<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03000036</url>
  </required_header>
  <id_info>
    <org_study_id>DOX-0675014600011</org_study_id>
    <nct_id>NCT03000036</nct_id>
  </id_info>
  <brief_title>Doxorubicin-associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients</brief_title>
  <official_title>Doxorubicin-associated Cardiac Tissue Remodeling Followed by CMR of Myocardial Extracellular Volume and Myocyte Size in Breast Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Campinas, Brazil</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundação de Amparo à Pesquisa do Estado de São Paulo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Campinas, Brazil</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Twenty-seven breast cancer women without heart failure, underwent CMR imaging (3T-Achieva,&#xD;
      Philips) before and 3 times serially after 4-cycles of adjuvant DOX (60mg/m2). CMR assessed&#xD;
      left ventricular (LV) ejection fraction (EF), T1 mapping pre and post gadolinium and late&#xD;
      gadolinium enhancement imaging. Biomarkers were obtained before and 72 hours after each&#xD;
      DOX-cycle.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective cohort study was performed at the State University of Campinas, Brazil. The&#xD;
      Institutional Review Board of the State University of Campinas approved the study and all&#xD;
      participants provided informed consent. Female patients with breast cancer who received&#xD;
      anthracycline (doxorubicin or daunorubicin or epirubicin) as part of their chemotherapy&#xD;
      protocol were enrolled in the study.&#xD;
&#xD;
      Detailed medical history, standard anthropometric data, and measurement hemogram, troponin,&#xD;
      CKMB, cholesterol, serum glucose, CRP and biomarkers were obtained.&#xD;
&#xD;
      As in adults, chronic anthracycline-related cardiotoxicity typically presents early, within&#xD;
      one year after termination of chemotherapy and the peak time for the appearance of symptoms&#xD;
      of heart failure is about three months after the last anthracycline dose, patients underwent&#xD;
      CMR before and three times serially after DOX (two, five and twelve months).&#xD;
&#xD;
      Patients were imaged in supine position in a 3T magnet (Achieva, Philips Medical Systems,&#xD;
      Best, The Netherlands). The CMR protocol consisted of electrocardiographically gated cine&#xD;
      imaging with steady state free-precession to assess left ventricular (LV) function and LV&#xD;
      mass. For imaging of late gadolinium enhancement (LGE) we used an&#xD;
      inversion-recovery-prepared, gradient-echo sequence with segmented acquisition, which was&#xD;
      triggered every other heartbeat. LGE images were acquired during end-expiratory&#xD;
      breath-holding for slices matching the slice locations for cine imaging, starting within 10&#xD;
      min after bolus administration of a cumulative dose of 0.2 mmol/Kg of gadoterate meglumine&#xD;
      (Dotarem, Guerbet, Aulnay-sous-Bois, France). T1 was performed with a Look-Locker sequence&#xD;
      with a non-slice-selective adiabatic inversion pulse, followed by segmented gradient-echo&#xD;
      acquisition for 17 times after inversion, covering approximately two cardiac cycles. The&#xD;
      Look-Locker sequence was performed in a single short-axis slice at the level of the mid left&#xD;
      ventricle. T1 imaging was repeated in the same LV short-axis slice, once before and five to&#xD;
      seven times after the injection of gadolinium to cover an approximately 30-min period of slow&#xD;
      contrast clearance.&#xD;
&#xD;
      All images were analyzed with MASS CMR software (Mass Research, Leiden University Medical&#xD;
      Center, Leiden, the Netherlands). For LV mass and function quantification, the endocardial&#xD;
      and epicardial borders of the LV myocardium were manually traced on short-axis cine images at&#xD;
      end-diastole and systole. Papillary muscles were excluded from LV mass, and LV mass was&#xD;
      indexed to body surface area.&#xD;
&#xD;
      For each Look-Locker image series, the endocardial and epicardial borders of the LV were&#xD;
      traced and divided into six standard segments. Signal intensity versus time curves for each&#xD;
      segment and the blood pool were used to determine segmental T1* by nonlinear, least-squares&#xD;
      fitting to an analytic expression for the magnitude signal measured during the inversion&#xD;
      recovery. T1 was calculated from the T1* and the amplitude parameters to correct for the&#xD;
      effects of radiofrequency pulses applied during the inversion recovery.&#xD;
&#xD;
      Pairs of R1 values for myocardial tissue and blood data were fit with a two-space&#xD;
      water-exchange model of equilibrium transcytolemmal water exchange. The myocardial&#xD;
      extracellular volume fraction (ECV) and the intracellular lifetime of water (τic), a cell&#xD;
      size-dependent parameter, were adjustable parameters of this model. The measured blood&#xD;
      hematocrit was a fixed parameter of the model. All R1 measurements for each patient were used&#xD;
      to fit the model to determine ECV and τic.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">January 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantification of fibrosis index by Cardiac Magnetic Resonance</measure>
    <time_frame>two years</time_frame>
    <description>Estimate the extracellular volume fraction derived from gadolinium-DTPA partition Coefficient of the myocardium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intracellular lifetime of water (τic) by Cardiac Magnetic Resonance</measure>
    <time_frame>two years</time_frame>
    <description>This metric estimates the myocyte size using Cardiac Magnetic Resonance T1 mapping data</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Left ventricular mass by Cardiac Magnetic Resonance</measure>
