López-Sendón José, Álvarez-Ortega Carlos, Zamora Auñon Pilar, Buño Soto Antonio, Lyon Alexander R, Farmakis Dimitrios, Cardinale Daniela, Canales Albendea Miguel, Feliu Batlle Jaime, Rodríguez Rodríguez Isabel, Rodríguez Fraga Olaia, Albaladejo Ainara, Mediavilla Guiomar, González-Juanatey Jose Ramón, Martínez Monzonis Amparo, Gómez Prieto Pilar, González-Costello José, Serrano Antolín José María, Cadenas Chamorro Rosalía, López Fernández Teresa
University Hospital La Paz, UAM, IdiPaz, CiberCV, CiberONC, Paseo de la Castellana 261, Madrid 28046, Spain.
Royal Brompton Hospital and Imperial College, Cardiology, London, United Kingdom of Great Britain and Northern Ireland.
Eur Heart J. 2020 May 7;41(18):1720-1729. doi: 10.1093/eurheartj/ehaa006.
Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking.
We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001).
The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.
心脏毒性（CTox）是癌症治疗的主要副作用，但缺乏统一的诊断标准来指导临床和研究实践。
我们前瞻性地研究了865例年龄为54.7±13.9岁的患者；男性占16.3%，计划接受与中度/高度CTox风险相关的抗癌治疗。根据现行指南，考虑了四组进行性心肌损伤/功能障碍：正常，生物标志物（高敏肌钙蛋白T和N末端脑钠肽前体）正常，左心室（LV）功能正常；轻度，生物标志物异常和/或LV功能障碍（LVD），左心室射血分数（LVEF）≥50%；中度，LVD且LVEF为40 - 49%；重度，LVD且LVEF≤40%或有症状性心力衰竭。心脏毒性定义为随访期间心肌损伤/心室功能较基线出现新的变化或恶化。患者的中位随访时间为24个月。随访期间37.5%的患者被确定存在心脏毒性[95%置信区间（CI）34.22 - 40.8%]，31.6%为轻度，2.8%为中度，3.1%为重度心肌损伤/功能障碍。重度CTox组的死亡率为每100患者年22.9例死亡，而其他组为每100患者年2.3例死亡，风险比为10.2（95% CI 5.5 - 19.2）（P < 0.001）。
大多数患者在癌症治疗期间或之后出现心肌损伤/功能障碍的客观数据。然而，具有强烈预后关系的重度CTox相对少见。这应在临床和研究实践方案中得到体现。
