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Semin Thromb Hemost 2021; 47(08): 899-906
DOI: 10.1055/s-0041-1729885
Review Article

The Growing Impact of Cardiovascular Oncology: Epidemiology and Pathophysiology

Antonella Tufano
1   Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy
,
Antonio Coppola
2   Hub Center for Inherited Bleeding Disorders, University Hospital, Parma, Italy
,
Maurizio Galderisi
3   Department of Advanced Biomedical Sciences, Federico II University Hospital, Naples, Italy
› Author Affiliations
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Abstract

Progress in the treatment of cancer has significantly improved survival of oncologic patients in recent decades. However, anticancer therapies, particularly some new, more potent and targeted agents, are potentially cardiotoxic. As a consequence, cardiovascular complications, including heart failure, arterial hypertension, coronary artery disease, venous thromboembolism, peripheral vascular disease, arrhythmias, pericardial disease, and pulmonary hypertension, as related to cancer itself or to anticancer treatments, are increasingly observed and may adversely affect prognosis in oncologic patients. Cardiovascular oncology is an emerging field in cardiology and internal medicine, which is rapidly growing, dealing with the prevention, the early detection, and the management of cardiovascular disease, in all stages of anticancer therapy and during the survivorship period, now crucial for reducing cardiovascular morbidity and mortality in cancer patients. In this narrative review, the existing literature regarding the epidemiology of cardiovascular oncology, the mechanisms of cardiovascular complications in cancer, and the pathophysiology of cardiotoxicity related to chemotherapeutic agents, targeted therapies, immunotherapies, and radiotherapy will be analyzed and summarized.

Keywords

cancer - cardiovascular disease - cardiotoxicity - cardiovascular oncology - epidemiology


