Abstract
Cardiac disease in patients with cancer or caused by cancer therapy is a clinical problem of emerging importance. Optimum management of cardiovascular disease can mean that patients with cancer can successfully receive therapies to treat their malignancy and can reduce morbidity and mortality due to cardiovascular disease in cancer survivors. The presence of cancer and cancer-related morbidities substantially complicates the management of cardiovascular disease in cancer patients. In this Review, we discuss management strategies for cardiovascular disease in patients with cancer, focusing on the prevention and treatment of congestive heart failure and myocardial infarction.
Key Points
-
In addition to alkylating agents and anthracyclines, some receptor tyrosine kinase inhibitors are potentially cardiotoxic
-
Patients with cancer who are treated with potentially cardiotoxic chemotherapy regimens represent a high-risk group for the development of heart failure, and should be treated in accordance with the new American Heart Association guidelines for the treatment of the stage A heart failure patient
-
Angiotensin-converting-enzyme inhibitors, beta blockers, and aldosterone antagonists have all been shown to improve morbidity and mortality related to heart failure in patients with cancer
-
Radiation-induced coronary artery disease is common and often presents many years after therapy; severe coronary artery disease induced by radiation therapy can be present in patients despite a paucity of symptoms
-
Aspirin therapy considerably reduces mortality in patients with myocardial infarction, including patients with cancer who have substantial thrombocytopenia
-
Interventional cardiologists should avoid the use of drug-eluting stents in patients with cancer
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hunt SA et al. (2005) ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to update the 2001 guidelines for the evaluation and management of heart failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 112: e154–e235
Schultz-Hector S and Trott KR (2007) Radiation-induced cardiovascular diseases: is the epidemiologic evidence compatible with the radiobiologic data? Int J Radiat Oncol Biol Phys 67: 10–18
Yeh ET (2006) Cardiotoxicity induced by chemotherapy and antibody therapy. Annu Rev Med 57: 485–498
Horenstein MS et al. (2000) Molecular basis of anthracycline-induced cardiotoxicity and its prevention. Mol Genet Metab 71: 436–444
Kwok JC and Richardson DR (2000) The cardioprotective effect of the iron chelator dexrazoxane (ICRF-187) on anthracycline-mediated cardiotoxicity. Redox Rep 5: 317–324
Lefrak EA et al. (1973) A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 32: 302–314
Steinherz LJ et al. (1991) Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 266: 1672–1677
Von Hoff DD et al. (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91: 710–717
Swain SM et al. (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97: 2869–2879
Schwartz RG et al. (1987) Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy: seven-year experience using serial radionuclide angiocardiography. Am J Med 82: 1109–1118
Cheitlin MD et al. (2003) ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ase committee to update the 1997 guidelines for the clinical application of echocardiography). Circulation 108: 1146–1162
Tassan-Mangina S et al. (2006) Tissue Doppler imaging and conventional echocardiography after anthracycline treatment in adults: early and late alterations of left ventricular function during a prospective study. Eur J Echocardiogr 7: 141–146
Bristow MR et al. (1982) Efficacy and cost of cardiac monitoring in patients receiving doxorubicin. Cancer 50: 32–41
Felker GM et al. (2000) Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 342: 1077–1084
Cardinale D et al. (2006) Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114: 2474–2481
Adams JE 3rd et al. (1993) Cardiac troponin I: a marker with high specificity for cardiac injury. Circulation 88: 101–106
Kilickap S et al. (2005) cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Ann Oncol 16: 798–804
Auner HW et al. (2003) Prolonged monitoring of troponin T for the detection of anthracycline cardiotoxicity in adults with hematological malignancies. Ann Hematol 82: 218–222
Cardinale D et al. (2002) Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol 13: 710–715
Cardinale D et al. (2000) Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 36: 517–522
Maisel AS et al. (2002) Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347: 161–167
Suzuki T et al. (1998) Elevated B-type natriuretic peptide levels after anthracycline administration. Am Heart J 136: 362–363
Aggarwal S et al. (2007) B-type natriuretic peptide as a marker for cardiac dysfunction in anthracycline-treated children. Pediatr Blood Cancer 49: 812–816
Burjonroppa SC et al. (2007) Cancer patients with markedly elevated B-type natriuretic peptide may not have volume overload. Am J Clin Oncol 30: 287–293
