2015 review of BAV and associated aortopathy, including morphology, natural history and brief overview of management.

1. Bicuspid AV &
Aortopathy
Dr Cheng He
Cardiothoracic Trainee,
Royal Australasian College of Surgeons

2. BAV - Anatomy
• 2 unequal-sized cusps
• Raphe - site of fusion identifiable
in most cases
• Size of cusps:
• Fused > non-fused
counterpart
• 2 ‘normal’ cusps > 1 fused
cusp
Morphologic patterns depend on
fusion configuration
Roberts, Am J Cardiol 1970;26:72-83
Sievers et al JTCS 2007;133:1226-33

3. BAV - Epidemiology
• Incidence: 0.5%-2%
• M:F 3:1
• Sporadically
• Familial
• Turner - 30% have BAV
• Occur with other congenital CVS malformations
• Coarctation of aorta - 50%
• Hypoplastic LHS
BAV represents a complex disease of the aorta and
cardiac development

4. BAV - Pathogenesis
Padang et al. Circ Cardiovasc Genet. 2012;5:569-580.

5. ClemenG et al. Am J Med Genet 1996;62:336-8.
Glick et al. Am J Cardiol 1994;73:400-4.
HunGngton et al. Am J Cardiol 1997:30;1809.
Padang et al. Circ Cardiovasc Genet. 2012;5:569-580.
Genetics
• Autosomal dominant, variable penetrance
• 9% prevalence in first-degree relatives
• 24% if >1 person affected
• Causal genes largely unknown
• NOTCH1 (9q34.3)
• BAV + accelerated calcium deposition
BAV - Pathogenesis

6. BAV - Classification
Sievers et al JTCS 2007;133:1226-33
Surgical - Sievers

7. BAV - Classification
Echo - Schaffers
Schaffers et al Heart 2008;94:1634–1638
Valve: PS SAX
R+L R+N L+N

8. BAV - Classification
Kang et al. JACC 2013;6:150-61
MDCT - Kang

9. BAV - Classification
Why?
• Valve morphology - Natural history
• Associated aortopathies
• Comparison of reports on BAV
• Appropriate surgical intervention

10. BAV - Diagnosis
Auscultation
• Functionally normal BAV - Ejection murmur/click
at LLSB or apex
• Murmurs of AS/AR/Coarctation

11. BAV - Diagnosis
Transthoracic Echo
• Sensitivity 92%, Specificity 96%
• Accuracy inverse to calcification
• Findings:
• Raphe
• Systolic doming & eccentric closure line
(LAX)
• Evaluate in systole; raphe may appear
trileaflet
Ayad et al. Am J Cardiol 2011; 108:1589.Diastole Systole
Raphe
Doming

12. BAV - Natural History
• Valvular dysfunction - AS, AR, endocarditis
• Aortopathy

13. BAV - Natural History
Michelena et al CirculaGon. 2008;117:2776-2784.)
Survival of asymptomatic patients with BAV
Identical to expected survival of matched population

14. BAV - Natural History
Michelena et al CirculaGon. 2008;117:2776-2784.)
Medical events

15. BAV - Natural History
Michelena et al CirculaGon. 2008;117:2776-2784.)
20-yr BAV
rate
BAV
incidence
rate*
Non-BAV
incidence
rate*
AVR 24% 1370 19
*In pt-yrs (per 100,000)
AVR performed at younger ages
49±20 (BAV) vs 67±16 yrs (tricuspid)
No aortic dissections during follow-up
Surgical events

16. BAV - Natural History
Michelena et al CirculaGon. 2008;117:2776-2784.)
Predictive factors (medical & surgery):
• Age ≥50 yrs
• Valve degeneration at diagnosis
Aorta surgery predicted by:
• Ascending aorta ≥40 mm at baseline

17. BAV - Natural History
Tzemos et al. JAMA;2008:300;11:1317-1325.
The largest study (n=642) in symptomatic/asymptomatic BAV pts:
10-year 96% survival
Similar to normal population

18. BAV - Natural History
Tzemos et al. JAMA;2008:300;11:1317-1325.
Independent predictors of primary cardiac events:
Age ≥30 yrs
Moderate/Severe AS
Moderate/Severe AR

19. BAV - Natural History
What is common in both these studies?
• Independent prognostic significance of age and baseline
valvular dysfunction
Many patients proceed to have some sort of intervention
Does surgery in BAV pts alter its presumed natural history?

20. BAV - Natural History
• Valvular dysfunction - AS, AR, endocarditis
• Aortopathy

21. Surgical series of 932 resected aortic valves for AS:
• 49% had BAV
• Age at intervention
• BAV: 67±11
• Tricuspid: 74±8
BAV - AS
Roberts et al. CirculaGon. 2005;111:920-925.

