1. Aortic Stenosis Randall Harada Echo conference: 12 Sep 2007

2. Etiology Echo conference: 12 Sep 2007 Age < 70Age ≥ 70

3. Pathophysiology Congential AS: turbulent flow → fibrosis, calcification Rheumatic AS: vascularization of leaflets → retraction, stiffening, adhesions, fusion Calcific / degenerative AS: Echo conference: 12 Sep 2007 Similarities to atherosclerosis: lipid accumulation, inflammatory cell infiltration, calcification Clinical factors mirror CAD risk factors (Dissimilarities: little SM cell proliferation, lack of neovascularization, and more prominent micro-calcification) Otto CM. Circulation 90; 1994

4. Pathophysiology Echo conference: 12 Sep 2007 Stewart BF, JACC 29(3) 1997 Stepwise multiple logistic regression

5. Pathophysiology Echo conference: 12 Sep 2007 Aortic stenosis Increased afterload LVH Increased preloadPreserved wall stress Normal systolic function Atrial contraction

6. Pathophysiology Echo conference: 12 Sep 2007 Aortic stenosis Increased afterload LVH LVH inadequate (afterload mismatch) Reduced myocardial contractility ↓ CBF per unit of mass ↑ O2 demand↓ coronary perfusion pressure Compression of intramyocardial arteries Myocardial ischemia

7. Natural history Long latent period: Mortality is low during the latent period; similar to age-matched Progression to symptomatic or severe aortic stenosis has marked individual variability –Average rate of progression 0.10 – 0.12 cm 2 per year Echo conference: 12 Sep 2007 10 years20 years25 years Mild88%63%38% Moderate4%15%25% Severe8%22%38% Horstkotte D, Eur Heart J 9(suppE) 1988

8. Natural history Severe stenosis with symptoms: Echo conference: 12 Sep 2007 Avg life expectancy (y) Angina5 Syncope3 Heart failure<2 Ross J, Circ 36(supp IV) 1968

9. Clinical care of AS Assessment of symptoms; patient education Careful exercise testing for asymptomatic patients with unclear medical histories: Serum BNP – non-specific marker Echo conference: 12 Sep 2007 ACC/AHA, Circ 114, 2006 Echocardiography: eval AS severity, LV function

10. Medical therapy Antibiotic prophylaxis no longer recommended No medical therapies proven to prevent or delay AS In severe AS, atrial fibrillation is often poorly tolerated Echo conference: 12 Sep 2007

11. Medical therapy Echo conference: 12 Sep 2007 Rajamannan NM, Circ 110, 2004

12. SALTIRE trial (atorvastatin 80 vs placebo) Echo conference: 12 Sep 2007 Cowell SJ, NEJM 352, 2005

13. RAAVE study 121 patients Not randomized –Active arm: patients who need statin due to hyperlipidemia Mean LDL 160 mg/dL → at end of study: 93 mg/dL Higher prevalence of HTN and diabetes –Control arm: patients who do not meet guidelines for a statin Mean LDL 119 mg/dL → at end of study: 118 mg/dL Echo conference: 12 Sep 2007 Moura LM, JACC 49, 2007

14. RAAVE study Echo conference: 12 Sep 2007 Moura LM, JACC 49, 2007

15. Ongoing Statin RCTs Echo conference: 12 Sep 2007 Stop Aortic Stenosis (STOP-AS) - U.S. Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) - Europe Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin (???) - Canada ASTRONOMER

16. Evaluation of AS severity Echo conference: 12 Sep 2007 Maximum aortic velocity Mean transvalvular gradient Aortic valve area by continuity equation

17. Evaluation of AS severity Echo conference: 12 Sep 2007 Maximum aortic velocity ← 4.2 m/s ↔ max instantaneous gradient ← 71 mmHg http://www.grc.nasa.gov/WWW/K-12/airplane/bern.html

18. Evaluation of AS severity Echo conference: 12 Sep 2007 Maximum aortic velocity↔ max instantaneous gradient Modified Bernoulli equation: ∆P = 4 [(V 2 ) 2 – (V 1 ) 2 ] Simplified equation (assuming V 2 >>> V 1 ) : ∆P = 4 V 2

19. Evaluation of AS severity Echo conference: 12 Sep 2007 Maximum aortic velocity Most reproducible Strongest predictor of clinical outcomes Mild: 2.6 – 3.0 m/s Moderate: 3 – 4 m/s Severe: >4 m/s