Forfia PR et al. (2005) Relationship between B-type natriuretic peptides and pulmonary capillary wedge pressure in the intensive care unit. J Am Coll Cardiol 45: 1667–1671
Lenihan DJ et al. (2007) Early detection of cardiotoxicity during chemotherapy using biomarkers. J Card Fail 13 (Supp): S151
Legha SS et al. (1982) Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med 96: 133–139
Levitt GA et al. (2004) Does anthracycline administration by infusion in children affect late cardiotoxicity? Br J Haematol 124: 463–468
Lipshultz SE et al. (2002) Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J Clin Oncol 20: 1677–1682
Coukell AJ and Faulds D (1997) Epirubicin: an updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of breast cancer. Drugs 53: 453–482
Nair R et al. (1998) A randomized comparison of the efficacy and toxicity of epirubicin and doxorubicin in the treatment of patients with non-Hodgkin's lymphoma. Cancer 82: 2282–2288
Posner LE et al. (1985) Mitoxantrone: an overview of safety and toxicity. Invest New Drugs 3: 123–132
Aviles A et al. (1993) Late cardiac toxicity of doxorubicin, epirubicin, and mitoxantrone therapy for Hodgkin's disease in adults. Leuk Lymphoma 11: 275–279
O'Brien ME et al. (2004) Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol 15: 440–449
Safra T et al. (2000) Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. Ann Oncol 11: 1029–1033
Speyer JL et al. (1992) ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J Clin Oncol 10: 117–127
van Dalen EC et al. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD003917. 10.1002/14651858.CD003917.pub3
Swain SM et al. (1997) Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol 15: 1318–1332
Schuchter LM et al. (2002) 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 20: 2895–2903
Cheng J et al. (2001) Carvedilol: molecular and cellular basis for its multifaceted therapeutic potential. Cardiovasc Drug Rev 19: 152–171
Spallarossa P et al. (2004) Carvedilol prevents doxorubicin-induced free radical release and apoptosis in cardiomyocytes in vitro. J Mol Cell Cardiol 37: 837–846
Matsui H et al. (1999) Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats. Life Sci 65: 1265–1274
Santos DL et al. (2002) Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy. Toxicol Appl Pharmacol 185: 218–227
Kalay N et al. (2006) Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 48: 2258–2262
Vaynblat M et al. (2002) Simultaneous angiotensin converting enzyme inhibition moderates ventricular dysfunction caused by doxorubicin. Eur J Heart Fail 4: 583–586
Sacco G et al. (2001) Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat. Eur J Pharmacol 414: 71–78
Zver S et al. (2007) Cardiac toxicity of high-dose cyclophosphamide in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Int J Hematol 85: 408–414
Gottdiener JS et al. (1981) Cardiotoxicity associated with high-dose cyclophosphamide therapy. Arch Intern Med 141: 758–763
Quezado ZM et al. (1993) High-dose ifosfamide is associated with severe, reversible cardiac dysfunction. Ann Intern Med 118: 31–36
Romond EH et al. (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353: 1673–1684
Slamon DJ et al. (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344: 783–792
Seidman A et al. (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20: 1215–1221
Guarneri V et al. (2006) Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol 24: 4107–4115
Tan-Chiu E et al. (2005) 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 23: 7811–7819
Gonzalez-Angulo AM et al. (2006) Adjuvant therapy with trastuzumab for HER-2/neu-positive breast cancer. Oncologist 11: 857–867
Yeh ET et al. (2004) Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation 109: 3122–3131
Ewer MS et al. (2005) Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol 23: 7820–7826
Force T et al. (2007) Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer 7: 332–344
Kantarjian H et al. (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346: 645–652
Demetri GD et al. (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347: 472–480
Kerkela R et al. (2006) Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12: 908–916
Atallah E et al. (2007) Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood 110: 1233–1237
Verweij J et al. (2007) Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. Eur J Cancer 43: 974–978
Maitland ML and Ratain MJ (2006) Terminal ballistics of kinase inhibitors: there are no magic bullets. Ann Intern Med 145: 702–703
Rock EP et al. (2007) Food and drug administration drug approval summary: sunitinib malate for the treatment of gastrointestinal stromal tumor and advanced renal cell carcinoma. Oncologist 12: 107–113
SUTENT® (sunitinib malate) package insert (Pfizer Inc. 2006) http://media.pfizer.com/files/products/uspi_sutent.pdf (accessed 9 January 2008)
Motzer RJ et al. (2006) Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295: 2516–2524
Lopez-Sendon J et al. (2004) Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J 25: 1341–1362
Pitt B et al. (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341: 709–717
