BICUSPID AORTIC VALVE

Brook A. June/2016
Braunwald 10th ed.
 AORTIC VALVE DISEASE
PATRICK T. O’GARA, JOSEPH
LOSCALZO
GLOBAL BURDEN OF VALVULAR HEART DISEASE

 Primary valvular heart disease ranks well below

coronary
heart disease, stroke, hypertension, obesity, and
diabetes as a
major threat to the public health.
 Nevertheless, it is the source
of significant morbidity and mortality rates.
 BICUSPID AORTIC VALVE  — It has been
estimated that a bicuspid aortic valve is present
in approximately 2 percent of the general
population , but a lower value (0.8 percent) was
noted in almost 21,000 men (mean age 18) in
Italy who underwent screening echocardiography
for the military . In these young men with a
bicuspid aortic valve, aortic regurgitation was
the most common hemodynamic lesion and was
moderate to severe in 12 percent. Mild aortic
stenosis was present in 5 percent, and ascending
aortic size was increased compared to normal
controls. uptodate
 Bicuspid aortic valve is the most common cause
of isolated valvular aortic stenosis in adults with
a male-to-female ratio of 3:1 . It is also the most
common cause of aortic valve replacement for
aortic stenosis up to age 70 (uptodate)
 Course in unoperated patients  — The bicuspid valve
may be functionally normal, ie, no significant pressure
gradient and no more than trace regurgitation.
However, thickening and focal calcification of the
functionally normal bicuspid valve can be detected
pathologically and on echocardiography as early as the
second decade
 Almost all patients with a bicuspid aortic valve
eventually develop symptoms due to aortic stenosis or
regurgitation, although many are now diagnosed when
asymptomatic due to the widespread use of
echocardiography. Occasionally, a minimally calcified
bicuspid aortic valve is discovered in patients ≥70
years of age. uptodte
 Progressive fibrocalcific stenosis requiring
surgery eventually occurs in over 75 percent of
patients. The nodular calcium deposits originate
at the base of the cusps and extend outward
toward the free edge, causing obstruction . In a
small number of patients, stenosis results from
excessive fibrosis alone . The pathogenesis of
valve calcification is discussed separately.
 The peak incidence of symptoms (angina,
syncope, or heart failure) occurs between the
ages of 40 and 60 . Once symptoms develop,
survival without valve replacement is less than
five years. The incidence of sudden death in
symptomatic patients, attributed to myocardial
ischemia and arrhythmias, is 15 to 20 percent.
 A bicuspid valve is a common cause of aortic
stenosis that requires surgery in all age groups.
This was illustrated in a report of 932 adults
with isolated nonrheumatic aortic stenosis who
underwent operative excision of the stenotic
valve; none underwent mitral valve replacement,
none had mitral stenosis, and none had undergone
previous aortic valvulotomy . A congenitally
malformed valve was present in 54 percent: 49
percent had a bicuspid valve and 4 percent had a
unicuspid valve (mostly in patients ≤50 years of
age).
 The causes according to age at the time of aortic
valve replacement were as follows:
 Among the 7 percent of patients who underwent
surgery at ≤50 years of age, approximately two-thirds
had a bicuspid valve and one-third had a unicuspid
valve.
 Among the 40 percent of patients who underwent
surgery between the ages of 50 and 70,
approximately two-thirds had a bicuspid valve and
one-third a tricuspid valve; a unicuspid valve was rare.
 Among the remaining patients over age 70,
approximately 60 percent had a tricuspid valve and 40
percent had a bicuspid valve.
 Risk factors for stenosis  — Nearly all bicuspid
valves eventually become stenotic . However, the
factors that affect the rate of valve narrowing
are incompletely defined. The clinical risk
factors for the development of calcific stenosis
are the same as those for the development of
atherosclerosis; of particular importance are
elevated total cholesterol, systemic
hypertension , and inherent cuspal inequality.