22. BAV - AS
Roberts et al. CirculaGon. 2005;111:920-925.
Disease progression
• Similar degenerative changes as seen in tricuspid
valves
• Exacerbated by BAV folding/creasing/turbulent flow
• Results in accelerated disease progression
• Most common reason for valve replacement

23. BAV - AS
Fernandes et al. JACC 2007:2211-4.
Influence of valve morphology
• 310 patients with BAV
• 202 (65%): R-L fusion, 108 (35%): R-N fusion
• Follow-up 14±7 yrs
• 49 (16%) had interventions
• Freedom from intervention: 64% R-N vs. 91% R-L
• AS more progressive in R-N pts

24. BAV - AR
Sabet et al. Mayo Clin Proc. 1999 Jan;74(1):14-26
Tzemos et al. JAMA;2008:300;11:1317-1325
Michelena et al CirculaGon. 2008;117:2776-2784.)
Less frequent occurrence than AS
• Surgical series of 542 pts who underwent AVR (1991-1996):
• 13% (pure AR) vs 75% (pure AS)
• Mean age:
• 46 yrs (AR) vs 65 yrs (AS)
Low intervention rates
• Olmsted county (Michelena): 47% had some degree of AR at baseline; 3% had
intervention for severe AR
• Toronto study (Tzemos): 21% had moderate/severe AR at baseline; 6% had
intervention for symptomatic AR
Mechanisms
• Valve prolapse
• Aortic root/annular dilatation
• Endocarditis

25. BAV - Endocarditis
Tzemos et al. JAMA;2008:300;11:1317-1325
Michelena et al CirculaGon. 2008;117:2776-2784.)
Recent studies suggest low incidence:
• Olmsted county:
• 2% per year incidence
• Toronto study:
• 0.3% per year incidence
AHA guidelines no longer suggest bacterial endocarditis
prophylaxis, except if prior history of endocarditis.

26. BAV - Aortopathy
Siu et al. J Am Coll Cardiol 2010;55:2789-800.
Tadros et al. CirculaGon 2009;119:880-90.
Prevalence of Aortic Dilation
• 20% - 84% amongst pts with BAV
• Differences in study populations
• Assessment techniques
• Aortic-size thresholds
• Heterogenous nature of the disease
• Children with BAV have larger ascending aorta & enlarges faster cf matched
tricuspid controls
• All segments of ascending aorta are larger in adults with BAV cf tricuspid
controls
• Independent of BP, peak aortic velocities, LV ejection time
• Prevalence of tubular ascending aorta dilation increases with age:
<30 yrs 30-39yrs 40-49yrs 50-60yrs >60yrs
56% 74% 85% 91% 88%

27. BAV - Aortopathy
Verma et al. NEJM 2014 370;20
Patterns of Aortic Dilation
Type 1: Dilation of tubular ascending aorta primarily
along convexity with mild-moderate root dilation.
Most common; associated with R-L cusp fusion & AS
Type 2: Isolated tubular ascending aorta dilation,
which may extend into the arch, with relative sparing of
aortic root.
Associated with R-N cusp fusion.
Type 3: Root phenotype - isolated root dilation, normal
tubular/arch dimensions.
Rarer; associated with younger age at diagnosis;
genetic.

28. BAV - Aortopathy
Verma et al. NEJM 2014 370;20
Yasuda et al. CirculaGon 2003; 108;supp;291-4
Pathophysiology
Genetic evidence
• Aortopathy prevalent in 1st degree relatives of BAV pts
• Aortic dimension differences in BAV cf controls in spite of
haemodynamic variable adjustments
• Aortic dilation in BAVs (incl. children) without AS/AR
• Progressive aortic dilation with or without AVR
Deficiency of Fibrillin 1;
Increased matrix metalloproteinases -
loss of integrity in extracellular matrix

29. BAV - Aortopathy
Barker et al. Circ Cardiovasc Imaging 2012;5:457-66.
Hope et al. Radiology 2010;255:53-61.
Michelena et al CirculaGon. 2008;117:2776-2784.)
Tzemos et al. JAMA;2008:300;11:1317-1325.
Verma et al. NEJM 2014 370;20
Pathophysiology
Haemodynamic evidence
Recent MRI studies -
• Abnormal transvalvular-flow patterns despite apparent normally
functioning BAVs
• Regional increases in wall-shear stress
However, valve morphology did not predict events in population studies

30. BAV - Aortopathy
Hardikar et al JACC: Cardiovascular Imaging 2013;6;12:1311-20
Robicesk et al. HSR Proc Intensive Care Cardiovasc Anaesth 2012;4:109-18.
Pathophysiology
Robicsek et al: No histological
differences of foetal BAV vs
control aortic tissue
Genetic predilection
compounded by
haemodynamic insults?