Publication History

Article published online:
12 July 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Zamorano JL, Lancellotti P, Rodriguez Muñoz D. et al; ESC Scientific Document Group. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: the Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J 2016; 37 (36) 2768-2801
    CrossrefPubMedGoogle Scholar
  • 2 Koutsoukis A, Ntalianis A, Repasos E, Kastritis E, Dimopoulos MA, Paraskevaidis I. Cardio-oncology: a focus on cardiotoxicity. Eur Cardiol 2018; 13 (01) 64-69
    CrossrefPubMedGoogle Scholar
  • 3 Farmakis D, Parissis J, Filippatos G. Insights into onco-cardiology: atrial fibrillation in cancer. J Am Coll Cardiol 2014; 63 (10) 945-953
    CrossrefPubMedGoogle Scholar
  • 4 Howard E, Steingart RM, Armstrong GT. et al. Cardiovascular events in cancer survivors. Semin Oncol 2019; 46 (06) 426-432
    CrossrefPubMedGoogle Scholar
  • 5 Larsen CM, Mulvagh SL. Cardio-oncology: what you need to know now for clinical practice and echocardiography. Echo Res Pract 2017; 4 (01) R33-R41
    CrossrefPubMedGoogle Scholar
  • 6 Curigliano G, Cardinale D, Suter T. et al; ESMO Guidelines Working Group. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol 2012; 23 (Suppl. 07) vii155-vii166
    CrossrefPubMedGoogle Scholar
  • 7 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. Eur Heart J Cardiovasc Imaging 2014; 15 (10) 1063-1093
    CrossrefPubMedGoogle Scholar
  • 8 Armenian SH, Lacchetti C, Barac A. et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2017; 35 (08) 893-911
    CrossrefPubMedGoogle Scholar
  • 9 Lancellotti P, Nkomo VT, Badano LP. et al; European Society of Cardiology Working Groups on Nuclear Cardiology and Cardiac Computed Tomography and Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, Society for Cardiovascular Magnetic Resonance, Society of Cardiovascular Computed Tomography. Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging 2013; 14 (08) 721-740
    CrossrefPubMedGoogle Scholar
  • 10 Markman TM, Markman M. Cardio-oncology: mechanisms of cardiovascular toxicity. F1000 Res 2018; 7: 113
    CrossrefPubMedGoogle Scholar
  • 11 Pudil R. The future role of cardio-oncologists. Card Fail Rev 2017; 3 (02) 140-142
    CrossrefPubMedGoogle Scholar
  • 12 Curigliano G, Cardinale D, Dent S. et al. Cardiotoxicity of anticancer treatments: epidemiology, detection, and management. CA Cancer J Clin 2016; 66 (04) 309-325
    CrossrefPubMedGoogle Scholar
  • 13 Narayan V, Ky B. Common cardiovascular complications of cancer therapy: epidemiology, risk prediction, and prevention. Annu Rev Med 2018; 69 (69) 97-111
    CrossrefPubMedGoogle Scholar
  • 14 Von Hoff DD, Layard MW, Basa P. et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979; 91 (05) 710-717
    CrossrefPubMedGoogle Scholar
  • 15 Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol 2009; 53 (24) 2231-2247
    CrossrefPubMedGoogle Scholar
  • 16 Simůnek T, Stérba M, Popelová O, Adamcová M, Hrdina R, Gersl V. Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 2009; 61 (01) 154-171
    CrossrefPubMedGoogle Scholar
  • 17 Ewer MS, Lippman SM. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol 2005; 23 (13) 2900-2902
    CrossrefPubMedGoogle Scholar
  • 18 de Azambuja E, Bedard PL, Suter T, Piccart-Gebhart M. Cardiac toxicity with anti-HER-2 therapies: what have we learned so far?. Target Oncol 2009; 4 (02) 77-88
    CrossrefPubMedGoogle Scholar
  • 19 Hahn VS, Lenihan DJ, Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. [serial online] J Am Heart Assoc 2014; 3 (02) e000665
    CrossrefPubMedGoogle Scholar
  • 20 Qi WX, Shen Z, Tang LN, Yao Y. Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: a systematic review and meta-analysis of 36 clinical trials. Br J Clin Pharmacol 2014; 78 (04) 748-762
    CrossrefPubMedGoogle Scholar
  • 21 Narayan V, Keefe S, Haas N. et al. Prospective evaluation of sunitinib-induced cardiotoxicity in patients with metastatic renal cell carcinoma. Clin Cancer Res 2017; 23 (14) 3601-3609
    CrossrefPubMedGoogle Scholar
  • 22 Ghatalia P, Morgan CJ, Je Y. et al. Congestive heart failure with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Crit Rev Oncol Hematol 2015; 94 (02) 228-237
    CrossrefPubMedGoogle Scholar
  • 23 Force T, Krause DS, Van Etten RA. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer 2007; 7 (05) 332-344
