Inflammatory/Familial Dilated Cardiomyopathy: Is There a Link to Autoimmune Diseases? TP9a
Condition: Non Ischemic Cardiomyopathy
MeSH terms: Cardiomyopathies; Cardiomyopathy, Dilated; Autoimmune Diseases
Study type: Observational

Summary: 
      In a hitherto ill-defined proportion of patients with inflammatory/familial cardiomyopathy,
      the phenotype dilative cardiomyopathy (DCM) is assumed to be the endstage of a multifactorial
      etiopathogenetic pathophysiology. Precipitating factors include enhanced autoimmunity,
      predisposition for viral infections, environmental factors in addition to a specific 'genetic
      background' of the individual patient. It is unresolved, whether the susceptibility to
      immunologically mediated myocardial damage reflects the presence of genetic risk factors
      shared by other autoimmune diseases, or is cardio-specific with individual predisposing
      factors. Aims of the project are the search for a genetic link or oredisposition to
      autoimmune diseases in patients with familial / inflammatory DCM.
    

Detailed description: 
      Epidemiological investigations in patients with autoimmune diseases have shown that in
      addition to a specific genetic alteration secondary inducing factors are responsible for the
      onset of the disease, which may lead to different phenotypes of autoimmune diseases in a
      single family. The working hypothesis has been derived that inflammatory DCM is the endstage
      of an autoimmune cardiac disease that goes along with the activation of succeptibility genes,
      which are common to other autoimmune diseases.

      Original aims of the project were:

        -  inclusion of patients with dilated cardiomyopathy (ejection fraction <45%, left
           ventricular enddiastolic diameter > 56mm) and in addition

        -  the inclusion of all relevant data regarding a possible familial, infectious or
           autoimmune etiology of the disease. A questionnaire was added to the CRFs, in order to
           ascertain data regarding a possible familial history for each patient not only for
           cardiac diseases, but also for autoimmune disorders. A pedigree of all patients was
           drawn. Data regarding a possible infectious or inflammatory etiology of the disease are
           available by investigation of the endomyocardial biopsy and peripheral blood. All data
           were included in the CRF. Derived from the data base, the biopsy and serum bank, further
           aims of the project are the search for a genetic link or genetic predisposition for
           autoimmune diseases in patients with DCM, especially inflammatory diseases.

      To reach these aims, peripheral blood of all included patients was sent to the biomaterial
      bank in Berlin. DNA extracted from peripheral blood was investigated for the detection of
      genetic abnormalities in the genes for structural proteins, which are known to be associated
      with DCM. In addition, screening was done for several candidate genes in endomyocardial
      biopsies of patients with DCM using microchip technology and the investigation for
      polymorphisms in the HLA class II DQ locus in the patient cohort. Data if this Investigation
      were correlated with clinical outcome of the patients, who clinically were followed in total
      for 10 years. Right now the 10 year follow-up is ongoing.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with non ischemic DCM: All patients underwent a careful history and clinical
        examination aswell as laboratory studies and echocardiographic assessment with
        2-dimensional echocardiography. The diagnosis of DCM was made according to criteria of the
        position statement from the European Society of Cardiology working group on myocardial and
        pericardial diseases