Coronary Artery Disease

  • Giuseppe Mercuro
  • Christian Cadeddu DessalviEmail author
  • Martino Deidda
  • Stephan Stöbe
  • Andreas Hagendorff
Part of the Current Clinical Pathology book series (CCPATH)


Cardiovascular complications during chemotherapy and radiotherapy are becoming an increasing problem because many patients with cancer are treated with agents that exert significant vascular toxicity. Coronary heart disease in patients with cancer presents particular challenges, which directly impact the management of both the coronary disease and malignancy.

Several chemotherapeutic agents have been shown to trigger ischemic heart disease, and as it has happened for myocardial cardiotoxicity, more attention should be dedicated to improving early recognition and prevention of cardiovascular toxicity. Cardiac imaging could facilitate early detection of vascular toxicity, but a thorough risk stratification should always be performed to identify patients at higher risk of vascular impairment.


Coronary artery disease Vascular toxicity Cardiotoxicity 


  1. 1.
    Heron M, Hoyert DL, Murphy S, , Xu J, Kochanek KD, Tejada-Vera B. Deaths: final data for 2006. Natl Vital Stat Rep 2009:57(14):1–134.PubMedGoogle Scholar
  2. 2.
    Suter TM, Ewer MS. Cancer drugs and the heart: importance and management. Eur Heart J. 2013;34:1102–11.CrossRefGoogle Scholar
  3. 3.
    Daher IN, Yeh ET. Vascular complications of selected cancer therapies. Nat Clin Pract Cardiovasc Med. 2008;5:797–805.CrossRefGoogle Scholar
  4. 4.
    Meinardi MT, Gietema JA. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000;18:1725–32.CrossRefGoogle Scholar
  5. 5.
    Vaughn DJ, Palmer SC, Carver JR, Jacobs LA, Mohler ER. Cardiovascular risk in long-term survivors of testicular cancer. Cancer. 2008;112:1949–53.CrossRefGoogle Scholar
  6. 6.
    Sorrentino MF, Kim J, Foderaro AE, Truesdell AG. 5-Fluorouracil induced cardiotoxicity: review of the literature. Cardiol J. 2012;19:453–8.CrossRefGoogle Scholar
  7. 7.
    Saif MW, Shah MM, Shah AR. Fluoropyrimidine-associated cardiotoxicity: revisited. Expert Opin Drug Saf. 2009;8:191–202.CrossRefGoogle Scholar
  8. 8.
    Focaccetti C, Bruno A, Magnani E, Bartolini D, Principi E, Dallaglio K, et al. Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes. PLoS One. 2015;10:e0115686.CrossRefGoogle Scholar
  9. 9.
    Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53:2231–47.CrossRefGoogle Scholar
  10. 10.
    Bronckaers A, Gago F, Balzarini J, Liekens S. The dual role of thymidine phosphorylase in cancer development and chemotherapy. Med Res Rev. 2009;29:903–53.CrossRefGoogle Scholar
  11. 11.
    Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, et al. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989;338:557–62.CrossRefGoogle Scholar
  12. 12.
    Ignatescu MC, Gharehbaghi-Schnell E, Hassan A, Rezaie-Majd S, Korschineck I, Schleef RR, et al. Expression of the angiogenic protein, platelet-derived endothelial cell growth factor, in coronary atherosclerotic plaques: in vivo correlation of lesional microvessel density and constrictive vascular remodeling. Arterioscler Thromb Vasc Biol. 1999;19:2340–7.CrossRefGoogle Scholar
  13. 13.
    Soultati A, Mountzios G, Avgerinou C, Papaxoinis G, Pectasides D, Dimopoulos MA, et al. Endothelial vascular toxicity from chemotherapeutic agents: preclinical evidence and clinical implications. Cancer Treat Rev. 2012;38:473–83.CrossRefGoogle Scholar
  14. 14.
    Meinardi MT, Gietema JA, van Veldhuisen DJ, van der Graaf WT, de Vries EG, Sleijfer DT. Long-term chemotherapy-related cardiovascular morbidity. Cancer Treat Rev. 2000;26:429–47.CrossRefGoogle Scholar
  15. 15.
