The Role of Biomarkers in Cardio-Oncology

Kajaluxy Ananthan, Alexander R Lyon, Kajaluxy Ananthan, Alexander R Lyon

Abstract

In the field of cardio-oncology, it is well recognised that despite the benefits of chemotherapy in treating and possibly curing cancer, it can cause catastrophic damage to bystander tissues resulting in a range of potentially of life-threatening cardiovascular toxicities, and leading to a number of damaging side effects including heart failure and myocardial infarction. Cardiotoxicity is responsible for significant morbidity and mortality in the long-term in oncology patients, specifically due to left ventricular dysfunction. There is increasing emphasis on the early use of biomarkers in order to detect the cardiotoxicity at a stage before it becomes irreversible. The most important markers of cardiac injury are cardiac troponin and natriuretic peptides, whilst markers of inflammation such as interleukin-6, C-reactive protein, myeloperoxidase, Galectin-3, growth differentiation factor-15 are under investigation for their use in detecting cardiotoxicity early. In addition, microRNAs, genome-wide association studies and proteomics are being studied as novel markers of cardiovascular injury or inflammation. The aim of this literature review is to discuss the evidence base behind the use of these biomarkers for the detection of cardiotoxicity.

Keywords: BNP; Biomarker; Brain natriuretic peptide; Cardio-Oncology; Cardiotoxicity; Heart failure; Troponin.

Conflict of interest statement

ARL has received speaker, advisory board or consultancy fees and/or research grants from Pfizer, Novartis, Servier, Amgen,Clinigen Group, Takeda, Roche, Eli Lily, Eisal, Bristol Myers Squibb, Ferring Pharmaceuticals and Boehringer Ingelheim. KA has no conflicts of interest.

Figures

Fig. 1
Fig. 1
Demonstrates the main mechanism of cardiotoxicity for most cytotoxic chemotherapy. Firstly, anthracycylines have direct mechanisms of damaging DNA resulting in cell cycle arrest leading to either: apopotosis, cell necrosis or cell autophagy. They also generate toxic reactive oxygen species (ROS). ROS trigger off a cascade of events which alters mitochondrial permeability and hence function which moderates calcium signalling and hence myocyte contraction. The mechansim of this invovles the SERCA2a protein which is at the centre of calcium homeostasis. Secondly the receptor tyrosine kinase inhibitors, namely bevacluzumab, trastuzumab, etc. function by inhibiting the activity of their receptor proteins: Vascular Endothelial Growth Factor Receptor (VEGFR), ErBb4/ErBb2 and Her2/Neu receptor resulting in cell cycle arrest in the Growth 1 (G1) phase of the cycle leading eventually to apoptosis, necrosis or cell autophagy. This transition is mediated by p53 (a nuclear DNA-binding phosphoprotein). [22, 155, 156]

References

    1. Dolci A, Panteghini M. The exciting story of cardiac biomarkers: from retrospective detection to gold diagnostic standard for acute myocardial infarction and more. Clinica Chimica Acta. 2006;369(2):179–187. doi: 10.1016/j.cca.2006.02.042.
    1. Zamorano JL, Lancellotti P, Rodriguez MD, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. European Heart Journal. 2016;37(36):2768–2801. doi: 10.1093/eurheartj/ehw211.
    1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the heart failure association (HFA) of the ESC. European Journal of Heart Failure. 2016;18(8):891–975. doi: 10.1002/ejhf.592.
    1. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE).Version 4.0. Available at: . Accessed December 25, 2019.
    1. Curigliano G, Lenihan D, Fradley M, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Annals of Oncology, the journal of the European Society for Medical Oncology. 2020;31(2):171–190. doi: 10.1016/j.annonc.2019.10.023.
    1. McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracycline chemotherapy and cardiotoxicity. Cardiovascular Drugs and Therapy. 2017;31(1):63–75. doi: 10.1007/s10557-016-6711-0.
    1. Feijen EAM, Leisenring WM, Stratton KL, Ness KK, van der Pal HJH, van Dalen EC, Armstrong GT, Aune GJ, Green DM, Hudson MM, Loonen J, Oeffinger KC, Robison LL, Yasui Y, Kremer LCM, Chow EJ. Derivation of anthracycline and anthraquinone equivalence ratios to doxorubicin for late-onset cardiotoxicity. JAMA Oncology. 2019;5(6):864. doi: 10.1001/jamaoncol.2018.6634.
    1. Fallah-Rad N, Walker JR, Wassef A, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II–positive breast cancer treated with adjuvant trastuzumab therapy. Journal of the American College of Cardiology. 2011;57(22):2263–2270. doi: 10.1016/j.jacc.2010.11.063.
    1. Pareek N, Cevallos J, Moliner P, et al. Activity and outcomes of a cardio-oncology service in the United Kingdom—a five-year experience. European Journal of Heart Failure. 2018;20(12):1721–1731. doi: 10.1002/ejhf.1292.
