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      Troponins and Natriuretic Peptides in Cardio-Oncology Patients—Data From the ECoR Registry

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          Abstract

          Background

          The long-term survival of cancer patients has significantly improved over the past years. Despite their therapeutic efficacy, various cancer therapies are associated with cardiotoxicity. Therefore, timely detection of cardiotoxic adverse events is crucial. However, the clinical assessment of myocardial damage caused by cancer therapy remains difficult.

          Methods

          This retrospective study was performed to evaluate the diagnostic value of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for monitoring cancer therapy-induced cardiomyopathy. A total of 485 cancer patients referred to our cardio-oncology unit between July 2018 and January 2020 were selected from our Essen Cardio-oncology Registry (ECoR). We included patients with all types of cancer. Plasma concentrations of cTnI and NT-proBNP were measured by radioimmunoassay, and two-dimensional left ventricular ejection fraction (2D-LVEF), diastolic function, and global longitudinal strain (GLS) were measured by transthoracic echocardiography. In 116 patients, assessment was conducted before the induction of cancer therapy and during a short-term follow-up period; n = 42 of these were treated for malignant melanoma, and n = 42 with serial measurements were under treatment for breast cancer.

          Results

          In cross-sectional data, elevated NT-proBNP was associated with reduced LVEF and pathological GLS in the total cohort. A total of 116 patients had serial LVEF and biomarker measurements, and changes in NT-proBNP and troponin correlated with changes in LVEF during follow-up investigations. Similar to the total cohort, a subgroup of patients treated for malignant melanoma showed a correlation between the change in cTnI and the change in LVEF. In a subgroup analysis of patients undergoing breast cancer therapy, a correlation between the change in NT-proBNP and the change in LVEF could be detected. Thirty patients presented with chemotherapy-induced cardiomyopathy, defined as a significant LVEF decrease (> 10%) to a value below 50%. The number of patients with increased cTnI and NT-proBNP was significantly higher in patients with chemotherapy-induced cardiomyopathy than in patients without cardiotoxicity. Patients with positive cTnI and NT-proBNP were more likely to have a history of coronary heart disease, atrial fibrillation, and arterial hypertension.

          Conclusion

          Our data suggest that cardiac biomarkers play an important role in the detection of cancer therapy-induced cardiotoxicity. Larger systematic assessment in prospective cohorts is mandatory.

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          Most cited references43

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          Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults: Recommendations from the American Society of Echocardiography

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            OUP accepted manuscript

            (2017)
            This European Association Cardiovascular Imaging (EACVI) Expert Consensus document aims at defining the main quantitative information on cardiac structure and function that needs to be included in standard echocardiographic report following recent ASE/EACVI chamber quantification, diastolic function, and heart valve disease recommendations. The document focuses on general reporting and specific pathological conditions such as heart failure, coronary artery and valvular heart disease, cardiomyopathies, and systemic diseases.
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              Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab.

              Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab. Eighty-one women with newly diagnosed human epidermal growth factor receptor 2-positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro-B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%-43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%-14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure. In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                19 May 2020
                2020
                : 11
                : 740
                Affiliations
                [1] Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, Medical Faculty, University Hospital Essen , Essen, Germany
                Author notes

                Edited by: Sebastian Szmit, Medical Centre for Postgraduate Education, Poland

                Reviewed by: Joachim Neumann, Institut für Pharmakologie und Toxikologie, Germany; Daniela Cardinale, European Institute of Oncology (IEO), Italy

                *Correspondence: Tienush Rassaf, tienush.rassaf@ 123456uk-essen.de

                This article was submitted to Cardiovascular and Smooth Muscle Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2020.00740
                7248256
                2a20ebd3-9c04-49d8-9860-20b46eb73373
                Copyright © 2020 Hinrichs, Mrotzek, Mincu, Pohl, Röll, Michel, Mahabadi, Al-Rashid, Totzeck and Rassaf

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 March 2020
                : 04 May 2020
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 57, Pages: 10, Words: 5558
                Funding
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                troponin,nt-probnp,cancer,cardiotoxicity,cardiomyopathy,cardio-oncology

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