 There are also some anatomic data indicating which
valves are more likely to become stenotic:
 Sclerotic changes may occur earlier in valves with
anterior/posterior leaflets as compared to those
with a right/left orientation .
 Bicuspid valves with asymmetrical leaflet sizes (ie,
greater cuspal inequality) are more prone to rapid
calcification. It has been proposed that valve
calcification is induced by excessive hemodynamic
stress, resulting from straightening and stretching
of the leaflets when they are open and close .
These permutations are more pronounced in a valve
with asymmetrical cusps.
 Familial disease  — There is increasing evidence
for familial clustering and therefore heritability
of bicuspid aortic valve. This was illustrated in a
report of 30 consecutive patients with bicuspid
aortic valve confirmed on echocardiography;
among 210 first-degree relatives, 190 agreed to
undergo echocardiography [ 14 ]. A bicuspid
aortic valve was present in 9.1 percent of first-
degree relatives, and 37 percent of the families
had at least one additional member with a
bicuspid aortic valve. The pattern in these
families was consistent with autosomal dominant
inheritance.
 Associated cardiovascular anomalies  — A
bicuspid aortic valve often is seen in patients
with other congenital aortic and cardiac
anomalies. In addition, a subset of patients with
an isolated bicuspid aortic valve develop dilation
of the ascending aorta which occasionally
progresses to aortic aneurysm and less
frequently to aortic dissection.
 In a series cited above, 22 of 74 patients with
bicuspid aortic valve (30 percent) had other
congenital anomalies or aortic root dilation [ 15 ].
The most common associated anomaly was
coarctation of the aorta. An autopsy series
found coexisting coarctation of the aorta in 6
percent of patients with bicuspid aortic valve
 On the other hand, as many as 30 to 40 percent
of patients with coarctation have a bicuspid
aortic valve . Less common concomitant
congenital anomalies include ventricular or atrial
septal defect, hypoplastic left heart syndrome,
patent ductus arteriosus, bicuspid pulmonic
valve, and Ebstein's anomaly
 Dilatation of the aortic root and ascending
thoracic aorta is associated with the presence of
a bicuspid aortic valve and the degree of aortic
dilation is independent of valve dysfunction
 Dilatation of the aortic root and ascending thoracic
aorta is associated with the presence of a bicuspid
aortic valve and the degree of aortic dilation is
independent of valve dysfunction . In a study of
young men with normally functioning bicuspid aortic
valves, dilation at the aortic root or ascending aortic
level compared to controls was noted in 52 percent;
this finding was independent of the functional state
of the bicuspid valve . In another series, ascending
aortic dimensions were significantly larger in patients
with bicuspid valves compared to those with tricuspid
valves with comparable degrees of aortic stenosis .
Aortic root dilatation in Turner syndrome occurs
with or without a coexisting bicuspid aortic valve
 Turner syndrome-Cardiovascular disease
 — There is an increased risk of cardiovascular
morbidity in women with Turner
syndrome(45,X/46,XX)), presumably due to their
risk of cardiovascular malformations, renal
abnormalities, and hypertension . Abnormalities
include coarctation, aortic valvular disease, aortic
dissection, hypertension, and other
cardiovascular anomalies. Mortality rates are also
increased.
 Aortic dissection  — Aortic dissection or rupture
is an increasingly recognized cause of death in
women with Turner syndrome
 Aortic root dilatation progressing to aortic
aneurysm is associated with increased risk of
aortic dissection [ 22,23 ]. (See
"Clinical features and diagnosis of thoracic aorti
c aneurysm"
and
"Clinical manifestations and diagnosis of aortic di
ssection"
.) The risk of aortic progression and
complications are illustrated by the following
observations from an Olmsted County study [ 24
]:
EPIDEMIOLOGY
 1% to 2% of the population

