CMI - Center for Medical Innovation

Being integrated in the
international biomedical
research and biobanking
world
Research platform
Sudden cardiac death
Dr. J. Saenen, CRC Antwerpen
CMI Center for Medical Innovation
Sudden Cardiac Death
CMI Center for Medical Innovation
CMI
Centrum voor Medische Innovatie
Sudden Cardiac Death
CMI Center for Medical Innovation
CMI
Centrum voor Medische Innovatie
Sudden Cardiac Death
CMI
Centrum voor Medische Innovatie
• A leading cause of death (Incidence = 1-2/1000/year)
• All ages
• Survival of out-of-hospital
arrest CPR is 5-10%
16/12/2014
CMI Center for Medical Innovation
4
Sudden Cardiac Death
CMI
Centrum voor Medische Innovatie
> 45 yrs: ischaemic heart disease until proven otherwise
< 45 yrs: up to 80% hereditary cause
16/12/2014
CMI Center for Medical Innovation
5
Etiology SCD
•
•
•
•
•
CMI
Centrum voor Medische Innovatie
60-80% coronary artery disease (CAD)
10-15% cardiomyopathy (CMP)
10-20% primary electrical disorder (PED)
1-2% aortic aneurysm/dissection (TAAD)
1-5% idiopathic ventricular fibrillation
16/12/2014
CMI Center for Medical Innovation
6
Etiology SCD
•
•
•
•
•
CMI
Centrum voor Medische Innovatie
60-80% coronary artery disease (CAD)
10-15% cardiomyopathy (CMP)
10-20% primary electrical disorder (PED)
1-2% aortic aneurysm/dissection (TAAD)
1-5% idiopathic ventricular fibrillation
3 Working groups
WG1 on coronary artery disease (CAD)
WG2 on primary electricial disorders and
cardiomyopathies (PED & CMP)
WG3 on aortic aneurysmal disorders (TAAD)
16/12/2014
CMI Center for Medical Innovation
7
CMI
Autosomal dominant inheritance
Centrum voor Medische Innovatie
II:1
II:2
I:1
I:2
II:3
II:4
III:1
III:2
II:5
II:6
?
?
III:3
III:4
First degree relatives: 50% affected
BUT opportunity for prevention
16/12/2014
CMI Center for Medical Innovation
8
Overall project objectives
CMI
Centrum voor Medische Innovatie
(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
(3) Prevention of sudden cardiac death through innovative technologies
• Risk stratification
• New pharmacological treatments
• Medical devices
(4) Sudden cardiac death registry
16/12/2014
CMI Center for Medical Innovation
9
Valorisation focus
CMI
Centrum voor Medische Innovatie
(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
16/12/2014
CMI Center for Medical Innovation
10
Valorisation focus
CMI
Centrum voor Medische Innovatie
(2) Economic
• Development of accurate risk stratification models
• Efficient genetic screening
• Optimal medical device therapy
• Advanced pharmacological design
16/12/2014
CMI Center for Medical Innovation
11
Biobank research platform
CMI
Centrum voor Medische Innovatie
(1) Flemish network
• University networks: VUBrussel, UGent, KULeuven, UAntwerpen
• Large peripheral centers: Jessa Hasselt, ZOL Genk, St. Jan Brugge
(2) Upload retrospective TAAD samples
• Aorta – aortic valve tissue
• DNA
(3) Upload prospective samples
• DNA
• Minimal dataset
• Extended dataset
• Customized for each working group
16/12/2014
CMI Center for Medical Innovation
12
Biobank research platform
CMI
Centrum voor Medische Innovatie
(4) Building on existing expertise & sample collection 2013-2014:
Claeys, MJ; Sinnaeve, PR; Convens, C; Dubois, P; Boland, J; Vranckx, P; Gevaert, S; Coussement, P; Beauloye, C; Renard, M; Vrints, C; Evrard, P Inter-hospital variation in
