RE

VIE

W

Review

Management of the Ascending Aorta in Patientswith Bicuspid Aortic Valve Disease

Michael P. Vallely, PhD, FRACS a,∗, Christopher Semsarian, PhD, FRACP b,c,d andPaul G. Bannon, PhD, FRACS a,d,e

a The Baird Institute, Sydney, Australiab Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia

c Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australiad Central Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia

e Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital, Sydney, Australia

Bicuspid aortic valve (BAV) disease is the most common form of congenital heart disease, affecting 1–2% of thepopulation. Only 20% of patients will maintain normal valve function throughout their life and more than 30% of patientswill develop serious morbidity. It is a highly heritable condition, with transmission likely to be autosomal dominant.Patients with BAV have a 10-fold risk of aortic dissection when compared to the normal population. Management of BAVassociated aortopathy represents a significant clinical challenge.

(Heart, Lung and Circulation 2008;17:357–363)© 2008 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New

K

I

Bicos

caraB

P

Btftlmsc

R2

∗E

©A

Zealand. Published by Elsevier Inc. All rights reserved.

eywords. Bicuspid aortic valve; Aortic dissection

ntroduction

icuspid aortic valve (BAV) disease occurs in 1–2% of thepopulation.1,2 It is the most common form of congen-

tal heart disease, compared to 0.8% for all other formsombined, and also results in more morbidity than allther congenital heart disease combined.3,4 BAV may beporadic or familial, with a 4:1 male predominance.5

More than 35% of patients with BAV will develop seriousomplications including aortic dissection, endocarditis,ortic stenosis and aortic regurgitation requiring valveeplacement.6 In patients older than age 15 years havingortic valve replacement, more than 50% of them will haveAV disease.7,8

athophysiology

icuspid aortic valves are the result of abnormal aor-ic cusp formation during valvulogenesis. Adjacent cuspsuse to form a single aberrant cusp, larger than its coun-erpart, yet smaller than two normal cusps combined. Theeaflets are usually oriented right to left with the true com-

issures oriented anterior and posterior. There can beignificant morphological variability in the BAV.9,10 Mostommonly the right and left coronary leaflets comprise the

larger fused leaflet and the non-coronary leaflet is separatewith true commissures. The coronary arteries usually arisein front of the cusp with a raphe.6,11 Bicuspid valves arelikely to be the result of a complex developmental process,not simply the fusion of two normal cusps. Congenitalaortic valve malformations may reflect a continuum ofpathology. Unicuspid valves may represent a more severeform of bicuspid disease. This is reflected by earlier onsetof aortic valve related symptoms and an 18-fold increasedrisk of aortic dissection when compared to case-matchedcontrols.6,12 Endocardial cushion defects and neural crestabnormalities may contribute to the severity of valvularand aortic complications in these patients.13

Only 20% of patients with a congenitally bicuspid aorticvalve will maintain a normally functioning valve through-out life.1 More than 30% of patients will develop seriousmorbidity throughout their life. Patients may develop pro-gressive calcification and stenosis. BAV disease is themajor cause of pure aortic stenosis in most series.3,14

Patients may develop pure regurgitation with or withoutinfection (40–60% of severe aortic regurgitation in the BAVpopulation is secondary to infective endocarditis).8 Thirtypercent of patients with a BAV will develop endocarditisin their lifetime.3,15 A bicuspid valve is present in 7–13%of unselected cases of aortic dissection.16,17 Importantly,

eceived 14 September 2007; received in revised form 5 December007; accepted 23 January 2008; available online 29 May 2008

aortic dissection usually occurs in the presence of a nor-mally functioning bicuspid aortic valve, having a 9–12-foldi 18

t

onsl righ

Corresponding author. Tel.: +61295502350.-mail address: michael.vallely@bigpond.com (M.P. Vallely).

2008 Australasian Society of Cardiac and Thoracic Surgeustralia and New Zealand. Published by Elsevier Inc. Al

ncreased risk of Stanford Type A aortic dissection.Bicuspid aortic valves have a heterogenous presentation

hat is age related. While some patients will present early

and the Cardiac Society ofts reserved.

1443-9506/04/$30.00doi:10.1016/j.hlc.2008.01.007

RE

VIE

W

358 Vallely et al. Heart, Lung and CirculationAscending aorta in patients with BAV disease 2008;17:357–363

with symptoms of aortic valve disease (angina, dyspnoeaand syncope) many patients will remain asymptomaticuntil late in life.19 Paediatric patients tend to presentwith aortic stenosis or endocarditis. Young adults presentwith pure aortic regurgitation, with or without endocardi-tis. There may be a subset of young patients with aorticregurgitation that may be at higher risk for aortic com-plications, including aortic root dilatation.20 Middle ageadults present with aortic dilatation and/or aortic dissec-tion or aortic stenosis. Elderly patients present with aorticstenosis.12

The nature of the valve lesion is different betweenpatients. Importantly, the severity of the aortic diseaseis different according to the type of valve lesion. Patientswith pure aortic incompetence have a higher rate of sinusdilatation than patients with stenotic disease.21 This groupof patients represents approximately 15% of patients withBAV disease.1

