Prevention of sudden death in surviving relatives of young sudden death victims through optimal postmortal, genetic and cardiologic evaluations in affected families.
01 / 2008 - onbekend
The first aim of this study is to evaluate the effectiveness and costs (cost-effectiveness) of the introduction and application of a new multidisciplinary intervention which consists of the following 4 elements: (1a) Initiate postmortal studies in sudden death victims <40 years, including (1b) the isolation and storage of DNA; (2) Stimulate fast track referral of first degree relatives at an early stage to the CGO clinic; (3) Classify relative s risk of SCD; (4) Initiate diagnostic follow-up (surveillance) and/or treatment of risk carrying relatives to prevent sudden cardiac death, compared to current daily practice. The second aim of this study is to evaluate which of the following two intervention modalities is the most (cost-)effective: optimal intervention modality or bottom up -approach (which is aimed at changing professional s behaviour) versus the maximal intervention modality or top-down approach (in which professionals receive central support to follow the protocol each time they are confronted with a sudden death under 40y. (see PDF 1). BACKGROUND: In the Netherlands each year about 1000 children and young adults die from cardiovascular causes, often suddenly and unexpectedly. In 50-70% of cases sudden death is not explained by external factors (so called natural deaths ) and irrespective of gender and ethnic background, but caused by hereditary diseases. A proven or suspected genetic cause puts relatives at considerable risk of sudden cardiac death (SCD) too: Each first degree relative (parents, sisters, brothers, offspring) has a 50% chance of having the same cardiac disease, implying an overall risk of dying suddenly of 0.5-2.5% per year for all first degree relatives. Elimination of sudden death risk (1%-5% per year) especially at young age in the first two groups is possible by regular cardiologic follow up and, if indicated, treatment with medication, rules of living and implantation of pacemakers or internal defibrillators (ICDs). Direct treatment of genetic mutations (gene therapy) is not yet possible. However, prevention of the phenotypic consequences (of which sudden death is the most important) is possible by stratification of relatives into three groups: (a) certainly affected (proved carriers of the familiar disease causing mutation and/or showing signs of disease by cardiologic screening), (b) possibly affected (no disease causing mutation identified in the family and not, yet, showing signs of cardiac disease) and (c) certainly not affected (proven non-carriers of the familial mutation). Surprisingly, first degree family members of SCD victims only rarely (about 10%) visit the cardiogenetics outpatient clinics (CGO clinic). As a result, opportunities for prevention of SCD are grossly neglected.OBJECTIVE: Introduction of a piloted preventive intervention consisting of the following 4 elements: (1a) thorough postmortal investigations in the deceased, aiming at identification of genetic heart disease; (1b) isolation, storage and analysis of DNA of the SCD victim; (2) systematic fast track referral of first family members to CGO clinics; and (3) genetic counselling and cardiologic and molecular investigations in relatives, after which (4) follow up and treatment in proven risk carriers (certainly/possibly affected family members) is initiated (see PDF1). The first objective is to evaluate the (cost)effectiveness of the introduction and application of the intervention, compared to current daily practice without that intervention.The second objective is to evaluate which of the following two intervention modalities is the most (cost-)effective: the optimal or bottom up intervention-approach which is aimed at changing professional s behaviour, versus the maximal or top-down approach in which professionals receive central support to follow the protocol each time they are confronted with a sudden death under 40y. (see study design below) STUDY DESIGN/INTERVENTION. Prospective follow-up study in three regions: (1) current daily practice (Leiden; control region; no specific intervention); (2) an optimal strategy (Amersfoort; introduction of multidisciplinary guideline to be used by all independent professionals involved); (3) a maximal strategy (Amsterdam; continuous 7x24h stand-by service to guide the application of the proposed strategy). STUDY-POPULATION:1. All sudden death cases <40y in three Dutch regions (Amsterdam, Amersfoort, Leiden), during three years follow-up. 2. in whom natural death cannot be excluded; 3. All living first degree relatives of the cases who satisfy criteria 1 and 2. OUTCOME MEASURES. Primary outcome (all regions): (1) Proportion of 1st degree relatives who attend the CGO clinic within 1 year after SCD, who are well-informed (no longer unaware); (2) Proportion of 1st degree relatives attending the OCG within 1 year after SCD, in whom a risk of SCD cannot be excluded (i.e. definitely/possibly at risk of SCD) and are therefore referred for cardiologic follow up and (if necessary) treatment. Secondary outcomes: (1) Proportion of index patients in whom (i) autopsy is performed, and/or (ii) DNA is sampled, stored and analysed; (2) No. of families/1st degree family members of index patients who received information through the index patient s GP; (3) Time to attendance, i.e. time interval between SCD event and attendance of 1st degree relatives at CGO clinic. (4) Economic evaluation of the three strategies: Amersfoort region (guidline) vs. Leiden (no intervention) [Objective 1] and Amsterdam region (stand-by service) vs. Amersfoort (guideline) [Objective 2].