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Cardiovascular effects of systemic cancer treatment

Published:December 02, 2010DOI:https://doi.org/10.1016/j.ctrv.2010.11.001

      Abstract

      Many methods of systemic anticancer treatment have detrimental effects on the cardiovascular system, thus limiting the possibility of further therapy, worsening patients’ quality of life and increasing mortality. The best recognized and most clinically relevant is the cardiotoxicity of anthracyclines. Other cytotoxic drugs associated with significant risk of cardiovascular complications include alkylating agents, 5-fluorouracil and paclitaxel. Cardiovascular adverse effects are also associated with the use of targeted therapies, such as trastuzumab, bevacizumab and tyrosine kinase inhibitors, and some of the drugs used in the treatment of hematological malignancies, such as all-trans-retinoic acid and arsenic trioxide.
      The most serious cardiac complication of anticancer therapy is congestive heart failure, associated predominantly with the use of anthracyclines, trastuzumab and high-dose cyclophosphamide. Myocardial ischemia is mainly caused by antimetabolite and interferon alpha treatment. Other adverse effects may include hypotension, hypertension, arrhythmias and conduction disorders, edema, pericarditis and thrombo-embolic complications.
      The aim of this review is to summarize and critically analyze the available evidence on the cardiovascular toxicity of systemic anticancer therapies, with particular attention to the recently recognized adverse effects of targeted therapies.

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      References

        • Yeh E.T.
        • Tong A.T.
        • Lenihan D.J.
        • et al.
        Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management.
        Circulation. 2004; 109: 3122-3131
        • Bonow R.O.
        • Bennett S.
        • Casey Jr., D.E.
        • et al.
        ACC/AHA clinical performance measures for adults with chronic heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Heart Failure Clinical Performance Measures): endorsed by the Heart Failure Society of America.
        Circulation. 2005; 112: 1853-1887
        • Yeh E.T.
        Cardiotoxicity induced by chemotherapy and antibody therapy.
        Annu Rev Med. 2006; 57: 485-498
        • Hanrahan E.O.
        • Gonzalez-Angulo A.M.
        • Giordano S.H.
        • et al.
        Overall survival and cause-specific mortality of patients with stage T1a, bN0M0 breast carcinoma.
        J Clin Oncol. 2007; 25: 4952-4960
        • Mertens A.C.
        • Yasui Y.
        • Neglia J.P.
        • et al.
        Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study.
        J Clin Oncol. 2001; 19: 3163-3172
        • Hooning M.J.
        • Aleman B.M.
        • van Rosmalen A.J.
        • Kuenen M.A.
        • Klijn J.G.
        • van Leeuwen F.E.
        Cause-specific mortality in long-term survivors of breast cancer: a 25-year follow-up study.
        Int J Radiat Oncol Biol Phys. 2006; 64: 1081-1091
        • Jurcut R.
        • Wildiers H.
        • Ganame J.
        • D’hooge J.
        • Paridaens R.
        • Voigt J.U.
        Detection and monitoring of cardiotoxicity-what does modern cardiology offer?.
        Support Care Cancer. 2008; 16: 437-445
        • Khakoo A.Y.
        • Yeh E.T.
        Therapy insight: management of cardiovascular disease in patients with cancer and cardiac complications of cancer therapy.
        Nat Clin Pract Oncol. 2008; 5: 655-667
        • Slordal L.
        • Spigset O.
        Heart failure induced by non-cardiac drugs.
        Drug Saf. 2006; 29: 567-586
        • Schimmel K.J.
        • Richel D.J.
        • Van den Brink R.B.
        • Guchelaar H.J.
        Cardiotoxicity of cytotoxic drugs.
        Cancer Treat Rev. 2004; 30: 181-191
        • Outomuro D.
        • Grana D.R.
        • Azzato F.
        • Milei J.
        Adriamycin-induced myocardial toxicity: new solutions for an old problem?.