    1. Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. The New England Journal of Medicine. 2016;375(15):1457–1467. doi: 10.1056/NEJMra1100265.
    1. Henriksen, P. A. (2018). Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention. Heart, 971–977. 10.1136/heartjnl-2017-312103.
    1. Nowsheen, S., Aziz, K., Park, J. Y., et al. (2018). Trastuzumab in female breast cancer patients with reduced left ventricular ejection fraction. Journal of the American Heart Association, 7(15). 10.1161/JAHA.118.008637.
    1. Abdel-Rahman O, ElHalawani H, Ahmed H. Risk of selected cardiovascular toxicities in patients with cancer treated with MEK inhibitors: a comparative systematic review and meta-analysis. J Glob Oncol. 2015;1(2):73–82. doi: 10.1200/jgo.2015.000802.
    1. Oyakawa, T., Nakashima, K., & Naito, T. (2017). Cardiac dysfunction caused by osimertinib. Journal of Thoracic Oncology, e159–e160. 10.1016/j.jtho.2017.05.016.
    1. O’Hare M, Sharma A, Murphy K, Mookadam F, Lee H. Cardio-oncology part I: chemotherapy and cardiovascular toxicity. Expert Review of Cardiovascular Therapy. 2015;13(5):511–518. doi: 10.1586/14779072.2015.1032940.
    1. Lyu YL, Kerrigan JE, Lin C-P, Azarova AM, Tsai Y-C, Ban Y, Liu LF. Topoisomerase II mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Research. 2007;67(18):8839–8846. doi: 10.1158/0008-5472.CAN-07-1649.
    1. Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131(22):1981–1988. doi: 10.1161/CIRCULATIONAHA.114.013777.
    1. Shakir D, Rasul KI. Chemotherapy induced cardiomyopathy: pathogenesis, monitoring and management. Journal of Clinical Medical Research. 2009;1(1):8–12. doi: 10.4021/jocmr2009.02.1225.
    1. Odiete O, Hill MF, Sawyer DB. Neuregulin in Cardiovascular Development and Disease. Circulation Research. 2012;111(10):1376–1385. doi: 10.1161/CIRCRESAHA.112.267286.
    1. Sawyer DB, Zuppinger C, Miller TA, Eppenberger HM, Suter TM. Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1beta and anti-erbB2: potential mechanism for trastuzumab-induced cardiotoxicity. Circulation. 2002;105(13):1551–1554. doi: 10.1161/01.CIR.0000013839.41224.1C.
    1. Bian Y, Sun M, Silver M, et al. Neuregulin-1 attenuated doxorubicin-induced decrease in cardiac troponins. American Journal of Physiology: Heart and Circulatory Physiology. 2009;297(6):H1974–H1983. doi: 10.1152/ajpheart.01010.2008.
    1. Molinaro M, Ameri P, Marone G, et al. Recent advances on pathophysiology, diagnostic and therapeutic insights in cardiac dysfunction induced by antineoplastic drugs. BioMed Research International. 2015;2015:1–14. doi: 10.1155/2015/138148.
    1. Sawyer DB, Zuppinger C, Miller TA, Eppenberger HM, Suter TM. Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1β and anti-erbB2. Circulation. 2002;105(13):1551–1554. doi: 10.1161/01.CIR.0000013839.41224.1C.
    1. Maitland ML, Bakris GL, Black HR, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. Journal of the National Cancer Institute. 2010;102(9):596–604. doi: 10.1093/jnci/djq091.
    1. Miller GD, Bruno BJ, Lim CS. Resistant mutations in CML and Ph(+)ALL - role of ponatinib. Biologics. 2014;8:243–254. doi: 10.2147/BTT.S50734.
    1. Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. Journal of the National Cancer Institute. 2007;99(16):1232–1239. doi: 10.1093/jnci/djm086.
    1. Choueiri TK, Schutz FAB, Je Y, Rosenberg JE, Bellmunt J. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. Journal of Clinical Oncology. 2010;28(13):2280–2285. doi: 10.1200/JCO.2009.27.2757.
    1. Ghatalia P, Je Y, Kaymakcalan MD, Sonpavde G, Choueiri TK. QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors. British Journal of Cancer. 2015;112(2):296–305. doi: 10.1038/bjc.2014.564.
    1. Ghatalia P, Morgan CJ, Je Y, et al. Congestive heart failure with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Critical Reviews in Oncology/Hematology. 2015;94(2):228–237. doi: 10.1016/j.critrevonc.2014.12.008.
    1. Schutz FAB, Je Y, Richards CJ, Choueiri TK. Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. Journal of Clinical Oncology. 2012;30(8):871–877. doi: 10.1200/JCO.2011.37.1195.
    1. Aparicio-Gallego G, Afonso-Afonso FJ, León-Mateos L, et al. Molecular basis of hypertension side effects induced by sunitinib. Anti-Cancer Drugs. 2011;22(1):1–8. doi: 10.1097/CAD.0b013e3283403806.
