Non Ischemic Cardiomyopathy Clinical Trial
Official title:
Inflammatory/Familial Dilated Cardiomyopathy: Is There a Link to Autoimmune Diseases? TP9a of the KNHI Associated to the DZHK
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.
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.
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