Mitral Valve

1721 CHAPTER 77: Mitral Valve Regurgitation
CHAPTER 77
MITRAL VALVE
REGURGITATION
David H. Adams, Blas A. Carabello, and Javier G. Castillo
MITRAL ANNULUS
The mitral annulus is a fibromuscular ring located in the left atrio-
ventricular groove that serves as an attachment and hinge point for
the mitral valve leaflets. The mitral annulus is subjectively divided
into anterior and posterior segments based on the attachments of the
anterior and posterior mitral leaflets, but it can also be segmented by
location into septal and lateral components. The anterior portion of the
mitral annulus is in continuity with the fibrous skeleton of the heart,
defined by the right and left fibrous trigones and the aortic mitral cur-
tain. This portion of the mitral annulus is thus fibrous in nature and is
much less prone to dilation in comparison to the posterior portion of
the annulus (Fig. 771). Because the fibrous skeleton is discontinuous
along the posterior portion of the mitral annulus, this portion dilates
or increases its circumference in the setting of chronic mitral valve
regurgitation, with associated atrial and ventricular dilatation.
12
The
resultant increase in mitral annular dimension makes the annulus more
circular in shape, compared with its normal kidney bean shape, which
in turn compromises the coaptation of the mitral leaflets due to the
increase in septal-lateral or anterior-posterior dimension.
13
The hinge
point of the posterior portion of the mitral annulus may become atrial-
ized in long-standing posterior leaflet prolapse and may also be affected
by diffuse pathologic calcification.
14
The normal mitral annulus also
has a three-dimensional saddle shape, and the anterior portion of the
annulus tends to bulge during systole to accommodate the aortic root.
The overall circumference of the annulus may decrease by as much as
20% during systole, promoting central leaflet coaptation.
15
MITRAL LEAFLETS AND COMMISSURES
The mitral valve has an anterior and posterior leaflet with similar sur-
face areas but markedly different shapes.
16
The anterior leaflet is taller
than the posterior leaflet but with a shorter base, attaching to one-
third of the annular circumference between the right and left fibrous
trigones. During systole, the anterior leaflet forms a portion of the
LV outflow tract through its continuity with the aorto-mitral curtain.
The posterior leaflet is broader based, extending along the remaining
two-thirds of the annulus, and has a shorter height. Despite their dif-
ferent shapes, the overall surface areas of the two leaflets are similar.
The different orientations of the two leaflets ensure during systole
that the closure line of the mitral valve will be located in the poste-
rior one-third of the valve orifice, which prevents systolic anterior
motion of the tip of the anterior leaflet into the outflow track.
17
Both
leaflets present two zones from their base to the free margin: the body
zone (smooth and translucent) and the coaptation zone (thicker and
rough due to the attachment of numerous chordae). During systole,
the coaptation zones of the respective leaflets join together to form a
seal from anywhere from a few millimeters to a centimeter, ensuring
mitral valve competence (Fig. 772). The leaflets of the mitral valve
can be segmented by location of the clefts or indentations in the
posterior leaflet, which subdivide it into individual scallops. The
middle scallop of the posterior leaflet is designated as P2, and the
adjacent lateral and medial scallops are designated as P1 and P3,
respectively (see Fig. 771). The anterior leaflet does not typically
have natural indentations, but the corresponding areas of this leaflet
are designated by opposition to the segments in the posterior leaflet
as A1, A2, and A3.
18
In addition to anterior and posterior leaflet segments, the mitral
valve has posterior medial and anterior lateral commissures, which rep-
resent small segments of leaflet tissue presenting at the insertional junc-
tion of the anterior and posterior leaflets. These distinct areas of leaflet
tissue are supported by chordal fans and are critical to ensure a good
MITRAL VALVE ANATOMY / 1721
Mitral Annulus / 1721
Mitral Leaflets and Commissures / 1721
Chordae Tendineae / 1722
Papillary Muscles and the Left Ventricle / 1722
DEGENERATIVE MITRAL VALVE REGURGITATION / 1723
Dysfunction / 1723
Etiology and Lesions / 1723
Pathophysiology / 1725
Clinical Presentation / 1727
Medical Therapy / 1729
Surgical Therapy / 1730
The normal mitral valve permits one-way blood flow from the left
atrium to the left ventricle (LV) in an efficient, nearly frictionless
fashion.
