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JACC CardioOncol
JACC CardioOncol
JACC: CardioOncology
2666-0873
Elsevier

S2666-0873(24)00199-6
10.1016/j.jaccao.2024.05.010
Letters
To the Editor
Reply
Probing the Anthracycline-Induced Myocardial Injury: A Glimpse Through the Lens of the PRADA Trial
Mecinaj Albulena MD
Gulati Geeta MD, PhD
Omland Torbjørn MD, PhD, MPH
Heck Siri Lagethon MD, PhD s.l.heck@medisin.uio.no
@siri_lh
∗
∗ Department of Diagnostic Imaging, Akershus University Hospital, 1478 Lørenskog, Norway s.l.heck@medisin.uio.no@siri_lh
25 6 2024
8 2024
25 6 2024
6 4 630630
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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pmcWe thank Drs Statescu and El Blidi-Rahmani for their interest in our study on the incidence and prognostic value of asymptomatic cancer therapy–related cardiac dysfunction (CTRCD) as defined by the recent European Society of Cardiology cardio-oncology guidelines.1 Our study demonstrated that mild, asymptomatic CTRCD was frequent at the end of anthracycline therapy and was not predictive of subsequent CTRCD. The diagnosis of asymptomatic CTRCD was driven mainly by cardiac troponin (cTn) elevation and was markedly influenced by the choice of cTn assay and sex-neutral vs sex-dependent upper reference limit. In their letter, the authors comment that protracted, low-grade myocellular damage may continue long after the last anthracycline cycle and propose that serial cTn assessments including later time points might improve the ability to predict significant decline in systolic function. We agree that multiple cTn assessments at different time points may provide interesting insights and a more complete overview of myocellular damage, but the reported predictive value of serial cTn measurement has been inconsistent.2,3 In a study by Demissei et al,2 high-sensitivity cTnT (hs-cTnT) greater than the upper reference limit at the end of anthracycline therapy had a borderline significant association with risk for CTRCD within 1 year after the completion of anthracycline therapy. However, change in hs-cTnT was not associated with change in left ventricular ejection fraction (LVEF) or CTRCD at subsequent visits. In a small study encompassing 40 patients with breast cancer receiving anthracycline or trastuzumab, of whom 4 had declines in LVEF of >10 percentage points from baseline, Kitayama et al3 found that the integration of hs-cTnT values greater than baseline from multiple time points predicted cardiotoxicity. In contrast, in the Cardiac CARE (High-Sensitivity Cardiac Troponin I–Guided Combination Angiotensin Receptor Blockade and Beta Blocker Therapy to Prevent Cardiac Toxicity in Cancer Patients Receiving Anthracycline Chemotherapy) study, there was an overall decline in LVEF after 6 months irrespective of changes in hs-cTnI concentration during chemotherapy.4 In our view, the currently available evidence should be considered hypothesis generating, and further investigations concerning the predictive role, optimal timing, and optimal decision thresholds for cTn measurement before, during, and after anthracycline therapy are warranted.

Dr Gulati has received speaker honoraria from Novartis, AstraZeneca, and Bristol Myers Squibb. Dr Omland has served on advisory boards for Abbott Diagnostics, Roche Diagnostics, and Bayer; has received research support from Abbott Diagnostics, Novartis, and Roche Diagnostics via Akershus University Hospital; and has received speaker or consulting honoraria from Roche Diagnostics, Siemens Healthineers, and CardiNor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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References

1 Mecinaj A. Gulati G. Ree A.H. Impact of the ESC cardio-oncology guidelines biomarker criteria in incidence of cancer therapy–related cardiac dysfunction J Am Coll Cardiol CardioOnc 6 1 2024 83 95
2 Demissei B.G. Hubbard R.A. Zhang L. Changes in cardiovascular biomarkers with breast cancer therapy and associations with cardiac dysfunction J Am Heart Assoc 9 2020 e014708
3 Kitayama H. Kondo T. Sugiyama J. High-sensitive troponin T assay can predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients Breast Cancer 24 2017 774 782 28434150
4 Henriksen P.A. Hall P. MacPherson I.R. Multicenter, prospective, randomized controlled trial of high-sensitivity cardiac troponin I-guided combination angiotensin receptor blockade and beta-blocker therapy to prevent anthracycline cardiotoxicity: the Cardiac CARE trial Circulation 148 2023 1680 1690 37746692