        Int J Cardiol. 2007; 117: 6-15
        • Floyd J.D.
        • Nguyen D.T.
        • Lobins R.L.
        • Bashir Q.
        • Doll D.C.
        • Perry M.C.
        Cardiotoxicity of cancer therapy.
        J Clin Oncol. 2005; 23: 7685-7696
        • Youssef G.
        • Links M.
        The prevention and management of cardiovascular complications of chemotherapy in patients with cancer.
        Am J Cardiovasc Drugs. 2005; 5: 233-243
        • Keefe D.L.
        Trastuzumab-associated cardiotoxicity.
        Cancer. 2002; 95: 1592-1600
        • Barrett-Lee P.J.
        • Dixon J.M.
        • Farrell C.
        • et al.
        Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk.
        Ann Oncol. 2009; 20: 816-827
        • Chen B.
        • Peng X.
        • Pentassuglia L.
        • Lim C.C.
        • Sawyer D.B.
        Molecular and cellular mechanisms of anthracycline cardiotoxicity.
        Cardiovasc Toxicol. 2007; 7: 114-121
        • Swain S.M.
        • Whaley F.S.
        • Ewer M.S.
        Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials.
        Cancer. 2003; 97: 2869-2879
        • Perez E.A.
        • Rodeheffer R.
        Clinical cardiac tolerability of trastuzumab.
        J Clin Oncol. 2004; 22: 322-329
        • Bonneterre J.
        • Roche H.
        • Kerbrat P.
        • et al.
        Long-term cardiac follow-up in relapse-free patients after six courses of fluorouracil, epirubicin, and cyclophosphamide, with either 50 or 100 mg of epirubicin, as adjuvant therapy for node-positive breast cancer: French adjuvant study group.
        J Clin Oncol. 2004; 22: 3070-3079
        • Ganz P.A.
        • Hussey M.A.
        • Moinpour C.M.
        • et al.
        Late cardiac effects of adjuvant chemotherapy in breast cancer survivors treated on Southwest Oncology Group protocol s8897.
        J Clin Oncol. 2008; 26: 1223-1230
        • Zambetti M.
        • Moliterni A.
        • Materazzo C.
        • et al.
        Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation.
        J Clin Oncol. 2001; 19: 37-43
        • Jensen B.V.
        • Skovsgaard T.
        • Nielsen S.L.
        Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients.
        Ann Oncol. 2002; 13: 699-709
        • Carver J.R.
        • Shapiro C.L.
        • Ng A.
        • et al.
        American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects.
        J Clin Oncol. 2007; 25: 3991-4008
        • Tjeerdsma G.
        • Meinardi M.T.
        • van der Graaf W.T.
        • et al.
        Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables.
        Heart. 1999; 81: 419-423
        • Deng S.
        • Wojnowski L.
        Genotyping the risk of anthracycline-induced cardiotoxicity.
        Cardiovasc Toxicol. 2007; 7: 129-134
        • Scully R.E.
        • Lipshultz S.E.
        Anthracycline cardiotoxicity in long-term survivors of childhood cancer.
        Cardiovasc Toxicol. 2007; 7: 122-128
        • Swain S.M.
        • Vici P.
        The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert panel review.
        J Cancer Res Clin Oncol. 2004; 130: 1-7
        • Lipshultz S.E.
        • Giantris A.L.
        • Lipsitz S.R.
        • et al.
        Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91–01 Acute Lymphoblastic Leukemia protocol.
        J Clin Oncol. 2002; 20: 1677-1682
        • Ryberg M.
        • Nielsen D.
        • Cortese G.
        • Nielsen G.
        • Skovsgaard T.
        • Andersen P.K.
        New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients.
        J Natl Cancer Inst. 2008; 100: 1058-1067
        • Myers C.E.
        • McGuire W.P.
        • Liss R.H.
        • Ifrim I.
        • Grotzinger K.
