Hemodynamic Theory. ⢠Altered valvular geometry leads to alterations in the hemodynamic environment, causing more mechanical abnormalities on the aortic ...
THE ROLE OF BICUSPID AORTIC VALVE HEMODYNAMICS IN THE DEVELOPMENT OF ACUTE AORTIC DILATION Samantha Ratley, Philippe Sucosky University of Notre Dame Department of Aerospace & Mechanical Engineering
THE BICUSPID AORTIC VALVE leftcoronary leaflet
rightcoronary leaflet
noncoronary leaflet
Tricuspid aortic valve (TAV)
raphe
fused leaflet
noncoronary leaflet
Type-I bicuspid aortic valve (BAV)
• BAV is the most common form of cardiac anomalies, affecting 2-3% of the population (Hoffman 2002; Basso 2004; Cozijnsen 2011) • BAV imparts the highest amount of disease compared to all other genetic heart diseases combined (Ward 2000; Siu & Silversides 2010)
BAV IS LINKED TO AORTIC DISEASE BAV Risks Associated Risk
Chance
BAV Inheritance (1st Degree Relative)
10-17%
Aortic Valve Stenosis
40-53% (80-95%*)
(2)
Aortic Valve Replacement
50-80%
(3)
Aortic Dilation
35-68%
(4)
Aortic Dissection
7-13%
(5)
Aortic Aneurysm
26-50%
(6)
Aortic Coarctation
20% (22-42%*)
(7)
(1) Cripe et al. 2004 (2) Lewin & Otto 2005; Losenno et al. 2012 (3) Etz et al. 2001 (4) Braverman et al. 1996; Tzemos et al. 2008; Nistri et al. 2008; Beroukhim et al. 2006 (5) Yuan et al. 2010 (6) Mayo Clinic; Lewin & Otto 2005 (7) Warnes 2003
(1)
ASCENDING AORTIC DILATION • Diameter > 4.0 cm (Cozijnsen 2011; Lu 2013) • Thinning of ascending aorta (AA) wall – Smooth muscle cell apoptosis (Della Corte 2007)
• Dilation can lead to dissection CT Scan of Dilated Ascending Aorta (Al Attar 2008)
– ≥ 5.0 cm (Lu 2013) – 50% mortality rate in the first 48 hours (Antanas 2011)
BAV AORTOPATHY: CONTROVERSIAL ETIOLOGIES Genetic Theory • Intrinsic weakening of the aortic wall is caused by the same congenital defect that causes BAV
Hemodynamic Theory •
•
Altered valvular geometry leads to alterations in the hemodynamic environment, causing more mechanical abnormalities on the aortic wall in BAV than TAV Asymmetric presentation of dilation at the aortic convexity spatial distribution in shear stress •
• Currently, there is no established genetic link between BAV inheritance and aortic wall weakness
4D MRI (Hope et al. 2010), FEA (Viscardi et al. 2010), FSI (Cao et al. 2013), PIV (Saikrishnan et al. 2012)
• The causality between abnormal wall stress and aortic medial degeneration has not yet been demonstrated
FLUID-STRUCTURE INTERACTION (FSI) COMPLIMENTS IN VIVO DATA FSI (Cao et al. 2013, submitted ATVB)
right
left
volume flow rate (L/min)
-5
left
right
TAV BAV
20
0
right
left
anterior posterior
right
anterior posterior
anteriorposterior
left
anterior posterior
right
time (s) 0.86
left
Velocity magnitude (m/s) 0
0.6
TAV anterior posterior
BAV
anteriorposterior
TAV
4D MRI (Hope et al. 2010)
1.2
right
left
BAV
HEMODYNAMIC THEORY OF BAV AORTOPATHY BAV anatomic abnormality
biological changes (inflammation, proteases and remodeling)
MOTIVATION
acceleration phase
deceleration phase
3
TAV AA BAV AA
2.5 2 1.5 1 0
peak systole
0.43 time (s)
0.86
surface-averaged longitudinal WSS (dyn/cm2)
surface-averaged circumferential stretch (%)
• FSI studies closely mimic clinical data • BAV anatomy mostly impacts fluid wall shear stress (WSS) in the ascending aorta acceleration phase
deceleration phase
40
TAV AA BAV AA
20 0 -20 0
peak systole
0.43 time (s)
• Previous studies focus on already dilated aortic tissue in patients that have BAV
0.86
HYPOTHESIS AND OBJECTIVES • Hypothesis: Abnormal wall shear stress (WSS) experienced by a BAV ascending aorta contributes to the development of acute aortic dilation
• Objective: To study the effect of BAV WSS on aortic remodeling in the absence of any underlying aortic wall congenital defect
EX VIVO METHODOLOGY WSS WAVEFORMS
Longitudinal WSS (dyn/cm2)
• Temporal variations of the longitudinal WSS predicted at the center of the TAV ascending aorta (AA) and BAV AA convexity over one cardiac cycle.
40
acceleration phase deceleration phase
TAV AA BAV AA
20
0
-20
0
peak systole
central region of wall convexity
0.43
0.86
time (s)
(Cao et al. 2013, Submitted ATVB)
EX VIVO METHODOLOGY TISSUE ISOLATION AND CONDITIONING • •
Biopsy punches were sutured to theexposed tissue Normal A longitudinal The endothelium ascending cut of was aortas the made aorta dissected along was the from top of mounting plate porcine the aorta hearts attained7for a local Tissue biopsy punches mm in diameter were slaughterhouse taken from the disease-prone convexity with a custom biopsy punch intact aorta
mounting plate
endothelial surface exposed to flow
tissue samples location tissue samples sutured on plate
(Cao et al. 2013, Submitted ATVB)
EX VIVO METHODOLOGY TISSUE CONDITIONING • Tissue mounting plate was inserted into cone and plate bioreactor to replicate WSS environments of TAV and BAV AAs servo motor reservoir
servo drive
pump rotating cone pump
laptop computer culture medium tissue samples
perfusion system
mounting plate
pump
pump
(Sucosky 2008, Sun 2011)
EX VIVO METHODOLOGY TISSUE CONDITIONING TAV AA WSS Waveform
BAV AA WSS Waveform
(Sucosky 2008, Sun 2011)
CULTURE CONDITIONS, BIOMARKERS, AND ASSAYS Sample Group Control TAV AA WSS BAV AA WSS