1
Although even a normal competent valve may allow a trivial
amount of reversed flow, more than a trace of mitral regurgitation is
considered pathologic.
2,3
Mild to moderate mitral regurgitation is toler-
ated indefinitely as long as it does not worsen.
4
However, severe mitral
regurgitation causes LV remodeling, reduced forward cardiac output,
neurohumoral activation, LV damage, heart failure, and ultimately
death.
5
The natural history of mitral regurgitation depends intimately
on its etiology, the severity of LV volume overload and its contractile
performance, and the appearance of overlapping clinical conditions
secondary to reversal of flow such as atrial fibrillation and pulmonary
hypertension.
6-8
In this setting, myxomatous degeneration of the mitral
valve, a common pathologic substrate of mitral valve billowing (normal
valve coaptation) and prolapse (deficient valve coaptation), is the most
prevalent cause of isolated severe mitral regurgitation requiring surgi-
cal intervention in the United States.
9
The following is a review of the
normal mitral valve anatomy, as well as a summary of causes, conse-
quences, and treatment of degenerative mitral valve regurgitation.
MITRAL VALVE ANATOMY
The mitral valve is located in the left atrioventricular groove and allows
unidirectional flow of oxygenated blood from the left atrium into the
relaxed LV during diastole. The valve is a very complex three-dimensional
assembly of separate anatomic components, including the annulus, the
leaflets and commissures, the chordae, the papillary muscles, and the
ventricle.
10
During systolic contraction, a coordinated interaction of
these anatomic components closes the valve against ventricular pres-
sure. Therefore, its anatomy should be scrutinized systematically to
identify the lesions (the abnormalities in valve structure) that lead to
the valves dysfunction (the alteration in closure that results in mitral
regurgitation).
11
77-Fuster_Ch77_p1721-1737.indd 1721 10/1/10 11:32:30 PM
1722 PART 11: Valvular Heart Disease
surface of coaptation at the junctions of the two leaflets. The height of
commissural leaflet tissue can vary from a few millimeters to >1 cm.
CHORDAE TENDINEAE
The chordae tendineae attach the mitral leaflets to the papillary muscles
and LV, creating a suspension system that allows full opening of the
leaflets during diastole and prevents a displacement of the leaflets above
the annular plane during systole. Chordae tendineae are classified
according to their attachment between the free margin and the base
of the leaflets.
19
Primary or marginal chordae attach along the margin
of the leaflets and are critical to prevent leaflet prolapse and to align
the rough zone of the anterior and posterior leaflets during systole.
Typically, primary chordae insert every 3 to 5 mm along the margin of
both leaflets. Secondary, or body chordae attach to the ventricular side
of the body of the leaflets and provide ventricular annular continuity
as well as balancing of leaflet tension during systole. Tertiary, or basal
chordae attach to the base of the leaflet hinge, providing additional
linkage to the ventricle.
20
PAPILLARY MUSCLES AND THE LEFT VENTRICLE
The mitral valve leaflets are attached by the chordae tendineae to the
papillary muscles, which are a part of the LV. The papillary muscles
vary in the number of heads and exact position in the ventricle, but
generally, there are two main groups comprising the anterior and
posterior papillary muscles. Each papillary muscle is identified accord-
ing to the relationship to the valve commissures, and each provides a
fan chord to its corresponding commissure as well as to both anterior
and posterior leaflets. The anterior papillary muscles blood supply
can originate from both the left anterior descending artery and the
circumflex artery, whereas the posterior papillary muscle is dependent
primarily on the posterior descending artery. This explains the relative
A1
A2
A3
P1
P2
P3
CS
PC
AC
HB
AL
PL
RFT
LFT
AMC
FIGURE 771. Anatomic view of the cardiac valves in diastole (left) and systole (right) with the left and right atrium cropped away and the great vessels transected. The illustration
highlights the anatomic relations of the mitral valve, particularly its continuation with the aortic valve through the aorto-mitral curtain. AC, anterior commissure; AL, anterior leaflet;
AMC, aorto-mitral curtain; CA, circumflex artery, CS, coronary sinus; HB, His bundle; LFT, left fibrous trigone (anterolateral trigone); PC, posterior commissure; PL, posterior leaflet;
RFT, right fibrous trigone (posteromedial). Modified from Carpentiers Reconstructive Valve Surgery by Carpentier AC, Adams DH, Filsoufi F (Saunders Elsevier, 2010).
