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. 2024 Jan 16;6(1):83-95.
doi: 10.1016/j.jaccao.2023.10.008. eCollection 2024 Feb.

Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy-Related Cardiac Dysfunction

Albulena Mecinaj  1   2 , Geeta Gulati  1   3   4 , Anne Hansen Ree  5   6 , Berit Gravdehaug  7 , Helge Røsjø  1   4 , Kjetil Steine  2   5 , Torbjørn Wisløff  5   8 , Jürgen Geisler  5   6 , Torbjørn Omland  1   2 , Siri Lagethon Heck  1   9
Affiliations

Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy-Related Cardiac Dysfunction

Albulena Mecinaj et al. JACC CardioOncol. .

Abstract

Background: The impact of recent consensus definitions of cancer therapy-related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed.

Objectives: The aim of this study was to assess the: 1) cumulative incidence; 2) point prevalence during and after adjuvant therapy; and 3) prognostic value of CTRCD as defined by different asymptomatic CTRCD guideline criteria.

Methods: The cumulative incidence and point prevalence of CTRCD were retrospectively assessed in 118 patients participating in the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial. Asymptomatic CTRCD was assessed using alternative cardiac troponin (cTn) 99th percentile upper reference limits (URLs) to define cTnT and cTnI elevation.

Results: The cumulative incidence of moderate or severe CTRCD was low (1.7%), whereas the cumulative incidence of mild asymptomatic CTRCD was higher and differed markedly according to the biomarker criteria applied, ranging from 49.2% of patients when cTnT greater than the sex-specific 99th percentile URL was used to define cTn elevation to 9.3% when sex-neutral cTnI was used. The point prevalence of CTRCD was highest at the end of anthracycline therapy (47.8%) and was driven primarily by asymptomatic cTn elevation. CTRCD during adjuvant therapy was not prognostic for CTRCD at extended follow-up of 24 months (Q1-Q3: 21-29 months) after randomization.

Conclusions: Mild asymptomatic CTRCD during adjuvant breast cancer therapy was frequent and driven mainly by cTn elevation and was not prognostic of subsequent CTRCD. The incidence of mild, asymptomatic CTRCD differed markedly depending on the cTn assay and whether sex-neutral or sex-dependent URLs were applied. (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy [PRADA]; NCT01434134).

Keywords: biomarkers; breast cancer; cardiac magnetic resonance; cardiomyopathy; guidelines; troponin.

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Conflict of interest statement

This work was supported by the South-Eastern Norway Regional Health Authority, the University of Oslo, the Extra Foundation for Health and Rehabilitation, Norway, the Norwegian Cancer Society, and Akershus University Hospital. Study medications and matching placebos were provided free of charge by AstraZeneca. Reagents for the analysis of high-sensitivity cTnI were provided by Abbott Diagnostics. 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.

Figures

None
Graphical abstract
Figure 1
Figure 1
CTRCD Definition Asymptomatic cancer therapy–related cardiac dysfunction (CTRCD) according to the International Cardio-Oncology Society. GLS = global longitudinal strain; LVEF = left ventricular ejection fraction.
Figure 2
Figure 2
Study Timeline and Procedures Overview of PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) study timeline and available measurements at each time point. BM = biomarkers; CMR = cardiac magnetic resonance imaging; HER2 = human epidermal growth factor receptor 2; other abbreviations as in Figure 1.
Central Illustration
Central Illustration
CTRCD According to cTn Assay and Upper Reference Limits (Top) Distribution of cancer therapy–related cardiac dysfunction (CTRCD) by cardiac troponin (cTn) definition. (Bottom) Distribution of CTRCD by cTn definition at the end of anthracycline therapy and at extended follow-up in the 115 patients with assessment at the end of anthracycline therapy. GLS = global longitudinal strain; LVEF = left ventricular ejection fraction; URL = upper reference limit.
Figure 3
Figure 3
Biomarker Concentrations and Systolic Function at Each Study Time Point Distribution of cardiac troponin (cTn) T and I, amino-terminal pro–B-type natriuretic peptide (NT-proBNP), LVEF, GLS, and relative change in GLS from baseline at baseline (visit 1), after 1 anthracycline cycle (visit 2), at the end of anthracyclines (visit 3), after trastuzumab or radiation therapy (visit 4), and at extended follow-up (visit 5). Horizontal lines represent the different cutoff values; x indicates an outlier (82.3 ng/L). Abbreviations as in Figure 1.
Figure 4
Figure 4
Troponin Levels After Anthracyclines by Systolic Function at Extended Follow-Up Distribution of cardiac troponin (cTn) T and I according to whether systolic function was reduced at extended follow-up. Reduced systolic function was defined as a left ventricular ejection decline of ≥10 percentage points to a value between 40% and 49% or a decline in global longitudinal strain of ≥15% from baseline. Horizontal orange and red lines represent sex-specific and sex-neutral upper reference limits, and x indicates an outlier (82.3 ng/L).
See this image and copyright information in PMC

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