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Current Oncology Reports
Published in: Current Oncology Reports 7/2020

Open Access 01-07-2020 | Heart Failure | Cardio-oncology (EH Yang, Section Editor)

Cardiac Biomarkers in Patients with Cancer: Considerations, Clinical Implications, and Future Avenues

Authors: Valentina Bracun, Joseph Pierre Aboumsallem, Peter van der Meer, Rudolf A. de Boer

Published in: Current Oncology Reports | Issue 7/2020

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Abstract

Purpose of the Review

As the number of cancer survivors increases due to early screening and modern (antineoplastic) treatments, cancer treatment associated cardiotoxicity (CTAC) is becoming an increasing health burden that affects survival and quality of life among cancer survivors. Thus, clinicians need to identify adverse events early, in an effort to take suitable measures before the occurrence of permanent or irreversible cardiac dysfunction.

Recent Findings

Cardiac troponin (cTn) and B-type natriuretic peptide (BNP) have been proven to detect subclinical cardiotoxicity during antineoplastic treatment. As such, these cardio-specific biomarkers could predict which patients are at risk of developing CTAC even before the start of therapy. Nevertheless, there are inconsistent data from published studies, and the recommendations regarding the use of these biomarkers and their validity are mostly based on expert consensus opinion.

Summary

In this review, we summarize available literature that evaluates biomarkers of CTAC, and we encourage strategies that integrate circulating biomarkers and cardiac imaging in identifying cancer patients that are at high risk.
Literature
1.
Dagenais GR, Leong DP, Rangarajan S, Lanas F, Lopez-Jaramillo P, Gupta R, et al. Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study. Lancet (London, England). 2019;19.
2.
Rossi S, Baili P, Capocaccia R, Caldora M, Carrani E, Minicozzi P, et al. The EUROCARE-5 study on cancer survival in Europe 1999–2007: database, quality checks and statistical analysis methods. Eur J Cancer. 2015;51:2104–19.PubMedCrossRef
3.
Ferrell BR, Temel JS, Temin S, Alesi ER, Balboni TA, Basch EM, et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017;35:96–112.PubMedCrossRef
4.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.PubMedCrossRef
5.
American Cancer Society. Facts & Figures 2019. Am Cancer Soc:2019.
6.
Boer RA, Meijers WC, Meer P, Veldhuisen DJ. Cancer and heart disease: associations and relations. Eur J Heart Fail. 2019:ejhf.1539.
7.
8.
Cardinale D, Biasillo G, Salvatici M, Sandri MT, Cipolla CM. Using biomarkers to predict and to prevent cardiotoxicity of cancer therapy. Expert Rev Mol Diagn Taylor & Francis. 2017;17:245–56.CrossRef
9.
Curigliano G, Cardinale D, Dent S, Criscitiello C, Aseyev O, Lenihan D, et al. Cardiotoxicity of anticancer treatments: epidemiology, detection, and management. CA Cancer J Clin. 2016;66:309–25.PubMedCrossRef
10.
Strongman H, Gadd S, Matthews A, Mansfield KE, Stanway S, Lyon AR, et al. Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases. Lancet. The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. 2019;394:1041–54.PubMedPubMedCentralCrossRef
11.
Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Eur Heart J. 2016;37:2768–801.PubMedCrossRef
12.
• Michel L, Mincu RI, Mahabadi AA, Settelmeier S, Al-Rashid F, Rassaf T, et al. Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis. Eur J Heart Fail. 2019:ejhf.1631. Elaborative meta- analysis of circulating cardiac biomarkers in patients treated with anthracyclines.
13.
Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131:1981–8.PubMedCrossRef
14.
Sweeney M, Yiu A, Lyon AR. Cardiac atrophy and heart failure in cancer. Card Fail Rev. 2017;03:62.CrossRef