CT
PM
CZ
FIGURE 772. The mitral valve apparatus consists of the mitral leaflets, mitral annu-
lus, chordae tendineae, the papillary muscles, and the left ventricle. Normal function of
the mitral apparatus brings both leaflets together in systole and creates the coaptation
zone. CT, chordae tendineae; CZ, coaptation zone; PM, papillary muscles. Modified
from Carpentiers Reconstructive Valve Surgery by Carpentier AC, Adams DH, Filsoufi
F (Saunders Elsevier, 2010).
vulnerability of the posterior papillary muscle to ischemia and subse-
quent involvement in localized remodeling in the setting of ischemic
mitral valve regurgitation. The LV supports the entire mitral apparatus
due to the papillary muscles, and thus, ventricular dimensional changes
in the setting of volume overload and remodeling, whether ischemic or
not, can lead to leaflet tethering and mitral valve regurgitation.
21
This
important relationship of volume overload and remodeling to mitral
valve dysfunction has led to the common observation that mitral
regurgitation begets mitral regurgitation.
DEGENERATIVE MITRAL
VALVE REGURGITATION
DYSFUNCTION
It is important to clarify the etiology and
lesions that lead to clinically significant mitral
valve regurgitation because treatment options
and long-term outcomes vary in different
clinical scenarios. It is also useful to identify
the valve dysfunction that results from the
lesions of the mitral valve apparatus. The
main dysfunctions, lesions, and etiologies
that can result in mitral valve regurgitation
are shown in Fig. 773. Carpentier described
this pathophysiologic triad, and it is a use-
ful tool in everyday practice when assessing
patients with mitral valve regurgitation.
11,22

Dysfunctions are classified based on the posi-
tion of the leaflet margins in relationship to
the plane of the mitral annulus. Type I dys-
function implies normal leaflet motion, and
the most common cause of significant mitral
valve regurgitation is leaflet perforation or
isolated annular dilatation, which is com-
mon in the setting of primary atrial fibril-
lation. Type II dysfunction implies excess
leaflet motion and is most commonly asso-
ciated with chordal elongation or rupture
in the setting of degenerative mitral valve
disease. Type IIIA dysfunction designates
restricted opening and closing leaflet motion
and results typically from rheumatic valve
disease or other inflammatory scenarios that
lead to chordal and leaflet scarring and calci-
fication. Type IIIB dysfunction is associated
with restricted leaflet motion in systole and
is most commonly associated with papillary
muscle displacement and associated leaflet
tethering in the setting of ischemic or nonis-
chemic dilated cardiomyopathy. Some others
have chosen to designate conditions associ-
ated with types I, II, and IIIA dysfunction
as primary or organic mitral regurgitation
because the valve components (annulus, leaf-
lets, and chords) are diseased, whereas type
IIIB dysfunction is classified as secondary
or functional mitral regurgitation because
it is caused by perturbations in ventricular
geometry.
23
ETIOLOGY AND LESIONS
Although rheumatic heart disease is still the most common cause of
mitral regurgitation worldwide, it is no longer a common cause of
mitral regurgitation in developed countries.
24
Additionally, although
ischemic mitral regurgitation resulting from myocardial infarction
FIGURE 773. Pathophysiologic triad of mitral valve regurgitation composed of etiology, valve lesions, and leaflet
dysfunction.