Uddin N and Patterson JH (2007) Current guidelines for treatment of heart failure: 2006 update. Pharmacotherapy 27: 12S–17S
The Digitalis Investigation Group (1997) The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 336: 525–533
Eichhorn EJ and Gheorghiade M (2002) Digoxin. Prog Cardiovasc Dis 44: 251–266
McAlister FA et al. (2007) Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA 297: 2502–2514
de Forni M et al. (1992) Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J Clin Oncol 10: 1795–1801
Tsavaris N et al. (2002) Cardiotoxicity following different doses and schedules of 5-fluorouracil administration for malignancy—a survey of 427 patients. Med Sci Monit 8: PI51–P157
Labianca R et al. (1982) Cardiac toxicity of 5-fluorouracil: a study on 1083 patients. Tumori 68: 505–510
Kosmas C et al. (2007) Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol 134: 75–82
Lejonc JL et al. (1980) Myocardial infarction following vinblastine treatment. Lancet 2: 692
Mandel EM et al. (1975) Vincristine-induced myocardial infarction. Cancer 36: 1979–1982
Yancey RS and Talpaz M (1982) Vindesine-associated angina and ECG changes. Cancer Treat Rep 66: 587–589
Lapeyre-Mestre M et al. (2004) Vinorelbine-related cardiac events: a meta-analysis of randomized clinical trials. Fundam Clin Pharmacol 18: 97–105
Gridelli C et al. (2005) Treatment of advanced non-small-cell lung cancer in the elderly: results of an international expert panel. J Clin Oncol 23: 3125–3137
Fajardo LF and Stewart JR (1972) Coronary artery disease after radiation. N Engl J Med 286: 1265–1266
Basavaraju SR and Easterly CE (2002) Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications. Med Phys 29: 2391–2403
Orzan F et al. (1993) Severe coronary artery disease after radiation therapy of the chest and mediastinum: clinical presentation and treatment. Br Heart J 69: 496–500
McEniery PT et al. (1987) Clinical and angiographic features of coronary artery disease after chest irradiation. Am J Cardiol 60: 1020–1024
Hull MC et al. (2003) Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy. JAMA 290: 2831–2837
Paszat LF et al. (1999) Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: a population-based study in Ontario, Canada. Int J Radiat Oncol Biol Phys 43: 755–762
Paszat LF et al. (2007) A population-based case-cohort study of the risk of myocardial infarction following radiation therapy for breast cancer. Radiother Oncol 82: 294–300
Rutqvist LE et al. (1992) Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. Int J Radiat Oncol Biol Phys 22: 887–896
Paszat LF et al. (1998) Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. J Clin Oncol 16: 2625–2631
Hancock SL et al. (1993) Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. JAMA 270: 1949–1955
Heidenreich PA et al. (2007) Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease. J Clin Oncol 25: 43–49
Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360: 7–22
Darby SC et al. (2005) Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol 6: 557–565
Prosnitz RG and Marks LB (2005) Radiation-induced heart disease: vigilance is still required. J Clin Oncol 23: 7391–7394
Patel B et al. (1987) 5-Fluorouracil cardiotoxicity: left ventricular dysfunction and effect of coronary vasodilators. Am J Med Sci 294: 238–243
Antman EM et al. (2004) ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). Circulation 110: e82–e292
Grines CL et al. for the Stent Primary Angioplasty in Myocardial Infarction Study Group (1999) Coronary angioplasty with or without stent implantation for acute myocardial infarction. N Engl J Med 341: 1949–1956
McFadden EP et al. (2004) Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 364: 1519–1521
Braunwald E et al. (2002) ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the management of patients with unstable angina). Circulation 106: 1893–1900
Sarkiss MG et al. (2007) Impact of aspirin therapy in cancer patients with thrombocytopenia and acute coronary syndromes. Cancer 109: 621–627
Cannon CP et al. (2004) Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 350: 1495–1504
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Khakoo, A., Yeh, E. Therapy Insight: management of cardiovascular disease in patients with cancer and cardiac complications of cancer therapy. Nat Rev Clin Oncol 5, 655–667 (2008). https://doi.org/10.1038/ncponc1225
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ncponc1225
This article is cited by
-
Approaches for monitoring and treating cardiomyopathy among cancer survivors following anthracycline or thoracic radiation treatment
Cardio-Oncology (2022)
-
Opportunities to Incorporate Osteopathic Manipulative Treatment Within Cancer Rehabilitation and the Current State of the Evidence
Current Physical Medicine and Rehabilitation Reports (2022)
-
Acute Coronary Syndrome Management in Cancer Patients
Current Oncology Reports (2018)
-
Cancer as a Risk Factor for Cardiovascular Disease
Current Oncology Reports (2017)
-
Lung cancer as a cardiotoxic state: a review
Medical Oncology (2017)