Preferences help
enabled [disable] Abstract
Number of results
2018 | 8 | 4 | 99-104
Article title

Role of biomarkers and electrocardiography assessment as individual predictors of anthracycline cardiotoxicity in lymphoma patients

Title variants
Languages of publication
The significant progress in the treatment of non-Hodgkin lymphomas, translating into prolongation of overall survival results in the manifestation of long-term adverse events, like anthracycline-related cardiotoxicity. Despite the dose-dependent cardiac dysfunction and the presence of risk factors, the increasing probability of cardiotoxicity arises from individual predisposition. Identification of high- -risk patients gives the opportunity to implement the prevention strategies to reduce the incidence of cardiac complications. The study evaluated the utility of biomarkers: N-terminal B-type natriuretic peptide, troponin I and electrocardiography with spatial QRS-T angle assessment, as indicators of individual sensitivity of cardiomyocytes to doxorubicin resulting in myocardial damage. Thirty-five treatment-naïve patients at increased risk of cardiotoxicity, were subjected prospectively during (R)-CHOP treatment to echocardiographic assessment and analysis of biomarkers: TnI and NT-proBNP plasma level and spatial QRS-T assessment before and 24 hours after each cycle of chemotherapy. The analysis of QRS-T angle was consistent with the results of NT-proBNP assessment and allowed to identify, after the first cycle of chemotherapy, patients at increased risk of developing cardiovascular complications, who require thorough echocardiographic analysis and primary cardioprotection implementation. Our data did not reveal the role of TnI in the identification of cardiac events. Our findings, though promising, should be confirmed in a larger group of patients in real-life or clinical trials.
Physical description
  • Department of Haematology, Jagiellonian University, Cracow, Poland
  • Department of Nephrology, Family Medicine and Geriatrics, Institute of Medical Sciences, Jan Kochanowski University, Kielce, Poland
  • Department of Haematology, Jagiellonian University, Cracow, Poland
  • 1. Minotti G, Menna P, Salvatorelli E et al. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004; 56(2): 185-229. DOI: 10.1124/pr.56.2.6.
  • 2. Limat S, Demesmay K, Voillat L et al. Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin’s lymphoma. Ann Oncol 2003; 14(2): 277-281.
  • 3. Hershman DL, McBride RB, Eisenberger A et al. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin’s lymphoma. J Clin Oncol 2008; 26(19): 3159-3165. DOI: 10.1200/JCO.2007.14.1242.
  • 4. Menna P, Calabrese V, Armento G et al. Pharmacology of Cardio-Oncology: Chronotropic and Lusitropic Effects of B-Type Natriuretic Peptide in Cancer Patients with Early Diastolic Dysfunction Induced by Anthracycline or Nonanthracycline Chemotherapy. J Pharmacol Exp Ther 2018; 366(1): 158-168. DOI: 10.1124/jpet.118.249235.
  • 5. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol 2014; 64(9): 938-945. DOI: 10.1016/j.jacc.2014.06.1167.
  • 6. Lipshultz SE, Lipsitz SR, Sallan SE et al. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 2005; 23(12): 2629-2636. DOI: 10.1200/JCO.2005.12.121.
  • 7. Scully RE, Lipshultz SE. Anthracycline cardiotoxicity in long-term survivors of childhood cancer. Cardiovasc Toxicol 2007; 7(2): 122-128. DOI: 10.1007/s12012-007-0006-4.
  • 8. Armstrong GT, Oeffinger KC, Chen Y et al. Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. J Clin Oncol 2013; 31(29): 3673-3680. DOI: 10.1200/JCO.2013.49.3205.
  • 9. Armenian SH, Ding Y, Mills G et al. Genetic susceptibility to anthracycline-related congestive heart failure in survivors of haematopoietic cell transplantation. Br J Haematol 2013; 163(2): 205-213. DOI: 10.1111/bjh.12516.
  • 10. Jensen BC, McLeod HL. Pharmacogenomics as a risk mitigation strategy for chemotherapeutic cardiotoxicity. Pharmacogenomics 2013; 14(2): 205-213. DOI: 10.2217/pgs.12.205.
  • 11. Jurczak W, Szmit S, Sobocinski M et al. Premature cardiovascular mortality in lymphoma patients treated with (R)-CHOP regimen – a national multicenter study. Int J Cardiol 2013; 168(6): 5212-5217. DOI: 10.1016/j.ijcard.2013.08.033.
  • 12. Curigliano G, Cardinale D, Suter T et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol 2012; 23(Suppl 7): vii155-66. DOI: 10.1093/annonc/mds293.
  • 13. Davidson NC, Naas AA, Hanson JK et al. Comparison of atrial natriuretic peptide B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide as indicators of left ventricular systolic dysfunction. Am J Cardiol 1996; 77(10): 828-831. DOI: 10.1016/S0002-9149(97)89176-X.
