Doxorubicin-associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients
Condition: Breast Cancer Female; Doxorubicin Induced Cardiomyopathy
MeSH terms: Breast Neoplasms; Cardiomyopathies
Study type: Interventional

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.
    

Detailed description: 
      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.
    

Intervention name(s): Doxorubicin; Achieva, Philips Medical Systems (3T magnet); Gadoterate Meglumine
Intervention type(s): Drug; Device; Drug
Intervention description(s): 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).; 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.; 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).
Other intervention name(s): Adriamycin; Cardiovascular Magnetic Resonance (CMR); Dotarem
Intervention MeSH terms: Doxorubicin; Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Breast cancer; Doxorubicin; Cardiovascular Magnetic Resonance; T1 mapping