Non-invasive functional and biochemical assessment of mitoxantrone cardiotoxicity in patients with multiple sclerosis.
As mitoxantrone is a recently approved immunosuppressant for managing multiple sclerosis, the number of patients treated with this effective but potentially cardiotoxic anthracenedione derivative will increase substantially. To detect subclinical mitoxantrone-induced cardiotoxicity, sensitive non-invasive diagnostic tools are required. Assuming that changes in myocardial high-energy phosphate metabolism and alterations in left ventricular (LV) diastolic performance might be early markers of mitoxantrone-induced cardiotoxicity we examined fifteen MS patients treated with mitoxantrone up to 100 mg/m2 compared with 15 matched control MS patients. 31P-magnetic resonance (MR) spectroscopy was employed to measure myocardial high-energy phosphate metabolism, MR imaging for morphometric evaluation of changes in LV geometry. Indices of diastolic performance were assessed by Doppler echocardiography. In this exploratory study, phosphocreatine/ATP ratios were comparable between mitoxantrone-treated and control patients (1.48 +/- 0.23 and 1.43 +/- 0.41). LV mass, LV end-diastolic and systolic volumes, wall motion score, EF and cardiac output did not differ between both groups. All parameters of diastolic performance (E/A-ratio, isovolumic relaxation time, and E-wave deceleration time) were not different and within normal limits.In conclusion, using advanced diagnostic methodology, including functional, morphometric, and biochemical measurements no cardiotoxic effect of mitoxantrone up to a cumulative dose range of 100 mg/m2 could be detected.
Department of Medicine, Würzburg University, Germany. m.spindler@medizin.uni-wuerzburg.de
Matthias
M
Spindler
Franz
F
Weilbach
Meinrad
M
Beer
Jörn
J
Sandstede
Herbert
H
Köstler
Jörg
J
Strotmann
Wolfram
W
Voelker
Dietbert
D
Hahn
Georg
G
Ertl
Ralf
R
Gold
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use* / Q000633:toxicity*; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D010865:Pilot Projects; D011859:Radiography; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D008942:Mitoxantrone