    CrossrefPubMedGoogle Scholar
  • 24 de Jesus-Gonzalez N, Robinson E, Moslehi J, Humphreys BD. Management of antiangiogenic therapy-induced hypertension. Hypertension 2012; 60 (03) 607-615
    CrossrefPubMedGoogle Scholar
  • 25 Izzedine H, Massard C, Spano JP, Goldwasser F, Khayat D, Soria JC. VEGF signalling inhibition-induced proteinuria: mechanisms, significance and management. Eur J Cancer 2010; 46 (02) 439-448
    CrossrefPubMedGoogle Scholar
  • 26 Johnson DB, Balko JM, Compton ML. et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 2016; 375 (18) 1749-1755
    CrossrefPubMedGoogle Scholar
  • 27 Jain V, Bahia J, Mohebtash M, Barac A. Cardiovascular complications associated with novel cancer immunotherapies. Curr Treat Options Cardiovasc Med 2017; 19 (05) 36
    CrossrefPubMedGoogle Scholar
  • 28 Zarifa A, Albittar A, Kim PY. et al. Cardiac toxicities of anticancer treatments: chemotherapy, targeted therapy and immunotherapy. Curr Opin Cardiol 2019; 34 (04) 441-450
    CrossrefPubMedGoogle Scholar
  • 29 Grandin EW, Ky B, Cornell RF, Carver J, Lenihan DJ. Patterns of cardiac toxicity associated with irreversible proteasome inhibition in the treatment of multiple myeloma. J Card Fail 2015; 21 (02) 138-144
    CrossrefPubMedGoogle Scholar
  • 30 Willis MS, Patterson C. Proteotoxicity and cardiac dysfunction--Alzheimer's disease of the heart?. N Engl J Med 2013; 368 (05) 455-464
    CrossrefPubMedGoogle Scholar
  • 31 Siegel D, Martin T, Nooka A. et al. Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica 2013; 98 (11) 1753-1761
    CrossrefPubMedGoogle Scholar
  • 32 Jaworski C, Mariani JA, Wheeler G, Kaye DM. Cardiac complications of thoracic irradiation. J Am Coll Cardiol 2013; 61 (23) 2319-2328
    CrossrefPubMedGoogle Scholar
  • 33 Hooning MJ, Botma A, Aleman BM. et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 2007; 99 (05) 365-375
    CrossrefPubMedGoogle Scholar
  • 34 Kosmas C, Kallistratos MS, Kopterides P. et al. Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol 2008; 134 (01) 75-82
    CrossrefPubMedGoogle Scholar
  • 35 Polk A, Vistisen K, Vaage-Nilsen M, Nielsen DL. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharmacol Toxicol 2014; 15: 47
    CrossrefPubMedGoogle Scholar
  • 36 Donnellan E, Khorana AA. Cancer and venous thromboembolic disease: a review. Oncologist 2017; 22 (02) 199-207
    CrossrefPubMedGoogle Scholar
  • 37 Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: burden, mechanisms, and management. Thromb Haemost 2017; 117 (02) 219-230
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Nasser NJ, Fox J, Agbarya A. Potential mechanisms of cancer-related hypercoagulability. Cancers (Basel) 2020; 12 (03) 566
    CrossrefPubMedGoogle Scholar
  • 39 Labianca A, Bosetti T, Indini A, Negrini G, Labianca RF. Risk prediction and new prophylaxis strategies for thromboembolism in cancer. Cancers (Basel) 2020; 12 (08) E2070
    CrossrefPubMedGoogle Scholar
  • 40 Kim AS, Khorana AA, McCrae KR. Mechanisms and biomarkers of cancer-associated thrombosis. Transl Res 2020; 225: 33-53
    CrossrefPubMedGoogle Scholar
  • 41 Fisher B, Dignam J, Wolmark N. et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 1997; 89 (22) 1673-1682
    CrossrefPubMedGoogle Scholar
  • 42 Seng S, Liu Z, Chiu SK. et al. Risk of venous thromboembolism in patients with cancer treated with cisplatin: a systematic review and meta-analysis. J Clin Oncol 2012; 30 (35) 4416-4426
    CrossrefPubMedGoogle Scholar
  • 43 Gugliotta L, Mazzucconi MG, Leone G. et al; The GIMEMA Group. Incidence of thrombotic complications in adult patients with acute lymphoblastic leukaemia receiving L-asparaginase during induction therapy: a retrospective study. Eur J Haematol 1992; 49 (02) 63-66
    CrossrefPubMedGoogle Scholar
  • 44 Caruso V, Iacoviello L, Di Castelnuovo A. et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood 2006; 108 (07) 2216-2222
    CrossrefPubMedGoogle Scholar
  • 45 Cabanillas ME, Schlumberger M, Jarzab B. et al. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: a clinical outcomes and biomarker assessment. Cancer 2015; 121 (16) 2749-2756
    CrossrefPubMedGoogle Scholar
  • 46 Prandoni P, Lensing AW, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100 (10) 3484-3488
    CrossrefPubMedGoogle Scholar
