How to Integrate Imaging and Biochemistry Into Risk ...
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How to Integrate Imaging and Biochemistry Into Risk Stratification of Bicuspid Aortopathy David G. Guzzardi, MD/PhD (candidate) on behalf of: Paul W.M. Fedak, MD PhD FRCSC FAHA Associate Professor, University of Calgary Libin Cardiovascular Institute of Alberta Adjunct Associate Professor, Northwestern University Director of Translational Research, Martha and Richard Melman Bicuspid Aortic Valve Program
Transcript of How to Integrate Imaging and Biochemistry Into Risk ...
How to Integrate Imaging and Biochemistry Into Risk Stratification of Bicuspid
Aortopathy
David G. Guzzardi, MD/PhD (candidate) on behalf of:Paul W.M. Fedak, MD PhD FRCSC FAHA
Associate Professor, University of CalgaryLibin Cardiovascular Institute of AlbertaAdjunct Associate Professor, Northwestern UniversityDirector of Translational Research,Martha and Richard Melman Bicuspid Aortic Valve Program
No Disclosures
Clinical Problem
• Burden of surgery for BAV patients in the USA exceeds 1 billion dollars per year
• Frequency of aortic interventions has doubled over the past decade
• There is limited scientific evidence for the timing and extent of these prophylactic interventions
Opotowsky et al, JTCVS 2013; 146:339-46
Uncertainty of Clinical Guidelines for BAV Aortopathy
Hardikar & Marwick, Int J Cardiol 2015; 199:150-3
1998 2014
Genetics
Hemodynamics
VS
Surgical approaches are aggressive for genetic aortopathy
• 52% believed genetics, 2% believed valve hemodynamics
• 61% believed in resection at 45mm at time of AVR
• 33% performed resection at <45mm at time of AVR
Verma … Fedak et al, JTCVS 2013; 146:1033-40
Itagaki et al, JACC 2015; 65:2363-69
Long-term incidence of
aortic dissection after AVR
Acquired
Aortic Valve
Disease
Marfan
Syndrome
BAV
Aortopathy
Is progression of BAV aortopathy
predictable for individual patients?
Fedak, Eur Heart J 2008;29:432-33
Variable Patterns of BAV Aortopathy
ROOT
MID ASCPROX ARCH
Variable BAV Cusp Morphology
Sabet et al, Mayo Clin Proc, 1994;74:14-26
The Need for Biomarker
Development
Imaging
Circulating
Genetic
Mahadevia et al, Circulation 2014; 129:673-82 / Verma & Siu, NEJM 2014; 370:1920-9
RL fusion RN fusion
Valve Fusion and Flow Pattern
Barker et al, Circ Cardiovasc Imaging 2012; 5:457-66
Tricuspid AV (TAV)
(No valve dysfunction)
Bicuspid AV (BAV)
(No valve dysfunction)
BAV without dysfunction has
significant flow eccentricity
Individual Patient: Detect regions with abnormal WSS
BAV patient
3D WSS 3D Ao geometry
WSS [Pa]
Normal WSS
Healthy Atlas
WSS heat map
WSS WSSNormal WSS
WSS WSSNormal WSS
WSS WSSNormal WSS
±95% CI
Registration & interpolation
van Ooij et al, ABME 2015; 43:1385-97
WSS [Pa]
WSS Atlases and Heatmaps
FLIRT
Mahadevia et al, Circulation 2014; 129:673-82
Mahadevia et al, Circulation 2014; 129:673-82
Valve-mediated hemodynamics
predict local tissue remodeling
Guzzardi, Barker et al … Fedak, JACC 2015; 66:892-900
Valve-mediated hemodynamics
predict local tissue remodeling
Guzzardi, Barker et al … Fedak, JACC 2015; 66:892-900
Preoperative 4D flow MRI (N=20)
WSS mapping onto patients’ aortic anatomy
Aortic wall sample collection – same aorta(ascending aortic reconstruction)
• elevated WSS• normal WSS
HISTOLOGY• VVG (elastin)
SIGNALING & PROTEOLYTIC PROFILE
• TGFβ-1• MMPs, TIMPs
Valve-mediated hemodynamics
predict local tissue remodeling
Guzzardi, Barker et al … Fedak, JACC 2015; 66:892-900
Normal Elevated0
20
40
60
80
Regional Wall Shear Stress
Mean %
are
a o
f ela
stin
P = 0.01
Normal Elevated2.0
2.5
3.0
3.5
4.0
Regional Wall Shear Stress
Mean e
lastin fib
er
thic
kness (
mm
)
P = 0.00007
Normal Elevated0
20
40
60
80
Regional Wall Shear Stress
Mean d
ista
nce b
etw
een
ela
stin fib
ers
(m
m)
P = 0.001
Total elastin Fiber thickness Fiber-to-fiber distance
Compromised Elastin Histology
Guzzardi, Barker et al … Fedak, JACC 2015; 66:892-900
Normal Elevated0
200
400
600
800
Regional Wall Shear Stress
TG
Fb-1
Concentr
ation (
pg/m
L) P = 0.04
↑ TGFβ-1 in regions of ↑ WSS
Guzzardi, Barker et al … Fedak, JACC 2015;
66:892-900
The Need for Biomarker
Development
Imaging
Circulating
Genetic
Naito et al, Thorac Cardiovas Surg 2016; epub ahead of print
Naito et al, Thorac Cardiovas Surg 2016; epub ahead of print
The Need for Biomarker
Development
Imaging
Circulating
Genetic
Genetic Biomarkers
Humphrey et al, Circ Res 2015; 116:1448-61
Is there a unified
approach?
Precision Surgery:
Individualized Aortic Resection Strategies
When and Where to
resect BAV aorta?
CirculatingBiomarkers
HemodynamicBiomarkers
GeneticBiomarkers
AcknowledgementsUniversity of Calgary (CANADA)
Cardiac Sciences
Paul Fedak Holly Mewhort
Daniyil Svystonyuk Sean Kang
Darrell Belke Yong-Xiang Chen
Jeannine Turnbull
Pathology
Amy Bromley Thomas Kryton
Civil Engineering
Elena Di Martino Giampaolo Martufi
Katherine Olsen
Northwestern University (Chicago, USA)
Radiology
Alex Barker Michael Markl
James Carr Jeremy Collins
Pim van Ooij Emilie Bollache
Cardiac Surgery
Chris Malaisrie Patrick McCarthy
Colleen Clennon
Cardiology
Jyothy Puthumana Robert Bonow
James Thomas
How to Integrate Imaging and
Biochemistry Into Risk Stratification of
Bicuspid Aortopathy
David Guzzardi
Libin Cardiovascular Institute of Alberta (Calgary, CANADA)Marlene & Don Campbell Family Cardiac Research Laboratory
Bluhm Cardiovascular Institute (Chicago, USA)Martha & Richard Melman Family Bicuspid Aortic Valve Program
