Patient case: 32-year-old male with dilated cardiomyopathy; genetic feature: LMNA

Clinical trial: Inflammatory/Familial Dilated Cardiomyopathy: Is There a Link to Autoimmune Diseases? TP9a

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.

Eligibility: Inclusion Criteria:
  Patients between 18 and 70 years of age were included if they had a left ventricular ejection fraction of 45% and a left ventricular end-diastolic diameter >56 mm estimated by echocardiography with no evidence of significant valve disease.
  Exclusion Criteria:
  Coronary artery disease (>50% diameter luminal stenosis in one or more epicardial vessels) was excluded in all patients by means of coronary angiography. Moreover, patients were excluded from the study if they demonstrated one or more of the following parameters: peripartum cardiomyopathy, history of myocardial infarction, severe systemic hypertension, alcohol abuse, and drug dependency.

Relevance to patient case: not relevant