15.
16.
Pavo N, Raderer M, Hülsmann M, Neuhold S, Adlbrecht C, Strunk G, et al. Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality. Heart. 2015;101:1874–80.PubMedCrossRef
17.
De Vito P. Atrial natriuretic peptide: an old hormone or a new cytokine? Peptides. 2014:108–16.
18.
• Meijers WC, Maglione M, Bakker SJL, Oberhuber R, Kieneker LM, De Jong S, et al. Heart failure stimulates tumor growth by circulating factors. Circulation. 2018;138:678–91. Study showing indesputable connection between heart failure and cancer. PubMedCrossRef
19.
Shi C, van der Wal HH, Silljé HHW, Dokter MM, van den Berg F, Huizinga L, et al. Tumor biomarkers: association with heart failure outcomes. J Intern Med. 2020.
20.
Aboumsallem JP, Moslehi J, De Boer RA. Reverse cardio-oncology: cancer development in patients with cardiovascular disease. J Am Heart Assoc. 2020 Jan 21;9(2):e013754.
21.
Yoldaş T, Yeşil Ş, Karademir S, Şahin G, Arman Örün U, Doǧan V, et al. Evaluation of long-term cardiac side effects of anthracycline chemotherapy by conventional and non-conventional echocardiographic methods in childhood cancer survivors. Cardiol Young. 2019;29:904–9.PubMedCrossRef
22.
Meijers WC, De Boer RA, Van Veldhuisen DJ, Jaarsma T, Hillege HL, Maisel AS, et al. Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH. Eur J Heart Fail. 2015;17:1271–82.PubMedCrossRef
23.
Du W, Piek A, Schouten EM, de van Kolk CWA, Mueller C, Mebazaa A, et al. Plasma levels of heart failure biomarkers are primarily a reflection of extracardiac production. Theranostics. 2018;8:4155–69.PubMedPubMedCentralCrossRef
24.
Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Russ J Cardiol. 2016;131:9–63.
25.
26.
Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). Circulation. 2018;138:e618–51.PubMedCrossRef
27.
Myhre PL, O’Meara E, Claggett BL, de Denus S, Jarolim P, Anand IS, et al. Cardiac troponin I and risk of cardiac events in patients with heart failure and preserved ejection fraction. Circ Heart Fail. 2018;11:e005312.PubMedCrossRef
28.
29.
Eggers KM, Jernberg T, Lindahl B. Cardiac troponin elevation in patients without a specific diagnosis. J Am Coll Cardiol. 2019;73:1–9.PubMedCrossRef
30.
Mahjoob MP, Sheikholeslami SA, Dadras M, Mansouri H, Haghi M, Naderian M, et al. Prognostic value of cardiac biomarkers assessment in combination with myocardial 2D strain echocardiography for early detection of anthracycline-related cardiac toxicity. Cardiovasc Hematol Disord Targets. 2019;19.
31.
Blaes A, Rehman A, Vock D, Luo X, Menge M, Yee D, et al. Utility of high-sensitivity cardiac troponin T in patients receiving anthracycline chemotherapy. Vasc Health Risk Manag. 2015;11:591.PubMedPubMedCentralCrossRef
32.
Zardavas D, Suter TM, Van Veldhuisen DJ, Steinseifer J, Noe J, Lauer S, et al. Role of troponins I and T and N-terminal prohormone of brain natriuretic peptide in monitoring cardiac safety of patients with early-stage human epidermal growth factor receptor 2-positive breast cancer receiving trastuzumab: a herceptin adjuvant study ca. J Clin Oncol. 2017;35:878–84.PubMedCrossRef
33.
Zhang CJ, Pei XL, Song FY, Guo Y, Zhang QL, Shu XH, et al. Early anthracycline-induced cardiotoxicity monitored by echocardiographic Doppler parameters combined with serum hs-cTnT. Echocardiography. 2017;34:1593–600.PubMedCrossRef
34.
Ky B, Putt M, Sawaya H, French B, Januzzi JL, Sebag IA, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2014;63:809–16.PubMedCrossRef
35.
Kitayama H, Kondo T, Sugiyama J, Kurimoto K, Nishino Y, Kawada M, et al. High-sensitive troponin T assay can predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients. Breast Cancer. 2017;24:774–82.PubMedCrossRef
36.
