Hemodynamic and Biomarkers for Clinical Risk Stratification of Ascending Thoracic Aortic Aneurysm with Bicuspid Aortic Valve Salvatore Pasta, PhD
The Significance of Bicuspid Aortic Valve • Cardiovascular diseases (CVD) causes each year over 4 million deaths in the EU countries (European CVD statistics 2012) • Overall CVD is estimated to cost the EU economy almost €196 billion a year! • Among CVD, the bicuspid aortic valve (BAV) is the most common cardiovascular defect with highest morbidity and mortality • In Italy, nearly 0.6 to 1.2 million of individuals have a BAV, and the majority is likely to develop valve- or aneurysm complications by the age of 70 (Istat; Ward et al 2000)
The Bicuspid Aortopathy An aneurysm is a virulent but silent • disease It is imperative to extirpate the • aneurysmal aorta before fatal complications occur Unfortunately, the heterogeneity of • disease makes surgeon predictions particularly challenging Bicuspid Valve
The Challenge in the Surgical Management When should an aortic aneurysm be repaired in presence? * Case Study 50-year-old male with: • Isolated aortic dilatation • Normal functioning BAV More Aggressive! More Conservative! High Surgical Risk Risk of Untreated Disease
Genetic or Hemodynamic? Genetic Theory Hemodynamic Theory Healthy Disease
The Research Project at ISMETT CT Imaging Echocardiography Biomechanics Mathematics Histology Epigenetic miRNA-29 (Pasta et al. 2012; Pasta et al, 2013; Tsamis 2013; Rinaudo et al. 2014; Pasta et al 2015)
The Research Project at ISMETT CT Imaging Echocardiography Histology Biomechanics Mathematics Epigenetic miRNA-29 (Pasta et al. 2012; Pasta et al, 2013; Tsamis 2013; Rinaudo et al. 2014; Pasta et al 2015)
Novel Hemodynamic Marker Computational predictors may perform better than the current clinical criterion and can be therefore used to identify new metrics to reliably distinguish the more from the less ‘malignant’ aneurysm BAV ATAA (n=16) AA3 TAV ATAA (n=10) 35 AA2 * indicate p <0.05 20 * * 30 * 18 Mises Stress (kPa) * * 16 WSS mean (N/m2) 25 * 14 * 20 12 * 10 15 AA1 8 10 6 4 5 STJ 2 0 0 Sinus Sinus STJ AA1 AA2 AA3 Sinus STJ AA1 AA2 AA3 Aortic Root Ascending Aorta => => Proximal Arch Aortic Root Ascending Aorta Proximal Arch => => Legend: BAV = bicuspid aortic valve; TAV = tricuspid aortic valve; ATAA = ascending thoracic aortic aneurysm; WSS = wall shear stress (Pasta, considering for publication)
Effect of Valve Morphology The heterogeneity of bicuspid valve reflect on flow dynamic and aneurysm patterns AP-BAV RL-BAV * indicate p <0.05 (Pasta, considering for publication)
The Facility and Research Team Surgery Unit: Radiology Unit: M. Pilato (chief), MD • • A. Luca (chief), MD • G. Raffa, MD • G. Gentile, MD • n.4 operating room, • n.7 radiologists and n.12 technicians • n.1 hybrid operating room CT, 1.5T MRI, 3T MRI, n.2 angiographer • Bioengineering: Cardiology Unit: • A. Rinaudo, PhD student • C. Scardulla (chief), MD • F. Scardulla, MEng • D. Bellavia, MD, PhD • n.3 high-end workstation, FE software • echo for TEE, TTE (Vivid-q,GE) Grant Division: real-time 3D echo (iE33,Philips) • • Daniela Ciraulo, hemo-lab and stress-lab • • Fabrizio Campisi, • n.10 cardiologists Regenerative Medicine Unit: Collaborators at UPMC: P.G. Conaldi (chief), MD D. Vorp, PhD • • A. Gallo, PhD T.G. Gleason, MD • • • V. Agnese, PhD • J.A. Phillippi, PhD • n.15 biologists and n.8 lab- technicians all instruments for gene and protein • expression in tissue and cells
Funding This research is funded by a grant from Fondazione RiMED Ricerca Finalizzata 2011-2012; Hemodynamic and Biomarkers for Clinical Risk Stratification of Ascending Thoracic Aortic Aneurysm with Bicuspid Aortic Valve (GR-2011-02348129); Principal Investigator: Salvatore Pasta
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