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Early mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis
  1. F Paul1,
  2. J Dörr2,
  3. J Würfel3,
  4. H-P Vogel4,
  5. F Zipp5
  1. 1Institute of Neuroimmunology, Charité – Universitaetsmedizin Berlin, Berlin, Germany
  2. 2Department of Neurology, Helios-Klinikum, Berlin, Germany
  3. 3Institute of Neuroimmunology, Charité – Universitaetsmedizin Berlin, Berlin, Germany
  4. 4Department of Neurology, Helios-Klinikum, Berlin, Berlin, Germany
  5. 5Institute of Neuroimmunology, Charité – Universitaetsmedizin Berlin, Berlin, Germany
  1. Correspondence to:
 Professor F Zipp
 Institute of Neuroimmunology, Clinical and Experimental Neuroimmunology, Neuroscience Research Center, Charité – Universitaetsmedizin Berlin, 10098 Berlin, Germany; frauke.zipp{at}charite.de

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Mitoxantrone is an anthracenedione antineoplastic agent approved as an escalating immunotherapy for multiple sclerosis. Owing to structural similarity with other anthracyclines, cardiotoxicity is a severe side effect of mitoxantrone. Cardiotoxicity from anthracycline is considered to be dose dependent and irreversible and to result in the reduction of left ventricular ejection fraction (LVEF) and congestive heart failure.1 The risk of mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis increases with cumulative doses >100 mg/m2 body surface area (BSA).2,3 However, the effect of mitoxantrone on cardiac function in the early phase of treatment with cumulative doses <100 mg/m2 BSA is unclear, and data on cardiac function regularly monitored from the beginning of treatment are rare.

From a total number of 18 patients with secondary progressive multiple sclerosis who were prospectively assessed at our institution during the past 2 years, we report on four patients with a temporary and considerable decrease in LVEF, and with additional echocardiographic findings of diastolic dysfunction after only one or two doses of mitoxantrone.

Monitoring of cardiac function and treatment procedures

All patients receiving mitoxantrone in our clinic undergo assessment of cardiac function according to the following protocol: from the beginning of treatment, transthoracic echocardiography is performed every 3 months before each infusion. Examinations are, whenever possible (i.e. in about 90% of cases) carried out by our cardiologists, who perform at least 600 echocardiograms per year. The quantitation of LVEF is based on Simpson’s rule, as described elsewhere.4 Further, left ventricular diastolic function is evaluated from the following parameters: ratio E (peak early filling velocity)/A (peak atrial velocity), isovolumetric relaxation time (IVRT) and E wave deceleration time (DT).5,6 In line with current recommendations,2 patients with an LVEF of <50% are excluded from mitoxantrone treatment, and treatment is discontinued if the LVEF drops to a value of <50% …

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