Bicuspid aortic valve pattern

review article
The new engl and jour nal of medicine
n engl j med 370;20 nejm.org may 15, 20141920
Edward W. Campion, M.D., Editor
Aortic Dilatation in Patients
with Bicuspid Aortic Valve
Subodh Verma, M.D., Ph.D., and Samuel C. Siu, M.D.
From the Division of Cardiac Surgery, St.
Michael’s Hospital, Department of Sur-
gery, University of Toronto, Toronto
(S.V.), and the Division of Cardiology, De-
partment of Medicine, Lawson Research
Institute, London Health Sciences Cen-
tre, Western University, London, ON
(S.C.S.) — both in Canada. Address re-
print requests to Dr. Verma at the Divi-
sion of Cardiac Surgery, St Michael’s
Hospital, 30 Bond St., Toronto, ON M5B
1W8, Canada, or at vermasu@smh.ca.
N Engl J Med 2014;370:1920-9.
DOI: 10.1056/NEJMra1207059
Copyright © 2014 Massachusetts Medical Society.
B
icuspid aortic valve is the most common congenital heart de-
fect in adults, affecting 1.3% of the population worldwide, and is responsible
for more deaths and complications than the combined effects of all the
other congenital heart defects.1,2 Although aortic stenosis and regurgitation are the
most common complications of a bicuspid aortic valve, dilatation of any or all seg-
ments of the proximal aorta from the aortic root to the aortic arch, called bicuspid
aortopathy, is also present in approximately 50% of affected persons.1-4 Accumulating
evidence suggests that the pattern of aortic dilatation in persons with a bicuspid aortic
valve is diverse, possibly reflecting heterogeneity in molecular, rheologic, and clinical
features.4-9 This article provides a brief overview of the basic principles, recent advances,
and recommendations for the treatment of adults with bicuspid aortopathy.
TERMINOLOGY AND DEFINITIONS
A normal aortic valve is composed of three aortic-valve cusps, each semilunar in
appearance. The leaflets are housed within a small dilatation of the proximal aorta
associated with each cusp, called the sinuses of Valsalva or aortic sinuses, and their
association with the respective coronary ostia identifies them: left, right, and non-
coronary sinuses. Each cusp is attached to the wall of the aorta by the outward
edges of its semicircular border, and the attachment point between each leaflet is
called a commissure.
A bicuspid aortic valve typically comprises two leaflets of unequal size.2 The
most common fusion pattern involves the right and left cusps (RL fusion pattern,
resulting in an anterior–posterior leaflet orientation; also called the typical pat-
tern), followed by fusion of the right and noncoronary cusps (RN fusion pattern,
resulting in a right–left leaflet orientation; also called the atypical pattern). The
least common pattern involves fusion of the left and noncoronary cusps. In rare
cases, the leaflets are symmetrical or there is no raphe.
The aorta is anatomically divided into the ascending aorta (approximately 5 cm
in length and 20 to 37 mm in diameter),10 aortic arch, thoracic aorta, and ab-
dominal aorta. The aortic root comprises the aortic sinuses, aortic valve, and
coronary ostia; the tubular portion of the ascending aorta begins at a point distal
to the aortic root (sinotubular junction) and ends at the origin of the innominate
artery. The aortic arch is composed of the origins of the innominate artery, the
left common carotid artery, and the left subclavian artery (Fig. 1).
PREVALENCE OF BICUSPID AORTIC DILATATION
The reported prevalence of dilatation of the ascending aorta among persons with a
bicuspid aortic valve ranges from 20 to 84%.1,2,7,11-15 This variation is related to dif-
ferences in study populations, assessment techniques, and aortic-size thresholds,
The New England Journal of Medicine
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Aortic Dilatation
n engl j med 370;20 nejm.org may 15, 2014 1921
Innominate
artery
Aortic
arch
Tubular
aorta
artery
AorticAortic
Thoracic
aorta
Sinotubular
junction
Sinus
of Valsalva
Aortic
root
Aortic
valve
Left
coronary
artery
AorticAortic
LeftLeft
Right
coronary
artery
RightRight
SinusSinus
Patterns of bicuspid aortopathyA
Type 1Type 1
Type 2
Type 3Type 3
Echocardiographic and magnetic resonance examples of bicuspid aortopathyB
Isolated aortic-root
involvement with normal
tubular ascending aorta
and arch dimensions
Arch dilatation with
involvement of tubular
ascending aorta, with
relative sparing of root
Dilatation of tubular
ascending aorta primarily
along convexity of aorta,
with mild-to-moderate
root dilatation
LV
AscAO
Figure 1. Patterns of Bicuspid Aortopathy, with Representative Findings on Echocardiography and Computed
Tomography (CT).