 More prevalent in men, accounting for 70% to

80% of cases.

 In a subset of patients with bicuspid aortic

valve, familial clustering consistent with an
autosomal dominant inheritance with incomplete
penetrance has been documented.
 In some families with bicuspid aortic valve and
associated congenital anomalies, a mutation in the
NOTCH1 gene has been described.
PATHOPHYSIOLOGY
 The most prevalent anatomy for a bicuspid valve
is two cusps with a right-left systolic opening,
consistent with congenital fusion of the right
and left coronary cusps, seen in 70% to 80% of
patients

 An anterior-posterior orientation, with fusion of

the right and noncoronary cusps, is less common,
seen in approximately 20% to 30% of cases.

 Fusion of the left and noncoronary cusps is

rarely seen.
PATHOPHYSIOLOGY
 A prominent ridge of tissue or raphe may be
present in the larger of the two cusps so that
the closed valve in diastole may mimic a
trileaflet valve.

 Echocardiographic diagnosis relies on imaging the

systolic leaflet opening with only two aortic
commissures.

 Unicuspid valves are distinguished from a

bicuspid valve by having only one aortic
commissure.
PATHOPHYSIOLOGY
 Bicuspid aortic valve disease is associated with an
aortopathy, with dilation of the ascending aorta
related to accelerated degeneration of the aortic
media
 The presence, location, and severity of aortic dilation is
related to valve morphology but does not appear to be
related to the severity of valve dysfunction per se
 The risk of aortic dissection in patients with a
bicuspid aortic valve is five to nine times higher
than the general population.
 Some studies have also suggested an association
between bicuspid aortic valve disease
(anteriorposterior leaflet opening) and mitral valve
prolapse (MVP)
CLINICAL PRESENTATION
 Patients with a bicuspid valve may be diagnosed at
any age on the basis of the presence of an aortic
ejection sound or a systolic or diastolic murmur.

 Some patients, however, initially are diagnosed on

echocardiography requested for other reasons,
and others are diagnosed through a family history
of bicuspid aortic valve disease

 Often, the diagnosis is unknown until the physical

examination reveals manifestations of valve
dysfunction or the patient develops symptoms.
DISEASE COURSE
 Most bicuspid valves function normally until late in life,
although a subset of patients present in childhood or
adolescence with valve dysfunction
 Overall, survival is not different from population
estimates.
 Risk factors for cardiac events are age older than 30
years, moderate or severe AR, and moderate or severe
AS.
 Over a mean follow-up period of 9 years, primary cardiac events
occurred in 25% of 642 ambulatory adults with a bicuspid valve.
 Events included aortic valve or root replacement (22%),
hospitalization for heart failure (2%), and cardiac death (3%)
 Over their lifetime, approximately 20% of patients with
bicuspid valves develop severe AR requiring AVR between
the ages of 10 and 40 years
DISEASE COURSE
 Patients with a bicuspid aortic valve also are at
increased risk for endocarditis (0.4/100,000),
accounting for approximately 1200 deaths/year
in the United States.

 However, most patients with a bicuspid valve

develop calcific valve stenosis later in life,
typically presenting with severe AS after the
age of 50 years
 Histopathologic features similar to calcific AS
 Accelerated valve changes explains the earlier
presentation than trileaflet stenotic valve
DISEASE COURSE
 Bicuspid valve disease accounts for greater than
50% of AVRs in the United States and is a
common cause of calcific AS, even in older
persons

 The aortopathy associated with bicuspid valve

disease often results in aortic dilation and
carries an increased risk of aortic dissection.

 The magnitude of risk appears to vary depending

on valve and aortic morphology and on a family
history of aortic involvement
MANAGEMENT
 The management of bicuspid aortic valve disease is
directed toward the hemodynamic consequences of
valve dysfunction—AS or AR

 Currently, there are no effective medical therapies

to prevent progressive valve deterioration when a
bicuspid valve is diagnosed.

 In addition to appropriate follow-up for valve

dysfunction, evaluation of the ascending aorta is
needed, often with CT or CMR to ensure adequate
visualization and accurate measurement of the
aortic sinuses and ascending aorta
MANAGEMENT
 If AVR is needed for stenosis or regurgitation,
concurrent aortic root replacement is
recommended if the maximum aortic dimension
(measured at end-diastole) exceeds 45 mm

 Even in the absence of aortic valve disease,

aortic root replacement is recommended when
the aortic dimension exceeds 55 mm in adults
with a bicuspid aortic valve and may be
considered with an aortic diameter of 50 mm if
there is a positive family history or evidence of
rapid progression
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