Genetics and Bicuspid Aortic Valve Disease

Several family-based studies have shown that BAVdisease, either alone or in combination with other cardio-vascular malformations, can be inherited in families, andis therefore likely to have a genetic basis. Most family stud-ies suggest inheritance is autosomal dominant, i.e. thereis a 50% chance an affected person with BAV passing on

an isolated VSD or Turner’s syndrome will have a BAV.27

Bicuspid pulmonary valve disease is common and hasimplications for the Ross procedure.28,29 Coronary anoma-lies are common (short left main coronary artery, 90% leftdominant coronary anatomy) and have implications forsurgery.30 Patients with congenital left ventricular outflowtract obstruction (Shone’s complex and others) are likelyto have relatives with BAV disease.31

BAV Disease and the Aorta

The exact cause of BAV disease remains unknown. Itis clearly a complex developmental process rather thanjust a case of simple cusp fusion. Cardiac cushion defor-mities may affect the valve cusps, the aortic root andthe ascending aorta. Neural crest abnormalities, deficien-cies in endothelial derived nitric oxide synthase (eNOS),fibrillin-1 deficiencies and increased matrix metallopro-teinase (MMP) levels and activity have all been implicatedin the development of BAV disease and associated aorticabnormalities.6

The natural history of aortic rupture is clearly relatedto the size of the aorta. Elefteriades and co-workers haveproduced several articles showing increased rupture ratesof the ascending aorta with aortic dimensions greater than60 mm.32 In a more recent article from the same authors,the natural history of patients (n = 514) with ascending

the disease to his/her offspring.In an echocardiography study of 50 patients with known

BAV disease, Cripe et al. screened 309 patients (includ-ing relatives). Seventy-four patients (24% prevalence; 89%inheritance) had a BAV. Ninety-seven patients (31% preva-lence) had a BAV and/or other congenital cardiac anomaly(74% inheritance). BAV disease was almost entirely geneticin this population with a pattern of inheritance sugges-tive of autosomal dominant transmission with variablepenetrance.5

The specific genetic basis of BAV and the associatedaortopathy has not been identified. Several family-basedstudies have identified chromosomal regions linked to dis-ease without identification of the causative gene to date.In a genetic study of 10 families with BAV and aorticaneurysms, Goh et al. demonstrated linkages to chromo-some 15 in 9 out of the 10 families.22 Most recently, Martinet al. have also identified three additional chromosomalloci (5, 13 and 18) linked to BAV associated with other car-diovascular malformations (but not aortopathy).23 Morerecently, McKellar et al. identified NOTCH 1 variants in10% of patients with BAV and thoracic aortic aneurysmscompared to only 2% of patients with TAV and thoracicaortic aneurysms.24

Collectively, based on family and genetic studies to date,the screening of at least first-degree and possibly second-degree relatives of patients with BAV disease should beconsidered.5

Bicuspid aortic valve disease is usually an isolateddefect. However, 20–50% of patients will have an addi-tional cardiovascular anomaly.25 Fifty percent of patientswith coarctation of the aorta, and 30% with an interruptedaortic arch will have a BAV.26 Up to 30% of patients with

aortic aneurysms (>35 mm) and tricuspid (n = 451; 86.6%)or bicuspid aortic valves (n = 70; 13.4%) were followed.Patients with BAV had higher growth rates (1.9 mm peryear) than patients with TAV (1.3 mm per year). A signif-icantly greater percentage of patients with BAV (78.8%)underwent replacement of their ascending aorta thanpatients with a TAV (44.8%; p < 0.0001). The BAV patientswere significantly younger than the TAV patients (48.9 vs.63.1 years). BAV related aortic stenosis was a negative pre-dictor for adverse aortic events.33

However, aortic dissection can (and often does) occur inpatients with aortic dimensions well under 60 mm. TypeA aortic dissection is a catastrophic event, with a 75%two-week mortality without surgical treatment.34 How-ever, the surgical management of acute type A dissectionis improving. Recent Australasian data has shown dra-matic improvements in the surgical management of acutetype A dissection. Surgical mortality in the early 1970s wasgreater than 50%, whilst mortality after 2000 has reducedto 11%.35 This data compares very favourably with recentdata from the International Registry of Acute Aortic Dis-section which reports surgical mortality varying from 7%to 30% between surgeons and surgical centres.34,36

In an autopsy study of patients with Type A aortic dissec-tion Neri et al. examined 220 patients including 94 patientswith a connective tissue disorder including BAV disease(mean aortic diameter, 41.8 mm) and 126 without a con-nective tissue disorder (mean aortic diameter, 41.3 mm).The authors demonstrated that aortic dissection occurredin one third of patients with a normal aortic diameter. Fifty-seven percent of patients had an aortic diameter greaterthan 40 mm and only 10% of patients had a true aneurysm.The authors concluded that dissection super-imposing on

RE

VIE

W

Heart, Lung and Circulation Vallely et al. 3592008;17:357–363 Ascending aorta in patients with BAV disease

near-normal aortic size might be an expression of func-tional wall changes other than dilatation.37

In an echo series of 139 patients with aortic dissection,Epperlein et al. demonstrated that 5/79 (6.3%) of patientswith Type A dissection had a BAV, representing a nine-foldrisk on the normal population. In contrast only 1/60 (1.7%)of the patients with a Type B dissection had BAV. This ishighly suggestive that BAV may affect the ascending aortapreferentially.17

There are two broad theories as to the cause of aorticdilatation in patients with aortic valve disease. The first ofthese theories is that ascending aortic dilatation may bea consequence of blood flow turbulence. This is thoughtto disturb vascular endothelial cells, which leads to apop-tosis and atherosclerosis in the aortic wall causing aorticdilatation.38 However, there is a growing body of evidencethat suggests a common pathogenic mechanism under-lying both bicuspid valve formation and its associatedaortopathy. This evidence includes:

