Doxorubicin-associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients

Summary

Twenty-seven breast cancer women without heart failure, underwent CMR imaging (3T-Achieva, Philips) before and 3 times serially after 4-cycles of adjuvant DOX (60mg/m2). CMR assessed left ventricular (LV) ejection fraction (EF), T1 mapping pre and post gadolinium and late gadolinium enhancement imaging. Biomarkers were obtained before and 72 hours after each DOX-cycle.

Timeline

Start

2012-07

Primary completion

2015-01

Completion

2016-07

Publications

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• Background Hunold P, Wieneke H, Bruder O, Krueger U, Schlosser T, Erbel R, Barkhausen J. Late enhancement: a new feature in MRI of arrhythmogenic right ventricular cardiomyopathy? J Cardiovasc Magn Reson. 2005;7(4):649-55. doi: 10.1081/jcmr-65608.
• Background Harris PA, Lorenz CH, Holburn GE, Overholser KA. Regional measurement of the Gd-DTPA tissue partition coefficient in canine myocardium. Magn Reson Med. 1997 Oct;38(4):541-5. doi: 10.1002/mrm.1910380406.
• Background Flacke SJ, Fischer SE, Lorenz CH. Measurement of the gadopentetate dimeglumine partition coefficient in human myocardium in vivo: normal distribution and elevation in acute and chronic infarction. Radiology. 2001 Mar;218(3):703-10. doi: 10.1148/radiology.218.3.r01fe18703.
• Background Elliott P. Pathogenesis of cardiotoxicity induced by anthracyclines. Semin Oncol. 2006 Jun;33(3 Suppl 8):S2-7. doi: 10.1053/j.seminoncol.2006.04.020.
• Background Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN, Kaye DM, Taylor AJ. Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol. 2008 Nov 4;52(19):1574-80. doi: 10.1016/j.jacc.2008.06.049.
• Background Ellinor PT, Sasse-Klaassen S, Probst S, Gerull B, Shin JT, Toeppel A, Heuser A, Michely B, Yoerger DM, Song BS, Pilz B, Krings G, Coplin B, Lange PE, Dec GW, Hennies HC, Thierfelder L, MacRae CA. A novel locus for dilated cardiomyopathy, diffuse myocardial fibrosis, and sudden death on chromosome 10q25-26. J Am Coll Cardiol. 2006 Jul 4;48(1):106-11. doi: 10.1016/j.jacc.2006.01.079. Epub 2006 Jun 21.
• Background Ong DS, Scherrer-Crosbie M, Coelho-Filho O, Francis SA, Neilan TG. Imaging methods for detection of chemotherapy-associated cardiotoxicity and dysfunction. Expert Rev Cardiovasc Ther. 2014 Apr;12(4):487-97. doi: 10.1586/14779072.2014.893824.
• Background Kehr E, Sono M, Chugh SS, Jerosch-Herold M. Gadolinium-enhanced magnetic resonance imaging for detection and quantification of fibrosis in human myocardium in vitro. Int J Cardiovasc Imaging. 2008 Jan;24(1):61-8. doi: 10.1007/s10554-007-9223-y. Epub 2007 Apr 12.
• Background Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, McGregor C, Moon JC. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010 Jul 13;122(2):138-44. doi: 10.1161/CIRCULATIONAHA.109.930636. Epub 2010 Jun 28.
• Background Swain SM. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1999 Feb 25;340(8):654; author reply 655. No abstract available.
• Background Aiken MJ, Suhag V, Garcia CA, Acio E, Moreau S, Priebat DA, Chennupati SP, Van Nostrand D. Doxorubicin-induced cardiac toxicity and cardiac rest gated blood pool imaging. Clin Nucl Med. 2009 Nov;34(11):762-7. doi: 10.1097/RLU.0b013e3181b7d76f.
• Background Ewer MS, O'Shaughnessy JA. Cardiac toxicity of trastuzumab-related regimens in HER2-overexpressing breast cancer. Clin Breast Cancer. 2007 Jun;7(8):600-7.
• Background Perez EA. Cardiac toxicity of ErbB2-targeted therapies: what do we know? Clin Breast Cancer. 2008 Mar;8 Suppl 3:S114-20. doi: 10.3816/cbc.2008.s.007.
• Background Chien AJ, Rugo HS. The cardiac safety of trastuzumab in the treatment of breast cancer. Expert Opin Drug Saf. 2010 Mar;9(2):335-46. doi: 10.1517/14740331003627441.
• Background Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, Civelli M, Peccatori F, Martinelli G, Fiorentini C, Cipolla CM. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004 Jun 8;109(22):2749-54. doi: 10.1161/01.CIR.0000130926.51766.CC. Epub 2004 May 17.
• Background Ewer MS, Lenihan DJ. Left ventricular ejection fraction and cardiotoxicity: is our ear really to the ground? J Clin Oncol. 2008 Mar 10;26(8):1201-3. doi: 10.1200/JCO.2007.14.8742. Epub 2008 Jan 28. No abstract available.
• Background Von Hoff DD, Rozencweig M, Layard M, Slavik M, Muggia FM. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am J Med. 1977 Feb;62(2):200-8. doi: 10.1016/0002-9343(77)90315-1.
• Background Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979 Nov;91(5):710-7. doi: 10.7326/0003-4819-91-5-710.
• Background Coelho-Filho OR, Mongeon FP, Mitchell R, Moreno H Jr, Nadruz W Jr, Kwong R, Jerosch-Herold M. Role of transcytolemmal water-exchange in magnetic resonance measurements of diffuse myocardial fibrosis in hypertensive heart disease. Circ Cardiovasc Imaging. 2013 Jan 1;6(1):134-41. doi: 10.1161/CIRCIMAGING.112.979815. Epub 2012 Nov 15.
• Background Rickers C, Wilke NM, Jerosch-Herold M, Casey SA, Panse P, Panse N, Weil J, Zenovich AG, Maron BJ. Utility of cardiac magnetic resonance imaging in the diagnosis of hypertrophic cardiomyopathy. Circulation. 2005 Aug 9;112(6):855-61. doi: 10.1161/CIRCULATIONAHA.104.507723.
• Background Landis CS, Li X, Telang FW, Molina PE, Palyka I, Vetek G, Springer CS Jr. Equilibrium transcytolemmal water-exchange kinetics in skeletal muscle in vivo. Magn Reson Med. 1999 Sep;42(3):467-78. doi: 10.1002/(sici)1522-2594(199909)42:33.0.co;2-0.
• Background Coelho-Filho OR, Shah RV, Mitchell R, Neilan TG, Moreno H Jr, Simonson B, Kwong R, Rosenzweig A, Das S, Jerosch-Herold M. Quantification of cardiomyocyte hypertrophy by cardiac magnetic resonance: implications for early cardiac remodeling. Circulation. 2013 Sep 10;128(11):1225-33. doi: 10.1161/CIRCULATIONAHA.112.000438. Epub 2013 Aug 2.
• Ferreira de Souza T, Quinaglia A C Silva T, Osorio Costa F, Shah R, Neilan TG, Velloso L, Nadruz W, Brenelli F, Sposito AC, Matos-Souza JR, Cendes F, Coelho OR, Jerosch-Herold M, Coelho-Filho OR. Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease. JACC Cardiovasc Imaging. 2018 Aug;11(8):1045-1055. doi: 10.1016/j.jcmg.2018.05.012.

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