From European Institute of Oncology, Milan, Italy (D.C., A.C., G.B., I.T., C.A.M., M.C., G.L., N.C., G.C., C.M.C.); and Centro Cardiologico Monzino (I.R.C.C.S.), Milan, Italy (F.V., C.F.).
Circulation. 2015 Jun 2;131(22):1981-8. doi: 10.1161/CIRCULATIONAHA.114.013777. Epub 2015 May 6.
Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity.
We assessed left ventricular ejection fraction (LVEF), at baseline, every 3 months during chemotherapy and for the following year, every 6 months over the following 4 years, and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%), heart failure therapy was initiated. Recovery from cardiotoxicity was defined as partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6-8.0) years. The overall incidence of cardiotoxicity was 9% (n=226). The median time elapsed between the end of chemotherapy and cardiotoxicity development was 3.5 (quartile 1 to quartile 3, 3-6) months. In 98% of cases (n=221), cardiotoxicity occurred within the first year. Twenty-five (11%) patients had full recovery, and 160 (71%) patients had partial recovery. At multivariable analysis, end-chemotherapy LVEF (hazard ratio, 1.37; 95% confidence interval, 1.33-1.42 for each percent unit decrement) and cumulative doxorubicin dose (hazard ratio, 1.09; 95% confidence interval, 1.04-1.15 for each 50 mg/m(2) increment) were independent correlates of cardiotoxicity.
Most cardiotoxicity after anthracycline-containing therapy occurs within the first year and is associated with anthracycline dose and LVEF at the end of treatment. Early detection and prompt therapy of cardiotoxicity appear crucial for substantial recovery of cardiac function.
目前公认的蒽环类药物诱导性心脏毒性有三种类型：急性、早期慢性和晚期慢性。然而，缺乏支持这种分类的数据。我们前瞻性地评估了心脏毒性的发生率、发生时间、临床相关性以及对心力衰竭治疗的反应。
我们评估了左心室射血分数（LVEF），在基线时、化疗期间每 3 个月一次、接下来的 1 年每 6 个月一次、接下来的 4 年每年一次、之后每年一次，在接受蒽环类药物治疗的异质队列 2625 例患者中进行。如果发生心脏毒性（LVEF 下降 >10 个绝对点，且 <50%），则开始心力衰竭治疗。心脏毒性的恢复定义为部分（LVEF 增加 >5 个绝对点和 >50%）或完全（LVEF 恢复到基线值）。中位随访时间为 5.2 年（四分位距 1 到 3，2.6-8.0）。心脏毒性的总发生率为 9%（n=226）。化疗结束与心脏毒性发展之间的中位时间为 3.5 个月（四分位距 1 到 3，3-6）。在 98%的情况下（n=221），心脏毒性发生在第一年。25 例（11%）患者完全恢复，160 例（71%）患者部分恢复。多变量分析显示，化疗结束时的 LVEF（风险比，1.37；每降低 1%单位，95%置信区间，1.33-1.42）和累积多柔比星剂量（风险比，1.09；每增加 50mg/m2，95%置信区间，1.04-1.15）是心脏毒性的独立相关因素。
蒽环类药物治疗后，大多数心脏毒性发生在第一年，与治疗结束时的蒽环类药物剂量和 LVEF 相关。早期发现和及时治疗心脏毒性对于心脏功能的显著恢复似乎至关重要。