(1) Patients with haemodynamically normal BAV havelarger aortic root and ascending aorta diameters thanpatients with normal tricuspid aortic valves.39

(2) BAV patients exhibit more histological abnormalitiesincluding cystic medial necrosis and apoptosis in theascending aorta media than patients with tricuspidaortic valves.40

(3) A reduced extracellular matrix components and

(

(

sGniooIprcsg

pasaaTo

B

nificant valvular lesions, Ferencik examined progressivedilatation of the aortic annulus, sinuses, sino-tubular junc-tion and the proximal ascending aorta. Progression ofaortic dilatation was independent of the presence of valvu-lar dysfunction. The proximal ascending aorta showed anincreased rate of dilatation when compared to the othersites. Therefore, it would appear that the proximal aorta ismost vulnerable to dilatation in BAV disease and the proxi-mal ascending aorta is the site of most type A dissections.46

This study has significance when examining the merits ofreplacing the whole aortic root or just the ascending aortain patients with BAV disease.

Yasuda and co-workers compared patients undergoingaortic valve replacement for aortic stenosis. They demon-strated that patients with tricuspid valves who underwentaortic valve replacement had regression of their aorticdilatation, suggesting that post-stenotic dilatation in thissetting has a predominantly haemodynamic pathogenesis.However, patients with BAV disease demonstrated pro-gression of their aortic dilatation, irrespective of whetherthey had their valve replaced or not. This suggests anintrinsic abnormality of the aortic wall causing aorticdilatation in the BAV group.43

In a similar study by Russo et al., the authors com-pared 50 patients with BAV (mean aortic diameter, 48 mm)undergoing AVR with 50 patients with TAV (mean aorticdiameter, 36 mm) undergoing AVR. In the BAV group, fivepslaed

B

Tcahtitaowhmmtc

B

Ccfsow

increased matrix degradation enzymes in the aorta ofBAV patients.41,42

4) BAV disease has high heritability with determinationbeing almost entirely genetic.5

5) Ascending aortic dilatation can occur even after thevalve is replaced, which is in contrast to patients witha tricuspid valve who demonstrate reduction in aorticsize over time after replacement of their haemodynam-ically significant valve.43

Greater than 50% of patients with BAV will demon-trate aortic dilatation. In an echocardiography study,urvitz et al. compared 76 children with BAV to 41ormal controls. Aortic root dilatation was significantly

ncreased in patients with BAV disease (with and with-ut haemodynamically significant lesion aortic stenosisr regurgitation) when compared to the control group.44

n another echocardiography study, Ben-Dor et al. com-ared the ascending aorta of 88 patients with degenerative,heumatic or bicuspid aortic stenosis to a group ofontrol patients. Patients with BAV aortic stenosis hadignificantly larger ascending aortas than the otherroups.45

In a large echocardiography-based series of 41,000atients from the University of Pennsylvania (patients withortic root pathology such as endocarditis and Marfan’syndrome were excluded), patients with BAV disease (118fter exclusions) were compared to the matched (for agend severity of the valve lesion) tricuspid valve controls.he degree of aortic dilatation in the BAV group was outf proportion to the severity of the valvular lesion.39

In an echocardiography-based study of 68 patients withAV disease, with and without haemodynamically sig-

atients suffered late aortic dissection and seven patientsuffered late sudden death. There were no incidents ofate-dissection or sudden death in the TAV group. Theuthors recommended an aggressive policy of replacingven normal looking ascending aortas in patients with BAVisease.47

AV and Other Aortic Anomalies

he association with other aortic anomalies reflects theontinuum of the aortic disease. In a study by Oliver etl. of 235 adults with coarctation, 57% of the patientsad a BAV. Thirty-seven patients developed serious aor-

ic complications. The prevalence of aortic complicationsn the BAV group was 22% compared to only 8% ofhe patients without a BAV. Aortic complications of BAVccount for 86% of ascending aortic aneurysms and 70%f descending aortic aneurysms, with 80% of the patientsith aneurysm recurrence at the coarctation repair siteaving a BAV. The combination of coarctation and BAVay represent a more extensive neural crest origin abnor-ality. Patients with both conditions co-existing should be

reated more aggressively to prevent catastrophic aorticomplications.48

AV and Marfan’s Aortopathy

ystic medial degeneration is the pathological entity asso-iated with BAV disease. Pathological observations includeragmentation and loss of elastic fibres, coagulative necro-is of medial smooth muscle, loss of cell nuclei and collapsef elastic lamellae and medial pooling of glycoproteinhich leads to intramedial aortic dissection.49

RE

VIE

W

360 Vallely et al. Heart, Lung and CirculationAscending aorta in patients with BAV disease 2008;17:357–363

While Marfan’s disease has many features in commonwith BAV disease, there are many differences. Fibrillin-1deficiency is a common defect. However, there are differ-ences in the expression of the subtypes of MMP enzymesbetween the two conditions (MMP-2 in BAV, MMP-9 inMarfan’s).42 The phenotypic expression is different. Mar-fan’s patients tend to have aortic sinus dilatation, whilstBAV patients demonstrate dilatation above the sinotubu-lar junction.50 Consequently aortic dissection occurs in40% of patients with Marfan’s and only 5% of patientswith BAV. However, because BAV is far more common thanMarfan’s, BAV is the underlying pathology in more casesof aortic dissection.51

Surgical Options for the Ascending Aorta in BAVDisease

In the setting of abnormal valve function, aortic valvereplacement is indicated. There are several options avail-able to patients with ascending aortic dilatation in thepresence of BAV disease. These include:

• Reduction aortoplasty, with or without wrap augmenta-tion.

