MR Imaging of Diffuse Myocardial Fibrosis in Transfusion-Dependent Anemias (MAFIO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bernd Winterspersper, University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT02090699
First received: February 28, 2014
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

Cardiac failure is the major cause of death in patients with thalassemia and chronic blood transfusion-related iron overload. The treatment of thalassemia has been revolutionized over the past decade with the implementation of cardiac MRI based assessment of iron overload. This has enabled detection of cardiac iron overload prior to symptomatic heart failure and now allows for timely therapy which has resulted in a substantial decrease in mortality. However, currently implemented MR imaging techniques assess for iron content only and not for iron related diffuse fibrosis which play a role in iron related heart failure. Histopathologic studies indicate that patients with iron overload have diffuse interstitial fibrosis. Quantitative MR techniques have shown that patients with various cardiomyopathies demonstrate diffuse myocardial fibrosis and that these changes correlate with changes in cardiac function. The investigators propose that quantitative cardiac MRI for assessment of diffuse myocardial fibrosis can further improve our ability to detect early damage to the myocardium and prevent morbidity and mortality from cardiac iron overload. Detection of fibrosis in patients with thalassemia may allow for earlier identification of cardiomyopathy when compared to other techniques in clinical use including T2* analysis. Identification of fibrosis could affect patient management as it would allow for tailoring of iron chelation therapy and may lead to better understanding of the disease processes contributing to heart failure and arrhythmia in these patients.


Condition
Thalassemia Major
Chronic Blood Transfusion Related Iron Overload

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Quantification of Diffuse Myocardial Iron Overload Related Interstitial Fibrosis With Cardiac Magnetic Resonance Imaging in Patients With Transfusion-Dependent Anemias

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Evidence of diffuse myocardial fibrosis (elevated extracellular volume fraction) confirmed by MRI [ Time Frame: at time of cardiac MR examination for each individual ] [ Designated as safety issue: No ]
    At the time of MRI respective imaging data will be collected to assess the extracellular volume fraction as a marker for diffuse myocardial fibrosis.


Secondary Outcome Measures:
  • Regional myocardial dysfunction as assessed by global longitudinal strain Echocardiography measurement [ Time Frame: at time of echocardiography examination for each individual ] [ Designated as safety issue: No ]
    At the time of echocardiography (same day as MRI) respective strain data with be gathered for outcome assessment.


Enrollment: 42
Study Start Date: July 2013
Study Completion Date: June 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Myocardial Iron Overload
chronic blood transfusion related myocardial iron overload
Healthy Volunteers
age matched healthy volunteers

Detailed Description:

Cardiac failure is the major cause of death in patients with transfusion-related iron overload. Histopathologic studies indicate that patients with myocardial siderosis have diffuse interstitial fibrosis. Cardiac MR assessment of the extracellular volume (ECV) fraction in other disease processes has been shown to accurately characterize diffuse myocardial fibrosis and to correlate with changes in diastolic function. No prior studies have assessed for diffuse interstitial myocardial fibrosis in patients with iron overload utilizing the proposed imaging techniques.

In this study, the investigators will assess the presence and extent of interstitial fibrosis in patients with transfusion-dependent anemias using cardiac MR techniques of T1 mapping and determination of ECV fraction. ECV values will be correlated with the severity of myocardial iron deposition determined by multi-echo T2*-weighted imaging, systolic ventricular function as determined by cardiac MR and diastolic function assessed by echocardiography. The investigators will recruit 35 patients with transfusion-related iron overload. Ten age-matched healthy subjects will be included as controls, to establish baseline values of myocardial T1 and ECV values. A modified Look-Locker with inversion recovery (MOLLI) sequence will be used to determine T1 values pre-, and post-administration of a gadolinium-based contrast agent (GBCA) at 1.5 Tesla. Calculated ECV values will be compared between iron-overload subjects and healthy controls, and will be correlated with left ventricular ejection fraction, measures of diastolic dysfunction and T2* values.

Detection of myocardial fibrosis in patients with iron overload would allow for improved prognostication and risk stratification. Elucidation of the relationship between myocardial fibrosis and myocardial iron deposition as well as cardiac functional parameters would provide valuable mechanistic insights and improved pathophysiological understanding of the disease. The results of the proposed study have the potential to significantly impact patient management including recommendations for earlier or more aggressive chelation therapy based on changes in ECV values.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients with transfusion dependent anemias Age-matched healthy subjects

Criteria

Inclusion Criteria (Patients):

Diagnosis of thalassemia Treatment with iron chelation therapy Referral for cardiac MR assessment of iron overload

Inclusion Criteria (Healthy Volunteers):

No significant past medical history and no evidence of cardiovascular or metabolic disease.

Exclusion Criteria (both groups):

Arrhythmia Claustrophobia Pregnancy and potential pregnancy (patient cannot exclude potential pregnancy) History of allergic reaction to Gadolinium based contrast agent (GBCA) Impaired renal function with eGFR < 30 ml/min/1.73m2 Any general MR contraindication such as pacemaker or defibrillators.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02090699

Locations
Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Sponsors and Collaborators
University Health Network, Toronto
  More Information

No publications provided

Responsible Party: Bernd Winterspersper, Dr. (MD), University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02090699     History of Changes
Other Study ID Numbers: RSNA-RR1318
Study First Received: February 28, 2014
Last Updated: July 16, 2014
Health Authority: Canada: University Health Network Research Ethics Board

Keywords provided by University Health Network, Toronto:
thalassemia major
chronic blood transfusion related iron overload
magnetic resonance imaging
myocardium
fibrosis

Additional relevant MeSH terms:
Beta-Thalassemia
Fibrosis
Thalassemia
Iron Overload
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Pathologic Processes
Iron Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 20, 2014