    <time_frame>two years</time_frame>
    <description>Electrocardiographically gated cine imaging with steady state free-precession to assess left ventricular mass.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular volumes by Cardiac Magnetic Resonance</measure>
    <time_frame>two years</time_frame>
    <description>Electrocardiographically gated cine imaging with steady state free-precession to assess left ventricular volume.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular ejection fraction by Cardiac Magnetic Resonance</measure>
    <time_frame>two years</time_frame>
    <description>Electrocardiographically gated cine imaging with steady state free-precession to assess left ventricular ejection fraction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular myocardial edema fraction by Cardiac Magnetic Resonance</measure>
    <time_frame>two years</time_frame>
    <description>Using T2-weighted sequences to visualize myocardial edema</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Ultra-sensitive troponin</measure>
    <time_frame>two years</time_frame>
    <description>Cardiac troponin (ng/mL)</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Breast Cancer Female</condition>
  <condition>Doxorubicin Induced Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Cardiovascular Magnetic Resonance</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Twenty-seven female patients were imaged in a 3T magnet after consecutively enrolled in the study if they had received a breast cancer diagnosis at the Center for Integral Attention to Women's Health (University of Campinas) and had prescribed endovenous doxorubicin as part of their chemotherapy regimen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Patients had prescribed endovenous doxorubicin as part of their chemotherapy regimen (mean cumulative dose 102,66 mg/m2, administered in 4 doses with 21 days interval).</description>
    <arm_group_label>Cardiovascular Magnetic Resonance</arm_group_label>
    <other_name>Adriamycin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Achieva, Philips Medical Systems (3T magnet)</intervention_name>
    <description>Patients were imaged in supine position in a 3T magnet (Achieva, Philips Medical Systems, Best, The Netherlands). The protocol consisted of electrocardiographically gated cine imaging with steady state free-precession to assess left ventricular (LV) ejection fraction and LV mass. For imaging of late gadolinium-DTPA enhancement (LGE) we used an inversion-recovery-prepared, gradient-echo sequence with segmented acquisition, which was triggered every other heartbeat. LGE images were acquired during end-expiratory breath-holding, after administration of Dotarem. T1 was performed with a Look-Locker sequence with a non-slice-selective adiabatic inversion pulse, followed by segmented gradient-echo acquisition for 17 times after inversion, covering approximately two cardiac cycles. T1 imaging was repeated in the same LV short-axis slice, once before and five to seven times after the injection of gadolinium to cover an approximately 30-min period of slow contrast clearance.</description>
    <arm_group_label>Cardiovascular Magnetic Resonance</arm_group_label>
    <other_name>Cardiovascular Magnetic Resonance (CMR)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gadoterate Meglumine</intervention_name>
    <description>LGE images were acquired starting within 10 min after bolus administration of a cumulative dose of 0.2 mmol/Kg of gadoterate meglumine (Dotarem, Guerbet, Aulnay-sous-Bois, France).</description>
    <arm_group_label>Cardiovascular Magnetic Resonance</arm_group_label>
    <other_name>Dotarem</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Breast cancer and had prescribed an anthracycline agent as part of their chemotherapy&#xD;
             regimen&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Strict contraindications to MRI&#xD;
&#xD;
          -  Acute or chronic kidney failure&#xD;
&#xD;
          -  Previously diagnosed myocardial infarction, heart failure, valvular disease or&#xD;
             cardiomyopathy.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Otávio R. Coelho-Filho, MD, MPH, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Campinas, Brazil</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>State University of Campinas</name>
      <address>
        <city>Campinas</city>
        <state>São Paulo</state>
        <zip>13083-887</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO, Judd RM. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000 Nov 16;343(20):1445-53. doi: 10.1056/NEJM200011163432003.</citation>
    <PMID>11078769</PMID>
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    <citation>Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999 Nov 9;100(19):1992-2002. doi: 10.1161/01.cir.100.19.1992.</citation>
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    <citation>Tandri H, Saranathan M, Rodriguez ER, Martinez C, Bomma C, Nasir K, Rosen B, Lima JA, Calkins H, Bluemke DA. Noninvasive detection of myocardial fibrosis in arrhythmogenic right ventricular cardiomyopathy using delayed-enhancement magnetic resonance imaging. J Am Coll Cardiol. 2005 Jan 4;45(1):98-103. doi: 10.1016/j.jacc.2004.09.053.</citation>
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    <citation>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.</citation>
    <PMID>16136854</PMID>
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    <citation>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.</citation>
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    <citation>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.</citation>
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  <reference>
    <citation>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.</citation>
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  <reference>
    <citation>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.</citation>
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    <citation>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.</citation>
    <PMID>16814656</PMID>
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  <reference>
    <citation>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.</citation>
    <PMID>24650314</PMID>
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    <citation>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.</citation>
    <PMID>17429755</PMID>
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    <citation>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.</citation>
    <PMID>20585010</PMID>
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  <reference>
    <citation>Swain SM. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1999 Feb 25;340(8):654; author reply 655. No abstract available.</citation>
    <PMID>10049087</PMID>
  </reference>
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    <citation>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.</citation>
    <PMID>19851170</PMID>
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    <citation>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.</citation>
    <PMID>17592672</PMID>
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    <citation>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.</citation>
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    <citation>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.</citation>
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    <citation>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.</citation>
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    <citation>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.</citation>
    <PMID>16087809</PMID>
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    <citation>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.</citation>
    <PMID>10467291</PMID>
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    <citation>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.</citation>
    <PMID>23912910</PMID>
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  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>December 18, 2016</last_update_submitted>
  <last_update_submitted_qc>December 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 21, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Campinas, Brazil</investigator_affiliation>
    <investigator_full_name>Otavio Rizzi Coelho Filho</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Breast cancer</keyword>
  <keyword>Doxorubicin</keyword>
  <keyword>Cardiovascular Magnetic Resonance</keyword>
  <keyword>T1 mapping</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Cardiomyopathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03000036
org study id: DOX-0675014600011
nct id: NCT03000036
lead sponsor: 
collaborator: 
has dmc: No
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.
This prospective cohort study was performed at the State University of Campinas, Brazil. The
      Institutional Review Board of the State University of Campinas approved the study and all
      participants provided informed consent. Female patients with breast cancer who received
      anthracycline (doxorubicin or daunorubicin or epirubicin) as part of their chemotherapy
      protocol were enrolled in the study.

      Detailed medical history, standard anthropometric data, and measurement hemogram, troponin,
      CKMB, cholesterol, serum glucose, CRP and biomarkers were obtained.

      As in adults, chronic anthracycline-related cardiotoxicity typically presents early, within
      one year after termination of chemotherapy and the peak time for the appearance of symptoms
      of heart failure is about three months after the last anthracycline dose, patients underwent
      CMR before and three times serially after DOX (two, five and twelve months).

      Patients were imaged in supine position in a 3T magnet (Achieva, Philips Medical Systems,
      Best, The Netherlands). The CMR protocol consisted of electrocardiographically gated cine
      imaging with steady state free-precession to assess left ventricular (LV) function and LV
      mass. For imaging of late gadolinium enhancement (LGE) we used an
      inversion-recovery-prepared, gradient-echo sequence with segmented acquisition, which was
      triggered every other heartbeat. LGE images were acquired during end-expiratory
      breath-holding for slices matching the slice locations for cine imaging, starting within 10
      min after bolus administration of a cumulative dose of 0.2 mmol/Kg of gadoterate meglumine
      (Dotarem, Guerbet, Aulnay-sous-Bois, France). T1 was performed with a Look-Locker sequence
      with a non-slice-selective adiabatic inversion pulse, followed by segmented gradient-echo
      acquisition for 17 times after inversion, covering approximately two cardiac cycles. The
      Look-Locker sequence was performed in a single short-axis slice at the level of the mid left
      ventricle. T1 imaging was repeated in the same LV short-axis slice, once before and five to
      seven times after the injection of gadolinium to cover an approximately 30-min period of slow
      contrast clearance.

      All images were analyzed with MASS CMR software (Mass Research, Leiden University Medical
      Center, Leiden, the Netherlands). For LV mass and function quantification, the endocardial
      and epicardial borders of the LV myocardium were manually traced on short-axis cine images at
      end-diastole and systole. Papillary muscles were excluded from LV mass, and LV mass was
      indexed to body surface area.