20. Evaluation of AS severity Echo conference: 12 Sep 2007 Maximum aortic velocity Mean transvalvular gradient Aortic valve area by continuity equation

21. Evaluation of AS severity Echo conference: 12 Sep 2007 Mean transvalvular gradient

22. Evaluation of AS severity Echo conference: 12 Sep 2007 Mean transvalvular gradient Mild: < 25 mm Hg Moderate: 25 – 40 mm Hg Severe: > 40 mm Hg

23. Evaluation of AS severity Echo conference: 12 Sep 2007 Maximum aortic velocity Mean transvalvular gradient Aortic valve area by continuity equation

24. Evaluation of AS severity Echo conference: 12 Sep 2007 Aortic valve area by continuity equation Volume flow proximal to valve = volume flow thru orifice CSA LVOT x VTI LVOT = AVA x VTI AV CSA LVOT x V LVOT = AVA x V AV AVA = (CSA LVOT x V LVOT ) / V AV Velocity ratio = V LVOT / V AV

25. Evaluation of AS severity Echo conference: 12 Sep 2007 Aortic valve area by continuity equation Severity by AHA criteria: –Mild:> 1.5 cm 2 –Moderate:1.0 – 1.5 cm 2 –Severe: < 1.0 cm 2 Severity by BIDMC criteria: –Mild:> 1.2 cm 2 –Moderate:0.8 – 1.2 cm 2 –Severe: < 0.8 cm 2 Dimensionless ratio < 0.25 corresponds to severe AS

26. Evaluation of AS severity Echo conference: 12 Sep 2007 Aortic valve area by continuity equation Assumes: –Geometry of the LVOT is round –Acquired imaging plane (PLAX) is parallel to the LVOT 3D-echo may improve measurements Doddamani S. Echocardiography 24;2007

27. Evaluation of AS severity Echo conference: 12 Sep 2007 55 consecutive patients w/ nl AV Estimations of LVOT area: a.2D-echo PLAX: (π r 2 ) b.3D-echo idealized PLAX: (π r 2 ) c.3D-echo planimetry in the “transverse plane” d.3D-echo “ellipse”: (π x LVOT long x LVOT short ) Doddamani S. Echocardiography 24;2007

28. Evaluation of AS severity Echo conference: 12 Sep 2007 Eccentricity index = 1 – ( LVOT short / LVOT long ) Doddamani S. Echocardiography 24;2007 ←RoundOblate → median

29. Evaluation of AS severity Echo conference: 12 Sep 2007 Comparison of LVOT area estimations Doddamani S. Echocardiography 24;2007

30. Evaluation of AS severity Echo conference: 12 Sep 2007 Comparison of LVOT area estimations Doddamani S. Echocardiography 24;2007

31. Timing of valve replacement Echo conference: 12 Sep 2007Otto CM, JACC 47, 2006

32. Timing of valve replacement Echo conference: 12 Sep 2007Otto CM, JACC 47, 2006

33. Asymptomatic patients Echo conference: 12 Sep 2007 Risk of sudden death with AS < 1% What is the risk of surgery?

34. In-hospital, post-op mortality Echo conference: 12 Sep 2007Ambler G, Circ 112, 2005

35. In-hospital, post-op mortality Echo conference: 12 Sep 2007Ambler G, Circ 112, 2005

36. Exceptions to the asymptomatic rule Echo conference: 12 Sep 2007Otto CM, JACC 47, 2006 Undergoing other cardiac sx

37. Problematic situations Echo conference: 12 Sep 2007 Hypertension –May mask the severity of AS For a given AVA, transaortic ∆P (velocity) decreases when systemic arterial compliance decreases. Otto CM, JACC 47, 2006

38. Problematic situations Echo conference: 12 Sep 2007 LV dysfunction –Primary cardiomyopathy vs. secondary due to true AS –Low stroke volume may reduce leaflet motion in a non-stenotic valve –Dobutamine stress echo to differentiate Flexible leaflets: increase in EF, leaflet excursion, and AVA Severe AS: increase in EF, no change in AVA “Lack of contractile reserve”: no increase in EF

39. Congenital AS Echo conference: 12 Sep 2007 Subvalvar Supravalvar Valvar

40. Subvalvar / Subaortic stenosis Dynamic stenosis: –HOCM Fixed stenosis: –Thin membrane –Thick fibromuscular ridge Echo conference: 12 Sep 2007

