Kuittinen Taru, Jantunen Esa, Vanninen Esko, Mussalo Hanna, Nousiainen Tapio, Hartikainen Juha
Hematology Research Unit, Helsinki University Central Hospital and University of Helsinki, Helsinki, Helsinki, Finland.
Clin Physiol Funct Imaging. 2010 May;30(3):175-80. doi: 10.1111/j.1475-097X.2009.00920.x. Epub 2010 Jan 28.
The most common cardiotoxic effects of high-dose cyclophosphamide (CY) are electrocardiographic changes and transient arrhythmias. Therefore, we prospectively assessed serial electrocardiogram (ECG) and signal-averaged electrocardiogram (SAECG) recordings in 30 adult patients with non-Hodgkin lymphoma (NHL) receiving high-dose CY as part of high-dose chemotherapy (HDT) regimen. All patients were treated with anthracyclines earlier. Heart-rate-corrected QT interval and QT dispersion (QTc and QTc dispersion) were measured from ECG. QRS duration and late potentials (LPs) were analysed from SAECG. Both ECG and SAECG were recorded 1 day (d) prior to HDT (d-7) at baseline, and 1 day (d-2), 7 days (d+7), 12 days (+12) and 3 months (m+3) after HDT. Stem cells were infused on day 0 (d0). Cardiac systolic and diastolic function were assessed on (d-7), (d+12) and (m+3) by radionuclide ventriculography. At baseline, four patients presented with LPs. Cardiac systolic function decreased significantly (53 +/- 2; 49 +/- 2%, P = 0.009 versus baseline), whilst no patient developed acute heart failure. QRS duration prolonged and RMS(40) reduced significantly versus baseline (104 +/- 3; 107 +/- 3 ms, P = 0.003; 41 +/- 4; 38 +/- 3 microV, P = 0.03), and six patients (21%) presented with LPs after CY treatment. Both QTc interval and QTc dispersion increased versus baseline (402 +/- 5; 423 +/- 5 ms, P<0.001; 32 +/- 2; 44 +/- 3 ms, P = 0.012), and six patients (20%) developed abnormal QT dispersion. In conclusion, high-dose CY causes subclinical and transient electrical instability reflected by occurrence of LPs as well as increased QTc interval and QT dispersion. Thus, longer follow-up is required to confirm the meaning of these adverse effects on cardiac function and quality of life.
高剂量环磷酰胺（CY）最常见的心脏毒性作用是心电图改变和短暂性心律失常。因此，我们前瞻性地评估了30例接受高剂量CY作为高剂量化疗（HDT）方案一部分的成年非霍奇金淋巴瘤（NHL）患者的系列心电图（ECG）和信号平均心电图（SAECG）记录。所有患者先前均接受过蒽环类药物治疗。从ECG测量心率校正的QT间期和QT离散度（QTc和QTc离散度）。从SAECG分析QRS时限和晚电位（LP）。在HDT前1天（d-7）即基线时，以及HDT后1天（d-2）、7天（d+7）、12天（+12）和3个月（m+3）记录ECG和SAECG。在第0天（d0）输注干细胞。在（d-7）、（d+12）和（m+3）通过放射性核素心室造影评估心脏收缩和舒张功能。在基线时，4例患者出现LP。心脏收缩功能显著下降（53±2；49±2%，与基线相比P=0.009），而无患者发生急性心力衰竭。与基线相比，QRS时限延长且RMS(40)显著降低（104±3；107±3 ms，P=0.003；41±4；38±3 μV，P=0.03），6例患者（21%）在CY治疗后出现LP。QTc间期和QTc离散度均较基线增加（402±5；423±5 ms，P<0.001；32±2；44±3 ms，P=0.012），6例患者（20%）出现异常QT离散度。总之，高剂量CY导致亚临床和短暂性电不稳定，表现为LP的出现以及QTc间期和QT离散度增加。因此，需要更长时间的随访来确认这些不良反应对心脏功能和生活质量的意义。