    1. Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. The New England Journal of Medicine. 2008;358(11):1129–1136. doi: 10.1056/NEJMoa0707330.
    1. Rini BI, Cohen DP, Lu DR, et al. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. Journal of the National Cancer Institute. 2011;103(9):763–773. doi: 10.1093/jnci/djr128.
    1. Meyer T, Robles-Carrillo L, Robson T, et al. Bevacizumab immune complexes activate platelets and induce thrombosis in FCGR2A transgenic mice. Journal of Thrombosis and Haemostasis. 2009;7(1):171–181. doi: 10.1111/j.1538-7836.2008.03212.x.
    1. Hong S, Fang W, Liang W, et al. Risk of treatment-related deaths with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis of 41 randomized controlled trials. OncoTargets and Therapy. 2014;7:1851–1867. doi: 10.2147/OTT.S68386.
    1. Hall PS, Harshman LC, Srinivas S, Witteles RM. The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC: Heart Failure. 2013;1(1):72–78. doi: 10.1016/j.jchf.2012.09.001.
    1. Catino AB, Hubbard RA, Chirinos JA, et al. Longitudinal assessment of vascular function with sunitinib in patients with metastatic renal cell carcinoma. Circulation. Heart Failure. 2018;11(3):e004408. doi: 10.1161/CIRCHEARTFAILURE.117.004408.
    1. Jain V, Bahia J, Mohebtash M, Barac A. Cardiovascular complications associated with novel cancer immunotherapies. Current Treatment Options in Cardiovascular Medicine. 2017;19(5):36. doi: 10.1007/s11936-017-0532-8.
    1. Touyz RM, Herrmann J. Cardiotoxicity with vascular endothelial growth factor inhibitor therapy. JCO Precision Oncology. 2018;2(1):13. doi: 10.1038/s41698-018-0056-z.
    1. Lenihan D. Cardio-oncology: what is the best practice we can all strive for? International Journal of Cardiology. 2017;241:393–394. doi: 10.1016/j.ijcard.2017.03.136.
    1. Guha A, Armanious M, Fradley MG. Update on cardio-oncology: novel cancer therapeutics and associated cardiotoxicities. Trends in Cardiovascular Medicine. 2019;29(1):29–39. doi: 10.1016/j.tcm.2018.06.001.
    1. Burstein DS, Maude S, Grupp S, Griffis H, Rossano J, Lin K. Cardiac profile of chimeric antigen receptor T cell therapy in children: A single-institution experience. Biology of Blood and Marrow Transplantation. 2018;24(8):1590–1595. doi: 10.1016/j.bbmt.2018.05.014.
    1. Alvi RM, Frigault MJ, Fradley MG, et al. Cardiovascular events among adults treated with chimeric antigen receptor T-cells (CAR-T) Journal of the American College of Cardiology. 2019;74(25):3099–3108. doi: 10.1016/j.jacc.2019.10.038.
    1. Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography. 2014;27(9):911–939. doi: 10.1016/j.echo.2014.07.012.
    1. Omland T, de Lemos JA, Sabatine MS, et al. A sensitive cardiac troponin T assay in stable coronary artery disease. The New England Journal of Medicine. 2009;361(26):2538–2547. doi: 10.1056/NEJMoa0805299.
    1. Cardinale D, Sandri MT, Martinoni A, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. Journal of the American College of Cardiology. 2000;36(2):517–522. doi: 10.1016/S0735-1097(00)00748-8.
    1. Cardinale D, Sandri MT, Colombo A, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109(22):2749–2754. doi: 10.1161/.
    1. Cardinale D, Colombo A, Torrisi R, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. Journal of Clinical Oncology. 2010;28(25):3910–3916. doi: 10.1200/JCO.2009.27.3615.
    1. Welsh P, Preiss D, Hayward C, et al. Cardiac troponin T and troponin i in the general population: comparing and contrasting their genetic determinants and associations with outcomes. Circulation. 2019;139(24):2754–2764. doi: 10.1161/CIRCULATIONAHA.118.038529.
    1. Sawaya H, Sebag IA, Plana JC, et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. The American Journal of Cardiology. 2011;107(9):1375–1380. doi: 10.1016/j.amjcard.2011.01.006.
    1. Lipshultz SE, Scully RE, Lipsitz SR, et al. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. The Lancet Oncology. 2010;11(10):950–961. doi: 10.1016/S1470-2045(10)70204-7.
    1. Sawaya H, Sebag IA, Plana JC, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circulation. Cardiovascular Imaging. 2012;5(5):596–603. doi: 10.1161/CIRCIMAGING.112.973321.
    1. Drafts BC, Twomley KM, D’Agostino R, et al. Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease. JACC: Cardiovascular Imaging. 2013;6(8):877–885. doi: 10.1016/j.jcmg.2012.11.017.
    1. Mornoş C, Petrescu L. Early detection of anthracycline-mediated cardiotoxicity: the value of considering both global longitudinal left ventricular strain and twist. Canadian Journal of Physiology and Pharmacology. 2013;91(8):601–607. doi: 10.1139/cjpp-2012-0398.