        • Young R.C.
        Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response.
        Science. 1977; 197: 165-167
        • Ewer M.S.
        • Lippman S.M.
        Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity.
        J Clin Oncol. 2005; 23: 2900-2902
        • Milei J.
        • Boveris A.
        • Llesuy S.
        • et al.
        Amelioration of adriamycin-induced cardiotoxicity in rabbits by prenylamine and vitamins A and E.
        Am Heart J. 1986; 111: 95-102
        • Gianni L.
        • Herman E.H.
        • Lipshultz S.E.
        • Minotti G.
        • Sarvazyan N.
        • Sawyer D.B.
        Anthracycline cardiotoxicity: from bench to bedside.
        J Clin Oncol. 2008; 26: 3777-3784
        • Sparano J.A.
        • Brown D.L.
        • Wolff A.C.
        Predicting cancer therapy-induced cardiotoxicity: the role of troponins and other markers.
        Drug Saf. 2002; 25: 301-311
        • Mordente A.
        • Meucci E.
        • Martorana G.E.
        • Giardina B.
        • Minotti G.
        Human heart cytosolic reductases and anthracycline cardiotoxicity.
        IUBMB Life. 2001; 52: 83-88
        • Vasquez-Vivar J.
        • Martasek P.
        • Hogg N.
        • Masters B.S.
        • Pritchard Jr., K.A.
        • Kalyanaraman B.
        Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin.
        Biochemistry. 1997; 36: 11293-11297
        • Billingham M.E.
        • Mason J.W.
        • Bristow M.R.
        • Daniels J.R.
        Anthracycline cardiomyopathy monitored by morphologic changes.
        Cancer Treat Rep. 1978; 62: 865-872
        • Mackay B.
        • Ewer M.S.
        • Carrasco C.H.
        • Benjamin R.S.
        Assessment of anthracycline cardiomyopathy by endomyocardial biopsy.
        Ultrastruct Pathol. 1994; 18: 203-211
        • Batist G.
        • Ramakrishnan G.
        • Rao C.S.
        • et al.
        Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.
        J Clin Oncol. 2001; 19: 1444-1454
        • Harris L.
        • Batist G.
        • Belt R.
        • et al.
        Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma.
        Cancer. 2002; 94: 25-36
      1. van Dalen EC, Caron HN, Dickinson HO, Kremer LC. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev 2008;CD003917.

        • Seymour L.
        • Bramwell V.
        • Moran L.A.
        Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer. The Provincial Systemic Treatment Disease Site Group.
        Cancer Prev Control. 1999; 3: 145-159
        • Bates M.
        • Lieu D.
        • Zagari M.
        • Spiers A.
        • Williamson T.
        A pharmacoeconomic evaluation of the use of dexrazoxane in preventing anthracycline-induced cardiotoxicity in patients with stage IIIB or IV metastatic breast cancer.
        Clin Ther. 1997; 19: 167-184
        • Hensley M.L.
        • Hagerty K.L.
        • Kewalramani T.
        • et al.
        American Society of Clinical Oncology 2008 Clinical Practice Guideline Update: Use of Chemotherapy, Radiation Therapy Protectants.
        J Clin Oncol. 2008; 2: 2
        • Legha S.S.
        • Wang Y.M.
        • Mackay B.
        • et al.
        Clinical and pharmacologic investigation of the effects of alpha-tocopherol on adriamycin cardiotoxicity.
        Ann NY Acad Sci. 1982; 393: 411-418
        • Myers C.
        • Bonow R.
        • Palmeri S.
        • et al.
        A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine.
        Semin Oncol. 1983; 10: 53-55
        • Jones S.
        • Holmes F.A.
        • O’Shaughnessy J.
        • et al.
        Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735.
        J Clin Oncol. 2009; 27: 1177-1183
        • Yeh E.T.
        • Bickford C.L.
        Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management.
