How to Integrate Imaging and Biochemistry Into Risk Stratification of Bicuspid Aortopathy

Transcription

1 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

2 No Disclosures

3 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

4 Uncertainty of Clinical Guidelines for BAV Aortopathy Hardikar & Marwick, Int J Cardiol 2015; 199:150-3

5 Surgical approaches are aggressive for genetic aortopathy Genetics VS Hemodynamics

6 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:

7 Itagaki et al, JACC 2015; 65:

8 Long-term incidence of aortic dissection after AVR Acquired Aortic Valve Disease Marfan Syndrome BAV Aortopathy

9 Is progression of BAV aortopathy predictable for individual patients? Fedak, Eur Heart J 2008;29:432-33

10 Variable Patterns of BAV Aortopathy ROOT MID ASC PROX ARCH

11 Variable BAV Cusp Morphology Sabet et al, Mayo Clin Proc, 1994;74:14-26

12 The Need for Biomarker Development Imaging Circulating Genetic

13 Valve Fusion and Flow Pattern RL fusion RN fusion Mahadevia et al, Circulation 2014; 129: / Verma & Siu, NEJM 2014; 370:1920-9

14 BAV without dysfunction has significant flow eccentricity Tricuspid AV (TAV) (No valve dysfunction) Bicuspid AV (BAV) (No valve dysfunction) Barker et al, Circ Cardiovasc Imaging 2012; 5:457-66

15 WSS Atlases and Heatmaps Individual Patient: Detect regions with abnormal WSS BAV patient Normal WSS WSS heat map WSS [Pa] Registration & interpolation FLIRT WSS [Pa] WSS WSS Normal WSS WSS WSS Normal WSS No W 3D WSS 3D Ao geometry Healthy Atlas ±95% CI van Ooij et al, ABME 2015; 43:

16 Mahadevia et al, Circulation 2014; 129:673-82

17 Mahadevia et al, Circulation 2014; 129:673-82

18 Valve-mediated hemodynamics predict local tissue remodeling Guzzardi, Barker et al Fedak, JACC 2015; 66:

19 Valve-mediated hemodynamics predict local tissue remodeling 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 Guzzardi, Barker et al Fedak, JACC 2015; 66:

20 Valve-mediated hemodynamics predict local tissue remodeling Guzzardi, Barker et al Fedak, JACC 2015; 66:

21 Compromised Elastin Histology Mean % area of elastin P = 0.01 Normal Elevated Mean elastin fiber thickness (mm) P = Normal Elevated Mean distance between elastin fibers (mm) P = Normal Elevated Regional Wall Shear Stress Regional Wall Shear Stress Regional Wall Shear Stress Total elastin Fiber thickness Fiber-to-fiber distance Guzzardi, Barker et al Fedak, JACC 2015; 66:

22 TGFβ-1 in regions of WSS TGFb-1 Concentration (pg/ml) 800 P = Normal Elevated Regional Wall Shear Stress Guzzardi, Barker et al Fedak, JACC 2015; 66:

23 The Need for Biomarker Development Imaging Circulating Genetic

24 Naito et al, Thorac Cardiovas Surg 2016; epub ahead of print

25 Naito et al, Thorac Cardiovas Surg 2016; epub ahead of print

26 The Need for Biomarker Development Imaging Circulating Genetic

27 Genetic Biomarkers Humphrey et al, Circ Res 2015; 116:

28 Is there a unified approach?

29 Precision Surgery: Individualized Aortic Resection Strategies Hemodynamic Biomarkers When and Where to resect BAV aorta? Genetic Biomarkers Circulating Biomarkers

30 Acknowledgements University of Calgary (CANADA) Cardiac Sciences Pathology Paul Fedak Daniyil Svystonyuk Darrell Belke Jeannine Turnbull Amy Bromley Civil Engineering Elena Di Martino Katherine Olsen Holly Mewhort Sean Kang Yong-Xiang Chen Thomas Kryton Giampaolo Martufi Northwestern University (Chicago, USA) Radiology Alex Barker James Carr Pim van Ooij Cardiac Surgery Chris Malaisrie Colleen Clennon Cardiology Jyothy Puthumana James Thomas Michael Markl Jeremy Collins Emilie Bollache Patrick McCarthy Robert Bonow 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