    1. Mavinkurve-Groothuis AMC, Marcus KA, Pourier M, et al. Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study. European Heart Journal Cardiovascular Imaging. 2013;14(6):562–569. doi: 10.1093/ehjci/jes217.
    1. Ky B, Putt M, Sawaya H, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. Journal of the American College of Cardiology. 2014;63(8):809–816. doi: 10.1016/j.jacc.2013.10.061.
    1. Putt M, Hahn VS, Januzzi JL, et al. Longitudinal changes in multiple biomarkers are associated with cardiotoxicity in breast cancer patients treated with doxorubicin, taxanes, and trastuzumab. Clinical Chemistry. 2015;61(9):1164–1172. doi: 10.1373/clinchem.2015.241232.
    1. Olivieri J, Perna GP, Bocci C, et al. Modern management of anthracycline-induced cardiotoxicity in lymphoma patients: low occurrence of cardiotoxicity with comprehensive assessment and tailored substitution by nonpegylated liposomal doxorubicin. Oncologist. 2017;22(4):422–431. doi: 10.1634/theoncologist.2016-0289.
    1. Kitayama H, Kondo T, Sugiyama J, et al. High-sensitive troponin T assay can predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients. Breast Cancer. 2017;24(6):774–782. doi: 10.1007/s12282-017-0778-8.
    1. Shafi A, Siddiqui N, Imtiaz S, Din Sajid MU. Left ventricular systolic dysfunction predicted by early troponin I release after anthracycline based chemotherapy in breast cancer patients. Journal of Ayub Medical College, Abbottabad. 2017;29(2):266–269.
    1. Lipshultz SE, Rifai N, Sallan SE, et al. Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. Circulation. 1997;96(8):2641–2648. doi: 10.1161/01.CIR.96.8.2641.
    1. Auner HW, Tinchon C, Linkesch W, et al. Prolonged monitoring of troponin T for the detection of anthracycline cardiotoxicity in adults with hematological malignancies. Annals of Hematology. 2003;82(4):218–222. doi: 10.1007/s00277-003-0615-3.
    1. Sandri MT, Cardinale D, Zorzino L, et al. Minor increases in plasma troponin I predict decreased left ventricular ejection fraction after high-dose chemotherapy. Clinical Chemistry. 2003;49(2):248–252. doi: 10.1373/49.2.248.
    1. Specchia G, Buquicchio C, Pansini N, et al. Monitoring of cardiac function on the basis of serum troponin I levels in patients with acute leukemia treated with anthracyclines. The Journal of Laboratory and Clinical Medicine. 2005;145(4):212–220. doi: 10.1016/j.lab.2005.02.003.
    1. Kilickap S, Barista I, Akgul E, et al. cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Annals of Oncology. 2005;16(5):798–804. doi: 10.1093/annonc/mdi152.
    1. Lee HS, Son CB, Shin SH, Kim YS. Clinical correlation between brain natriutetic peptide and anthracyclin-induced cardiac toxicity. Cancer Research and Treatment. 2008;40(3):121. doi: 10.4143/crt.2008.40.3.121.
    1. Schmidinger M, Zielinski CC, Vogl UM, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology. 2008;26(32):5204–5212. doi: 10.1200/JCO.2007.15.6331.
    1. Ylänen K, Poutanen T, Savukoski T, Eerola A, Vettenranta K. Cardiac biomarkers indicate a need for sensitive cardiac imaging among long-term childhood cancer survivors exposed to anthracyclines. Acta Paediatrica. 2015;104(3):313–319. doi: 10.1111/apa.12862.
    1. Mavinkurve-Groothuis AMC, Groot-Loonen J, Bellersen L, et al. Abnormal NT-pro-BNP levels in asymptomatic long-term survivors of childhood cancer treated with anthracyclines. Pediatric Blood & Cancer. 2009;52(5):631–636. doi: 10.1002/pbc.21913.
    1. Pourier MS, Kapusta L, van Gennip A, et al. Values of high sensitive troponin T in long-term survivors of childhood cancer treated with anthracyclines. Clinica Chimica Acta. 2015;441:29–32. doi: 10.1016/j.cca.2014.12.011.
    1. Zardavas D, Suter TM, Van Veldhuisen DJ, 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 cardiac marker substudy. Journal of Clinical Oncology. 2017;35(8):878–884. doi: 10.1200/JCO.2015.65.7916.
    1. Christenson ES, James T, Agrawal V, Park BH. Use of biomarkers for the assessment of chemotherapy-induced cardiac toxicity. Clinical Biochemistry. 2015;48(4–5):223–235. doi: 10.1016/j.clinbiochem.2014.10.013.
    1. Cardinale D, Biasillo G, Cipolla CM. Curing cancer, saving the heart: a challenge that cardioncology should not miss. Current Cardiology Reports. 2016;18(6):51. doi: 10.1007/s11886-016-0731-z.