        J Am Coll Cardiol. 2009; 53: 2231-2247
        • Saif M.W.
        • Shah M.M.
        • Shah A.R.
        Fluoropyrimidine-associated cardiotoxicity: revisited.
        Expert Opin Drug Saf. 2009; 8: 191-202
        • Albini A.
        • Pennesi G.
        • Donatelli F.
        • Cammarota R.
        • De F.S.
        • Noonan D.M.
        Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention.
        J Natl Cancer Inst. 2010; 102: 14-25
        • Manojlovic N.
        • Babic D.
        • Stojanovic S.
        • Filipovic I.
        • Radoje D.
        Capecitabine cardiotoxicity – case reports and literature review.
        Hepatogastroenterology. 2008; 55: 1249-1256
        • Dasanu C.A.
        Gemcitabine: vascular toxicity and prothrombotic potential.
        Expert Opin Drug Saf. 2008; 7: 703-716
        • Gianni L.
        • Salvatorelli E.
        • Minotti G.
        Anthracycline cardiotoxicity in breast cancer patients: synergism with trastuzumab and taxanes.
        Cardiovasc Toxicol. 2007; 7: 67-71
        • Vallis K.A.
        • Pintilie M.
        • Chong N.
        • et al.
        Assessment of coronary heart disease morbidity and mortality after radiation therapy for early breast cancer.
        J Clin Oncol. 2002; 20: 1036-1042
        • Slamon D.J.
        • Leyland-Jones B.
        • Shak S.
        • et al.
        Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that over expresses HER2.
        N Engl J Med. 2001; 344: 783-792
        • Hayes D.F.
        • Picard M.H.
        Heart of darkness: the downside of trastuzumab.
        J Clin Oncol. 2006; 24: 4056-4058
        • Ewer M.S.
        • Vooletich M.T.
        • Durand J.B.
        • et al.
        Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment.
        J Clin Oncol. 2005; 23: 7820-7826
        • de A.E.
        • Bedard P.L.
        • Suter T.
        • Piccart-Gebhart M.
        Cardiac toxicity with anti-HER-2 therapies: what have we learned so far?.
        Target Oncol. 2009; 4: 77-88
        • Yavas O.
        • Yazici M.
        • Eren O.
        • Oyan B.
        The acute effect of trastuzumab infusion on ECG parameters in metastatic breast cancer patients.
        Swiss Med Wkly. 2007; 137: 556-558
        • Telli M.L.
        • Hunt S.A.
        • Carlson R.W.
        • Guardino A.E.
        Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility.
        J Clin Oncol. 2007; 25: 3525-3533
        • Suter T.M.
        • Cook-Bruns N.
        • Barton C.
        Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer.
        Breast. 2004; 13: 173-183
      2. Slamon D, Eiermann W, Robert N, et al. Phase III Trial Comparing AC-T with AC-TH and with TCH in the Adjuvant Treatment of HER2 positive Early Breast Cancer Patients: Second Interim Efficacy Analysis. Abstr.29th Annual San Antonio Breast Cancer Symposium 2006.

        • Joensuu H.
        • Kellokumpu-Lehtinen P.L.
        • Bono P.
        • et al.
        Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.
        N Engl J Med. 2006; 354: 809-820
        • Piccart-Gebhart M.J.
        • Procter M.
        • Leyland-Jones B.
        • et al.
        Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
        N Engl J Med. 2005; 353: 1659-1672
        • Romond E.H.
        • Perez E.A.
        • Bryant J.
        • et al.
        Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
        N Engl J Med. 2005; 353: 1673-1684
        • Perez E.A.
        • Suman V.J.
        • Davidson N.E.
        • et al.
        Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial.
        J Clin Oncol. 2008; 26: 1231-1238
        • Speyer J.
        Cardiac dysfunction in the trastuzumab clinical experience.
        J Clin Oncol. 2002; 20: 1156-1157
        • Grazette L.P.