• Supra-sinus ascending aorta replacement.• Ascending aorta replacement with sinus resection and

remodelling.• Valve sparing root replacement.

(2) Aorta 40–45 mm.(3) Aorta 45–50 mm.

The authors noted that there was a significantly higherincidence of aortic complications at 15 years in the groupof patients with aortas greater than 45 mm (>45 mm: 43%;40–45 mm: 78%; <40 mm: 81% freedom from ascendingaortic complications). This correlated with decreased sur-vival in this group.53

Patients with connective tissue diseases that culminatein aortic pathology tend to be younger than those patientswith atherosclerotic and/or hypertensive aortic pathol-ogy. Elective aortic procedures can be performed with lowmortality in these groups. This is highlighted in a studyof 675 patients undergoing elective aortic root replace-ment for Marfan’s syndrome related aortic pathology in 10high-volume aortic centres in North America. The electivemortality was 1.5% (7/455 patients) and the emergent mor-tality was 11.7% (12/103 patients). The eight-fold increasein mortality in the emergent group highlights the need forpreventative surgery.54

Aortic root replacement using the modified Bentallapproach with re-implantation of the coronary arteriesas buttons is a reproducible procedure with excellentlong-term results. In a European study of 72 aorticroot replacements performed over 20 years, the authorsreported a 0% elective (53/72) 30-day mortality and a

• Aortic root replacement with a valved conduit.o Mechanical valve.o Stented xenograft.

- Porcine.- Pericardial.

o Stentless xenograft.- Porcine.

o Allograft.o Pulmonary autograft (Ross procedure).

In a study from the Cleveland Clinic of 430 patients witha BAV, the risk of aortic dissection was 12.5% with an aor-tic size less than 50 mm. Patients with Marfan’s syndromeand an aortic diameter less than 50 mm had a 15% risk ofdissection, a rate not dissimilar to those with BAV aortopa-thy. The authors suggested that if all patients with an aorticdiameter greater than 40 mm had their ascending aortareplaced then 95% of dissections would be avoided.51

In a prospective study of 35 patients (20 patients withBAV) undergoing aortic valve replacement with aorticdiameters greater than 40 mm the authors noted that 5patients had a subsequent aortic event. The recommenda-tion arising from this paper is for all patients undergoingAVR with an ascending aorta greater than 40 mmshould have their ascending aorta replaced at the sametime.52

In a study from Dr. Tirone David’s group, 201 patientswith BAV disease and ascending aorta less than 50 mmundergoing AVR were followed. Patients with an aortagreater than 50 mm had their aorta replaced. The studypatients were divided into three groups:

(1) Aorta <40 mm (normal aorta).

21% emergent (19/72) 30-day mortality. Long-term resultsincluded a 91% freedom from death at 16 years with 0%endocarditis, thrombosis, haemorrhage or structural valvedeterioration.55 This study clearly demonstrates the ben-efits of elective surgery and the longevity achievable witha composite graft.

The relative preservation of the sinuses in the BAV aor-topathy may indicate that replacement of the ascendingaorta with or without sinus remodelling may eliminate theneed for a formal aortic root replacement and its associ-ated increased morbidity.51 In a 30-year review (1965–1995)by the Stanford group, patients undergoing treatment foraortic valve disease and aortic aneurysm or aortic dissec-tion (n = 390) with ascending aortic replacement (n = 255) oraortic root replacement (n = 135) were studied. The authorsreported improvements in morbidity and mortality associ-ated with aortic surgery in that time (15% for whole series,7% for last decade). There have been even further improve-ments in the last decade.

The authors observed no differences in early or latemortality between the two groups. The seven patients inthe ascending aorta replacement group who required re-operation for sinus of Valsalva aneurysms were noted tohave gross sinus dilatation at the time of their initial opera-tion. In this group of patients, the current recommendationwould be to perform an aortic root replacement at thetime of the initial operation. The authors also observedno difference in the two groups at early or late follow-up. However, they did recommend sinus resection withpreservation of tongues of aorta around the coronary ostiafor patients undergoing ascending aortic replacement.56

In a similar, smaller study of 45 patients, Sundt etal. demonstrated no difference in the management of

RE

VIE

W

Heart, Lung and Circulation Vallely et al. 3612008;17:357–363 Ascending aorta in patients with BAV disease

patients with a haemodynamically significant BAV andassociated dilated ascending aorta with a composite graftaortic root replacement or a valve and ascending aorticreplacement.57

Reduction ascending aortoplasty is a controversial treat-ment for dilatation of the ascending aorta in the presenceof aortic valve disease. In a recent study, the authors exam-ined 68 patients with a mean aortic diameter of 50.9 ± 7 mmundergoing reduction aortoplasty. Only 10 patients in thestudy had BAV disease, which limits the power of the study.The authors suggested that BAV was not a predictor of lateaortic events after reduction aortoplasty.58

However, in a recent review article on reduction aorto-plasty, Robicsek made two important observations. Firstly,he recommended that the technique not to be used inpatients with cystic medial degeneration, which is thepathology of the aortic dilatation seen in patients withBAV disease. Secondly, reduction aortoplasty does noteliminate the risk of type A dissection, that resectionand replacement of the ascending aorta virtually does.59

Therefore, we should question the role of reduction aor-toplasty in patients with BAV associated aortic dilatation.