Dysfunction Lesions Etiology
Type I
Normal leaflet motion Annular dilatation
Annular deformation
Leaflet perforation
Leaflet cleft
Ischemic cardiomyopathy
Dilated cardiomyopathy
Endocarditis
Congenital
Type II
Myxomatous degeneration
Chordal elongation
Chordal rupture
Papillary muscle elongation
Papillary muscle rupture
Degenerative disease
Fibroelastic deficiency
Marfan syndrome
Forme fruste Barlow
Barlow disease
Endocarditis
Rheumatic disease
Trauma
Ehler-Danlos syndrome
Type IIIA
Restricted leaflet motion
(restricted opening)
Leaflet thickening
Leaflet retraction
Chordal thickening
Chordal retraction
Chordal fusion
Calcification
Commissural fusion
Ventricular fibrosis
Rheumatic disease
Carcinoid disease
Radiation
Lupus eythematosus
Ergotamine use
Hypereosinophilic syndrome
Mucopolysaccharidosis
Type IIIB
Restricted leaflet motion
(restricted closure)
Leaflet tethering
Papillary muscle displacement
Ventricular dilatation
Ventricular aneurysm
Ventricular fibrosis
Dilated cardiomyopathy
Increased leaflet motion
(leaflet prolapse)
still accounts for 10% to 20% of mitral regur-
gitation earlier intervention in acute coronary
syndromes may be limiting the number of such
cases in the future.
25
degenerative mitral valve
disease is now the leading cause of mitral valve
disease and regurgitation.
26
Degenerative mitral
valve disease is defined by a spectrum of lesions,
varying from simple chordal rupture involving
prolapse of an isolated segment (particularly P2
or the middle scallop of the posterior leaflet) in
an otherwise normal valve to multisegmental pro-
lapse involving one or both leaflets in a valve with
significant excess tissue and a large annular size
(Fig. 774). Thus, the spectrum of degenerative
disease is evident in clinical practice, which car-
ries important surgical and clinical implications.
Furthermore, based on this spectrum of lesions,
degenerative disease may be further divided into
two main entitiesfibroelastic deficiency and
Barlow disease
27-29
(Fig. 775). Other terms used
to describe degenerative mitral valve disease,
including floppy valve syndrome, mitral valve
prolapse, click-murmur syndrome, and parachute
valve, cause much more confusion.
30
For instance,
mitral valve prolapse can cause a click and murmur
on physical examination, but the terms
fail to clarify etiology.
31
Fibroelastic deficiency generally occurs
in patients over the age of 60 years.
32

Generally, patients present with a rela-
tively short history of valve disease, and
mitral regurgitation is usually holosys-
tolic and severe. Fibroelastic deficiency
describes a condition associated with
fibrillin deficiency that often leads to
a rupture of one or more thinned and
elongated chordae, usually involving the
middle scallop of the posterior leaflet.
Chordal rupture is the most common
lesion causing mitral regurgitation in
fibroelastic deficiency. Leaflets are usually
thin and translucent, although the pro-
lapsing segment may show myxomatous
degeneration with leaflet segment thick-
ening and distension in long-standing
regurgitation. The key characteristic to
make a distinction of fibroelastic defi-
ciency within the spectrum of degen-
erative disease rests in the condition of
the adjacent segments to the prolapsing
segment, which are generally normal in
size, height, and character.
22,28,29
The valve
annular size, as defined by anterior leaflet
surface area, is generally 32 mm.
In contrast, patients with Barlow dis-
ease are generally younger (<60 years old)
at the time of surgical referral and often
present with a long history of follow-up
for a murmur. Barlow valve disease causes
a more diffuse and complex redundancy
(A) (B)
(C) (D)
FIGURE 774. Valve lesions in degenerative mitral valve disease. A. Fibroelastic deficiency; isolated P2 prolapse second-
ary to chordal rupture and mild segmental thickening. B. Fibroelastic deficiency; anterior leaflet prolapse due to multiple
ruptured chordae. C. Barlow disease; very tall and thickened P2 segment with otherwise normal P1 and P3 segments.