      For each Look-Locker image series, the endocardial and epicardial borders of the LV were
      traced and divided into six standard segments. Signal intensity versus time curves for each
      segment and the blood pool were used to determine segmental T1* by nonlinear, least-squares
      fitting to an analytic expression for the magnitude signal measured during the inversion
      recovery. T1 was calculated from the T1* and the amplitude parameters to correct for the
      effects of radiofrequency pulses applied during the inversion recovery.

      Pairs of R1 values for myocardial tissue and blood data were fit with a two-space
      water-exchange model of equilibrium transcytolemmal water exchange. The myocardial
      extracellular volume fraction (ECV) and the intracellular lifetime of water (τic), a cell
      size-dependent parameter, were adjustable parameters of this model. The measured blood
      hematocrit was a fixed parameter of the model. All R1 measurements for each patient were used
      to fit the model to determine ECV and τic.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Quantification of fibrosis index by Cardiac Magnetic Resonance
time frame: two years
description: Estimate the extracellular volume fraction derived from gadolinium-DTPA partition Coefficient of the myocardium
measure: Intracellular lifetime of water (τic) by Cardiac Magnetic Resonance
time frame: two years
description: This metric estimates the myocyte size using Cardiac Magnetic Resonance T1 mapping data
measure: Left ventricular mass by Cardiac Magnetic Resonance
time frame: two years
description: Electrocardiographically gated cine imaging with steady state free-precession to assess left ventricular mass.
measure: Left ventricular volumes by Cardiac Magnetic Resonance
time frame: two years
description: Electrocardiographically gated cine imaging with steady state free-precession to assess left ventricular volume.
measure: Left ventricular ejection fraction by Cardiac Magnetic Resonance
time frame: two years
description: Electrocardiographically gated cine imaging with steady state free-precession to assess left ventricular ejection fraction.
measure: Left ventricular myocardial edema fraction by Cardiac Magnetic Resonance
time frame: two years
description: Using T2-weighted sequences to visualize myocardial edema
measure: Ultra-sensitive troponin
time frame: two years
description: Cardiac troponin (ng/mL)
arm group label: Cardiovascular Magnetic Resonance
arm group type: Other
description: Twenty-seven female patients were imaged in a 3T magnet after consecutively enrolled in the study if they had received a breast cancer diagnosis at the Center for Integral Attention to Women's Health (University of Campinas) and had prescribed endovenous doxorubicin as part of their chemotherapy regimen.
intervention type: Drug
intervention name: Doxorubicin
description: Patients had prescribed endovenous doxorubicin as part of their chemotherapy regimen (mean cumulative dose 102,66 mg/m2, administered in 4 doses with 21 days interval).
arm group label: Cardiovascular Magnetic Resonance
other name: Adriamycin
intervention type: Device
intervention name: Achieva, Philips Medical Systems (3T magnet)
description: Patients were imaged in supine position in a 3T magnet (Achieva, Philips Medical Systems, Best, The Netherlands). The protocol consisted of electrocardiographically gated cine imaging with steady state free-precession to assess left ventricular (LV) ejection fraction and LV mass. For imaging of late gadolinium-DTPA enhancement (LGE) we used an inversion-recovery-prepared, gradient-echo sequence with segmented acquisition, which was triggered every other heartbeat. LGE images were acquired during end-expiratory breath-holding, after administration of Dotarem. T1 was performed with a Look-Locker sequence with a non-slice-selective adiabatic inversion pulse, followed by segmented gradient-echo acquisition for 17 times after inversion, covering approximately two cardiac cycles. T1 imaging was repeated in the same LV short-axis slice, once before and five to seven times after the injection of gadolinium to cover an approximately 30-min period of slow contrast clearance.
arm group label: Cardiovascular Magnetic Resonance
other name: Cardiovascular Magnetic Resonance (CMR)
intervention type: Drug
intervention name: Gadoterate Meglumine
description: LGE images were acquired starting within 10 min after bolus administration of a cumulative dose of 0.2 mmol/Kg of gadoterate meglumine (Dotarem, Guerbet, Aulnay-sous-Bois, France).
arm group label: Cardiovascular Magnetic Resonance
other name: Dotarem
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Otávio R. Coelho-Filho, MD, MPH, PhD
role: Principal Investigator
affiliation: University of Campinas, Brazil
facility: 
country: Brazil
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PMID: 16814656
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PMID: 23912910
responsible party type: Principal Investigator
investigator affiliation: University of Campinas, Brazil
investigator full name: Otavio Rizzi Coelho Filho
investigator title: Professor
mesh term: Breast Neoplasms
mesh term: Cardiomyopathies
mesh term: Doxorubicin
mesh term: Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
sharing ipd: No