    1. Cardinale D, Biasillo G, Salvatici M, Sandri MT, Cipolla CM. Using biomarkers to predict and to prevent cardiotoxicity of cancer therapy. Expert Review of Molecular Diagnostics. 2017;17(3):245–256. doi: 10.1080/14737159.2017.1283219.
    1. Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, Donaldson SS, Green DM, Sklar CA, Robison LL, Leisenring WM. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ. 2009;339(dec08 1):b4606. doi: 10.1136/bmj.b4606.
    1. Tukenova M, Guibout C, Oberlin O, Doyon F, Mousannif A, Haddy N, Guérin S, Pacquement H, Aouba A, Hawkins M, Winter D, Bourhis J, Lefkopoulos D, Diallo I, de Vathaire F. Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. Journal of Clinical Oncology. 2010;28(8):1308–1315. doi: 10.1200/JCO.2008.20.2267.
    1. Armstrong GT, Liu Q, Yasui Y, Neglia JP, Leisenring W, Robison LL, Mertens AC. Late mortality among 5-year survivors of childhood cancer: a summary from the childhood cancer survivor study. Journal of Clinical Oncology. 2009;27(14):2328–2338. doi: 10.1200/JCO.2008.21.1425.
    1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews. Cancer. 2012;12(4):252–264. doi: 10.1038/nrc3239.
    1. Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in patients treated with immune checkpoint inhibitors. Journal of the American College of Cardiology. 2018;71(16):1755–1764. doi: 10.1016/j.jacc.2018.02.037.
    1. Bonaca MP, Olenchock BA, Salem JE, et al. Myocarditis in the setting of cancer therapeutics: proposed case definitions for emerging clinical syndromes in cardio-oncology. Circulation. 2019;140(1):80–91. doi: 10.1161/CIRCULATIONAHA.118.034497.
    1. Lyon, A. R., Yousaf, N., Battisti, N. M. L., Moslehi, J., & Larkin, J. (2018). Immune checkpoint inhibitors and cardiovascular toxicity. The Lancet Oncology, e447–e458. 10.1016/S1470-2045(18)30457-1.
    1. Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. The New England Journal of Medicine. 2016;375(18):1749–1755. doi: 10.1056/NEJMoa1609214.
    1. Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188–195. doi: 10.1182/blood-2014-05-552729.
    1. Daugaard G, Lassen U, Bie P, et al. Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction. European Journal of Heart Failure. 2005;7(1):87–93. doi: 10.1016/j.ejheart.2004.03.009.
    1. Lenihan DJ, Massey MR, Baysinger KB, et al. Superior detection of cardiotoxicity during chemotherapy using biomarkers. Journal of Cardiac Failure. 2007;13(6):S151. doi: 10.1016/j.cardfail.2007.06.634.
    1. Dodos F, Halbsguth T, Erdmann E, Hoppe UC. Usefulness of myocardial performance index and biochemical markers for early detection of anthracycline-induced cardiotoxicity in adults. Clinical Research in Cardiology. 2008;97(5):318–326. doi: 10.1007/s00392-007-0633-6.
    1. De Iuliis F, Salerno G, Taglieri L, De Biase L, Lanza R, Cardelli P, Scarpa S. Serum biomarkers evaluation to predict chemotherapy-induced cardiotoxicity in breast cancer patients. Tumor Biology. 2016;37(3):3379–3387. doi: 10.1007/s13277-015-4183-7.
    1. Sandri MT, Salvatici M, Cardinale D, Zorzino L, Passerini R, Lentati P, Leon M, Civelli M, Martinelli G, Cipolla CM. N-terminal Pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? Clinical Chemistry. 2005;51(8):1405–1410. doi: 10.1373/clinchem.2005.050153.
    1. Mukoyama M, Nakao K, Hosoda K, et al. Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. Journal of Clinical Investigation. 1991;87:1402–1412. doi: 10.1172/JCI115146.
    1. Kjaer A, Hesse B. Heart failure and neuroendocrine activation: diagnostic, prognostic and therapeutic perspectives. Clinical Physiology. 2001;21(6):661–672. doi: 10.1046/j.1365-2281.2001.00371.x.
    1. Romano S, Fratini S, Ricevuto E, et al. Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients. British Journal of Cancer. 2011;105(11):1663–1668. doi: 10.1038/bjc.2011.439.
    1. Lenihan DJ, Stevens PL, Massey M, et al. The utility of point-of-care biomarkers to detect cardiotoxicity during anthracycline chemotherapy: a feasibility study. Journal of Cardiac Failure. 2016;22(6):433–438. doi: 10.1016/j.cardfail.2016.04.003.
    1. Wieshammer S, Dreyhaupt J, Müller D, Momm F, Jakob A. Limitations of N-terminal pro-B-type natriuretic peptide in the diagnosis of heart disease among cancer patients who present with cardiac or pulmonary symptoms. Oncology. 2016;90(3):143–150. doi: 10.1159/000443505.