Advani P, Hoyne J, Moreno-Aspita A, Dubin M, Brock S, Harlow C, et al. High-sensitivity troponin T and NT-proBNP kinetics in breast cancer chemotherapy. Chemotherapy. 2017;62:334–8.PubMedCrossRef
37.
• Cardinale D, Ciceri F, Latini R, Franzosi MG, Sandri MT, Civelli M, et al. Anthracycline-induced cardiotoxicity: a multicenter randomised trial comparing two strategies for guiding prevention with enalapril: the International CardioOncology Society-one trial. Eur J Cancer. 2018;94:126–37. Study showing the benefits of enalapril in patients with CTIC. PubMedCrossRef
38.
• Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016;37:1671–80. Study showing a benefit of candesartan in patients with CTIC. PubMedPubMedCentralCrossRef
39.
• Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR, das Dores Cruz F, Gonçalves Brandão SM, Rigaud VOC, et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J Am Coll Cardiol. 2018;71:2281–90. Study showing the benefits of carvedilol in patients with CTIC. PubMedCrossRef
40.
Lenihan DJ, Stevens PL, Massey M, Plana JC, Araujo DM, Fanale MA, et al. The utility of point-of-care biomarkers to detect cardiotoxicity during anthracycline chemotherapy: a feasibility study. J Card Fail Elsevier Inc. 2016;22:433–8.CrossRef
41.
Palumbo I, Palumbo B, Fravolini ML, Marcantonini M, Perrucci E, Latini ME, et al. Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: a prospective study. Breast. 2016;25:45–50.PubMedCrossRef
42.
Bouwer NI, Liesting C, Kofflard MJM, Sprangers-van Campen SM, Brugts JJ, Kitzen JJEM, et al. NT-proBNP correlates with LVEF decline in HER2-positive breast cancer patients treated with trastuzumab. Cardio-Oncol. 2019;5:1–10.CrossRef
43.
Demissei B, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, et al. Changes in cardiovascular biomarkers with breast cancer therapy and associations with cardiac dysfunction. J Am Coll Cardiol. 2019;73:678.CrossRef
44.
Alvi RM, Frigault MJ, Fradley MG, Jain MD, Mahmood SS, Awadalla M, et al. Cardiovascular events among adults treated with chimeric antigen receptor T-cells (CAR-T). J Am Coll Cardiol. 2019;74:3099–108.PubMedCrossRefPubMedCentral
45.
Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet Elsevier Ltd. 2017;389:1195–205.CrossRef
46.
Mohan N, Jiang J, Dokmanovic M, Wu WJ. Trastuzumab-mediated cardiotoxicity: current understanding, challenges, and frontiers. Antib Ther. 2018;1:13–7.PubMedPubMedCentral
47.
Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018;71:1755–64.PubMedPubMedCentralCrossRef
48.
Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018:933.
49.
Upadhrasta S, Elias H, Patel K, Zheng L. Managing cardiotoxicity associated with immune checkpoint inhibitors. Chronic dis Transl med. Elsevier Masson SAS. 2019;5:6–14.
50.
Salem JE, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018;19:1579–89.PubMedPubMedCentralCrossRef
51.
Dolladille C, Ederhy S, Allouche S, Dupas Q, Gervais R, Madelaine J, et al. Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors. J Immunother cancer. 2020;8:e000261.PubMedPubMedCentralCrossRef
52.
Lancellotti P, Moonen M, Galderisi M. Chimeric antigen receptor T-cells and cardiovascular toxicity: cause for concern? J Am Coll Cardiol. 2019:3109–11.
53.
Pareek N, Cevallos J, Moliner P, Shah M, Tan LL, Chambers V, et al. Activity and outcomes of a cardio-oncology service in the United Kingdom—a five-year experience. Eur J Heart Fail. 2018;20:1721–31.PubMedCrossRef
54.
Kappel C, Rushton M, Johnson C, Aseyev O, Small G, Law AJ, et al. Clinical experience of patients referred to a multidisciplinary cardio-oncology clinic: an observational cohort study. Curr Oncol. 2019;26:322–7.CrossRef
55.
Jaffe AS, Ordonez-Llanos J. High-sensitivity cardiac troponin: from theory to clinical practice. Rev Esp Cardiol. 2013.
56.
