Anthracycline Dose, Myocardial Injury, and Change in Left Ventricular Function in the Cardiac CARE Trial

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology Pub Date : 2025-10-01 DOI:10.1016/j.jaccao.2025.06.003

Krithika Loganath MBBS ∗ , Kuan Ken Lee PhD ∗ , Olga Oikonomidou MD, BSc, MSc, MRes, PhD , Peter Hall PhD , Nicholas L. Mills BSc Hons, MBChB, PhD , Shruti Joshi PhD , Trisha Singh PhD , Tom McGillivray PhD , Scott Semple PhD , Ninian N. Lang BSc (Hons), MB ChB, PhD , Marc R. Dweck BSc (Hons), MBChB, PhD , Peter A. Henriksen BSc, MB ChB, PhD

{"title":"Anthracycline Dose, Myocardial Injury, and Change in Left Ventricular Function in the Cardiac CARE Trial","authors":"Krithika Loganath MBBS ∗ , Kuan Ken Lee PhD ∗ , Olga Oikonomidou MD, BSc, MSc, MRes, PhD , Peter Hall PhD , Nicholas L. Mills BSc Hons, MBChB, PhD , Shruti Joshi PhD , Trisha Singh PhD , Tom McGillivray PhD , Scott Semple PhD , Ninian N. Lang BSc (Hons), MB ChB, PhD , Marc R. Dweck BSc (Hons), MBChB, PhD , Peter A. Henriksen BSc, MB ChB, PhD","doi":"10.1016/j.jaccao.2025.06.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Anthracycline-induced toxicity contributes to long-term cardiovascular morbidity in cancer survivors. Cardiac troponin is recommended for risk stratification and diagnosis, but the relationship between troponin concentrations—particularly those measured using high-sensitivity assays—and subsequent cardiac dysfunction remains unclear.</div></div><div><h3>Objectives</h3><div>The authors sought to examine associations between high-sensitivity cardiac troponin I (hs-cTnI), cumulative anthracycline dose, number of treatment cycles, and changes in left ventricular (LV) function.</div></div><div><h3>Methods</h3><div>The Cardiac CARE trial was a prospective, multicenter, randomized, open-label, blinded-endpoint study of cardioprotective therapy in patients with elevated baseline hs-cTnI undergoing high-dose anthracycline chemotherapy. Hs-cTnI was measured before each chemotherapy cycle and at 2, 4, and 6 months after treatment. LV function was assessed by cardiac magnetic resonance at baseline and 6 months post-chemotherapy.</div></div><div><h3>Results</h3><div>Of the 175 participants (mean age 52 ± 11 years; 86.5% women), 171 received ≥3 anthracycline cycles. The median cumulative epirubicin-equivalent dose was 600 mg/m<sup>2</sup> (Q1-Q3: 513-660 mg/m<sup>2</sup>). Peak hs-cTnI concentrations were observed 2 months after chemotherapy (median 14.0 ng/L [Q1-Q3: 9.0-30.5 ng/L]) and statistically correlated with the number of treatment cycles, but not with cumulative dose. No participants developed an LV ejection fraction (LVEF) <50%, although 24 of 171 patients (14.0%) experienced a decline in LVEF >10%. Hs-cTnI showed a weak correlation with LVEF change and was not predictive of global longitudinal strain by cardiac magnetic resonance.</div></div><div><h3>Conclusions</h3><div>Hs-cTnI levels were not associated with cumulative anthracycline dose and were only weakly associated with LVEF decline at 6 months. These findings suggest that mild myocardial injury, as reflected by hs-cTnI elevation, may not reliably predict subsequent cardiac dysfunction following anthracycline chemotherapy.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 725-735"},"PeriodicalIF":12.8000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jacc: Cardiooncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666087325002467","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Anthracycline-induced toxicity contributes to long-term cardiovascular morbidity in cancer survivors. Cardiac troponin is recommended for risk stratification and diagnosis, but the relationship between troponin concentrations—particularly those measured using high-sensitivity assays—and subsequent cardiac dysfunction remains unclear.

Objectives

The authors sought to examine associations between high-sensitivity cardiac troponin I (hs-cTnI), cumulative anthracycline dose, number of treatment cycles, and changes in left ventricular (LV) function.