    1. Pavo N, Raderer M, Hülsmann M, et al. Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality. Heart. 2015;101(23):1874–1880. doi: 10.1136/heartjnl-2015-307848.
    1. Sandri MT, Salvatici M, Cardinale D, et al. N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? Clinical Chemistry. 2005;51(8):1405–1410. doi: 10.1373/clinchem.2005.050153.
    1. Hayakawa H, Komada Y, Hirayama M, Hori H, Ito M, Sakurai M. Plasma levels of natriuretic peptides in relation to doxorubicin-induced cardiotoxicity and cardiac function in children with cancer. Medical and Pediatric Oncology. 2001;37(1):4–9. doi: 10.1002/mpo.1155.
    1. Palumbo I, Palumbo B, Fravolini ML, 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. doi: 10.1016/j.breast.2015.10.004.
    1. Cornell RF, Ky B, Weiss BM, et al. Prospective study of cardiac events during proteasome inhibitor therapy for relapsed multiple myeloma. Journal of Clinical Oncology. 2019;37(22):1946–1955. doi: 10.1200/JCO.19.00231.
    1. Cowie M. Clinical applications of B-type natriuretic peptide (BNP) testing. European Heart Journal. 2003;24(19):1710–1718. doi: 10.1016/S0195-668X(03)00476-7.
    1. Galasko GIW, Lahiri A, Barnes SC, Collinson P, Senior R. What is the normal range for N-terminal pro-brain natriuretic peptide? How well does this normal range screen for cardiovascular disease? European Heart Journal. 2005;26(21):2269–2276. doi: 10.1093/eurheartj/ehi410.
    1. Takase H, Dohi Y. Kidney function crucially affects B-type natriuretic peptide (BNP), N-terminal proBNP and their relationship. European Journal of Clinical Investigation. 2014;44(3):303–308. doi: 10.1111/eci.12234.
    1. Bando S, Soeki T, Matsuura T, et al. Plasma brain natriuretic peptide levels are elevated in patients with cancer. PLoS One. 2017;12(6):e0178607. doi: 10.1371/journal.pone.0178607.
    1. Mair J, Artner-Dworzak E, Lechleitner P, Smidt J, Wagner I, Dienstl F, Puschendorf B. Cardiac troponin T in diagnosis of acute myocardial infarction. Clinical Chemistry. 1991;37(6):845–852. doi: 10.1093/clinchem/37.6.845.
    1. Katus HA, Remppis A, Neumann FJ, Scheffold T, Diederich KW, Vinar G, Noe A, Matern G, Kuebler W. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation. 1991;83(3):902–912. doi: 10.1161/01.CIR.83.3.902.
    1. Cardinale D, Sandri MT, Martinoni A, Borghini E, Civelli M, Lamantia G, Cinieri S, Martinelli G, Fiorentini C, Cipolla CM. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Annals of Oncology. 2002;13(5):710–715. doi: 10.1093/annonc/mdf170.
    1. Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR, Colan SD, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Gelber RD, Sallan SE. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. New England Journal of Medicine. 2004;351(2):145–153. doi: 10.1056/NEJMoa035153.
    1. Rosenberg S., De Vita V., DeVita, L.T. (2015). Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology.
    1. Libby P. Inflammation and cardiovascular disease mechanisms. The American Journal of Clinical Nutrition. 2006;83(2):456S–460S. doi: 10.1093/ajcn/83.2.456S.
    1. Hartman J, Frishman WH. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiology in Review. 2014;22(3):147–151. doi: 10.1097/CRD.0000000000000021.
    1. Ridker PM, Lüscher TF. Anti-inflammatory therapies for cardiovascular disease. European Heart Journal. 2014;35(27):1782–1791. doi: 10.1093/eurheartj/ehu203.
    1. Onitilo AA, Engel JM, Stankowski RV, Liang H, Berg RL, Doi SAR. High-sensitivity C-reactive protein (hs-CRP) as a biomarker for trastuzumab-induced cardiotoxicity in HER2-positive early-stage breast cancer: a pilot study. Breast Cancer Research and Treatment. 2012;134(1):291–298. doi: 10.1007/s10549-012-2039-z.
    1. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188–195. doi: 10.1182/blood-2014-05-552729.
    1. Frantz S, Falcao-Pires I, Balligand J-L, et al. The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC. European Journal of Heart Failure. 2018;20(3):445–459. doi: 10.1002/ejhf.1138.
    1. Zhang Y, Huang Z, Li H. Insights into innate immune signalling in controlling cardiac remodelling. Cardiovascular Research. 2017;113(13):1538–1550. doi: 10.1093/cvr/cvx130.
    1. Hofmann U, Frantz S. Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction. Circulation Research. 2015;116(2):354–367. doi: 10.1161/CIRCRESAHA.116.304072.