    Schwartz EL. Antivascular actions of microtubule-binding drugs. Clin Cancer Res. 2009;15:2594–601.CrossRefGoogle Scholar
  16. 16.
    Wood SC, Tang X, Tesfamariam B. Paclitaxel potentiates inflammatory cytokine-induced prothrombotic molecules in endothelial cells. J Cardiovasc Pharmacol. 2010;55:276–85.CrossRefGoogle Scholar
  17. 17.
    Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–76.CrossRefGoogle Scholar
  18. 18.
    Small HY, Montezano AC, Rios FJ, Savoia C, Touyz RM. Hypertension due to antiangiogenic cancer therapy with vascular endothelial growth factor inhibitors: understanding and managing a new syndrome. Can J Cardiol. 2014;30:534–43.CrossRefGoogle Scholar
  19. 19.
    Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet. 2007;370:2011–9.CrossRefGoogle Scholar
  20. 20.
    Ranpura V, Hapani S, Chuang J, Wu S. Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncol. 2010;49:287–97.CrossRefGoogle Scholar
  21. 21.
    Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125–34.CrossRefGoogle Scholar
  22. 22.
    Herrmann J, Lerman A. An update on cardio-oncology. Trends Cardiovasc Med. 2014;24:285–95.CrossRefGoogle Scholar
  23. 23.
    Raghunathan D, Khilji MI, Hassan SA, Yusuf SW. Radiation-induced cardiovascular disease. Curr Atheroscler Rep. 2017;19:22.CrossRefGoogle Scholar
  24. 24.
    Yusuf SW, Sami S, Daher IN. Radiation-induced heart disease: a clinical update. Cardiol Res Pract. 2011;2011:317659. Scholar
  25. 25.
    Tungjai M, Whorton EB, Rithidech KN. Persistence of apoptosis and inflammatory responses in the heart and bone marrow of mice following whole-body exposure to 28Silicon (28Si) ions. Radiat Environ Biophys. 2013;52(3):339–50.CrossRefGoogle Scholar
  26. 26.
    Koene RJ, Prizment AE, Bleas A, Konety SH. Shared risk factors in cardiovascular disease and cancer. Circulation. 2016;133:1104–14.CrossRefGoogle Scholar
  27. 27.
    Zöller B, Ji J, Sundquist J, Sundquist K. Risk of coronary artery disease in patients with cancer: a nationwide follow-up study from Sweden. Eur J Cancer. 2012;48:121–8.CrossRefGoogle Scholar
  28. 28.
    Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006;83:456S–60S.CrossRefGoogle Scholar
  29. 29.
    Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119–31. Scholar
  30. 30.
    Franchini M, Montagnana M, Favaloro EJ, Lippi G. The bidirectional relationship of cancer and hemostasis and the potential role of anticoagulant therapy in moderating thrombosis and cancer spread. Semin Thromb Hemost. 2009;35:644–53.CrossRefGoogle Scholar
  31. 31.
    de Forni M, Bugat R, Sorbette F, Delay M, Bachaud JM, Chevreau C. Cardiotoxicity of continuous intravenous infusion of 5-fluorouracil: clinical study, prevention and physiopathology. Apropos of 13 cases. Bull Cancer. 1990;77:429–38.PubMedGoogle Scholar
  32. 32.
    Südhoff T, Enderle MD, Pahlke M, Petz C, Teschendorf C, Graeven U, et al. 5-fluorouracil induces arterial vasocontractions. Ann Oncol. 2004;15:661–4.CrossRefGoogle Scholar
  33. 33.
    Sestito A, Sgueglia GA, Pozzo C, Cassano A, Barone C, Crea F, et al. Coronary artery spasm induced by capecitabine. J Cardiovasc Med (Hagerstown). 2006;7:136–8. Scholar
  34. 34.
    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. Scholar
  35. 35.
    Schrader C, Keussen C, Bewig B, von Freier A, Lins M. Symptoms and signs of an acute myocardial ischemia caused by chemotherapy with Paclitaxel (Taxol) in a patient with metastatic ovarian carcinoma. Eur J Med Res. 2005;10:498–501.PubMedGoogle Scholar
  36. 36.
    Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors. Cancer Treat Rev. 2013;39:974–84. Scholar
  37. 37.
    Gallagher H, Carroll WM, Dowd M, Rochev Y. The effects of vinblastine on endothelial cells. Endothelium. 2008;15:9–15. Scholar
  38. 38.
    Pantaleo MA, Mandrioli A, Saponara M, Nannini M, Erente G, Lolli C, et al. Development of coronary artery stenosis in a patient with metastatic renal cell carcinoma treated with sorafenib. BMC Cancer. 2012;12:231. Scholar
  39. 39.
    Weinberg BA, Conces DJ Jr, Waller BF. Cardiac manifestations of noncardiac tumors. Part I: direct effects. Clin Cardiol. 1989;12:289–96.CrossRefGoogle Scholar
  40. 40.
    Orban M, Tousek P, Becker I, Augustin N, Firschke C. Cardiac malignant tumor as a rare cause of acute myocardial infarction. Int J Cardiovasc Imaging. 2004;20:47–51.CrossRefGoogle Scholar
  41. 41.
    Ito D, Shiraishi J, Nakamura T, Maruyama N, Iwamura Y, Hashimoto S, et al. Primary percutaneous coronary intervention and intravascular ultrasound imaging for coronary thrombosis after cisplatin-based chemotherapy. Heart Vessel. 2012;27:634–8. Scholar
  42. 42.
    Togna GI, Togna AR, Franconi M, Caprino L. Cisplatin triggers platelet activation. Thromb Res. 2000;99:503–9.CrossRefGoogle Scholar
  43. 43.
    Karabay KO, Yildiz O, Aytekin V. Multiple coronary thrombi with cisplatin. J Invasive Cardiol. 2014;26:E18–20.PubMedGoogle Scholar
  44. 44.
    Scappaticci FA, Skillings JR, Holden SN, Gerber HP, Miller K, Kabbinavar F, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. 2007;99:1232–9. Scholar
  45. 45.
    Kushiyama S, Ikura Y, Iwai Y. Acute myocardial infarction caused by coronary tumour embolism. Eur Heart J. 2013;34:3690. Scholar
  46. 46.
    Diaz Castro O, Bueno H, Nebreda LA. Acute myocardial infarction caused by paradoxical tumorous embolism as a manifestation of hepatocarcinoma. Heart. 2004;90:e29.CrossRefGoogle Scholar
  47. 47.
    Mir MA, Patnaik MM, Herrmann J. Spontaneous coronary artery dissection during hematopoietic stem cell infusion. Blood. 2013;122:3388–9. Scholar
  48. 48.
    Ghosh N, Chow CM, Korley V, Chisholm R. An unusual case of chronic coronary artery dissection: did cisplatin play a role? Can J Cardiol. 2008;24:795–7.CrossRefGoogle Scholar
  49. 49.
    Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery; European Society of Cardiology (ESC); Poldermans D, Bax JJ, Boersma E, De Hert S, et al. Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. Eur Heart J. 2009;30:2769–812.CrossRefGoogle Scholar
  50. 50.
    Tornio A, Pasanen MK, Laitila J, , Neuvonen PJ, Backman JT. Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8. Basic Clin Pharmacol Toxicol 2005;97:104–108.CrossRefGoogle Scholar
  51. 51.
    Khaidakov M, Wang W, Khan JA, Kang BY, Hermonat PL, Mehta JL. Statins and angiogenesis: is it about connections? Biochem Biophys Res Commun. 2009;387:543–7.CrossRefGoogle Scholar
  52. 52.
    Elewa HF, El-Remessy AB, Somanath PR, Fagan SC. Diverse effects of statins on angiogenesis: new therapeutic avenues. Pharmacotherapy. 2010;30:169–76.CrossRefGoogle Scholar
  53. 53.
    Mehta NG, Mehta M. Overcoming multidrug resistance in cancer: statins offer a logical candidate. Med Hypotheses. 2010;74:237–9.CrossRefGoogle Scholar
  54. 54.