D. Barlow disease; large valve with redundant, thick, bulky leaflets. Note the fissures blurring of the junction between
atrium and leaflet.
FIGURE 775. Characteristic clinical and surgical differences between fibroelastic deficiency and Barlow
disease.
(36 mm) ( 32 mm)
Fibroelastic deficiency Barlow disease
Age at diagnosis > 60 y old < 60 y old
History of mitral regurgitation < 5 y > 10 y
Annular dilation
Leaet tissue Thin translucent with some
excess tissue
Thickened with diffuse
excess tissue
Segmental distribution Usually single segment (P2) Multisegmental
Chordae tendinae Thin and ruptured Irregular and elongated
Calcication + +++
of the valve, producing prolapse and myxomatous degeneration of mul-
tiple segments in one or both leaflets (see Fig. 775). The most common
lesions are excess leaflet tissue and leaflet thickening and distention, with
diffuse chordal elongation, thickening, and/or rupture. Severe annular
dilatation with giant valve size is evident (36 mm).
33
Additionally,
varying degrees of annular calcification are often observed, as are sub-
valvular fibrosis and calcification of the papillary muscles, in particular
the anterior papillary muscle.
34
Histologically, no specific cause of these abnormalities has been
defined, although increased incidence has been associated with some
genetic abnormalities (Fig. 776). However, no one genetic variation
still explains the pathology seen.
35-37
There are clear abnormalities
in the extracellular matrix and leaflet, and chordal strength is below
normal
38-40
(Fig. 777). Furthermore, increased activation of matrix
metalloproteases (MMP), which seem to play an important role in
leaflet enlargement, has been also observed. In this regard, a murine
model of overexpression of MMP2 produced a phenotype similar
to human degenerative mitral valve disease.
41
It is likely that genetic
abnormalities render the valve susceptible to the degenerative process,
and after mitral regurgitation develops, it places progressively more
hemodynamic stress on the valve, perpetually worsening the disease.
At present, no useful strategies have emerged for preventing or slowing
the progression of degenerative mitral regurgitation.
PATHOPHYSIOLOGY
Mitral regurgitation imparts a volume overload on the LV
because it must compensate for the volume lost to regurgi-
tation. Mild to moderate mitral regurgitation is well toler-
ated, possibly indefinitely, as long as the severity of mitral
regurgitation does not increase. The grades of severity as
suggested by the American College of Cardiology (ACC)/
American Heart Association (AHA) Guidelines for the
Management of Valvular Heart Disease
42
are listed in
(Table 771). Although these are only guidelines, they
stem in part from the fact that when regurgitant fraction
has been calculated for patients requiring mitral valve
surgery, it almost always exceeds 50%.
Severe mitral regurgitation can be divided into three
stages: acute, chronic compensated, and chronic decom-
pensated
43
(Fig. 778). In acute mitral regurgitation as
might occur from rupture of marginal chordae tendineae,
a small unprepared LV is suddenly confronted with a
FIGURE 776. Surgical view of the mitral valve with Barlow disease (left) and histology
(right) demonstrating cellular myxoid degeneration (hematoxylin and eosin, 100).
C
e
l
l

d
e
n
s
i
t
y

(
#
/
h
p
f
)
0
0
20
40
60
80
T
h
i
c
k
n
e
s
s

(
m
m
)
0
0
1
2
P < .001 P < .001
(A) (B)
Normal Normal Myxomatous Myxomatous
FIGURE 777. Quantitative analysis of mitral posterior leaflet tissue demonstrating significant thickening
and increased cellularity of myxomatous valves. Hpf, high-power field. Data from Rabkin E, Aikawa M,
Stone JR, et al. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remod-
eling in myxomatous heart valves. Circulation. 2001;104:2525-2532.