        • Boecker W.
        • Matsui T.
        • et al.
        Inhibition of ErbB2 causes mitochondrial dysfunction in cardiomyocytes: implications for herceptin-induced cardiomyopathy.
        J Am Coll Cardiol. 2004; 44: 2231-2238
        • Perez E.A.
        • Koehler M.
        • Byrne J.
        • Preston A.J.
        • Rappold E.
        • Ewer M.S.
        Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials.
        Mayo Clin Proc. 2008; 83: 679-686
        • Spector N.L.
        • Yarden Y.
        • Smith B.
        • et al.
        Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells.
        Proc Natl Acad Sci USA. 2007; 104: 10607-10612
        • Azim H.
        • Azim Jr., H.A.
        • Escudier B.
        Trastuzumab versus lapatinib: the cardiac side of the story.
        Cancer Treat Rev. 2009; 35: 633-638
        • Veronese M.L.
        • Mosenkis A.
        • Flaherty K.T.
        • et al.
        Mechanisms of hypertension associated with BAY 43–9006.
        J Clin Oncol. 2006; 24: 1363-1369
        • Zhu X.
        • Wu S.
        • Dahut W.L.
        • Parikh C.R.
        Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis.
        Am J Kidney Dis. 2007; 49: 186-193
        • Shih T.
        • Lindley C.
        Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies.
        Clin Ther. 2006; 28: 1779-1802
        • Scappaticci F.A.
        • Skillings J.R.
        • Holden S.N.
        • et al.
        Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab.
        J Natl Cancer Inst. 2007; 99: 1232-1239
        • Escudier B.
        • Eisen T.
        • Stadler W.M.
        • et al.
        Sorafenib in advanced clear-cell renal-cell carcinoma.
        N Engl J Med. 2007; 356: 125-134
        • Motzer R.J.
        • Hutson T.E.
        • Tomczak P.
        • et al.
        Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.
        N Engl J Med. 2007; 356: 115-124
        • Chu T.F.
        • Rupnick M.A.
        • Kerkela R.
        • et al.
        Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib.
        Lancet. 2007; 370: 2011-2019
        • Pouessel D.
        • Culine S.
        High frequency of intracerebral hemorrhage in metastatic renal carcinoma patients with brain metastases treated with tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor.
        Eur Urol. 2008; 53: 376-381
        • Hutson T.E.
        • Figlin R.A.
        • Kuhn J.G.
        • Motzer R.J.
        Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies.
        Oncologist. 2008; 13: 1084-1096
        • Schmidinger M.
        • Zielinski C.C.
        • Vogl U.M.
        • et al.
        Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma.
        J Clin Oncol. 2008; 26: 5204-5212
        • Joensuu H.
        Cardiac toxicity of sunitinib.
        Lancet. 2007; 370: 1978-1980
        • Strevel E.L.
        • Ing D.J.
        • Siu L.L.
        Molecularly targeted oncology therapeutics and prolongation of the QT interval.
        J Clin Oncol. 2007; 25: 3362-3371
        • Kerkela R.
        • Grazette L.
        • Yacobi R.
        • et al.
        Cardiotoxicity of the cancer therapeutic agent imatinib mesylate.
        Nat Med. 2006; 12: 908-916
        • Atallah E.
        • Durand J.B.
        • Kantarjian H.
        • Cortes J.
        Congestive heart failure is a rare event in patients receiving imatinib therapy.
        Blood. 2007; 110: 1233-1237
        • Vogelvang T.E.
        • van der Mooren M.J.
        • Mijatovic V.
        • Kenemans P.
        Emerging selective estrogen receptor modulators: special focus on effects on coronary heart disease in postmenopausal women.
        Drugs. 2006; 66: 191-221
        • Nandur R.
        • Kumar K.
        • Villablanca A.C.
        Cardiovascular actions of selective estrogen receptor modulators and phytoestrogens.
