评估心肌性能指数在早期检测多发性硬化症患者米托蒽醌诱导的心脏毒性中的应用。

Pattoneri Paolo, Pelà Giovanna, Montanari Enrico, Pesci Ilaria, Moruzzi Paolo, Borghetti Alberico

Department of Internal Medicine, Nephrology and Health Sciences, University of Parma, Via Gramsci 14, 43100 Parma, Italy.

Eur J Echocardiogr. 2007 Mar;8(2):144-50. doi: 10.1016/j.euje.2006.02.009. Epub 2006 Apr 5.

AIMS

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.

METHODS AND 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.

CONCLUSION

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.

目的

多发性硬化症是年轻成年人神经功能障碍最常见的病因。米托蒽醌是一种合成蒽二酮，最近被批准用于治疗病情恶化的多发性硬化症，已知其可诱发心脏毒性。本研究旨在通过使用心肌性能指数（一种评估整体（收缩期和舒张期）心室功能的新参数）来评估接受米托蒽醌治疗的多发性硬化症患者左心室功能的早期改变。

方法与结果

本研究纳入了29例接受米托蒽醌治疗的白种多发性硬化症患者（平均年龄41.8±9.3岁，男性12例，女性17例），平均累积剂量为30.8±18.2mg/m²，并与28例健康受试者（平均年龄37.8±11.8岁，男性13例，女性15例）进行比较。两组均接受了完整的二维和多普勒超声心动图检查，包括评估二尖瓣血流和左心室流出模式，以估算多普勒衍生的心肌性能指数。该参数定义为等容收缩时间与等容舒张时间之和除以心室射血时间。与对照组相比，多发性硬化症患者的血压、心率、左心室直径、质量和射血分数均未观察到差异。二尖瓣血流模式显示，患者的E波以峰值速度（E(pv)）计算显著降低（63.3±13.4对77.2±17.2，P<0.002），时间速度积分（E(tvi)）也显著降低（8.8±1.9对10.3±2.4，P<0.02），E(pv)/A(pv)比值显著降低，E(tvi)/A(tvi)比值无显著降低。此外，与对照组相比，多发性硬化症患者的E波减速时间显著延长（178.2±30.2对137.9±14.7，P<0.0001）。患者的心肌性能指数平均值为0.55±0.1，而对照组为0.37±0.06（P<0.0001）。米托蒽醌的给定累积剂量与心肌性能指数（r=0.67，P<0.001）和E波减速时间（r=0.45，P<0.001）之间分别存在显著相关性。