T1 Mapping of Diffuse Myocardial Fibrosis in Congenital Heart Disease
Condition: Cardiomyopathy
MeSH terms: Heart Diseases; Cardiomyopathies; Heart Defects, Congenital
Study type: Interventional

Summary: 
      Diffuse fibrosis (or scarring) of the heart muscle is found in a variety of congenital heart
      diseases and in cardiomyopathies (heart muscle disease), and is considered a mediator of
      decreased cardiac function. The detection and quantification of diffuse myocardial fibrosis
      has recently become feasible non-invasively, using cardiac magnetic resonance (CMR), applying
      a new technique labeled T1 mapping. With this technique, the part of the heart tissue which
      is not made up of muscle cells (extracellular volume) can be quantified, as long as the
      individual's hematocrit (cellular volume in the blood) is known. The extracellular volume in
      the heart tissue is regarded as a quantifiable marker for the extent of diffuse myocardial
      fibrosis.

      In the proposed study this new T1 mapping technique shall be applied in patients with
      different forms of congenital heart disease (n=130), cardiomyopathies (n=40) and in control
      subjects (n=30). The additional scan time due to participation in the study will be
      approximately 5-10 minutes, without changing the clinical protocol.

      The main objective is to study the presence and extent of myocardial fibrosis by T1 mapping
      CMR in pediatric patients with congenital heart disease and cardiomyopathies, in comparison
      to cardiovascularly healthy controls.
    

Detailed description: 
      A better understanding of the mechanisms by which the heart muscle fails in pediatric heart
      disease may result in novel therapies directed at preventing rather than treating ventricular
      failure. The most likely mediator candidate for cardiac demise in congenital heart disease as
      well as the cardiomyopathies is diffuse myocardial fibrosis and non-favorable chronic
      biventricular remodeling. As such, fibrosis may be a marker, if not a mediator, preceding the
      onset of actual echocardiographic and clinical deterioration, opening opportunities for more
      timely and targeted treatment. Chronic stressors of myocardial function (hypoxemia, abnormal
      afterload or preload) appear to promote fibrosis. In some groups of patients, a genetically
      upregulated collagen metabolism seems to play a role. In adult patients with dilated
      cardiomyopathy the extent of myocardial fibrosis is predictive of outcome.

      With cardiac magnetic resonance imaging, the characterization of myocardial tissue is
      possible. Whereas standard late gadolinium enhancement (LGE) CMR can only identify patchy
      scars neighboring healthy tissue, quantification of diffuse myocardial fibrosis in the living
      has become feasible with the T1 mapping technique. Both techniques (T1 mapping and LGE) are
      based on the principle that MR contrast medium (gadolinium) is trapped in between collagen
      fibres and is retained in areas of fibrosis while it is quickly washed out of healthy
      myocardium. As gadolinium is a T1 shortening agent, the fibrosed tissue with its 'trapped'
      gadolinium has a shorter T1 time than healthy tissue. T1 mapping measures the T1 time
      constant, which has been shown to correlate with the degree of fibrosis. In a refined
      approach of this technique, which we will use, it is now possible to quantify the
      extracellular space (equivalent to the degree of fibrosis) by T1 mapping. This method has
      been validated against the current gold standard of surgical myocardial biopsy.
    

Intervention name(s): Cardiac magnetic resonance sequence T1 mapping
Intervention type(s): Other
Intervention description(s): Adding T1 mapping sequence to the clinical cardiac magnetic resonance scan Obtaining bloodwork for assessment of hematocrit and collagen biomarkers
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic