrated a significant continuous reduction of mean left ventricular pump function with increasing cumulative doses of mitoxantrone. We conclude that mitoxantrone may exert a progressive cardiac damage requiring a more detailed discussion of potential side effects with the patient and a more aggressive monitoring of left ventricular pump function.