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Unexplained cardiac arrest registry of Europe. The molecular counterpart


1) To identify, within the patients survived to an episode of Idiopathic Ventricular Fibrillation (IVF), those who may not require an automatic Implantable Cardioverter Defibrillator because a treatable disease has been identified by a molecular approach. 2) To further define the true IVF population by excluding those patients in whom this novel approach allows the diagnosis of a definite disease. 3) To attempt the genetic characterisation, and possibly the identification of the gene, of the so called "Brugada's syndrome" which is currently included in the diagnosis of IVF. 4) To continue the successful experience of UCARE, the Unexplained Cardiac Arrest Registry of Europe, in order to provide definitive information on the natural history and on the long term effect of therapy in IVF patients.

Brief description:
Cases of IVF will be referred by any physician willing to comply with the enrolment and follow up procedures. Data on individual patients are collected on standardised forms, specifically: a) Enrolment, b) Follow-up and c) Terminal event/change of diagnosis. Each individual enrolled is requested to have a follow-up visit every year or whenever an arrhythmic event occurs.
For each patient blood (20 ml) will be collected in heparin for implementation of lymphoblastoid cell lines that will provide a continuous source of DNA for the present as well as future studies on IVF. Myocardial biopsy is already routinely performed in 70% of the IVF patients and it is evaluated by conventional histopathology. Paraffin embedded slices will be used for DNA extraction. DNA is isolated from immortalised cells lines of lymphoblasts. A fraction of extracted DNA will be stored at -20°C and will represent a DNA bank for IVF survivors. Identified genes associated to Long QT Syndrome and to hypertrophic cardiomyopathy will be screened for mutations. In situ hybridisation to assess regional and transmural distribution of Ito channels will be performed using oligonucletides directed to a unique portion of the cDNA of Kv4.2/3 and Kv1.4 cDNA specifically developed. PCR protocols for the identification of adenovirus, enterovirus, cytomegalovirus, herpes simplex virus, parvovirus, Ebstein-Barr virus and respiratory sincitial virus will be performed.
Data analysis is performed via interrogation of the data base through the QUEST software. Statistical analysis is performed using the SPSS (Statistical Package for the Social Sciences II) statistical package.

Idiopathic ventricular fibrillation, Sudden cardiac death, Long QT syndrome, Hypertrophic cardiomyopathy, Brugada's syndrome, Molecular biology, Gene mutations, Genotype-phenotype correlation.

Call for proposal

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Via Mentana 4
27100 Pavia

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