  • 14. Gegenhuber A, Mueller T, Dieplinger B et al. B-type natriuretic peptide and amino terminal proBNP predict one-year mortality in short of breath patients independently of the baseline diagnosis of acute destabilized heart failure. Clin Chim Acta 2006; 370(1-2): 174-179. DOI: 10.1016/j. cca.2006.02.010.
  • 15. Pavri BB, Hillis MB, Subacius H et al. Prognostic value and temporal behavior of the planar QRS-T angle in patients with nonischemic cardiomyopathy. Circulation 2008; 117(25): 3181-3186. DOI: 10.1161/CIRCULATIONAHA.107.733451.
  • 16. Borleffs CJ, Scherptong RW, Man SC et al. Predicting ventricular arrhythmias in patients with ischemic heart disease: clinical application of the ECG-derived QRS-T angle. Circ Arrhythm Electrophysiol 2009; 2(5): 548-554. DOI: 10.1161/CIRCEP.109.859108.
  • 17. Piotrowski G, Gawor R, Gawor Z et al. [Role of echocardiography in monitoring of cardiac toxicity of cancer pharmacotherapy. Expert consensus statement of the Polish Clinical Forum for Cardiovascular Imaging]. Kardiol Pol 2014; 72(6): 558-575. DOI: 10.5603/KP.2014.0126.
  • 18. Seidman A, Hudis C, Pierri MK et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 2002; 20(5): 1215-1221. DOI: 10.1200/JCO.2002.20.5.1215.
  • 19. Dlugosz-Danecka M, Gruszka AM, Szmit S et al. Primary Cardioprotection Reduces Mortality in Lymphoma Patients with Increased Risk of Anthracycline Cardiotoxicity, Treated by R-CHOP Regimen. Chemotherapy 2018; 63(4): 238-245. DOI: 10.1159/000492942.
  • 20. Billingham ME, Mason JW, Bristow MR, Daniels JR. Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep 1978; 62(6): 865-872.
  • 21. Druck MN, Gulenchyn KY, Evans WK et al. Radionuclide angiography and endomyocardial biopsy in the assessment of doxorubicin cardiotoxicity. Cancer 1984; 53(8): 1667-1674.
  • 22. Cardinale D, Sandri MT, Martinoni A et al. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol 2002; 13(5): 710-715.
  • 23. Cardinale D, Sandri MT, Colombo A et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 2004; 109(22): 2749-2754. DOI: 10.1161/01.CIR.0000130926.51766.CC.
  • 24. Dolci A, Dominici R, Cardinale D et al. Biochemical markers for prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use. Am J Clin Pathol 2008; 130(5): 688-695. DOI: 10.1309/AJCPB66LRIIVMQDR.
  • 25. Ekstein S, Nir A, Rein AJ et al. N-terminal-proB-type natriuretic peptide as a marker for acute anthracycline cardiotoxicity in children. J Pediatr Hematol Oncol 2007; 29(7): 440-444. DOI: 10.1097/MPH.0b013e3180640d42.
  • 26. Horacek JM, Vasatova M, Pudil R et al. Biomarkers for the early detection of anthracycline-induced cardiotoxicity: current status. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158(4): 511-517. DOI: 10.5507/bp.2014.004.
  • 27. Sandri MT, Salvatici M, Cardinale D et al. N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? Clin Chem 2005; 51(8): 1405-1410. DOI: 10.1373/clinchem.2005.050153.
  • 28. Zamorano JL, Lancellotti P, Rodriguez Munoz D et al. 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 J Heart Fail 2017; 19(1): 9-42. DOI: 10.1002/ejhf.654.
  • 29. Okumura H, Iuchi K, Yoshida T et al. Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity. Acta Haematol 2000; 104(4): 158-163. DOI: 10.1159/000046508.
  • 30. Nousiainen T, Jantunen E, Vanninen E et al. Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients. Eur J Haematol 1998; 61(5): 347-353.
  • 31. Suzuki T, Hayashi D, Yamazaki T et al. Elevated B-type natriuretic peptide levels after anthracycline administration. Am Heart J 1998; 136(2): 362- -363. DOI: 10.1053/hj.1998.v136.89908.
  • 32. Bagnes C, Panchuk PN, Recondo G. Antineoplastic chemotherapy induced QTc prolongation. Curr Drug Saf 2010; 5(1): 93-96.
  • 33. Trinkley KE, Page RL 2nd, Lien H et al. QT interval prolongation and the risk of torsades de pointes: essentials for clinicians. Curr Med Res Opin 2013; 29(12): 1719-1726. DOI: 10.1185/03007995.2013.840568.
  • 34. Cortez D, Schlegel TT, Ackerman MJ, Bos JM. ECG-derived spatial QRS-T angle is strongly associated with hypertrophic cardiomyopathy. J Electrocardiol 2017; 50(2): 195-202. DOI: 10.1016/j.jelectrocard.2016.10.001.
  • 35. Naing A, Veasey-Rodrigues H, Hong DS et al. Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs. Ann Oncol 2012; 23(11): 2960-2963. DOI: 10.1093/annonc/mds130.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.