Lipshultz SE, Rifai N, Sallan SE, Lipsitz SR, Dalton V, Sacks DB, et al. Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. Circulation. 1997;96:2641–8.PubMedCrossRef
57.
Cardinale D, Sandri MT, Martinoni A, Tricca A, Civelli M, Lamantia G, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol. 2000;36:517–22.PubMedCrossRef
58.
Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109:2749–54.PubMedCrossRef
59.
Rocco E, La Rosa G, Liuzzo G, Biasucci LM. High-sensitivity cardiac troponin assays and acute coronary syndrome: a matter of sex? J Cardiovasc Med. 2019:504–9.
60.
Goel S, Liu J, Guo H, Barry W, Bell R, Murray B, et al. Decline in left ventricular ejection fraction following anthracyclines predicts trastuzumab cardiotoxicity. JACC Hear Fail. 2019;7:795–804.CrossRef
61.
Cadeddu Dessalvi C, Pepe A, Penna C, Gimelli A, Madonna R, Mele D, et al. Sex differences in anthracycline-induced cardiotoxicity: the benefits of estrogens. Heart Fail Rev. 2019:915–25.
62.
Kurz K, Giannitsis E, Zehelein J, Katus HA. Highly sensitive cardiac troponin T values remain constant after brief exercise- or pharmacologic-induced reversible myocardial ischemia. Clin Chem. 2008;54:1234–8.PubMedCrossRef
63.
Samaha E, Avila A, Helwani MA, Ben Abdallah A, Jaffe AS, Scott MG, et al. High-sensitivity cardiac troponin after cardiac stress test: a systematic review and meta-analysis. J Am Heart Assoc. 2019;8:e008626.PubMedPubMedCentralCrossRef
64.
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016, 2016:2129–2200m.
65.
Mueller C, McDonald K, de Boer RA, Maisel A, Cleland JGF, Kozhuharov N, et al. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. Eur J Heart Fail. 2019;21:715–31.PubMedCrossRef
66.
Wolsk E, Claggett B, Pfeffer MA, Diaz R, Dickstein K, Gerstein HC, et al. Role of B-type natriuretic peptide and N-terminal prohormone BNP as predictors of cardiovascular morbidity and mortality in patients with a recent coronary event and type 2 diabetes mellitus. J Am Heart Assoc. 2017;6.
67.
Suthahar N, Meijers WC, Ho JE, Gansevoort RT, Voors AA, van der Meer P, et al. Sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide levels in the general population. Eur J Heart Fail. 2018;20:1205–14.PubMedCrossRef
68.
DErrico MP, Petruzzelli MF, Gianicolo EAL, Grimaldi L, Loliva F, Tramacere F, et al. Kinetics of B-type natriuretic peptide plasma levels in patients with left-sided breast cancer treated with radiation therapy: results after one-year follow-up. Int J Radiat Biol. 2015;91:804–9.CrossRef
69.
Ponde N, Bradbury I, Lambertini M, Ewer M, Campbell C, Ameels H, et al. Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06). Breast Cancer Res Treat. 2018;168:631–8.PubMedCrossRef
70.
De Iuliis F, Salerno G, Taglieri L, Lanza R, Cardelli P, Scarpa S. Circulating neuregulin-1 and galectin-3 can be prognostic markers in breast cancer. Int J Biol Markers. 2017;32:e333–6.PubMedCrossRef
71.
Dessì M, Madeddu C, Piras A, Cadeddu C, Antoni G, Mercuro G, et al. Long-term, up to 18 months, protective effects of the angiotensin II receptor blocker telmisartan on Epirubin-induced inflammation and oxidative stress assessed by serial strain rate. Springerplus. 2013;2:1–10.CrossRef
72.
Riddell E, Lenihan D. The role of cardiac biomarkers in cardio-oncology. Curr Probl Cancer. 2018:375–85.
73.
Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010:463–6.
Metadata
Title
Cardiac Biomarkers in Patients with Cancer: Considerations, Clinical Implications, and Future Avenues
Authors
Valentina Bracun
Joseph Pierre Aboumsallem
Peter van der Meer
Rudolf A. de Boer
Publication date
01-07-2020
Publisher
Springer US
Published in
Current Oncology Reports / Issue 7/2020
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-020-00930-x

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