  • 47 Weitz JI, Haas S, Ageno W. et al; GARFIELD-VTE Investigators. Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE. J Thromb Thrombolysis 2020; 50 (02) 267-277
    CrossrefPubMedGoogle Scholar
  • 48 Key NS, Khorana AA, Kuderer NM. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline update. J Clin Oncol 2020; 38 (05) 496-520
    CrossrefPubMedGoogle Scholar
  • 49 Lenihan DJ, Kowey PR. Overview and management of cardiac adverse events associated with tyrosine kinase inhibitors. Oncologist 2013; 18 (08) 900-908
    CrossrefPubMedGoogle Scholar
  • 50 Mery B, Guichard JB, Guy JB. et al. Atrial fibrillation in cancer patients: hindsight, insight and foresight. Int J Cardiol 2017; 240: 196-202
    CrossrefPubMedGoogle Scholar
  • 51 López-Fernández T, Martín-García A, Roldán Rabadán I. et al; Expert Reviewers. Atrial fibrillation in active cancer patients: expert position paper and recommendations. Rev Esp Cardiol (Engl Ed) 2019; 72 (09) 749-759
    CrossrefPubMedGoogle Scholar
  • 52 Tufano A, Galderisi M, Esposito L. et al. Anticancer drug-related nonvalvular atrial fibrillation: challenges in management and antithrombotic strategies. Semin Thromb Hemost 2018; 44 (04) 388-396
    Article in Thieme ConnectPubMedGoogle Scholar
  • 53 Imperatori A, Mariscalco G, Riganti G, Rotolo N, Conti V, Dominioni L. Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study. J Cardiothorac Surg 2012; 7: 4
    CrossrefPubMedGoogle Scholar
  • 54 Onaitis M, D'Amico T, Zhao Y, O'Brien S, Harpole D. Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database. Ann Thorac Surg 2010; 90 (02) 368-374
    CrossrefPubMedGoogle Scholar
  • 55 O'Neal WT, Lakoski SG, Qureshi W. et al. Relation between cancer and atrial fibrillation (from the REasons for Geographic And Racial Differences in Stroke Study). Am J Cardiol 2015; 115 (08) 1090-1094
    CrossrefPubMedGoogle Scholar
  • 56 Ostenfeld EB, Erichsen R, Pedersen L, Farkas DK, Weiss NS, Sørensen HT. Atrial fibrillation as a marker of occult cancer. PLoS One 2014; 9 (08) e102861
    CrossrefPubMedGoogle Scholar
  • 57 Erichsen R, Christiansen CF, Mehnert F, Weiss NS, Baron JA, Sørensen HT. Colorectal cancer and risk of atrial fibrillation and flutter: a population-based case-control study. Intern Emerg Med 2012; 7 (05) 431-438
    CrossrefPubMedGoogle Scholar
  • 58 Glanzmann C, Huguenin P, Lütolf UM, Maire R, Jenni R, Gumppenberg V. Cardiac lesions after mediastinal irradiation for Hodgkin's disease. Radiother Oncol 1994; 30 (01) 43-54
    CrossrefPubMedGoogle Scholar
  • 59 Montani D, Bergot E, Günther S. et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation 2012; 125 (17) 2128-2137
    CrossrefPubMedGoogle Scholar
  • 60 Ranchoux B, Günther S, Quarck R. et al. Chemotherapy-induced pulmonary hypertension: role of alkylating agents. Am J Pathol 2015; 185 (02) 356-371
    CrossrefPubMedGoogle Scholar
  • 61 Herrmann J. Vascular toxic effects of cancer therapies. Nat Rev Cardiol 2020; 17 (08) 503-522
    CrossrefPubMedGoogle Scholar
  • 62 Guignabert C, Phan C, Seferian A. et al. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension. J Clin Invest 2016; 126 (09) 3207-3218
    CrossrefPubMedGoogle Scholar
  • 63 Weatherald J, Chaumais MC, Montani D. Pulmonary arterial hypertension induced by tyrosine kinase inhibitors. Curr Opin Pulm Med 2017; 23 (05) 392-397
    CrossrefPubMedGoogle Scholar
  • 64 Weatherald J, Chaumais MC, Savale L. et al. Long-term outcomes of dasatinib-induced pulmonary arterial hypertension: a population-based study. Eur Respir J 2017; 50 (01) 1700217
    CrossrefPubMedGoogle Scholar
  • 65 Ala CK, Klein AL, Moslehi JJ. Cancer treatment-associated pericardial disease: epidemiology, clinical presentation, diagnosis, and management. Curr Cardiol Rep 2019; 21 (12) 156
    CrossrefPubMedGoogle Scholar
  • 66 Tan-Chiu E, Yothers G, Romond E. et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol 2005; 23 (31) 7811-7819
    CrossrefPubMedGoogle Scholar
  • 67 Markman TM, Markman M. Cardio-oncology: management of cardiovascular toxicity. F1000 Res 2019; 8: 120
    CrossrefPubMedGoogle Scholar
  • 68 Carrier M, Abou-Nassar K, Mallick R. et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019; 380 (08) 711-719
    CrossrefPubMedGoogle Scholar
  • 69 Khorana AA, Soff GA, Kakkar AK. et al; CASSINI Investigators. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med 2019; 380 (08) 720-728
    CrossrefPubMedGoogle Scholar