Panel A shows the biologic features of the aorta and the three types of bicuspid aortopathy. The transthoracic echo-
cardiogram at the left in Panel B shows normal dimensions of the sinuses of Valsalva (arrow) and a dilated ascend-
ing aorta. AscAO denotes proximal ascending aorta, and LV left ventricle. The CT images in the middle and at the
right show dilatation of the aortic root and dilatation of the ascending aorta and proximal arch, respectively.

as well as the heterogeneous nature of the dis-
ease. All the segments of the ascending aorta are
larger in adults with a bicuspid valve than in those
with a tricuspid aortic valve.
Aortic dilatation begins in childhood and is
progressive. Children born with a bicuspid aortic
valve have a larger ascending aorta that increases
in size at a higher rate than that of matched con-
trols with a tricuspid aortic valve.2 The prevalence
of dilatation at the level of the tubular ascending
aorta increases with age and has been reported to
be 56%, 74%, 85%, 91%, and 88% at the respec-
tive age quintiles of younger than 30 years, 30 to
39 years, 40 to 49 years, 50 to 60 years, and older
than 60 years of age.11 The prevalence also varies
widely according to the site of dilatation (annulus,
aortic root, or tubular ascending aorta).7
PATTERNS OF BICUSPID AORTIC
DILATATION
Classification schemes that are based on histo-
logic features,16 morphologic valve-fusion pat-
terns, and hierarchical cluster analyses17 have
been proposed for describing bicuspid aortopa-
thy, but none have been widely adopted.1,4,7,8,17-20
The patterns of aortic involvement can be classi-
fied into three types to guide future manage-
ment. Type 1, the most common type, involves
dilatation of the tubular ascending aorta (par-
ticularly along its convexity), accompanied by
varying degrees of aortic-root dilatation (Fig. 1).
This type has been associated with an older age
at diagnosis (>50 years), valvular stenosis, and
the RL fusion pattern.4,8,21,22 Type 2 involves iso-
lated involvement of the tubular ascending aorta
(with relative sparing of the aortic root), fre-
quently extending into the transverse aortic arch
(Fig. 1), and has been associated with the pres-
ence of the RN fusion pattern.4,8,17,21,22 Type 3,
also called the root phenotype, involves isolated
dilatation of the aortic root (Fig. 1). This rare type
has been associated with a younger age at diag-
nosis (<40 years), male sex, and aortic regurgita-
tion and has been proposed to be the form of
bicuspid aortopathy that is most likely to be as-
sociated with a genetic cause.4,7,23
PATHOPHYSIOLOGICAL FEATURES
The development of bicuspid aortopathy has been
attributed to genetic and hemodynamic bases.
Although the relative contribution of genetics
and hemodynamics remains debated,1,2,4,7,24 both
factors are probably operative.
The evidence supporting a genetic basis in-
cludes the following observations: aortopathy is
prevalent in first-degree relatives of patients with
a bicuspid aortic valve25; differences in aortic di-
mensions in persons with a bicuspid aortic valve
persist even after adjustment for blood pressure,
peak aortic-jet velocity, and left ventricular ejection
time and are also observed in persons with appar-
ently normal-functioning bicuspid valves1,2,7; and
the prevalence of aortic dilatation among per-
sons with a bicuspid aortic valve is greater than
that predicted according to the severity of aortic
stenosis or aortic regurgitation.1,4,7,12,13,26 Auto-
somal dominant, X-linked, and familial modes
of inheritance have been reported.1,4,7 Abnormal
migration of neural-crest cells has been postulated
as a common pathway that results in a bicuspid
aortic valve and aortopathy.2,7
The histologic changes observed in bicuspid
aortopathy, previously called cystic medial ne-
crosis, are the end result of abnormal regulatory
pathways of vascular smooth-muscle cells within
the aortic media. Abnormal processing of the
extracellular matrix protein fibrillin 1 by vascu-
lar smooth-muscle cells initiates detachment of
vascular smooth-muscle cells from the extracel-
lular matrix, leading to the release of matrix
metalloproteinases (MMPs) together with their
tissue inhibitors. The resulting matrix disruption
and elastin and lamellar fragmentation lead to
increased apoptosis of vascular smooth-muscle
cells and disruption of the media layer, adversely
affecting the structural integrity and flexibility
of the aorta (Fig. 2).1,2,7,27,28
The concept that abnormal valve dynamics
lead to bicuspid aortopathy is supported by the
observation that even normally functioning bi-
cuspid aortic valves can have abnormal transval-
vular-flow patterns, resulting in regional increas-