TABLE 771. Classification of the Severity of Mitral Valve Regurgitation
in Adults
Mitral Valve Regurgitation
Mild Moderate Severe
Qualitative
Angiographic grade 1+ 2+ 3-4+
Color Doppler jet
area
Small central
jet (< 4 cm
2

or <20% LA
size)
Signs of MR
greater than
mild but no
severe MR
Vena contracta
width >0.7 cm
with large central
jet (area >40%
of LA) or with a
wall-impinging jet
swirling in LA
Doppler vena con-
tracta width (cm)
<0.3 0.3-0.69 0.70
Quantitative
Regurgitant volume
(mL-beat)
<30 30-59 60
Regurgitant fraction
(%)
<30 30-49 50
Regurgitant orifice
area (cm
2
)
<0.20 0.20-0.39 0.40
Additional criteria
Left atrial size Enlarged
Left ventricular size Enlarged
LA, left atrium; MR, mitral regurgitation.
Data from Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated
into the ACC/AHA 2006 guidelines for the management of patients with valvular heart
disease: a report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the man-
agement of patients with valvular heart disease). Endorsed by the Society of Cardiovascular
Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of
Thoracic Surgeons. J Am Coll Cardiol. 2008;52(13):e1-e1.
large volume overload from blood returning from the pulmonary
veins summed with the regurgitant volume from the LV. The volume
overload causes existing sarcomeres to stretch maximally, increasing
end-diastolic volume and also stroke work through the Frank-Starling
mechanism. The extra pathway for ejection into the left atrium unloads
the LV, reducing end-systolic volume. Increased preload, decreased
afterload, and a reflexive sympathetically
mediated increase in contractility act in
concert to increase total stroke volume
and ejection fraction. However, because
50% or more of the total stroke volume is
regurgitated into the left atrium, forward
stroke volume and cardiac output are
reduced. Additionally, the left atrium,
which is of normal size and compliance,
receives its very high total volume at
high filling pressure, in turn leading to
pulmonary congestion. Thus although
LV function is normal or even supernor-
mal, the patient suffers the low output
and pulmonary congestion typical of LV
failure. Many patients will require imme-
diate corrective surgery at the time acute
severe mitral regurgitation develops. In
others, there may be a more gradual pro-
gression to severe mitral regurgitation so
that it is better tolerated. Such patients
may enter a chronic compensated phase.
In this phase, eccentric hypertrophy
has developed, increasing LV volume.
Because the radius term in the Laplace
equation for wall stress has increased
(stress = p r/2th, where p = LV
pressure, r = radius, and th = thick-
ness), afterload returns from subnormal
to normal. However, increased preload
and normal contractility permit a higher
than normal ejection fraction of a large
end-diastolic volume so that total stroke
volume is greatly increased.
44
This per-
mits forward stroke volume to return to
normal. Left atrial size is now enlarged,
permitting it to accept the large regurgi-
tant volume at nearly normal pressure.
Thus the patient now has a near-normal
cardiac output and filling pressure and
is likely to be asymptomatic even dur-
ing exercise. Although the patient may
enjoy a period of compensation for years,
eventually, contractile dysfunction sus-
tained from prolonged hemodynamic
overload ensues, and decompensation
becomes manifest.
45,46
Impaired contrac-
tility causes increased end-systolic vol-
ume and reduced stroke volume and
cardiac output. Filling pressure is re-
elevated, and the patient may develop
heart failure symptoms. Although mitral
regurgitation is usually thought to be
a phenomenon that unloads the LV,
in decompensated mitral regurgitation,
the increased radius term in the Laplace
equation causes systolic wall stress to
increase, and afterload is greater than normal, contributing to LV
dysfunction.
47
In mitral regurgitation, increased LV radius is not
offset by increased thickness, leading to the increase in wall stress.