Pulmonary autograft (Ross procedure) replacement ofthe aortic root for aortic root dilatation in the setting ofBAV disease remains controversial. The incidence of bicus-pid pulmonary valve disease is high in these patients.28

This has implications for long-term valve function and ford 29

ts

apae

pcmtoarrtr

itmooeTtpnivg

Recommendations for Australian Surgical Practice

Management of the aorta in bicuspid aortic valve dis-ease remains controversial. Resection of the ascendingaorta will eliminate the vast majority of patients fromthe risk of type A dissection. This risk must of coursebe balanced against the risk of aortic surgery. Datafrom the Australian Institute for Health and Welfaresuggests that aortic root replacement, even in the elec-tive setting, does not have the same low mortality aswe see from the large volume North American units(5.6% vs. 1.5%).54,64 Therefore, recommendations for theaverage volume unit in the Australian environment areneeded.

The relative sparing of the aortic sinuses in bicuspidaortic valve disease and the proven long-term benefits ofreplacing the ascending aorta in patients with BAV diseasemay reduce the necessity of aortic root replacement in thissetting.

In terms of clinical evaluation, the growing evidence fora familial genetic basis in BAV disease should warrant athorough family history to be taken, and consideration ofclinical screening of at least all first-degree relatives of theBAV affected patient.

Recommendations for the management of the BAVascending aorta in the Australian environment are as fol-lows.

N

Puetu

dgdwm

A

Irrt

rfrf

pymamt

ilatation of the pulmonary autograft. It is a procedurehat should be used highly selectively and in high volume,pecialised centres.

A “watch and wait” policy for patients with ascendingortas over 40 mm in the setting of BAV disease exposes theatient to the risk of aortic dissection and to re-operativeortic surgery with its high mortality (particularly in themergent setting).60

Aortic root and ascending aortic replacement afterrevious cardiac surgery remains a very challenging pro-edure with a high mortality. In high-volume centres,ortality has improved. In a recent North American series,

he authors reported 147 patients who underwent re-perations on the ascending aorta and aortic root with5.4% mortality.61 However, this is contrasted with a

ecent European study of 56 patients undergoing aorticoot replacement after previous surgical intervention onhe aortic valve, aortic root or ascending aorta. The authorseported an in-hospital mortality of 17% in this series.62

In a recent European study of 73 patients undergo-ng re-operations on the ascending aorta or aortic root,he elective 30 day mortality was 8% whilst the emergent

ortality was 35%.63 In a published series from our unitf patients having aortic root replacements after previ-us cardiac surgery, we reported an 11% (3/26) 30-daylective mortality with a 100% (6/6) emergent mortality.60

hese two studies highlight the disparity between mor-ality associated with elective and emergent re-operativerocedures on the ascending aorta and aortic root. Theeed for elective first time replacement of the ascend-

ng aorta or aortic root or a planned reintervention isital in ensuring acceptable mortality figures in thisroup.

ormal Bicuspid Aortic Valve Function

atients with normal bicuspid aortic valve function shouldndergo ascending aortic replacement with sinus remod-lling if the aorta is greater than 45 mm in diameter. Ifhe aortic sinuses are abnormal then the patient shouldndergo an aortic root replacement.The mechanical valved conduit remains the gold stan-

ard for this procedure. However, consideration can beiven for xenograft, homograft or valve sparing proce-ures to avoid Warfarin. Provision for safe re-do surgery,ith closure of the pericardium or the use of a pericardialembrane, should be made in this setting.

bnormal Bicuspid Aortic Valve Function

n the setting of abnormal bicuspid aortic valve functionequiring aortic valve replacement we would recommendeplacement of the ascending aorta if the aorta is greaterhan 40 mm in diameter.

In the setting of normal aortic sinuses then a sinusemodelling ascending aortic replacement should be per-ormed. In the setting of abnormal sinuses, then an aorticoot replacement with a valved conduit should be per-ormed.

Consideration should also be given to stratifyingatients according to their valve lesion. For example,oung patients with pure aortic incompetence have auch higher dissection risk and rate of root aneurysms

nd consideration should be given to elective root replace-ent in these patients, irrespective of the dimensions of

he ascending aorta.

RE

VIE

W

362 Vallely et al. Heart, Lung and CirculationAscending aorta in patients with BAV disease 2008;17:357–363

Endovascular treatment of the descending thoracicaorta in the acute and chronic setting is becoming moreincreasingly utilised. The role of endovascular techniquesin the management of disease in the ascending thoracicaorta remains controversial. With future developmentsthese techniques may become more widely applicable tothe management of ascending aortic aortopathy.34

Conclusion

Bicuspid aortic valve disease remains a common condi-tion seen in Australian cardiothoracic surgical practice.The associated aortopathy and predisposition to aorticdissection (with or without aortic dilatation) remains achallenging clinical problem.