es in wall shear stress that are predicted largely
by the morphologic features of the bicuspid valve.4-6
Magnetic resonance imaging (MRI) studies have
shown that an RL fusion pattern results in a flow
jet directed toward the right anterior aortic wall,
which is then propagated in a right-handed heli-
cal direction (Fig. 3, and Fig. S1 in the Supple-
mentary Appendix, available with the full text of
this article at NEJM.org).5,6 The increase in re-
gional wall shear stress might be the basis of the

Aortic Dilatation
association of the RL fusion pattern with dilata-
tion of the aortic root and asymmetric dilatation
of the tubular ascending aorta. Conversely, an RN
fusion pattern results in a flow toward the pos-
terior aorta, with increased wall shear stress at
the right posterior aspect of the aorta (Fig. 3),
leading to dilatation of the aortic arch. These
preliminary observations in small samples of pa-
tients are intriguing but require further clarifica-
tion in unselected populations and linkage to out-
comes. Indeed, valve orientation did not predict
events in the three largest outcome studies.29-31
NATUR AL HISTORY
Aortic aneurysm formation and aortic dissection
are the two major complications of bicuspid aor-
topathy. The rate of growth of the ascending aorta
Elastin and collagen
Smooth-muscle
cells
Fibrillin 1
microfibril
Loss of fibrillin 1
microfibrils
A
B
Smooth-muscleSmooth-muscle
Fibrillin 1
Disrupted
elastin and collagen
Smooth-muscle
cell losscell losscell loss
MMP
release
Figure 2. Pathophysiological Features of Bicuspid Aortopathy.
Structural support and elasticity are afforded to the aorta by means of alternating layers of elastic lamellae and
smooth-muscle cells. At the histologic level, the smooth-muscle cells in the aorta in persons with tricuspid valves are
secured to the adjacent elastin and collagen matrix by fibrillin 1 microfibrils (Panel A). The aorta in persons with bi-
cuspid valves may be deficient in fibrillin 1. This deficiency culminates in a disrupted architecture whereby smooth-
muscle cells detach, accompanied by a surge in local levels of matrix metalloproteinases (MMPs), leading to loss
of integrity in the extracellular matrix and the accumulation of apoptotic cells. These events may lead to an aorta
with weakened structural integrity and reduced elasticity (Panel B).

in persons with a bicuspid aortic valve (range,
0.2 to 1.9 mm per year) is considerably higher
than the rate in persons with a tricuspid aortic
valve.7,14,32-38
The aortic diameter at baseline is an important
predictor of aortic expansion. A study involving
88 patients showed expansion rates of approxi-
mately 2.1 mm per year among patients with a
bicuspid aortic valve that had an initial aortic di-
ameter of 35 to 40 mm, as compared with a rate
of 5.6 mm per year among patients with an
aortic diameter of more than 60 mm.39 A recent
study involving 416 consecutive patients with a
bicuspid aortic valve showed that an aortic diam-
eter of 40 mm or more at baseline independently
predicted the subsequent development of an an-
eurysm, as compared with a baseline diameter
of less than 40 mm (hazard ratio, 3.3; 95% con-
fidence interval, 1.5 to 7.2).29 Other predictors of
progression of bicuspid aortopathy include older
age, male sex, elevated systolic blood pressure,
coexisting aortic-valve stenosis or regurgitation,
and morphologic features of the valve (RL fusion
pattern).2 Prior coarctation repair may provide
protection against rapid aortic dilatation.15
The incidence of aortic dissection, the most-
feared complication of bicuspid aortopathy, was
once estimated to be as high as 5% but has been
much lower in contemporary studies. The inci-
dence of aortic dissection was 0.1% per patient-
year of follow-up in a Toronto study involving
642 patients with a bicuspid aortic valve.30 Like-
wise, in an Olmsted County, Minnesota, study in-
volving 416 patients with a bicuspid aortic valve,
there were two aortic dissections during a mean
(±SD) follow-up of 16±7 years, with an incidence
of 3.1 cases per 10,000 person-years and an age-
adjusted relative risk of 8.4.29 The incidence of
aortic dissection was 17.4 cases per 10,000 person-
years among patients 50 years of age or older
and 44.9 cases per 10,000 person-years among
patients with a baseline echocardiogram show-
ing an aneurysm. There were no dissections in
patients with an aortic diameter of less than
45 mm at baseline or in those with a normally
functioning aortic valve. Thus, despite a high rela-
Right–left fusion patternA
RapheRapheRaphe
Right–noncoronary fusion patternB
Figure 3. Morphologic Features of the Bicuspid Aortic Valve That Influence the Pattern of Aortopathy.
