Biochemical markers for prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use.

Chemotherapy is a well-established therapeutic approach for several malignancies, but its clinical efficacy is often limited by its related cardiotoxicity, which leads to cardiomyopathy, possibly evolving into heart failure. To detect cardiac damage, the adopted diagnostic approach is the estimation of left ventricular ejection fraction by echocardiography. This approach shows low sensitivity toward early prediction of cardiomyopathy, when the possibilities of appropriate treatments could still improve the patient's outcome. Cardiac troponins, however, show high diagnostic efficacy as early as 3 months before the clinical onset of cardiomyopathy. The increase in their concentrations is correlated with disease severity and may predict the new onset of major cardiac events during follow-up. Negative troponin concentrations may identify patients with a very low risk of cardiomyopathy (negative predictive value, 99%). Concerning cardiac natriuretic peptides, definitive evidence in regard to a diagnostic or prognostic role in predicting chemotherapy-induced cardiomyopathy is still lacking.

[1]  E. V. D. Wall Guidelines for clinical use in nuclear cardiology , 1992 .

[2]  H. Hayakawa,et al.  Plasma levels of natriuretic peptides in relation to doxorubicin-induced cardiotoxicity and cardiac function in children with cancer. , 2001, Medical and pediatric oncology.

[3]  A. Tiran,et al.  Prolonged monitoring of troponin T for the detection of anthracycline cardiotoxicity in adults with hematological malignancies , 2003, Annals of Hematology.

[4]  M. Kervancıoğlu,et al.  Plasma concentrations of NT-pro-BNP and cardiac troponin-I in relation to doxorubicin-induced cardiomyopathy and cardiac function in childhood malignancy. , 2005, Saudi medical journal.

[5]  V. Ferrans,et al.  The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity , 2001, Cancer Chemotherapy and Pharmacology.

[6]  P. Riikonen,et al.  Long-term prospective follow-up study of cardiac function after cardiotoxic therapy for malignancy in children. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  J. Hartikainen,et al.  Natriuretic peptides during the development of doxorubicin‐induced left ventricular diastolic dysfunction , 2002, Journal of internal medicine.

[8]  V. Ferrans,et al.  Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  B. Hesse,et al.  Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction , 2004, European journal of heart failure.

[10]  Brian Walters,et al.  Cardiotoxicity of the cancer therapeutic agent imatinib mesylate , 2006, Nature Medicine.

[11]  S. Lipsitz,et al.  The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. , 2004, The New England journal of medicine.

[12]  K. Lee,et al.  Value of serial troponin T measures for early and late risk stratification in patients with acute coronary syndromes. The GUSTO-IIa Investigators. , 1998, Circulation.

[13]  M. Nahata,et al.  Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. , 2000, Drug safety.

[14]  G. Martinelli,et al.  Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  J. Berkhof,et al.  The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study , 2007, British Journal of Cancer.

[16]  J. Verweij,et al.  Results of plasma N-terminal pro B-type natriuretic peptide and cardiac troponin monitoring in GIST patients do not support the existence of imatinib-induced cardiotoxicity. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  Shinobu Nakamura,et al.  Brain Natriuretic Peptide Is a Predictor of Anthracycline-Induced Cardiotoxicity , 2001, Acta Haematologica.

[18]  Tsuneyuki Nakamura,et al.  Troponin-T and brain natriuretic peptide as predictors for adriamycin-induced cardiomyopathy in rats. , 2004, Circulation journal : official journal of the Japanese Circulation Society.

[19]  P. Sager,et al.  Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. , 1987, The American journal of medicine.

[20]  M. Garami,et al.  Doxorubicin selectively inhibits brain versus atrial natriuretic peptide gene expression in cultured neonatal rat myocytes. , 1999, Hypertension.

[21]  V. Ferrans,et al.  Use of cardiac troponin T levels as an indicator of doxorubicin-induced cardiotoxicity. , 1998, Cancer research.

[22]  E J Orav,et al.  Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. , 1995, The New England journal of medicine.

[23]  B. Zaret,et al.  Doxorubicin cardiotoxicity: Prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era , 2003, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[24]  C. Pui,et al.  Cancer survivorship--genetic susceptibility and second primary cancers: research strategies and recommendations. , 2006, Journal of the National Cancer Institute.

[25]  E. D. de Vries,et al.  Detection of anthracycline-induced cardiotoxicity. , 1999, Cancer treatment reviews.

[26]  Giovanni Martinelli,et al.  Prevention of High-Dose Chemotherapy-Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme Inhibition , 2006, Circulation.

[27]  M. Štěrba,et al.  Troponin as a marker of myocardiac damage in drug-induced cardiotoxicity , 2005, Expert opinion on drug safety.

[28]  L. Liaudet,et al.  Pharmacological inhibition of CB1 cannabinoid receptor protects against doxorubicin-induced cardiotoxicity. , 2007, Journal of the American College of Cardiology.

[29]  池上 英 Edaravone, a potent free radical scavenger, prevents anthracycline-induced myocardial cell death , 2008 .

[30]  Yumin Chen,et al.  Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury. , 2007, Free radical biology & medicine.

