Bicuspid AV & Aortopathy

Dr Cheng He

Cardiothoracic Trainee, Royal Australasian College of Surgeons

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,AmJCardiol1970;26:72-83SieversetalJTCS2007;133:1226-33

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

BAV - Pathogenesis

Padangetal.CircCardiovascGenet.2012;5:569-580.

ClemenGetal.AmJMedGenet1996;62:336-8.Glicketal.AmJCardiol1994;73:400-4.HunGngtonetal.AmJCardiol1997:30;1809.Padangetal.CircCardiovascGenet.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

BAV - Classification

SieversetalJTCS2007;133:1226-33

Surgical - Sievers

BAV - ClassificationEcho - Schaffers

SchaffersetalHeart2008;94:1634–1638

Valve: PS SAX

R+L R+N L+N

BAV - Classification

Kangetal.JACC2013;6:150-61

MDCT - Kang

BAV - ClassificationWhy?

• Valve morphology - Natural history

• Associated aortopathies

• Comparison of reports on BAV

• Appropriate surgical intervention

BAV - DiagnosisAuscultation

• Functionally normal BAV - Ejection murmur/click at LLSB or apex

• Murmurs of AS/AR/Coarctation

BAV - DiagnosisTransthoracic Echo

• Sensitivity 92%, Specificity 96% • Accuracy inverse to calcification

• Findings: • Raphe • Systolic doming & eccentric closure line

(LAX) • Evaluate in systole; raphe may appear

trileaflet

Ayadetal.AmJCardiol2011;108:1589.Diastole Systole

Raphe

Doming

BAV - Natural History• Valvular dysfunction - AS, AR, endocarditis

• Aortopathy

BAV - Natural History

MichelenaetalCirculaGon.2008;117:2776-2784.)

Survival of asymptomatic patients with BAV

Identical to expected survival of matched population

BAV - Natural History

MichelenaetalCirculaGon.2008;117:2776-2784.)

Medical events

BAV - Natural History

MichelenaetalCirculaGon.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 ages49±20 (BAV) vs 67±16 yrs (tricuspid)

No aortic dissections during follow-up

Surgical events

BAV - Natural History

MichelenaetalCirculaGon.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

BAV - Natural History

Tzemosetal.JAMA;2008:300;11:1317-1325.

The largest study (n=642) in symptomatic/asymptomatic BAV pts: 10-year 96% survival

Similar to normal population

BAV - Natural History

Tzemosetal.JAMA;2008:300;11:1317-1325.

Independent predictors of primary cardiac events: Age ≥30 yrs

Moderate/Severe ASModerate/Severe AR

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?

BAV - Natural History• Valvular dysfunction - AS, AR, endocarditis

• Aortopathy

Surgical series of 932 resected aortic valves for AS:

• 49% had BAV

• Age at intervention • BAV: 67±11 • Tricuspid: 74±8

BAV - AS

Robertsetal.CirculaGon.2005;111:920-925.

BAV - AS

Robertsetal.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

BAV - AS

Fernandesetal.JACC2007:2211-4.

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

BAV - AR

Sabetetal.MayoClinProc.1999Jan;74(1):14-26Tzemosetal.JAMA;2008:300;11:1317-1325MichelenaetalCirculaGon.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

BAV - Endocarditis

Tzemosetal.JAMA;2008:300;11:1317-1325MichelenaetalCirculaGon.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.

BAV - Aortopathy

Siuetal.JAmCollCardiol2010;55:2789-800.Tadrosetal.CirculaGon2009;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%

BAV - Aortopathy

Vermaetal.NEJM2014370;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.

BAV - Aortopathy

Vermaetal.NEJM2014370;20Yasudaetal.CirculaGon2003;108;supp;291-4

PathophysiologyGenetic 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

BAV - Aortopathy

Barkeretal.CircCardiovascImaging2012;5:457-66.Hopeetal.Radiology2010;255:53-61.MichelenaetalCirculaGon.2008;117:2776-2784.)Tzemosetal.JAMA;2008:300;11:1317-1325.Vermaetal.NEJM2014370;20

PathophysiologyHaemodynamic 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

BAV - Aortopathy

HardikaretalJACC:CardiovascularImaging2013;6;12:1311-20Robicesketal.HSRProcIntensiveCareCardiovascAnaesth2012;4:109-18.

Pathophysiology

Robicsek et al: No histological differences of foetal BAV vs

control aortic tissue

Genetic predilection compounded by

haemodynamic insults?

BAV - Aortopathy

MichelenaetalCirculaGon.2008;117:2776-2784.)Tzemosetal.JAMA;2008:300;11:1317-1325.Vermaetal.NEJM2014370;20

Natural HistoryAscending 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

BAV - Aortopathy

HardikaretalJACC:CardiovascularImaging2013;6;12:1311-20

Natural HistoryAscending 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

BAV - Aortopathy

Michelenaetal.JAMA2011;306(10):1104-1113

Natural HistoryAscending aortic aneurysm: Predictors

BAV - Aortopathy

Michelenaetal.JAMA2011;306(10):1104-1113Tzemosetal.JAMA;2008:300;11:1317-1325.

Natural HistoryAortic 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

BAV - Aortopathy

Girdauskasetal.JThoracCardiovascSurg2014;147:276-82

Natural HistoryAortic 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%

BAV - AortopathyNatural HistoryAortic 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

BAV - ManagementSurveillanceClass 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

BAV - ManagementMedical• 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

BAV - ManagementRepair 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

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

BAV - ManagementRepair of BAV - TechniquesRestore 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

BAV - ManagementRepair of BAV - TechniquesDeficient tissue • Overcorrecting free margin of the conjoint cusp to a length

shorter than free margin of reference cusp • Increases systolic doming

BAV - ManagementRepair of BAV - TechniquesCommissural repair

Resuspension of detached commissure -pledgeted sutures & plication

Misalignment & splaying -pledgeted oblique Cabrol-like stitch

BAV - ManagementBAV repair with dilated annulus:

Bavariaetal.STS2013.AnnThorSurg.Aicheretal.CirculaGon2011;123:178-185

BAV - ManagementFailure of BAV repair in dilated annulus irrespective of SCA or Remodelling style root

Aicheretal.CirculaGon2011;123:178-185

BAV - ManagementBentall's

Survival similar to age/sex matched controls at 12 yrs

Etzetal.AnnThoracSurg2007;84:1186-94

BAV - Management

Ross ProcedureConcern regarding intrinsic wall abnormalities of the pulmonary artery in BAV pts

Etzetal.AnnThoracSurg2007;84:1186-94

BAV - ManagementAHA 2014: Surgical Intervention Class 1Diameter of the aortic sinuses or ascending aorta is greater than 5.5 cm [B]

Class 2aDiameter 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]