The fusion configuration of the aortic-valve cusps lays the foundation for changes in aortic wall shear stress and the resultant flow pat-
tern. In the right–left fusion pattern (Panel A), the jet is directed toward the right anterior wall of the ascending aorta, where it travels in
a right-handed helical direction to promote dilatation predominantly of the ascending aorta. In the pattern with fusion of the right and
noncoronary cusps (Panel B), the jet is directed toward the posterior wall of the aorta, whereby the pattern of wall shear stress it causes
may promote aortic dilatation within the proximal arch. Further details regarding the influence of morphologic features of bicuspid aor-
tic valve on patterns of aortopathy are provided in Figure S1 in the Supplementary Appendix.

Aortic Dilatation
tive risk that increased with age, the absolute risk
of aortic dissection was quite low. Furthermore,
the 25-year survival rate in the entire cohort was
80% — identical to the survival rate in the gen-
eral population of Olmsted County.
The low rates of aortic dissection in contem-
porary series reflect the practice of serial surveil-
lance and surgical intervention once aortic size
exceeds a threshold.29,30 The actual risk in the
absence of surgery is probably higher, since pa-
tients with a large aorta will have undergone
surgery. For example, among the 32 patients in
the Olmsted County study who had an aortic
diameter of 45 mm or more at baseline, the
long-term rate of aortic dissection was 7%, but
46% of the patients underwent aortic surgery.29
In the entire study group, the rates of aneurysm
formation and aortic surgery at 25 years were
26% and 25%, respectively, reflecting the effect
of aortopathy on morbidity (Fig. S2 in the Sup-
plementary Appendix).
Patients with a bicuspid aortic valve and an
aortic diameter of less than 50 mm at baseline
who underwent isolated aortic-valve replacement
continued to be at risk for future aortic compli-
cations. In a mixed group of patients with aortic
stenosis and those with aortic regurgitation, the
rate of freedom from aortic complications (need
for surgery, aortic dissection, or death) at 15 years
was 43% among patients with an aortic diameter
of 45 to 49 mm, as compared with 86% among
those with an aortic diameter of less than 40 mm,
suggesting that moderate aortic dilatation is an
important risk factor for aortic complications,
even after valve replacement.40 No aortic dissec-
tion was observed during follow-up in a more
recent series of patients with aortic stenosis and
concomitant mild-to-moderate dilatation of the
ascending aorta at the time of aortic-valve replace-
ment.23 However, patients with aortic regurgita-
tion and mild-to-moderate dilatation of the aortic
root (root phenotype) were at risk for aortic com-
plications after aortic-valve replacement.
ASSESSMENT AND TREATMENT
DIAGNOSIS
The initial diagnosis of bicuspid aortopathy is
likely to be made with the use of transthoracic
echocardiography (TTE). Although TTE is usu-
ally adequate in assessing the aortic root and
proximal ascending aorta, visualization of the
mid-distal ascending aorta and the arch may be
difficult in adults, in which case either a comput-
ed tomographic (CT) or MRI study should be
considered for comprehensive assessment of the
ascending aorta. If there are contraindications to
CT or MRI, then a transesophageal echocardio-
gram can be obtained.41 MRI is preferable to CT
for serial surveillance since it is not associated
with radiation exposure.
DECISION-MAKING ALGORITHM
Figure 4 outlines a proposed approach to the man-
agement of bicuspid aortopathy in asymptomatic
adults. This algorithm integrates U.S., European,
and Canadian recommendations, which are based
largely on expert opinion and observational stud-
ies.41-45 Risk factors, particularly smoking and
hypertension, should be aggressively addressed in
all patients with bicuspid aortopathy. Beta-adren-
ergic blockers, angiotensin-converting–enzyme
inhibitors, and angiotensin-receptor blockers are
the antihypertensive agents of choice. Beta-adren-
ergic blockers have the theoretical advantage of
reducing aortic wall shear stress, whereas angio-
tensin-receptor blockers have been shown to re-
duce the rate of aortic growth in patients with
Marfan’s syndrome.46
Yearly echocardiographic surveillance is rec-
ommended in patients who have an aortic root
or an ascending aorta with a diameter of more
than 40 mm, as assessed by means of TTE, and
no concomitant indication for valvular replace-
ment or repair. In patients who have an aortic
root or ascending aorta with a diameter of 40 to
44 mm and no concomitant valvular indication
for intervention, a baseline CT or MRI scan may
be obtained. If ongoing imaging surveillance, by
means of echocardiography, CT, or MRI, reveals
a growth rate exceeding 5 mm per year, surgical
management may be considered.