        Prev Cardiol. 2004; 7: 73-79
        • Braithwaite R.S.
        • Chlebowski R.T.
        • Lau J.
        • George S.
        • Hess R.
        • Col N.F.
        Meta-analysis of vascular and neoplastic events associated with tamoxifen.
        J Gen Intern Med. 2003; 18: 937-947
        • Meier C.R.
        • Jick H.
        Tamoxifen and risk of idiopathic venous thromboembolism.
        Br J Clin Pharmacol. 1998; 45: 608-612
        • Bushnell C.D.
        • Goldstein L.B.
        Risk of ischemic stroke with tamoxifen treatment for breast cancer: a meta-analysis.
        Neurology. 2004; 63: 1230-1233
        • Cushman M.
        • Costantino J.P.
        • Bovill E.G.
        • et al.
        Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer Prevention Trial.
        Br J Haematol. 2003; 120: 109-116
        • Keating N.L.
        • O’Malley A.J.
        • Smith M.R.
        Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer.
        J Clin Oncol. 2006; 24: 4448-4456
        • D’Amico A.V.
        • Denham J.W.
        • Crook J.
        • et al.
        Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions.
        J Clin Oncol. 2007; 25: 2420-2425
        • Nabholtz J.M.
        • Gligorov J.
        Cardiovascular safety profiles of aromatase inhibitors: a comparative review.
        Drug Saf. 2006; 29: 785-801
        • Lenihan D.J.
        • Esteva F.J.
        Multidisciplinary strategy for managing cardiovascular risks when treating patients with early breast cancer.
        Oncologist. 2008; 13: 1224-1234
        • Altena R.
        • Perik P.J.
        • van Veldhuisen D.J.
        • de Vries E.G.
        • Gietema J.A.
        Cardiovascular toxicity caused by cancer treatment: strategies for early detection.
        Lancet Oncol. 2009; 10: 391-399
        • Galderisi M.
        • Marra F.
        • Esposito R.
        • Lomoriello V.S.
        • Pardo M.
        • de Divitiis O.
        Cancer therapy and cardiotoxicity: the need of serial Doppler echocardiography.
        Cardiovasc Ultrasound. 2007; 5: 4
        • Karakurt C.
        • Kocak G.
        • Ozgen U.
        Evaluation of the left ventricular function with tissue tracking and tissue Doppler echocardiography in pediatric malignancy survivors after anthracycline therapy.
        Echocardiography. 2008; 25: 880-887
        • Mavinkurve-Groothuis A.M.
        • Groot-Loonen J.
        • Bellersen L.
        • et al.
        Abnormal NT-pro-BNP levels in asymptomatic long-term survivors of childhood cancer treated with anthracyclines.
        Pediatr Blood Cancer. 2009; 52: 631-636
        • Jones A.L.
        • Barlow M.
        • Barrett-Lee P.J.
        • et al.
        Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring.
        Br J Cancer. 2009; 100: 684-692
        • Blaes A.H.
        • Gaillard P.
        • Peterson B.A.
        • Yee D.
        • Virnig B.
        Angiotensin converting enzyme inhibitors may be protective against cardiac complications following anthracycline chemotherapy.
        Breast Cancer Res Treat. 2010;
        • van Heeckeren W.J.
        • Ortiz J.
        • Cooney M.M.
        • Remick S.C.
        Hypertension, proteinuria, and antagonism of vascular endothelial growth factor signaling: clinical toxicity, therapeutic target, or novel biomarker?.
        J Clin Oncol. 2007; 25: 2993-2995
        • Wadhwa D.
        • Fallah-Rad N.
        • Grenier D.
        • et al.
        Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study.
        Breast Cancer Res Treat. 2009; 117: 357-364
        • Hershman D.L.
        • Neugut A.I.
        Anthracycline cardiotoxicity: one size does not fit all!.
        J Natl Cancer Inst. 2008; 100: 1046-1047