    1. Meng X, Yang J, Dong M, et al. Regulatory T cells in cardiovascular diseases. Nature Reviews. Cardiology. 2016;13(3):167–179. doi: 10.1038/nrcardio.2015.169.
    1. Nahrendorf M, Frantz S, Swirski FK, et al. Imaging systemic inflammatory networks in ischemic heart disease. Journal of the American College of Cardiology. 2015;65(15):1583–1591. doi: 10.1016/j.jacc.2015.02.034.
    1. Baldus S, Heeschen C, Meinertz T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003;108(12):1440–1445. doi: 10.1161/01.CIR.0000090690.67322.51.
    1. Reichlin T, Socrates T, Egli P, et al. Use of myeloperoxidase for risk stratification in acute heart failure. Clinical Chemistry. 2010;56(6):944–951. doi: 10.1373/clinchem.2009.142257.
    1. Hampton MB, Kettle AJ, Winterbourn CC. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood. 1998;92(9):3007–3017. doi: 10.1182/blood.V92.9.3007.
    1. Mukhopadhyay P, Rajesh M, Bátkai S, et al. Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro. American Journal of Physiology. Heart and Circulatory Physiology. 2009;296(5):H1466–H1483. doi: 10.1152/ajpheart.00795.2008.
    1. Anatoliotakis N, Deftereos S, Bouras G, et al. Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease. Current Topics in Medicinal Chemistry. 2013;13(2):115–138. doi: 10.2174/1568026611313020004.
    1. van Boxtel W, Bulten BF, Mavinkurve-Groothuis AMC, et al. New biomarkers for early detection of cardiotoxicity after treatment with docetaxel, doxorubicin and cyclophosphamide. Biomarkers. 2015;20(2):143–148. doi: 10.3109/1354750X.2015.1040839.
    1. Chen A, Hou W, Zhang Y, Chen Y, He B. Prognostic value of serum galectin-3 in patients with heart failure: a meta-analysis. International Journal of Cardiology. 2015;182:168–170. doi: 10.1016/j.ijcard.2014.12.137.
    1. Schindler EI, Szymanski JJ, Hock KG, Geltman EM, Scott MG. Short- and long-term biologic variability of galectin-3 and other cardiac biomarkers in patients with stable heart failure and healthy adults. Clinical Chemistry. 2016;62(2):360–366. doi: 10.1373/clinchem.2015.246553.
    1. Fu J, Chen Y, Li F. Attenuation of MicroRNA-495 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy. Cardiol. 2018;139(4):245–254. doi: 10.1159/000487044.
    1. Huang ZP, Chen J, Seok HY, et al. MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress. Circulation Research. 2013;112(9):1234–1243. doi: 10.1161/CIRCRESAHA.112.300682.
    1. Colpaert RMW, Calore M. MicroRNAs in cardiac diseases. Cells. 2019;8(7):737. doi: 10.3390/cells8070737.
    1. Tao L, Bei Y, Chen P, et al. Crucial role of miR-433 in regulating cardiac fibrosis. Theranostics. 2016;6(12):2068–2083. doi: 10.7150/thno.15007.
    1. Fichtlscherer S, Zeiher AM, Dimmeler S. Circulating MicroRNAs. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(11):2383–2390. doi: 10.1161/ATVBAHA.111.226696.
    1. Mendell JT, Olson EN. MicroRNAs in stress signaling and human disease. Cell. 2012;148(6):1172–1187. doi: 10.1016/j.cell.2012.02.005.
    1. Horie T, Ono K, Nishi H, et al. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovascular Research. 2010;87(4):656–664. doi: 10.1093/cvr/cvq148.
    1. Wang J, Yu M, Yu G, et al. Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochemical and Biophysical Research Communications. 2010;394(1):184–188. doi: 10.1016/j.bbrc.2010.02.145.
    1. Brase JC, Wuttig D, Kuner R, Sültmann H. Serum microRNAs as non-invasive biomarkers for cancer. Molecular Cancer. 2010;9(1):306. doi: 10.1186/1476-4598-9-306.
    1. Serie DJ, Crook JE, Necela BM, et al. Genome-wide association study of cardiotoxicity in the NCCTG N9831 (Alliance) adjuvant trastuzumab trial. Pharmacogenetics and Genomics. 2017;27(10):378–385. doi: 10.1097/FPC.0000000000000302.
    1. Haney, S., Cresti, N., Verrill, M., & Plummer, C. J. (2013). Cardiac troponin release following standard dose anthracycline-based adjuvant chemotherapy. European Heart Journal, 34(suppl 1), P5752–P5752.
    1. Katsurada K, Ichida M, Sakuragi M, Takehara M, Hozumi Y, Kario K. High-sensitivity troponin T as a marker to predict cardiotoxicity in breast cancer patients with adjuvant trastuzumab therapy. SpringerPlus. 2014;3(1):620. doi: 10.1186/2193-1801-3-620.
