蒽环类药物所致心血管毒性：心力衰竭协会和国际心脏肿瘤学会风险评分的验证

Anthracycline-induced cardiovascular toxicity: validation of the Heart Failure Association and International Cardio-Oncology Society risk score.

作者信息

Rivero-Santana Borja, Saldaña-García Jesús, Caro-Codón Juan, Zamora Pilar, Moliner Pedro, Martínez Monzonis Amparo, Zatarain Eduardo, Álvarez-Ortega Carlos, Gómez-Prieto Pilar, Pernas Sonia, Rodriguez Isabel, Buño Soto Antonio, Cadenas Rosalía, Palacios Ozores Patricia, Pérez Ramírez Sara, Merino Salvador María, Valbuena Silvia, Fernández Gasso Lucía, Juárez Victor, Severo Andrea, Terol Belén, de Soto Álvarez Teresa, Rodríguez Olaia, Brion María, González-Costello José, Canales Albendea Miguel, González-Juanatey José R, Moreno Raúl, López-Sendón José, López-Fernández Teresa

机构信息

Cardiology Department, La Paz University Hospital, IdiPAZ Research Institute, C/Paseo de la Castellana n° 261, 28046 Madrid, Spain.

Oncology Department, La Paz University Hospital, IdiPAZ Research Institute, CIBER ONC, Madrid, Spain.

出版信息

Eur Heart J. 2025 Jan 16;46(3):273-284. doi: 10.1093/eurheartj/ehae496.

DOI:10.1093/eurheartj/ehae496

PMID:39106857

Abstract

BACKGROUND AND AIMS

Baseline cardiovascular toxicity risk stratification is critical in cardio-oncology. The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) score aims to assess this risk but lacks real-life validation. This study validates the HFA-ICOS score for anthracycline-induced cardiovascular toxicity.

METHODS

Anthracycline-treated patients in the CARDIOTOX registry (NCT02039622) were stratified by the HFA-ICOS score. The primary endpoint was symptomatic or moderate to severe asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), with all-cause mortality and cardiovascular mortality as secondary endpoints.

RESULTS

The analysis included 1066 patients (mean age 54 ± 14 years; 81.9% women; 24.5% ≥65 years). According to the HFA-ICOS criteria, 571 patients (53.6%) were classified as low risk, 333 (31.2%) as moderate risk, 152 (14.3%) as high risk, and 10 (0.9%) as very high risk. Median follow-up was 54.8 months (interquartile range 24.6-81.8). A total of 197 patients (18.4%) died, and 718 (67.3%) developed CTRCD (symptomatic: n = 45; moderate to severe asymptomatic: n = 24; and mild asymptomatic: n = 649). Incidence rates of symptomatic or moderate to severe symptomatic CTRCD and all-cause mortality significantly increased with HFA-ICOS score [hazard ratio 28.74, 95% confidence interval (CI) 9.33-88.5; P < .001, and hazard ratio 7.43, 95% CI 3.21-17.2; P < .001) for very high-risk patients. The predictive model demonstrated good calibration (Brier score 0.04, 95% CI 0.03-0.05) and discrimination (area under the curve 0.78, 95% CI 0.70-0.82; Uno's C-statistic 0.78, 95% CI 0.71-0.84) for predicting symptomatic or severe/moderate asymptomatic CTRCD at 12 months.

CONCLUSIONS

The HFA-ICOS score effectively categorizes patients by cardiovascular toxicity risk and demonstrates strong predictive ability for high-risk anthracycline-related cardiovascular toxicity and all-cause mortality.

摘要

背景与目的

在心脏肿瘤学中，基线心血管毒性风险分层至关重要。心力衰竭协会（HFA）和国际心脏肿瘤学会（ICOS）评分旨在评估此风险，但缺乏现实生活中的验证。本研究验证了HFA-ICOS评分在蒽环类药物所致心血管毒性方面的有效性。

方法

CARDIOTOX注册研究（NCT02039622）中接受蒽环类药物治疗的患者按HFA-ICOS评分进行分层。主要终点为有症状的或中度至重度无症状的癌症治疗相关心脏功能障碍（CTRCD），全因死亡率和心血管死亡率作为次要终点。

结果

分析纳入了1066例患者（平均年龄54±14岁；81.9%为女性；24.5%年龄≥65岁）。根据HFA-ICOS标准，571例患者（53.6%）被分类为低风险，333例（31.2%）为中度风险，152例（14.3%）为高风险，10例（0.9%）为极高风险。中位随访时间为54.8个月（四分位间距24.6 - 81.8）。共有197例患者（18.4%）死亡，718例（67.3%）发生了CTRCD（有症状的：n = 45；中度至重度无症状的：n = 24；轻度无症状的：n = 649）。有症状的或中度至重度有症状的CTRCD以及全因死亡率的发生率随HFA-ICOS评分显著增加[极高风险患者的风险比为28.74，95%置信区间（CI）9.33 - 88.5；P <.001，以及风险比7.43，95% CI 3.21 - 17.2；P <.001]。该预测模型在预测12个月时有症状的或重度/中度无症状的CTRCD方面显示出良好的校准（Brier评分0.04，95% CI 0.03 - 0.05）和区分能力（曲线下面积0.78，95% CI 0.70 - 0.82；Uno氏C统计量0.78，95% CI 0.71 - 0.84）。