References

1. Roberts WC. The congenitally bicuspid aortic valve. A studyof 85 autopsy cases. Am J Cardiol 1970;26(1):72–83.

2. Basso C, Boschello M, Perrone C, Mecenero A, Cera A, BicegoD, Thiene G, De Dominicis E. An echocardiographic survey ofprimary school children for bicuspid aortic valve. Am J Cardiol2004;93(5):661–3.

3. Ward C. Clinical significance of the bicuspid aortic valve. Heart2000;83(1):81–5.

4. Wauchope G. The clinical significance of variations in the

14. Roberts WC, Ko JM. Frequency by decades of unicuspid,bicuspid, and tricuspid aortic valves in adults having isolatedaortic valve replacement for aortic stenosis, with or withoutassociated aortic regurgitation. Circulation 2005;111(7):920–5.

15. Lewis T, Grant RT. Observations relating to subacute infectiveendocarditis. Heart 1928;10:21–9.

16. Januzzi JL, Isselbacher EM, Fattori R, Cooper JV, Smith DE,Fang J, Eagle KA, Mehta RH, Nienaber CA, Pape LA. Charac-terizing the young patient with aortic dissection: results fromthe International Registry of Aortic Dissection (IRAD). J AmColl Cardiol 2004;43(4):665–9.

17. Epperlein S, Mohr-Kahaly S, Erbel R, Kearney P, Meyer J.Aorta and aortic valve morphologies predisposing to aor-tic dissection. An in vivo assessment with transoesophagealechocardiography. Eur Heart J 1994;15(11):1520–7.

18. Larson EW, Edwards WD. Risk factors for aortic dissection: anecropsy study of 161 cases. Am J Cardiol 1984;53(6):849–55.

19. Lewin MB, Otto CM. The bicuspid aortic valve: adverse out-comes from infancy to old age. Circulation 2005;111(7):832–4.

20. Della Corte A, Bancone C, Quarto C, Dialetto G, Covino FE,Scardone M, Caianiello G, Cotrufo M. Predictors of ascendingaortic dilatation with bicuspid aortic valve: a wide spectrum ofdisease expression. Eur J Cardiothorac Surg 2007;31(3):397–404,discussion 404-5.

21. Pachulski RT, Chan KL. Progression of aortic valve dysfunc-tion in 51 adult patients with congenital bicuspid aortic valve:assessment and follow up by Doppler echocardiography. BrHeart J 1993;69(3):237–40.

22. Goh DLHLF, Judge DP. Linkage of familial bicuspid aorticvalve with aortic aneurysm to chromosome. Am Soc Hum Genet

number of cusps forming the aortic and pulmonary valves.Quart J Med 1928;21:383–99.

5. Cripe L, Andelfinger G, Martin LJ, Shooner K, BensonDW. Bicuspid aortic valve is heritable. J Am Coll Cardiol2004;44(1):138–43.

6. Fedak PW, Verma S, David TE, Leask RL, Weisel RD, ButanyJ. Clinical and pathophysiological implications of a bicuspidaortic valve. Circulation 2002;106(8):900–4.

7. Beppu S, Suzuki S, Matsuda H, Ohmori F, Nagata S, Miy-atake K. Rapidity of progression of aortic stenosis in patientswith congenital bicuspid aortic valves. Am J Cardiol 1993;71(4):322–7.

8. Roberts WC, Ko JM, Moore TR, Jones 3rd WH. Causes of pureaortic regurgitation in patients having isolated aortic valvereplacement at a single US tertiary hospital (1993–2005). Cir-culation 2006;114(5):422–9.

9. Angelini A, Ho SY, Anderson RH, Devine WA, ZuberbuhlerJR, Becker AE, Davies MJ. The morphology of the normal aor-tic valve as compared with the aortic valve having two leaflets.J Thorac Cardiovasc Surg 1989;98(3):362–7.

10. Fernandes SM, Sanders SP, Khairy P, Jenkins KJ, GauvreauK, Lang P, Simonds H, Colan SD. Morphology of bicuspidaortic valve in children and adolescents. J Am Coll Cardiol2004;44(8):1648–51.

11. Sabet HY, Edwards WD, Tazelaar HD, Daly RC. Congenitallybicuspid aortic valves: a surgical pathology study of 542 cases(1991–1996) and a literature review of 2,715 additional cases.Mayo Clin Proc 1999;74(1):14–26.

12. Borger MA, David TE. Management of the valve and ascend-ing aorta in adults with bicuspid aortic valve disease. SeminThorac Cardiovasc Surg 2005;17(2):143–7.

13. Kappetein AP, Gittenberger-de Groot AC, Zwinderman AH,Rohmer J, Poelmann RE, Huysmans HA. The neural crestas a possible pathogenetic factor in coarctation of the aortaand bicuspid aortic valve. J Thorac Cardiovasc Surg 1991;102(6):830–6.

2002;(71):A239.23. Martin LJ, Ramachandran V, Cripe LH, Hinton RB, Andelfin-

ger G, Tabangin M, Shooner K, Keddache M, Benson DW.Evidence in favor of linkage to human chromosomal regions18q, 5q and 13q for bicuspid aortic valve and associated car-diovascular malformations. Hum Genet 2007;121(2):275–84.

24. McKellar SH, Tester DJ, Yagubyan M, Majumdar R, AckermanMJ, Sundt 3rd TM. Novel NOTCH1 mutations in patients withbicuspid aortic valve disease and thoracic aortic aneurysms. JThorac Cardiovasc Surg 2007;134(2):290–6.