31. BAV - Aortopathy
Michelena et al CirculaGon. 2008;117:2776-2784.)
Tzemos et al. JAMA;2008:300;11:1317-1325.
Verma et al. NEJM 2014 370;20
Natural History
Ascending aortic aneurysm:
• At 25yrs: 26% will develop aneurysm
(≥45 mm ascending aorta)
BAV: 84.9/10,000 pt-yrs
All population: 1.04/10,000 pt-yrs
Age-adjusted RR: 86.2

32. BAV - Aortopathy
Hardikar et al JACC: Cardiovascular Imaging 2013;6;12:1311-20
Natural History
Ascending aortic aneurysm:
• Rate of growth higher in persons with BAV c/f tricuspid valve
• Tricuspid: 0.16 mm/yr uniformly over 6 decades
• BAV: 0.20 - 1.9 mm/yr
Accelerating rate of aortic
dimension increase with
increasing age

33. BAV - Aortopathy
Michelena et al. JAMA 2011;306(10):1104-1113
Natural History
Ascending aortic aneurysm: Predictors

34. BAV - Aortopathy
Michelena et al. JAMA 2011;306(10):1104-1113
Tzemos et al. JAMA;2008:300;11:1317-1325.
Natural History
Aortic dissection
• Toronto study:
• 0.1% per pt-yrs over 9yrs
• 5/642 pts (3 type A, 2 type B)
• Olmsted County study:
• At 25yrs: 0.5% risk of dissection
• 2/416 pts (1 type A, 1 type B)
• 3.1 cases/10,000 person-yrs
• Pts >50yrs age: 17.4 cases/10,000 person-yrs
• Baseline aneurysm: 44.9 cases/10,000 person-yrs
• 7% longer-term rate of dissection
• RR 8.4
No dissections when aortic diameter <45mm or
normal functioning aortic valve

35. BAV - Aortopathy
Girdauskas et al. J Thorac Cardiovasc Surg 2014; 147:276-82
Natural History
Aortic dissection
Risk after AVR - 153 BAV pts vs 172 TAV pts:
• 3 dissections over 3566 pt-yrs
• All in TAV group
• Reoperation rates lower in BAV cf TAV: 3% vs 5%

36. BAV - Aortopathy
Natural History
Aortic dissection
Low rates in contemporary series -
• Serial surveillance
• Surgery changes natural history of BAV
Does size really matter?
• Changes in 2014 AHA guidelines reflect the low incidence observed

37. BAV - Management
Surveillance
Class I [AHA]
• Annual aortic imaging if
• Aortic dilation >4.5 cm
• Rapid rate of change in aortic diameter
• Family history of dissection
Screening
• First-degree family members of pts with BAV

38. BAV - Management
Medical
• Scarce evidence of efficacy
• No evidence for altering natural history in BAV
• AHA recommendation
• Dilated aortic root/ascending aorta:
• ACEI/ARB & BB to reduce SBP to the lowest tolerated
levels
• AS/AR:
• Treatment of systemic hypertension
Current trial:
Atenolol and Telmisartan in BAV aortopathy - RCT

39. BAV - Management
Repair of BAV
• Attractive given young cohort of BAV pts with AI
• No RCTs of repair vs replacement
• When to consider:
• Regurgitant valves
• Pliable leaflets
• Minimal fibrosis/calcification
• No more than mild cusp thickening
• Minor fenestrations

40. BAV - Management
Repair of BAV
• Effective height:
• Height to which central free
margin of cusp rises over the
aortic insertion line of cusp
• N = 9-10mm
• Prolapse: <6-7mm

41. BAV - Management
Repair of BAV - Techniques
Restore cusp integrity
• Closing tears/perforations by direct suture or autologous
pericardial patching
Line-up discloses presence of tissue redundancy
Sufficient tissue; closure of cleft
Excess tissue; triangular resection, plication

42. BAV - Management
Repair of BAV - Techniques
Deficient tissue
• Overcorrecting free margin of the conjoint cusp to a length
shorter than free margin of reference cusp
• Increases systolic doming

43. BAV - Management
Repair of BAV - Techniques
Commissural repair
Resuspension of detached commissure
-pledgeted sutures & plication
Misalignment & splaying
-pledgeted oblique Cabrol-like stitch

44. BAV - Management
BAV repair with dilated annulus:
Bavaria et al. STS 2013. Ann Thor Surg.
Aicher et al. CirculaGon 2011;123:178-185

45. BAV - Management
Failure of BAV repair in dilated annulus irrespective of SCA or Remodelling style root
Aicher et al. CirculaGon 2011;123:178-185

46. BAV - Management
Bentall's
Survival similar to age/sex matched controls at 12 yrs
Etz et al. Ann Thorac Surg 2007;84:1186-94

47. BAV - Management
Ross Procedure
Concern regarding intrinsic wall abnormalities of
the pulmonary artery in BAV pts
Etz et al. Ann Thorac Surg 2007;84:1186-94

48. BAV - Management
AHA 2014: Surgical Intervention
Class 1
Diameter of the aortic sinuses or ascending aorta is greater than 5.5 cm [B]
Class 2a
Diameter of the aortic sinuses or ascending aorta is greater than 5.0 cm and a
risk factor for dissection is present (family history of aortic dissection or if the
rate of increase in diameter is 0.5 cm per year) [C]
Replacement of the ascending aorta is reasonable in patients with a bicuspid
aortic valve who are undergoing aortic valve surgery because of severe AS or
AR if the diameter of the ascending aorta is greater than 4.5 cm. [C]