In patients who have an aortic root or ascend-
ing aorta with a diameter of 45 to 49 mm, a CT
or MRI scan should be obtained. If there are
concomitant indications for either valvular or cor-
onary surgery, then a tailored surgical approach
will be required, dictated largely by the aor-
topathy pattern, perioperative risk, and surgeon
and center experience. In patients with dilata-
tion of the tubular ascending aorta, surgical
options include supracoronary replacement of
the ascending aorta, or if substantial aortic-valve
dysfunction and aortic-root dilatation are also
present, then replacement of the aortic valve, aor-
tic root, and ascending aorta is indicated. In

Transthoracicechocardiogram
Aorticrootorascending
aorta<40mm
Valvularindication
Serialtransthoracic
echocardiography
MayconsiderCT
orMRIinpatients
withaorticrootor
ascendingaorta
dimensionsof
35–39mm
Proceedtoisolated
aortic-valve
replacement
aorta40–44mm
Valvularindication
BaselineCTorMRI
Proceedtoisolated
aortic-valve
replacement
aorta45–49mm
Valvularindication
Evaluatethepresence
ofriskmodifiers
Familyhistory
ofaorticdissec-
tion,aneurysm,
rupture,or
suddendeath
Growthrate
≥5mm/yr
Ratioofaortic
areatobody
height>10
Tailoredsurgical
approachbasedon
typeofaortopathy
pattern,perioperative
riskassessment,
surgeonorcenter
experience,anti-
coagulationtherapy,
andpatientpreference
(e.g.,aortic-valve
replacementwith
supracoronary
replacementof
ascendingaorta,
hemiarch,totalarch
replacement,aortic-
valverepair,sparing
rootreplacement,or
valvedconduitrepair)
Tailoredsurgical
approachbasedon
typeofaortopathy
riskassessment,
surgeonorcenter
experience,anti-
coagulationtherapy,
andpatientpreference
(e.g.,aortic-valve
replacementwith
supracoronary
replacementof
ascendingaorta,
hemiarch,totalarch
replacement,aortic-
valverepair,sparing
rootreplacement,or
valvedconduitrepair)
aorta50–55mm
Valvularindication
MayconsidersurgeryConsidersurgery
Yearlyechocardi-
ography,CT,or
MRItoevaluate
ascendingaorta
Yearlysurveillance
withechocardi-
ography,CT,orMRI
Yearlyechocardi-
ography,CT,or
MRItoevaluate
ascendingaorta
Tailoredsurgical
approachbasedon
typeofaortopathy
risk,andsurgeonor
centerexperience
Ifrapidprogression
(≥5mm/yr),
considersurgery
Considertailored
surgicalapproach
basedontypeof
aortopathypattern,
perioperativerisk,
andsurgeonor
centerexperience
NoYesNoYesNoYesNoYes
Figure4.Decision-MakingAlgorithmfortheManagementofBicuspidAortopathy.
Managementincludesrisk-factormodificationinallpersonsandincludesthetreatmentofhypertension,treatmentofdyslipidemia,andsmokingcessation.Iftheentireascending
aorta(fromaorticroottoarch)isnotcompletelyvisualizedbymeansoftransthoracicechocardiography,supplementalMRIorCTisrecommended.CTorMRIisalsorecommend-
edinplanningthesurgicalapproach.

Aortic Dilatation
patients with a dilated ascending aorta and aortic
arch, surgical options may include aortic-valve
replacement with supracoronary replacement of
the ascending aorta and hemiarch. In most in-
stances, this intervention will require deep hy-
pothermic circulatory arrest and the potential
use of antegrade cerebral perfusion.
