Evaluation of the myocardial performance index for early detection of mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis.
OBJECTIVE
Multiple sclerosis is the most common cause of neurological disability in young adults. Mitoxantrone is a synthetic anthracenedione, recently approved for the treatment of worsening multiple sclerosis, which is known to induce cardiotoxicity. This study was designed to evaluate the early alterations in left ventricular function in patients with multiple sclerosis receiving mitoxantrone, by the use of the myocardial performance index, a new parameter of global (systolic and diastolic) ventricular function.


RESULTS
The study included 29 Caucasian patients with multiple sclerosis (mean age 41.8+/-9.3 years, 12 males and 17 females) treated with mitoxantrone (mean cumulative dose 30.8+/-18.2 mg/m(2)) who were compared with 28 healthy subjects (mean age 37.8+/-11.8 years, 13 males and 15 females). Both groups underwent a complete two-dimensional and Doppler echocardiography including assessment of the mitral inflow and left ventricular outflow patterns for estimation of the Doppler-derived myocardial performance index. This parameter is defined as the sum of isovolumic contraction time and isovolumic relaxation time, divided by ventricular ejection time. No differences were observed in blood pressure, heart rate, left ventricular diameters, mass and ejection fraction in multiple sclerosis patients compared to the controls. The mitral flow pattern showed a significant decrease of E wave calculated as peak velocity (E(pv)) (63.3+/-13.4 vs. 77.2+/-17.2, P<0.002) and time velocity integral (E(tvi)) (8.8+/-1.9 vs. 10.3+/-2.4, P<0.02), with a significant decrease of E(pv)/A(pv) ratio and a non-significant decrease of E(tvi)/A(tvi) ratio in the patients. In addition, E-wave deceleration time was significantly increased in multiple sclerosis patients compared to controls (178.2+/-30.2 vs. 137.9+/-14.7, P<0.0001). The mean value of myocardial performance index was 0.55+/-0.1 in patients compared to 0.37+/-0.06 in the controls (P<0.0001). A significant correlation between the given cumulative dose of mitoxantrone and myocardial performance index (r=0.67, P<0.001) and E-wave deceleration time (r=0.45, P<0.001) respectively were demonstrated.


CONCLUSIONS
The myocardial performance index represents a parameter of combined systolic and diastolic myocardial performance strongly correlated with the given cumulative dose of mitoxantrone. The myocardial performance index may be an adjunctive parameter to conventional echocardiography for detecting sub-clinical cardiotoxicity of mitoxantrone in the clinical management of the multiple sclerosis patients.
Pattoneri
Paolo
P
Department of Internal Medicine, Nephrology and Health Sciences, University of Parma, Via Gramsci 14, 43100 Parma, Italy. pattopaolo@libero.it
Pelà
Giovanna
G
Montanari
Enrico
E
Pesci
Ilaria
I
Moruzzi
Paolo
P
Borghetti
Alberico
A
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015150:Echocardiography, Doppler; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy*; D013599:Systole; D016277:Ventricular Function, Left
D000970:Antineoplastic Agents; D008942:Mitoxantrone