Innovation Platform: Sudden Cardiac Death Prof. dr. Bart Loeys CRC Antwerp
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
Clinical Research Center Antwerp: A strategic choice
TRANSLATIONAL AND CLINICAL RESEARCH TOWARDS BIOMEDICAL INNOVATION Multidisciplinary Supportive Integration with patient care Collaboration
Storage and management of biological samples Tissue, blood products, DNA Resource for scientific research Virtual connection of biobank with hospital and patient data
Cardiovascular pathology: mean reason for hospitalisation in Antwerp University Hospital
Sudden cardiac death (SCD) 4/07/2013 7
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
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
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 4/07/2013 10
Etiology SCD AGE is THE triage marker > 45 yrs: ischaemic heart disease until proven otherwise < 45 yrs: up to 80% hereditary cause 4/07/2013 11
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 4/07/2013 12
Paradigm shift cardiogenetics 4/07/2013 13
What s needed for SCD research? DNA, serum, tissue Diagnostics Pathogenesis Biobanks DNA, serum, tissue Therapeutics DNA, serum, tissue 4/07/2013 14
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 4/07/2013 15
Outcome 4/07/2013 16
Outcome 4/07/2013 17
Outcome 1 st line Genetic diagnosis Known loci 2 nd line Genetic diagnosis Unknown loci Genetic variant found!.but what does it mean? 4/07/2013 18
Outcome 3 rd line Gene function Molecular diagnosis I AP /C m (pa/pf) 50 40 30 20 10 0 WT p.pro347ser Co-expression -80-60 -40-20 0 20 40 60 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 4/07/2013 19
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 4/07/2013 20
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 4/07/2013 21
Thank you! innovatieplatformen@cmi-vzw.be http://www.cmi-vzw.be/