In patients with isolated involvement of the
aortic root, surgical options may include aortic-
valve and aortic-root replacement with the use of
a composite valved conduit (Bentall procedure). In
most cases, surgical repair for bicuspid aortopathy
can be achieved with excellent results at an ex-
perienced center.47 If aortic-valve surgery will be
performed concurrently with ascending-aorta
replacement, it is important to incorporate non-
surgical factors into the decision-making process,
such as the lifestyle of the patient, need for long-
term anticoagulation, and in the case of female
patients, future reproductive plans. A summary of
surgical results from various publications are pro-
vided in Table S1 in the Supplementary Appendix.
In the absence of a valvular indication, pa-
tients who have an aortic root or ascending aorta
with a diameter of 45 to 50 mm may be consid-
ered for surgery only if they have high-risk fea-
tures such as a family history of aortic dissec-
tion, rupture, or sudden death and an aortic
growth rate of more than 5 mm per year. A ratio
of aortic area to body height of more than 10 cm2
per meter has also been recommended for pa-
tients of short stature.41 In the absence of these
factors, yearly reassessment of the risk stratifica-
tion with the use of CT or MRI is suggested.7,37
Surgery has previously been recommended
for patients with an aortic root or ascending aorta
that has a diameter of 5.0 cm or more, with
guidelines recommending a threshold of 5.5 cm
and a more individualized approach.41,42 Euro-
pean guidelines recommend that the aorta be
replaced when the diameter of the aortic root or
ascending aorta is 5.0 cm or more and in the
presence of risk factors including coarctation of
the aorta, systemic hypertension, family history
of dissection, or an increase in the aortic diam-
eter of more than 2 mm per year.43 European
guidelines are in agreement with U.S. guidelines
that recommend a lower threshold for ascend-
ing-aorta replacement in patients who are under-
going aortic-valve surgery (aortic diameter, 45 mm)
and when valve repair will be performed at an
experienced center with high rates of success.43
The 2014 Canadian guidelines recommended
a threshold range (aortic diameter, 50 to 55 mm),
recognizing the importance of also incorporat-
ing patient size and patient-specific factors when
deciding on the timing and nature of elective
aorta replacment.45 Prophylactic surgery at the
lower threshold limit of 50 mm would be ap-
propriate in patients with risk factors for aortic
complications (e.g., rapid aortic growth or con-
comitant aortic-valve disease, connective-tissue
disorders, or genetic syndromes) but may not be
prudent in those at increased risk for complica-
tions during surgery. These recommendations
are based on the premise that aortic complica-
tions, representing a long-term risk that in-
creases with time, will be avoided if elective
aortic-valve replacement is performed at experi-
enced centers with low mortality (≤1%).45
SPECIAL POPULATIONS
During pregnancy, there are changes in hemody-
namic variables as well as changes in the aortic
media, and pregnant women who have a bicuspid
aortic valve and concomitant aortic dilatation are
therefore at increased risk for complications. In
general, women with a bicuspid aortic valve and
an aortic diameter of more than 45 mm should
be advised against pregnancy. Summary recom-
mendations regarding treatment during pregnan-
cy are provided in Table S2 in the Supplementary
Appendix.
Athletes with or without valvular disease who
have a dilated aortic root or ascending aorta
(diameter ≥45 mm) should be advised to par-
ticipate only in low-intensity competitive sports
(Table S3 in the Supplementary Appendix).
First-degree relatives of patients with a bicuspid
aortic valve should be screened for the presence
of a bicuspid aortic valve and asymptomatic
aortic disease.25,41,43
UNANSWERED QUESTIONS
AND FUTURE DIRECTIONS
Advances in imaging, biomarker-based risk as-
sessments, and genetics should be used to gain a
better understanding of the mechanisms under-
lying the development and progression of bicus-
pid aortopathy. The Beta Blockers and Angioten-
sin Receptor Blockers in Bicuspid Aortic Valve
Disease Aortopathy (BAV) study (ClinicalTrials
.gov number, NCT01202721) is an ongoing trial

that is being conducted by the Canadian Network
and Centre for Trials Internationally. The purpose
of this study is to evaluate the efficacy of atenolol
and telmisartan in slowing the progression of
bicuspid aortopathy. A trial of medical versus
surgical management in patients with a moder-
ately dilated ascending aorta (45 to 50 mm) would
be highly informative. Future studies should fo-
cus on improving the selection of subgroups of
patients who are most likely to benefit from ear-
lier intervention, as well as those for whom watch-
ful waiting is appropriate.
No potential conflict of interest relevant to this article was
reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
We thank Dr. Hwee Teoh for editorial assistance with an ear-
lier version of the manuscript.
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