[31]  T. Stokłosa,et al.  Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[32]  S. Lipshultz,et al.  Protecting against anthracycline‐induced myocardial damage: a review of the most promising strategies , 2005, British journal of haematology.

[33]  M. Gad,et al.  Increased plasma endothelin-1 and cardiac nitric oxide during doxorubicin-induced cardiomyopathy. , 2001, Pharmacology & toxicology.

[34]  J. Horáček,et al.  The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. , 2004, Neoplasma.

[35]  R. Calabro',et al.  Anthracycline-Induced Cardiotoxicity in Children with Cancer , 2005, Paediatric drugs.

[36]  P. Ponka,et al.  Study of daunorubicin cardiotoxicity prevention with pyridoxal isonicotinoyl hydrazone in rabbits. , 2005, Pharmacological research.

[37]  G. Martinelli,et al.  Prognostic Value of Troponin I in Cardiac Risk Stratification of Cancer Patients Undergoing High-Dose Chemotherapy , 2004, Circulation.

[38]  S. Takai,et al.  Beneficial effects of angiotensin-converting enzyme inhibition in adriamycin-induced cardiomyopathy in hamsters. , 2002, Japanese journal of pharmacology.

[39]  B. Jensen Cardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer. , 2006, Seminars in oncology.

[40]  M. Panteghini,et al.  10% CV concentration for the fourth generation Roche cardiac troponin T assay derived from Internal Quality Control data , 2006, Clinical chemistry and laboratory medicine.

[41]  G. Martinelli,et al.  Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. , 2000, Journal of the American College of Cardiology.

[42]  M. Panteghini The new definition of myocardial infarction and the impact of troponin determination on clinical practice. , 2006, International journal of cardiology.

[43]  G. Martinelli,et al.  N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? , 2005, Clinical chemistry.

[44]  J. Bryant,et al.  Use of cardiac markers to assess the toxic effects of anthracyclines given to children with cancer: a systematic review. , 2007, European journal of cancer.

[45]  M. P. van den Berg,et al.  Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  S. Aksöyek,et al.  cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[47]  S. Edge,et al.  Is MUGA Scan Necessary in Patients With Low‐Risk Breast Cancer Before Doxorubicin‐Based Adjuvant Therapy? , 2001, American journal of clinical oncology.

[48]  R. Schwartz,et al.  Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group. , 1992, Pediatrics.

[49]  P. Singal,et al.  Doxorubicin-induced cardiomyopathy. , 1998, The New England journal of medicine.

[50]  C. Cipolla,et al.  Troponin I and cardiovascular risk stratification in patients with testicular cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[51]  J. Delaunay,et al.  Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide assays and radionuclide ventriculography. , 2005, In vivo.

[52]  P. Morandi,et al.  Chemotherapy-related cardiotoxicity: new diagnostic and preventive strategies. , 2003, Italian heart journal : official journal of the Italian Federation of Cardiology.

[53]  A. Wolff,et al.  Predicting Cancer Therapy-Induced Cardiotoxicity , 2002, Drug safety.

[54]  P. Dombernowsky,et al.  Epirubicin cardiotoxicity: a study of 135 patients with advanced breast cancer. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[55]  S. Lipsitz,et al.  Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. , 1997, Circulation.

[56]  R. Nagai,et al.  Elevated B-type natriuretic peptide levels after anthracycline administration. , 1998, American heart journal.

[57]  P. Morandi,et al.  Cardiac toxicity of high-dose chemotherapy , 2005, Bone Marrow Transplantation.

[58]  M. Coleman,et al.  Cancer prevalence in European registry areas. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[59]  L. Zanolla,et al.  Cardiac troponin I as diagnostic and prognostic marker in severe heart failure. , 2000, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[60]  A. Rosowsky,et al.  Cyclophosphamide pharmacokinetics: correlation with cardiac toxicity and tumor response. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  B. Jensen,et al.  Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[62]  J. Hartikainen,et al.  Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients , 1998, European journal of haematology.

[63]  E. Perez,et al.  Clinical cardiac tolerability of trastuzumab. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  A. Burnett,et al.  Chemotherapy‐induced cardiotoxicity: current practice and prospects of prophylaxis , 2002, European journal of heart failure.

[65]  David Zurakowski,et al.  Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib , 2007, The Lancet.

[66]  T. Merchant,et al.  Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[67]  M. Emdin,et al.  [Recommendations for the clinical use of cardiac natriuretic peptides]. , 2005, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology.

[68]  C. Cipolla,et al.  Troponins in prediction of cardiotoxic effects. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[69]  V. Ferrans,et al.  The Use of Cardiac Biomarkers to Detect Myocardial Damage Induced by Chemotherapeutic Agents , 2003 .

[70]  Giovanni Martinelli,et al.  Minor increases in plasma troponin I predict decreased left ventricular ejection fraction after high-dose chemotherapy. , 2003, Clinical chemistry.

[71]  J. Hartikainen,et al.  Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non‐Hodgkin's lymphoma , 1999, European journal of haematology.

[72]  S. Colan,et al.  Monitoring for anthracycline cardiotoxicity. , 1994, Pediatrics.

[73]  M. Goris,et al.  Sensitivity and specificity of radionuclide ejection fractions in doxorubicin cardiotoxicity. , 1983, American heart journal.