25. Braverman AC, Guven H, Beardslee MA, Makan M, KatesAM, Moon MR. The bicuspid aortic valve. Curr Probl Cardiol2005;30(9):470–522.

26. Duran AC, Frescura C, Sans-Coma V, Angelini A, Basso C,Thiene G. Bicuspid aortic valves in hearts with other congen-ital heart disease. J Heart Valve Dis 1995;4(6):581–90.

27. Miller MJ, Geffner ME, Lippe BM, Itami RM, Kaplan SA,DiSessa TG, Isabel-Jones JB, Friedman WF. Echocardiogra-phy reveals a high incidence of bicuspid aortic valve in Turnersyndrome. J Pediatr 1983;102(1):47–50.

28. Niwa K, Perloff JK, Bhuta SM, Laks H, Drinkwater DC, ChildJS, Miner PD. Structural abnormalities of great arterial wallsin congenital heart disease: light and electron microscopicanalyses. Circulation 2001;103(3):393–400.

29. David TE, Omran A, Ivanov J, Armstrong S, de Sa MP, Sonnen-berg B, Webb G. Dilation of the pulmonary autograft after theRoss procedure. J Thorac Cardiovasc Surg 2000;119(2):210–20.

30. Hutchins GM, Nazarian IH, Bulkley BH. Association of leftdominant coronary arterial system with congenital bicuspidaortic valve. Am J Cardiol 1978;42(1):57–9.

31. Bolling SF, Iannettoni MD, Dick 2nd M, Rosenthal A, BoveEL. Shone’s anomaly: operative results and late outcome. AnnThorac Surg 1990;49(6):887–93.

32. Elefteriades JA. Natural history of thoracic aortic aneurysms:indications for surgery, and surgical versus nonsurgical risks.Ann Thorac Surg 2002;74(5):S1877–80 (discussion S1892-8).

RE

VIE

W

Heart, Lung and Circulation Vallely et al. 3632008;17:357–363 Ascending aorta in patients with BAV disease

33. Davies RR, Kaple RK, Mandapati D, Gallo A, Botta Jr DM,Elefteriades JA, Coady MA. Natural history of ascending aor-tic aneurysms in the setting of an unreplaced bicuspid aorticvalve. Ann Thorac Surg 2007;83(4):1338–44.

34. Atkins Jr MD, Black 3rd JH, Cambria RP. Aortic dissec-tion: perspectives in the era of stent-graft repair. J Vasc Surg2006;43(Suppl A):30A–43A.

35. Suehiro K, Pritzwald-Stegmann P, West T, Kerr AR, HaydockDA. Surgery for acute type a aortic dissection a 37-year expe-rience in Green Lane Hospital. Heart Lung Circ 2006;15(2):105–12.

36. Trimarchi S, Nienaber CA, Rampoldi V, Myrmel T, SuzukiT, Mehta RH, Bossone E, Cooper JV, Smith DE, MenicantiL, Frigiola A, Oh JK, Deeb MG, Isselbacher EM, Eagle KA.Contemporary results of surgery in acute type A aortic dis-section: The International Registry of Acute Aortic Dissectionexperience. J Thorac Cardiovasc Surg 2005;129(1):112–22.

37. Neri E, Barabesi L, Buklas D, Vricella LA, Benvenuti A, TucciE, Sassi C, Massetti M. Limited role of aortic size in the gen-esis of acute type A aortic dissection. Eur J Cardiothorac Surg2005;28(6):857–63.

38. Freyberg MA, Kaiser D, Graf R, Buttenbender J, Friedl P.Proatherogenic flow conditions initiate endothelial apopto-sis via thrombospondin-1 and the integrin-associated protein.Biochem Biophys Res Commun 2001;286(1):141–9.

39. Keane MG, Wiegers SE, Plappert T, Pochettino A, Bavaria JE,Sutton MG. Bicuspid aortic valves are associated with aor-tic dilatation out of proportion to coexistent valvular lesions.Circulation 2000;102(19 Suppl 3):III35–9.

40. Bonderman D, Gharehbaghi-Schnell E, Wollenek G, Maurer

48. Oliver JM, Gallego P, Gonzalez A, Aroca A, Bret M, Mesa JM.Risk factors for aortic complications in adults with coarctationof the aorta. J Am Coll Cardiol 2004;44(8):1641–7.

49. Hinton Jr RB, Lincoln J, Deutsch GH, Osinska H, Manning PB,Benson DW, Yutzey KE. Extracellular matrix remodeling andorganization in developing and diseased aortic valves. Circ Res2006;98(11):1431–8.

50. Beroukhim RS, Roosevelt G, Yetman AT. Comparison of thepattern of aortic dilation in children with the Marfan’s syn-drome versus children with a bicuspid aortic valve. Am JCardiol 2006;98(8):1094–5.

51. Svensson LG, Kim KH, Lytle BW, Cosgrove DM. Relationshipof aortic cross-sectional area to height ratio and the risk of aor-tic dissection in patients with bicuspid aortic valves. J ThoracCardiovasc Surg 2003;126(3):892–3.

52. Matsuyama K, Usui A, Akita T, Yoshikawa M, Murayama M,Yano T, Takenaka H, Katou W, Toyama M, Okada M, SawakiM, Ueda Y. Natural history of a dilated ascending aorta afteraortic valve replacement. Circ J 2005;69(4):392–6.

