Lipshultz S E, Lipsitz S R, Mone S M, Goorin A M, Sallan S E, Sanders S P, Orav E J, Gelber R D, Colan S D
Department of Cardiology, Children's Hospital, Boston, MA 02115, USA.
N Engl J Med. 1995 Jun 29;332(26):1738-43. doi: 10.1056/NEJM199506293322602.
Late cardiotoxic effects of doxorubicin are increasingly a problem for patients who survive childhood cancer. Cardiotoxicity is often progressive, and some patients have disabling symptoms. Our objective was to identify risk factors for late cardiotoxicity.
We examined echocardiograms from 120 children and adults who had received cumulative doses of 244 to 550 mg of doxorubicin per square meter of body-surface area for the treatment of acute lymphoblastic leukemia or osteogenic sarcoma in childhood, a mean of 8.1 years earlier. Measurements of blood pressure and left ventricular function, contractility (measured as the stress-velocity index), end-diastolic posterior-wall thickness, end-diastolic dimension, mass, and afterload (measured as end-systolic wall stress) were compared with sex-specific values from a cohort of 296 normal subjects.
All echocardiographic measurements were abnormal at follow-up a minimum of two years after the end of therapy, with more frequent and severe abnormalities in female patients. In a multivariate analysis, female sex and a higher cumulative dose of doxorubicin were associated with depressed contractility (P < or = 0.001), and there was an interaction between these two variables. Independent and significant associations were found between a higher rate of administration of doxorubicin and increased afterload (P < or = 0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P < or = 0.001); between a younger age at diagnosis and reduced left-ventricular-wall thickness and mass and increased afterload; and between a longer time since the completion of doxorubicin therapy and reduced left-ventricular-wall thickness and increased afterload (P < or = 0.001).
Female sex and a higher rate of administration of doxorubicin were independent risk factors for cardiac abnormalities after treatment with doxorubicin for childhood cancer; the prevalence and severity of abnormalities increased with longer follow-up.
对于童年癌症幸存者而言，阿霉素的晚期心脏毒性作用日益成为一个问题。心脏毒性通常呈进行性发展，一些患者会出现致残症状。我们的目标是确定晚期心脏毒性的危险因素。
我们检查了120名儿童和成人的超声心动图，这些患者曾接受每平方米体表面积累积剂量为244至550毫克阿霉素的治疗，用于治疗儿童急性淋巴细胞白血病或骨肉瘤，平均时间为8.1年前。将血压、左心室功能、收缩性（以应力-速度指数衡量）、舒张末期后壁厚度、舒张末期内径、质量和后负荷（以收缩末期壁应力衡量）的测量值与296名正常受试者队列中的性别特异性值进行比较。
在治疗结束后至少两年的随访中，所有超声心动图测量值均异常，女性患者的异常情况更频繁且更严重。在多变量分析中，女性性别和更高的阿霉素累积剂量与收缩性降低相关（P≤0.001），并且这两个变量之间存在相互作用。发现阿霉素给药速率较高与后负荷增加（P≤0.001）、左心室扩张和左心室功能降低之间存在独立且显著的关联；较高的累积剂量与左心室功能降低之间存在关联（P≤0.001）；诊断时年龄较小与左心室壁厚度和质量降低以及后负荷增加之间存在关联；阿霉素治疗完成后时间较长与左心室壁厚度降低和后负荷增加之间存在关联（P≤0.001）。
女性性别和较高的阿霉素给药速率是儿童癌症患者接受阿霉素治疗后心脏异常的独立危险因素；随着随访时间延长，异常的发生率和严重程度增加。