Methods

The Cardiac CARE trial was a prospective, multicenter, randomized, open-label, blinded-endpoint study of cardioprotective therapy in patients with elevated baseline hs-cTnI undergoing high-dose anthracycline chemotherapy. Hs-cTnI was measured before each chemotherapy cycle and at 2, 4, and 6 months after treatment. LV function was assessed by cardiac magnetic resonance at baseline and 6 months post-chemotherapy.

Results

Of the 175 participants (mean age 52 ± 11 years; 86.5% women), 171 received ≥3 anthracycline cycles. The median cumulative epirubicin-equivalent dose was 600 mg/m² (Q1-Q3: 513-660 mg/m²). Peak hs-cTnI concentrations were observed 2 months after chemotherapy (median 14.0 ng/L [Q1-Q3: 9.0-30.5 ng/L]) and statistically correlated with the number of treatment cycles, but not with cumulative dose. No participants developed an LV ejection fraction (LVEF) <50%, although 24 of 171 patients (14.0%) experienced a decline in LVEF >10%. Hs-cTnI showed a weak correlation with LVEF change and was not predictive of global longitudinal strain by cardiac magnetic resonance.

Conclusions

Hs-cTnI levels were not associated with cumulative anthracycline dose and were only weakly associated with LVEF decline at 6 months. These findings suggest that mild myocardial injury, as reflected by hs-cTnI elevation, may not reliably predict subsequent cardiac dysfunction following anthracycline chemotherapy.

查看原文本刊更多论文

心脏CARE试验中蒽环类药物剂量、心肌损伤和左心室功能改变。

背景：蒽环类药物引起的毒性有助于癌症幸存者的长期心血管发病率。心肌肌钙蛋白被推荐用于风险分层和诊断，但是肌钙蛋白浓度（特别是那些使用高灵敏度测定法测量的）与随后的心功能障碍之间的关系尚不清楚。目的：作者试图研究高敏感性心肌肌钙蛋白I （hs-cTnI）、蒽环类药物累积剂量、治疗周期数和左心室（LV）功能变化之间的关系。方法：Cardiac CARE试验是一项前瞻性、多中心、随机、开放标签、盲终点的研究，对接受大剂量蒽环类药物化疗的基线hs-cTnI升高的患者进行心脏保护治疗。在每个化疗周期前和治疗后2、4和6个月测量Hs-cTnI。在基线和化疗后6个月通过心脏磁共振评估左室功能。结果：175名参与者(平均年龄52±11岁；86.5%女性)，171例接受≥3个蒽环类药物周期。中位累积表柔比星当量剂量为600 mg/m2 （Q1-Q3: 513-660 mg/m2）。化疗后2个月观察到hs-cTnI浓度峰值（中位数14.0 ng/L [Q1-Q3: 9.0-30.5 ng/L]），与治疗周期数有统计学相关性，但与累积剂量无关。没有参与者出现左室射血分数（LVEF） 10%。Hs-cTnI与LVEF变化呈弱相关，可预测心脏磁共振整体纵向应变。结论：Hs-cTnI水平与累积蒽环类药物剂量无关，仅与6个月时LVEF下降弱相关。这些发现表明，hs-cTnI升高所反映的轻度心肌损伤可能不能可靠地预测蒽环类药物化疗后的心功能障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Jacc: Cardiooncology Multiple-

CiteScore

12.50

自引率

6.30%

发文量

106

期刊介绍： JACC: CardioOncology is a specialized journal that belongs to the esteemed Journal of the American College of Cardiology (JACC) family. Its purpose is to enhance cardiovascular care for cancer patients by publishing high-quality, innovative scientific research and sharing evidence-based knowledge. The journal aims to revolutionize the field of cardio-oncology and actively involve and educate professionals in both cardiovascular and oncology fields. It covers a wide range of topics including pre-clinical, translational, and clinical research, as well as best practices in cardio-oncology. Key areas of focus include understanding disease mechanisms, utilizing in vitro and in vivo models, exploring novel and traditional therapeutics (across Phase I-IV trials), studying epidemiology, employing precision medicine, and investigating primary and secondary prevention. Amyloidosis, cardiovascular risk factors, heart failure, and vascular disease are some examples of the disease states that are of particular interest to the journal. However, it welcomes research on other relevant conditions as well.