    Gonyeau MJ, Yuen DW. A clinical review of statins and cancer: helpful or harmful? Pharmacotherapy. 2010;30:177–94.CrossRefGoogle Scholar
  55. 55.
    Serebruany VL. Platelet inhibition with prasugrel and increased cancer risks: potential causes and implications. Am J Med. 2009;122:407–8.CrossRefGoogle Scholar
  56. 56.
    Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2018;9(2):119–77. Scholar
  57. 57.
    Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 215 ESC guidelines for the management of acute coronary syndrome in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:267–315.CrossRefGoogle Scholar
  58. 58.
    Thygesen K, Alpert JS, White HD. Third universal definition of myocardial infarction. Eur Heart J. 2012;33:2551–67.CrossRefGoogle Scholar
  59. 59.
    Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34:2949–3003.CrossRefGoogle Scholar
  60. 60.
    Sedlis SP, Hartigan PM, Teo KK, Maron DJ, Spertus JA, Mancini GB, et al. Effect of PCI on long-term survival in patients with stable ischemic heart disease. N Engl J Med. 2015;373:1937–46.CrossRefGoogle Scholar
  61. 61.
    Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, 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;15:1063–93.CrossRefGoogle Scholar
  62. 62.
    Jiji RS, Kramer CM, Salerno M. Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs. J Nucl Cardiol. 2012;19:377–88.CrossRefGoogle Scholar
  63. 63.
    Nagueh SF, Smiseth OA, Appleton BFB, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29:277–314.CrossRefGoogle Scholar
  64. 64.
    Thavendiranathan P, Poulin F, Lim KD, Plana JC, Woo A, Marwick TH. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol. 2014;63:2751–68.CrossRefGoogle Scholar
  65. 65.
    Cadeddu C, Piras A, Dessi M, Madeddu C, Mantovani G, Scartozzi M, et al. Timing of the negative effects of trastuzumab on cardiac mechanics after anthracycline chemotherapy. Int J Cardiovasc Imaging. 2017;33:197–207.CrossRefGoogle Scholar
  66. 66.
    Lethen H, P Tries T, Kersting S, Lambertz H. Validation of noninvasive assessment of coronary flow velocity reserve in the right coronary artery. A comparison of transthoracic echocardiographic results with intracoronary Doppler flow wire measurements. Eur Heart J. 2003;24:1567–75.CrossRefGoogle Scholar
  67. 67.
    Wada T, Hirata K, Shiono Y, Orii M, Shimamura K, Ishibashi K, et al. Coronary flow velocity reserve in three major coronary arteries by transthoracic echocardiography for the functional assessment of coronary artery disease: a comparison with fractional flow reserve. Eur Heart J Cardiovasc Imaging. 2014;15:399–408.CrossRefGoogle Scholar
  68. 68.
    Holte E, Vegsundvag J, Hegborn K, Hole T, Wiseth R. Transthoracic Doppler echocardiography for detection of stenoses in the left coronary artery by use of poststenotic coronary flow profiles: a comparison with quantitative coronary angiography and coronary flow reserve. J Am Soc Echocardiogr. 2013;26:77–85.CrossRefGoogle Scholar
  69. 69.
    Holte E, Vegsundvag J, Hegborn K, Hole T, Wiseth R. Transthoracic Doppler for detection of stenoses in the three main coronary arteries by use of stenotic to prestenotic velocity ratio and aliased coronary flow. Eur Heart J Cardiovasc Imaging. 2015;16:1323–30.PubMedGoogle Scholar
  70. 70.
    Zamorano JL, Lancelotti 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.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Giuseppe Mercuro
    • 1
  • Christian Cadeddu Dessalvi
    • 1
    Email author
  • Martino Deidda
    • 1
  • Stephan Stöbe
    • 2
  • Andreas Hagendorff
    • 3
  1. 1.Department of Medical Science and Public HealthUniversity Hospital of CagliariMonserrato (CA)Italy
  2. 2.Division of Cardiology and AngiologyUniversity of LeipzigLeipzigGermany
  3. 3.CardiologyUniversity of LeipzigLeipzigGermany

Personalised recommendations