length of hospital stay after ST-elevation myocardial infarction: results from the Belgian STEMI registry ACTA CARDIOLOGICA (2013), 68(3): 235-239
Aantal cases: 2079
Conraads, VM; Van Craenenbroeck, EM; Pattyn, N; Cornelissen, VA; Beckers, PJ; Coeckelberghs, E; De Maeyer, C; Denollet, J; Frederix, G; Goetschalckx, K; Hoymans, VY;
Possemiers, N; Schepers, D; Shivalkar, B; Vanhees, L Rationale and design of a randomized trial on the effectiveness of aerobic interval training in patients with coronary
artery disease: The SAINTEX-CAD study INTERNATIONAL JOURNAL OF CARDIOLOGY (2013), 168(4): 3532-3536
van Ierssel, SH; Van Craenenbroeck, EM; Hoymans, VY; Vrints, CJ; Conraads, VM; Jorens, PG Endothelium Dependent Vasomotion and In Vitro Markers of
Endothelial Repair in Patients with Severe Sepsis: An Observational Study PLOS ONE (2013), 8(8)
McInerney-Leo, A.M., Marshall, M.S., Gardiner, B., Coucke, P.J., Van Laer, L., Loeys, B.L., Summers, K.M., Symoens, S., West, J.A., West, M.J., Paul Wordsworth, B.,
Zankl, A., Leo, P.J., Brown, M.A., and Duncan, E.L. (2013). Whole exome sequencing is an efficient, sensitive and specific method of mutation detection in
osteogenesis imperfecta and Marfan syndrome. Bonekey Rep. 2, 456. doi: 10.1038/bonekey.2013.190. eCollection 2013
Wischmeijer, A; Van Laer, L; Tortora, G; Bolar, NA; Van Camp, G; Fransen, E; Peeters, N; di Bartolomeo, R; Pacini, D; Gargiulo, G; Turci, S; Bonvicini, M; Mariucci, E;
Lovato, L; Brusori, S; Ritelli, M; Colombi, M; Garavelli, L; Seri, M; Loeys, BL Thoracic Aortic Aneurysm in Infancy in Aneurysms-Osteoarthritis Syndrome Due to a
Novel SMAD3 Mutation: Further Delineation of the Phenotype AMERICAN JOURNAL OF MEDICAL GENETICS PART A (2013), 161A(5): 1028-1035
Soender TK, De Backer T. Non-invasively estimated end-systolic elastance in patients with resistant hypertension and type 2 diabetes mellitus
Heart Vessels 2014; 29(3): 375-83
Bossuyt J, Van Bortel LM, De Backer TL, Van De Velde S, Azermai M, Segers P, De Buyzere M, Van Daele C, Rietzschel E. Asymmetry in prevalence of femoral but not
carotid atherosclerosis
J Hypertens 2014
De Wandele I, Rombaut L, Malfait F, De Backer T, De Paepe A, Calders P. Clinical heterogeneity in patients with the hypermobility type of Ehlers-Danlos syndrome
Res Dev Disabil 2013; 34(3): 873-81
16/12/2014
CMI Center for Medical Innovation
13
Biobank research platform
CMI
Centrum voor Medische Innovatie
(4) Building on existing expertise & sample collection 2013-2014:
Bossuyt J, Van De Velde S, Azermai M, Vermeersch SJ, De Backer TL, De Vos DG, Heyse C, Filipovsky J, Segers P, Van Bortel LM. Noninvasive assessment of carotid-femoral
pulse wave velocity: the influence of body side and body contours
J Hypertens 2013; 31(5): 946-51
De Backer TL, Vander Stichele R. Buflomedil for intermittent claudication
Cochrane Database Syst Rev 2013; 3: CD000988
Peterson GE, de Backer T, Contreras G, Wang X, Kendrick C, Greene T, Apple LJ, Randall OS, Lea J, Smogorzewski M, Vagaonescu T, Phillips RA; African American Study of
Kidney Disease Investigators. Relationship of left ventricular hypertrophy and diastolic function with cardiovascular and renal outcomes in African Americans with
hypertensive chronic kidney disease
Hypertension 2013; 62(3): 518-25
Campens L, Vanakker O, Trachet B, Segers P, Leroy BP, De Zaeytijd J, Voet D, De Paepe A, De Backer T, De Backer J
Characterization of cardiovascular involvement in pseudoxanthoma elesticum families
Arterioscler Thromb vasc Biol 2013; 33(11): 2646-52
De Wandele I, Rombaut l, Leybaert L, Van de Borne P, De Backer T, Malfait F, De Paepe A, Calders P. Dysautonomia and its underlying mechanisms in the hypermobility
type of Ehlers-Danlos syndrome
Semin Arthitis Rheum 2013; S0049-0172(13)00292-8
16/12/2014
CMI Center for Medical Innovation
14
Enrichment projects
CMI
Centrum voor Medische Innovatie
(1) WG1 on coronary artery disease
• Recruitment from and integration with Belgian STEMI registry
• New research initiatives underway
(2) WG2 on PED and CMP
• Systematic screening of large numbers of genes involved
• Targeted Next generation sequencing technology
• Exome/genome screening
• Gathering clinical data
• Composing clinical registry
• 51 gene diagnostic PED panel was created
• CMP panel under construction
16/12/2014
CMI Center for Medical Innovation
15
Enrichment projects
CMI
Centrum voor Medische Innovatie
(2) WG2 on PED and CMP
(1) Evaluation of ambulatory ECG screening system
Athletes
Ambulatory
ECG Screening
Clinical
assessment
16/12/2014
(2) Screening of athlete population for PED & CMP
(3) ECG – clinical - genetic
(4) Prevention of SCD
(5) Collaboration with industry
CMI Center for Medical Innovation
16
CMI
Enrichment projects
Centrum voor Medische Innovatie
(2) WG2 on PED and CMP
(1) Broad screening of PED and CMP
PED
patients
CMP
patients
(2) Study of overlap syndromes
(3) Collaboration with industry
16/12/2014
CMI Center for Medical Innovation
17
CMI
Enrichment projects
Centrum voor Medische Innovatie
(2) WG2 on PED and CMP
Athletes
PED
patients
CMP
patients
Ambulatory
ECG Screening
Clinical
assessment
16/12/2014
CMI Center for Medical Innovation
18
CMI
Enrichment projects
Centrum voor Medische Innovatie
(2) WG2 on PED and CMP
Athletes
Ambulatory
ECG Screening
Clinical
assessment
PED
patients
CMP
patients
Diagnostic PED & CMP gene panel
Biobank
Clinical registry
16/12/2014
CMI Center for Medical Innovation
19
CMI
Enrichment projects
Centrum voor Medische Innovatie
(2) WG2 on PED and CMP
Athletes
Ambulatory
ECG Screening
PED
patients
CMP
patients
Diagnostic PED & CMP gene panel
Clinical
assessment
Biobank
Clinical registry
Improved risk stratification models
Prevention
relatives
16/12/2014
CMI Center for Medical Innovation
20
Enrichment projects
CMI
Centrum voor Medische Innovatie
(3) WG3 on TAAD
• Retrospective samples
• Diagnostic TAAD panel was created in CRC Antwerpen
• New research initiatives underway
16/12/2014
CMI Center for Medical Innovation
21
CMI
Future steps SCD research platform
Centrum voor Medische Innovatie
(1) Consolidate collaboration
• Research grants
• Functional analysis
(2) Flemish cardiogenetic network
• Information exchange
• Uniform Flemish management
(3) Collaboration with international registries and biobank initiatives
(4) Participation in international GWAS efforts
16/12/2014
CMI Center for Medical Innovation
22
SCD Research Platform
CMI Center for Medical Innovation
CMI
Centrum voor Medische Innovatie

Download Report