41. Subvalvar / Subaortic stenosis Echo conference: 12 Sep 2007

42. Subvalvar / Subaortic stenosis Echo conference: 12 Sep 2007

43. Subaortic stenosis Echo conference: 12 Sep 2007 Pathophysiology –Underlying abnormality of LVOT structure –Turbulent flow → progressive LVOT fibrosis →AV leaflet thickening → AR 55% –Infectious endocarditis 12% Timing of surgery –Children: gradient ≥ 30 mm Hg –Adults: gradient ≥ 50 mm Hg –AR Recurrence rate: 15 - 27% reoperation

44. Supravalvar stenosis Echo conference: 12 Sep 2007 Hourglass deformity (discrete constriction) 60-75% Diffuse narrowing of variable length in ascending aorta 25-40%

45. Supravalvar stenosis Echo conference: 12 Sep 2007 Etiologies –Homozygous familial hypercholesterolemia –Familial autosomal dominant form – mutation of elastin gene –Sporadic mutation form –As a feature of Williams syndrome Gene deletions (including elastin) Short stature, facial abnormalities, visuospatial cognition defects, renovascular HTN, mental retardation Endocarditis prophylaxis Indications for surgery uncertain

46. Valvar AS Echo conference: 12 Sep 2007 Unicuspid or unicommissural valve Bicuspid or bicommissural valve Aortic annular hypoplasia

47. Bicuspid AV Echo conference: 12 Sep 2007 Prevalence estimate: 0.5-2% 3:1 male:female Peak age of symptom onset: 40 – 60 years-old Familial –Present in ~9% 1 st degree relatives Huntington K, JACC 30, 1997

48. Bicuspid AV Echo conference: 12 Sep 2007

49. Bicuspid AV Echo conference: 12 Sep 2007

50. Bicuspid AV Echo conference: 12 Sep 2007 Aortic abnormalities –Coarctation: 6% –Dilatation of aortic root and/or ascending aorta: ~50% –Predictor of ascending aorta aneurysm or dissection –Presence is independent of the functional state of the AV –Defects in aortic media

51. Bicuspid AV – aortic media Echo conference: 12 Sep 2007de Sa M, J Thorac Cardiovasc Surg 118, 1999 Tricuspid valve Bicuspid valve

52. Bicuspid AV – aortic media Echo conference: 12 Sep 2007Cotrufo M, J Thorac Cardiovasc Surg 130, 2005

53. Percutaneous AVR (CoreValve) Echo conference: 12 Sep 2007 86 consecutive patients –8/05-9/06: 2 nd generation 21-F device (n=50) –9/06-2/07: 3 rd generation 18-F device (n=36) Required less access site surgical cut-down, lower procedural time, and less frequent hemodynamic support (i.e. ECMO, bypass, cardiac assist) Grube E, JACC 50; 2007 Age82 ± 6 years Women65% CAD56% Prior CABG19% Prior stroke11% NYHA III/IV83% LVEF54 ± 16% EuroSCORE22 ± 13% Peak grad71 ± 13 mmHg AVA0.60 ± 0.16 cm 2

54. Percutaneous AVR (CoreValve) Echo conference: 12 Sep 2007 Grube E, JACC 50; 2007

55. Percutaneous AVR (CoreValve) Echo conference: 12 Sep 2007 Grube E, JACC 50; 2007 Acute device success88% Conversion to surgery6% Only valvuloplasty2% Valve in valve placement2% 48-hour AE Death6% Stroke10% MI0% Cardiac tamponade9% Coronary flow impairment0% 30-day AE Death12% Stroke10% MI1%

56. Percutaneous AVR (Cribier Edwards) Echo conference: 12 Sep 2007 50 consecutive patients Webb JG, Circulation 116; 2007 Age82 ± 7 years Women40% CAD72% Prior stroke12% NYHA III/IV90% EuroSCORE28% Mean grad46 ± 17 mmHg AVA0.6 ± 0.2 cm 2

57. Percutaneous AVR (Cribier Edwards) Echo conference: 12 Sep 2007 Webb JG, Circulation 116; 2007

58. Percutaneous AVR (Cribier Edwards) Echo conference: 12 Sep 2007 Webb JG, Circulation 116; 2007 Procedural success43 (86%) Inability to pass iliac artery1 Inability to cross AV3 Defect in prototype delivery catheter1 Malpositioning of the prosthesis2 Procedural death (aortic injury)1 (2%) Emergent cardiac surgery0 30-day death6 (12%) Stroke2 (4%) MI1 (2%)