    1. Groenning BA, Nilsson JC, Sondergaard L, Kjaer A, Larsson HBW, Hildebrandt PR. Evaluation of impaired left ventricular ejection fraction and increased dimensions by multiple neurohumoral plasma concentrations. European Journal of Heart Failure. 2001;3(6):699–708. doi: 10.1016/S1388-9842(01)00181-7.
    1. Morris PG, Chen C, Steingart R, Fleisher M, Lin N, Moy B, Come S, Sugarman S, Abbruzzi A, Lehman R, Patil S, Dickler M, McArthur HL, Winer E, Norton L, Hudis CA, Dang CT. Troponin I and C-reactive protein are commonly detected in patients with breast cancer treated with dose-dense chemotherapy incorporating trastuzumab and lapatinib. Clinical Cancer Research. 2011;17(10):3490–3499. doi: 10.1158/1078-0432.CCR-10-1359.
    1. Wollert KC, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Allhoff T, Peter T, Siegbahn A, Venge P, Drexler H, Wallentin L. Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non–ST-elevation acute coronary syndrome. Circulation. 2007;116(14):1540–1548. doi: 10.1161/CIRCULATIONAHA.107.697714.
    1. Wells QS, Veatch OJ, Fessel JP, et al. Genome-wide association and pathway analysis of left ventricular function after anthracycline exposure in adults. Pharmacogenetics and Genomics. 2017;27(7):247–254. doi: 10.1097/FPC.0000000000000284.
    1. Aminkeng F, Bhavsar AP, Visscher H, et al. A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer. Nature Genetics. 2015;47(9):1079–1084. doi: 10.1038/ng.3374.
    1. Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, et al. Genetic variants associated with cancer therapy-induced cardiomyopathy. Circulation. 2019;140(1):31–41. doi: 10.1161/CIRCULATIONAHA.118.037934.
    1. Beer LA, Kossenkov AV, Liu Q, et al. Baseline immunoglobulin E levels as a marker of doxorubicin- and trastuzumab-associated cardiac dysfunction. Circulation Research. 2016;119(10):1135–1144. doi: 10.1161/CIRCRESAHA.116.309004.
    1. Ngo D, Sinha S, Shen D, et al. Aptamer-based proteomic profiling reveals novel candidate biomarkers and pathways in cardiovascular disease. Circulation. 2016;134(4):270–285. doi: 10.1161/CIRCULATIONAHA.116.021803.
    1. Lind L, Ärnlöv J, Lindahl B, Siegbahn A, Sundström J, Ingelsson E. Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis. Atherosclerosis. 2015;242(1):205–210. doi: 10.1016/j.atherosclerosis.2015.07.023.
    1. Jensen BV, Nielsen SL, Skovsgaard T. Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy. Lancet. 1996;347(8997):297–299. doi: 10.1016/S0140-6736(96)90469-9.
    1. Okumura K, Jin D, Takai S, Miyazaki M. Beneficial effects of angiotensin-converting enzyme inhibition in adriamycin-induced cardiomyopathy in hamsters. Japanese Journal of Pharmacology. 2002;88(2):183–188. doi: 10.1254/jjp.88.183.
    1. Cardinale D, Ciceri F, Latini R, et al. Anthracycline-induced cardiotoxicity: a multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial. European Journal of Cancer. 2018;94:126–137. doi: 10.1016/J.EJCA.2018.02.005.
    1. Gulati, G., Heck, S. L., Røsjø, H., et al. (2017). Neurohormonal blockade and circulating cardiovascular biomarkers during anthracycline therapy in breast cancer patients: results from the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) study. Journal of the American Heart Association, 6(11). 10.1161/JAHA.117.006513.
    1. Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR, et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: The CECCY trial. Journal of the American College of Cardiology. 2018;71(20):2281–2290. doi: 10.1016/j.jacc.2018.02.049.
    1. ISRCTN24439460. The Cardiac CARE Trial – can heart muscle injury related to chemotherapy be prevented? . Available at: . Accessed December 22, 2019.
    1. Cardinale D, Cipolla CM. Chemotherapy-induced cardiotoxicity: importance of early detection. Expert Review of Cardiovascular Therapy. 2016;14(12):1297–1299. doi: 10.1080/14779072.2016.1239528.
    1. Cardinale D, Sandri MT. Detection and monitoring of cardiotoxicity by using biomarkers: pros and cons: remarks on the international colloquium on cardioncology. Progress in Pediatric Cardiology. 2015;39(2):77–84. doi: 10.1016/J.PPEDCARD.2015.10.004.
    1. Tocchetti CG, Molinaro M, Angelone T, et al. Nitroso-redox balance and modulation of basal myocardial function: an update from the Italian Society of Cardiovascular Research (SIRC) Current Drug Targets. 2015;16(8):895–903. doi: 10.2174/1389450116666150304103517.
    1. Zuppinger C, Suter TM. Cancer therapy-associated cardiotoxicity and signaling in the myocardium. Journal of Cardiovascular Pharmacology. 2010;56(2):141–146. doi: 10.1097/FJC.0b013e3181e0f89a.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi