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

Bicuspid Valve

• 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

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!

High Surgical Risk

More Conservative!

Risk of Untreated Disease

Genetic or Hemodynamic?

Hemodynamic TheoryGenetic 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 Biomechanics Mathematics Histology Epigenetic

miRNA-29

(Pasta et al. 2012; Pasta et al, 2013; Tsamis 2013; Rinaudo et al. 2014; Pasta et al 2015)

Sinus STJ AA1 AA2 AA3

WS

Sm

ea

n (

N/m

2)

0

2

4

6

8

10

12

14

16

18

20

*

*

* *

Aortic Root Ascending Aorta Proximal Arch=> =>

Sinus STJ AA1 AA2 AA3

Mis

es

Str

es

s (

kP

a)

0

5

10

15

20

25

30

35

Aortic Root Ascending Aorta Proximal Arch=> =>

** *

*

AA3

AA2

AA1

STJ

Sinus

BAV ATAA (n=16)

TAV ATAA (n=10)

(Pasta, considering for publication)

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

Legend: BAV = bicuspid aortic valve; TAV = tricuspid aortic valve; ATAA = ascending thoracic aortic aneurysm; WSS = wall shear stress

* indicate p<0.05

Novel Hemodynamic Marker

(Pasta, considering for publication)

Effect of Valve Morphology

AP-BAV RL-BAV

* indicate p<0.05

The heterogeneity of bicuspid valve reflect on flow dynamic and

aneurysm patterns

Radiology Unit:

• A. Luca (chief), MD

• G. Gentile, MD

• n.7 radiologists and n.12 technicians

• CT, 1.5T MRI, 3T MRI, n.2 angiographer

Cardiology Unit:

• C. Scardulla (chief), MD

• D. Bellavia, MD, PhD

• echo for TEE, TTE (Vivid-q,GE)

• real-time 3D echo (iE33,Philips)

• hemo-lab and stress-lab

• n.10 cardiologists

Surgery Unit:

• M. Pilato (chief), MD

• G. Raffa, MD

• n.4 operating room,

• n.1 hybrid operating room

Regenerative Medicine Unit:

• P.G. Conaldi (chief), MD

• A. Gallo, PhD

• V. Agnese, PhD

• n.15 biologists and n.8 lab-

technicians

• all instruments for gene and protein

expression in tissue and cells

Bioengineering:

• A. Rinaudo, PhD student

• F. Scardulla, MEng

• n.3 high-end workstation, FE software

Collaborators at UPMC:

• D. Vorp, PhD

• T.G. Gleason, MD

• J.A. Phillippi, PhD

The Facility and Research Team

Grant Division:

• Daniela Ciraulo,

• Fabrizio Campisi,

Funding

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

This research is funded by a grant from Fondazione RiMED

Thanks