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Borja Rivero-Santana, Jesús Saldaña-García, Juan Caro-Codón, Pilar Zamora, Pedro Moliner, Amparo Martínez Monzonis, Eduardo Zatarain, Carlos Álvarez-Ortega, Pilar Gómez-Prieto, Sonia Pernas, Isabel Rodriguez, Antonio Buño Soto, Rosalía Cadenas, Patricia Palacios Ozores, Sara Pérez Ramírez, María Merino Salvador, Silvia Valbuena, Lucía Fernández Gasso, Victor Juárez, Andrea Severo, Belén Terol, Teresa de Soto Álvarez, Olaia Rodríguez, María Brion, José González-Costello, Miguel Canales Albendea, José R González-Juanatey, Raúl Moreno, José López-Sendón, Teresa López-Fernández, on behalf of the CARDIOTOX Registry Investigators, Anthracycline-induced cardiovascular toxicity: validation of the Heart Failure Association and International Cardio-Oncology Society risk score, European Heart Journal, Volume 46, Issue 3, 14 January 2025, Pages 273–284, https://doi.org/10.1093/eurheartj/ehae496
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Abstract
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.
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.
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.
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.

This study aimed to validate the Heart Failure Association and International Cardio-Oncology Society score for anthracycline-induced cardiovascular toxicity in a real-world cohort, the CARDIOTOX registry (NCT02039622). The Heart Failure Association and International Cardio-Oncology Society score effectively categorized patients based on their cardiovascular toxicity risk, demonstrating strong predictive capabilities for high-risk anthracycline-related cardiovascular toxicity and all-cause mortality.