Cardiac and noncardiac biomarkers in patients undergoing anthracycline chemotherapy – a prospective analysis

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Abstract

Background

Biomarkers represent a potential tool to identify individuals at risk for anthracycline-induced cardiotoxicity (AICT) prior to symptom onset or left ventricular dysfunction.

Methods

This study examined the levels of cardiac and noncardiac biomarkers before, after the last dose of, and 3–6 months after completion of doxorubicin chemotherapy. Cardiac biomarkers included 5th generation high-sensitivity cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide, growth/differentiation factor-15 (GDF-15), and soluble suppression of tumorigenesis-2 (sST2). Noncardiac biomarkers included activated caspase-1 (CASP-1), activated caspase-3, C-reactive protein, tumor necrosis factor-α, myeloperoxidase (MPO), galectin-3, and 8-hydroxy-2’-deoxyguanosine. Echocardiographic data (LVEF and LVGLS) were obtained at pre- and post-chemotherapy. Subanalysis examined interval changes in biomarkers among high (cumulative doxorubicin dose ≥ 250 mg/m ²) and low exposure groups.

Results

The cardiac biomarkers cTnT, GDF-15, and sST2 and the noncardiac biomarkers CASP-1 and MPO demonstrated significant changes over time. cTnT and GDF-15 levels increased after anthracycline exposure, while CASP-1 and MPO decreased significantly. Subanalysis by cumulative dose did not demonstrate a larger increase in any biomarker in the high-dose group.

Conclusions

The results identify biomarkers with significant interval changes in response to anthracycline therapy. Further research is needed to understand the clinical utility of these novel biomarkers.

Supplementary Information

The online version contains supplementary material available at 10.1186/s40959-023-00174-1.

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Most cited references 2

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BNP Predicts Chemotherapy-Related Cardiotoxicity and Death: Comparison with Gated Equilibrium Radionuclide Ventriculography

Dorthe Skovgaard, Philip Hasbak, Andreas Kjaer (2014)

Cardiotoxicity is a dose-limiting side-effect of cancer chemotherapeutics such as anthracyclines. The drug-induced cardiac toxicity is currently monitored with repeated assessments of the left ventricular ejection fraction (LVEF) using multigated equilibrium radionuclide ventriculography (MUGA) or echocardiography. However, the plasma cardiac biomarker B-type natriuretic peptide (BNP) has been suggested for early identification of cardiac dysfunction. The aim of the study was to compare LVEF obtained by MUGA and plasma BNP as predictors of developing congestive heart failure (CHF) or death in a population of anthracycline-treated cancer patients. Methods We prospectively followed 333 cancer patients referred to our department for routine monitoring of LVEF with MUGA and measurement of BNP, January-December 2004. Study end points were hospitalization for CHF and death during follow-up 2004-2010. Data were obtained from the Danish National Patient Registry. Results During follow-up (mean 1,360 days), 21 of the patients were admitted to hospital with a diagnosis of CHF and 194 of the patients died. BNP levels were significantly higher and LVEF lower in the group of patients that developed CHF. Using cut-off points of BNP>100 pg/ml (HR 5.5; CI 1.8–17.2; p = 0.003) and LVEF <50% (HR 7.9; CI 3.0–21.4; p<0.001) both significantly predicted CHF. Using the same cut-off points only BNP (HR 1.9; CI 1.3-2.9; p = 0.002) and not LVEF (HR 1.1; CI 0.7–1.8; p = 0.58) was predictive of overall death. In multivariate Cox analysis both BNP and LVEF were independent predictors of CHF while age remained the only independent predictor of overall death. Conclusion In cancer patients treated with cardiotoxic chemotherapy both BNP and LVEF can significantly predict subsequent hospitalization with CHF. In addition, BNP and not LVEF has a prognostic value in detecting overall death. This prospective study based on the hitherto largest study population supports BNP as a clinical relevant method for monitoring chemotherapy-related cardiac failure and death.

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Role of Biomarkers in Prediction of Cardiotoxicity During Cancer Treatment

Li-Ling Tan, Alexander R Lyon (2018)

Purpose of review As cancer survivor rates improve with early screening and modern treatment options, cardiotoxicity is becoming an increasing problem. It is imperative for physicians to recognize adverse events early so that appropriate measures can be taken before advanced and permanent cardiac dysfunction ensues. In this review, we will evaluate the literature surrounding current cardiac biomarkers in the detection of cardiotoxicity during cancer treatment as well as discuss the role of emerging novel biomarkers. Recent findings Troponin and brain natriuretic peptides show promise in the detection of subclinical cardiotoxicity during cancer treatment. In addition to identifying late complications among cancer survivors, they have the potential to predict patients who are at risk of developing cardiotoxicity prior to the initiation of cancer therapy. However, there are also conflicting data due to varying study design. Summary Although biomarkers are an attractive option in the detection of cardiotoxicity among cancer patients, current recommendations surrounding its role are based on expert consensus opinion. Further research with appropriately designed prospective trials is required to guide optimal clinical practice.

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Author and article information

Contributors

Matthew Dean: matthew.dean@vcuhealth.org

Min Jung Kim: mikim@uchc.edu

Sharon Dimauro: dimauro@uchc.edu

Susan Tannenbaum: stannenbaum@uchc.edu

Garth Graham: gnsgraham@gmail.com

Bruce T. Liang: bliang@uchc.edu

Agnes S. Kim: akim@uchc.edu

Journal

Journal ID (nlm-ta): Cardiooncology

Journal ID (iso-abbrev): Cardiooncology

Title: Cardio-oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 2057-3804

Publication date (Electronic): 27 April 2023

Publication date PMC-release: 27 April 2023

Publication date Collection: 2023

Volume: 9

Electronic Location Identifier: 23

Affiliations

[1 ]GRID grid.208078.5, ISNI 0000000419370394, Department of Medicine, Calhoun Cardiology Center, , University of Connecticut School of Medicine, ; 263 Farmington Avenue, Farmington, CT 06030 USA

[2 ]GRID grid.224260.0, ISNI 0000 0004 0458 8737, Virginia Commonwealth University Health System Internal Medicine Residency, ; 1101 E. Marshall St, Richmond, VA 23298 USA

[3 ]GRID grid.208078.5, ISNI 0000000419370394, Pat and Jim Calhoun Cardiology Center, , UConn Health, ; 300 UConn Health Boulevard, Farmington, CT USA

[4 ]GRID grid.208078.5, ISNI 0000000419370394, Carole & Ray Neag Comprehensive Cancer Center, , UConn Health, ; 263 Farmington Avenue, Farmington, CT 06030 USA

Article

Publisher ID: 174

DOI: 10.1186/s40959-023-00174-1

PMC ID: 10133897

PubMed ID: 37106424

SO-VID: 7954ed40-6a32-4681-896e-b4daa0cfd6e9

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 11 January 2023

Date accepted : 18 April 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000045, Aetna Foundation;

Award ID: 15-0285

Custom metadata

Keywords: anthracycline,chemotherapy,cardiotoxicity,biomarker,troponin,growth/differentiation factor-15,s oluble suppression of tumorigenesis-2,myeloperoxidase,caspase,ejection fraction

Data availability:

Keywords: anthracycline, chemotherapy, cardiotoxicity, biomarker, troponin, growth/differentiation factor-15, s oluble suppression of tumorigenesis-2, myeloperoxidase, caspase, ejection fraction