53. Borger MA, Preston M, Ivanov J, Fedak PW, DavierwalaP, Armstrong S, David TE. Should the ascending aorta bereplaced more frequently in patients with bicuspid aorticvalve disease? J Thorac Cardiovasc Surg 2004;128(5):677–83.

54. Gott VL, Greene PS, Alejo DE, Cameron DE, Naftel DC, MillerDC, Gillinov AM, Laschinger JC, Pyeritz RE. Replacement ofthe aortic root in patients with Marfan’s syndrome. N Engl JMed 1999;340(17):1307–13.

55. Gelsomino S, Morocutti G, Frassani R, Masullo G, Da Col P,Spedicato L, Livi U. Long-term results of Bentall compositeaortic root replacement for ascending aortic aneurysms and

G, Baumgartner H, Lang IM. Mechanisms underlying aorticdilatation in congenital aortic valve malformation. Circulation1999;99(16):2138–43.

41. Nataatmadja M, West M, West J, Summers K, Walker P,Nagata M, Watanabe T. Abnormal extracellular matrix pro-tein transport associated with increased apoptosis of vascularsmooth muscle cells in marfan syndrome and bicuspid aor-tic valve thoracic aortic aneurysm. Circulation 2003;108(Suppl1):II329–34.

42. Fedak PW, de Sa MP, Verma S, Nili N, Kazemian P, ButanyJ, Strauss BH, Weisel RD, David TE. Vascular matrix remod-eling in patients with bicuspid aortic valve malformations:implications for aortic dilatation. J Thorac Cardiovasc Surg2003;126(3):797–806.

43. Yasuda H, Nakatani S, Stugaard M, Tsujita-Kuroda Y, BandoK, Kobayashi J, Yamagishi M, Kitakaze M, Kitamura S, Miy-atake K. Failure to prevent progressive dilation of ascendingaorta by aortic valve replacement in patients with bicuspidaortic valve: comparison with tricuspid aortic valve. Circula-tion 2003;108(Suppl 1):II291–4.

44. Gurvitz M, Chang RK, Drant S, Allada V. Frequency of aorticroot dilation in children with a bicuspid aortic valve. Am JCardiol 2004;94(10):1337–40.

45. Ben-Dor I, Sagie A, Weisenberg D, Ben Zekry S, Fraser A,Sahar G, Iakobishvili Z, Battler A, Shapira Y. Comparisonof diameter of ascending aorta in patients with severe aorticstenosis secondary to congenital versus degenerative versusrheumatic etiologies. Am J Cardiol 2005;96(11):1549–52.

46. Ferencik M, Pape LA. Changes in size of ascending aorta andaortic valve function with time in patients with congenitallybicuspid aortic valves. Am J Cardiol 2003;92(1):43–6.

47. Russo CF, Mazzetti S, Garatti A, Ribera E, Milazzo A, BruschiG, Lanfranconi M, Colombo T, Vitali E. Aortic complicationsafter bicuspid aortic valve replacement: long-term results.Ann Thorac Surg 2002;74(5):S1773–6, discussion S1792-9.

dissections. Chest 2003;124(3):984–8.56. Yun KL, Miller DC, Fann JI, Mitchell RS, Robbins RC, Moore

KA, Oyer PE, Stinson EB, Shumway NE, Reitz BA. Compositevalve graft versus separate aortic valve and ascending aorticreplacement: is there still a role for the separate procedure?Circulation 1997;96(9 Suppl):II368–75.

57. Sundt III TM, Mora BN, Moon MR, Bailey MS, Pasque MK,Gay Jr WA. Options for repair of a bicuspid aortic valve andascending aortic aneurysm. Ann Thorac Surg 2000;69(5):1333–7.

58. Polvani G, Barili F, Dainese L, Topkara VK, Cheema FH, PenzaE, Ferrarese S, Parolari A, Alamanni F, Biglioli P. Reductionascending aortoplasty: midterm follow-up and predictors ofredilatation. Ann Thorac Surg 2006;82(2):586–91.

59. Robicsek F, Cook JW, Reames Sr MK, Skipper ER. Sizereduction ascending aortoplasty: is it dead or alive? J ThoracCardiovasc Surg 2004;128(4):562–70.

60. Vallely MP, Hughes CF, Bannon PG, Hendel PN, French BG,Bayfield MS. Composite graft replacement of the aortic rootafter previous cardiac surgery: a 20-year experience. Ann Tho-rac Surg 2000;70(3):851–5.

61. Girardi LN, Krieger KH, Mack CA, Lee LY, Tortolani AJ, IsomOW. Reoperations on the ascending aorta and aortic rootin patients with previous cardiac surgery. Ann Thorac Surg2006;82(4):1407–12.

62. Kirsch EW, Radu NC, Mekontso-Dessap A, Hillion ML, Loi-sance D. Aortic root replacement after previous surgicalintervention on the aortic valve, aortic root, or ascendingaorta. J Thorac Cardiovasc Surg 2006;131(3):601–8.

63. Pacini D, Di Marco L, Loforte A, Angeli E, Dell’amore A,Bergonzini M, Di Bartolomeo R. Reoperations on the ascend-ing aorta and aortic root. Early and late results? J CardiovascSurg (Torino) 2005;46(5):491–8.

64. Davies, J, Senes S, Cardiac surgery in Australia 1999. AustralianInstitute of Health and Welfare, Cardiovascular Disease seriesno. 21. AIHW Cat. no. CVD 22; 2003.