Innovation Platform: Sudden Cardiac Death

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1 Innovation Platform: Sudden Cardiac Death Prof. dr. Bart Loeys CRC Antwerp

2 General Assembly VzW Board of Directors Strategic Advisory Board Staff: 1 executive director 1 ICT manager 1 financial administration Biobank facility management CRC focal point Translational Biomedical Research Programme CRC Antwerp CRC CRC CRC CRC Loca l biobanks Local biobanks Local biobanks Local biobanks Research projects Blue = governance; green = activities at operational level; orange = decentralized

3 Clinical Research Center Antwerp: A strategic choice

4 TRANSLATIONAL AND CLINICAL RESEARCH TOWARDS BIOMEDICAL INNOVATION Multidisciplinary Supportive Integration with patient care Collaboration

5 Storage and management of biological samples Tissue, blood products, DNA Resource for scientific research Virtual connection of biobank with hospital and patient data

6 Cardiovascular pathology: mean reason for hospitalisation in Antwerp University Hospital

7 Sudden cardiac death (SCD) 4/07/2013 7

8 Sudden cardiac death (SCD) A leading cause of death with estimated incidence of 1-2/1000/year. Affects all ages Also in the very young Survival our of hospital arrest/cpr very poor Efficacy AED availability in private and public places very poor 4/07/2013 8

9 Sudden cardiac death (SCD) 1/3 sudden death is the first sign of underlying disease 2/3 acute CV events in patients considered low risk Vast majority (up to 93%) due to arrhythmias 4/07/2013 9

10 Etiology SCD 60-80% coronary artery disease 10-15% cardiomyopathy 10-20% primary electrical disorder (longqt, Brugada, CPVT, ) 1-2% aortic aneurysm/dissection 1-5% idiopathic ventricular fibrillation 4/07/

11 Etiology SCD AGE is THE triage marker > 45 yrs: ischaemic heart disease until proven otherwise < 45 yrs: up to 80% hereditary cause 4/07/

12 Autosomal Dominant Inheritance I:1 I:2? II:1 II:2 II:3 II:4 II:5 II:6???? III:1 III:2 III:3 III:4 On average: implications for eight other family members 4/07/

13 Paradigm shift cardiogenetics 4/07/

14 What s needed for SCD research? DNA, serum, tissue Diagnostics Pathogenesis Biobanks DNA, serum, tissue Therapeutics DNA, serum, tissue 4/07/

15 Overall project objectives (1) Translating genetic technology into improved clinical care Next generation sequencing Biomarkers (2) In vitro and in vivo diagnostics of sudden cardiac death Invasive and non-invasive imaging Functional testing (3) Prevention of sudden cardiac death through innovative technologies Risk stratification New pharmacological treatments Medical devices (4) Sudden cardiac death registry 4/07/

16 Outcome 4/07/

17 Outcome 4/07/

18 Outcome 1 st line Genetic diagnosis Known loci 2 nd line Genetic diagnosis Unknown loci Genetic variant found!.but what does it mean? 4/07/

19 Outcome 3 rd line Gene function Molecular diagnosis I AP /C m (pa/pf) WT p.pro347ser Co-expression Em (mv) Functional analysis of mutations Saenen et al. JMCC. 2007;43(1):63-72 suppl. From probability of pathogenicity to personalized medicine tailored to the molecular diagnosis 4/07/

20 Expertise, samples and network (1) Research projects, publications, internationally recognized clinical expertise (Brugada syndrome, Loeys-Dietz syndrome, ) (2) DNA, serum/plasma samples and aortic valve and aortic aneurysm wall tissue (3) Translational and clinical research collaborations; clinical trials (4) Creation of working groups - WG on coronary artery disease - WG on primary electrical disorders - WG on aortic aneurysmal disorders - WG on cardiomyopathies 4/07/

21 Valorisation (1) Societal Individual patient: lifestyle modification, pharmacological/surgical treatment or internal cardioverter defibrillator First degree relatives: primary prevention through clinical and molecular, cardiogenetic cascade screening Flemish society: psychosocial and socio-economic impact (2) Economic Improved imaging techniques Optimal medical device design Development of accurate biomarkers Advanced pharmacological design 4/07/

22 Thank you!

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