Thus, the relatively thin wall of the mitral regurgitant ventricle is
beneficial to diastolic function and LV filling but is detrimental to LV
Preload
(SL)
Afterload
(ESS)
Contractile
function
Ejection
fraction
Regurgitant
fraction
Stroke
volume (cc)
Control (A)
Acute MR (B)
Compensated MR (C)
N
N
N
Decompensated MR (D)
2.07
2.25
2.19
2.19
90
60
90
100
0.67
0.82
0.79
0.58
0.0
0.5
0.5
0.7
100
70
95
65
100 cc
10 mm Hg
EDV 150
ESV 50
95 cc
15 mm Hg / 95 cc
EDV 260
ESV 110
EDV 170
ESV 30
EDV 240
ESV 50
70 cc
25 mm Hg / 70 cc 25 mm Hg / 85 cc
65 cc
(A)
(C)
(B)
(D)
FIGURE 778. Normal physiology (control) is compared with that of acute mitral regurgitation (chordal rupture), com-
pensated mitral regurgitation, and decompensated chronic mitral regurgitation starting with the upper left hand panel
and going counterclockwise. The sudden opening of a new pathway for regurgitant flow into the left atrium increases left
atrial pressure and preload (sarcomere length), in turn mildly increasing end-diastolic volume because resting sarcomere
length is still 90% of maximum length. Afterload (end-systolic stress) is decreased, allowing more complete left ventricular
ejection fraction and reducing end-systolic volume. These changes in loading increase ejection fraction and total stroke
volume, but because 50% of the total stroke volume is lost to regurgitation (regurgitant fraction), forward stroke volume
is decreased. Therefore, despite normal contractile fraction and increased ejection fraction, the patient presents with the
hemodynamics of congestive heart failure. In chronic compensated mitral regurgitation (upper right), eccentric hypertro-
phy leads to substantial LV enlargement allowing it to pump extra volume, in turn resetting forward stroke volume toward
normal. Enlargement of the left atrium allows it to accommodate the regurgitant volume at lower filling pressure. In the
presence of decompensated chronic mitral regurgitation, muscle damage caused by prolonged severe volume overload
reduces the effectiveness of ventricular ejection, and end-systolic volume increases. There is a further increase in diastolic
volume, which is not compensatory, resulting in a decrease in total and forward stroke volumes. EDV, end-diastolic volume;
ESS, end-systolic stress; ESV, end-systolic volume; MR, mitral regurgitation; SL, sarcomere length. Adapted from OGara
P, Sugeng L, Lang R, et al. The role of imaging in chronic degenerative mitral regurgitation. JACC Cardiovasc Imaging.
2008;1(2):221-237.
systolic function because maladaptive LV remodeling causes increased
afterload.
48,49
It is important to note that ejection fraction may be held
in the normal range by enhanced preload despite contractile dysfunc-
tion and afterload excess.
The LV dysfunction caused by severe mitral regurgitation stems
from multiple pathologic processes. At the cellular level, there is loss
of contractile elements in the endocardium in experimental models of
mitral regurgitation and in the papillary muscles of humans.
50,51
This
abnormality can be reversed by valve repair/replacement in the experi-
mental animal and in man and also by administration of -blockers
in the experimental animal.
52-54
These data suggest that sympathetic
overdrive, which is present in both human and experimental mitral
regurgitation, contributes to the cellular pathology of the disease.
55,56

In addition, the force-frequency relationship of the mitral regurgitant
ventricle is depressed but can be normalized by the administration of
forskolin, suggesting that abnormalities in calcium handling contribute
to LV dysfunction.
57
The LV remodeling of mitral regurgitation is unique and probably
dictated by the loading conditions present. Mitral regurgitation stands
out as a pure volume overload.
58
In most other volume overloads such
as anemia, heart block, and aortic regurgitation, the extra volume
generated by the LV is ejected into the aorta, where the high stroke
volume generates a widened pulse pressure and an element of systolic
hypertension. Thus, most volume overloads are in fact a combination
of volume and pressure overload, and the LV remodels accordingly.
In aortic regurgitation, for instance, not only is LV volume increased
to compensate for the regurgitated volume, but also LV thickness is
greater than normal.
59
Conversely, in mitral regurgitation, the extra
volume is ejected into the left atrium, and systolic pressure is often low-
normal. In turn, LV thickness is low-normal, producing a thin-walled,
large LV, as noted earlier.
Several decades ago, Grossman et al
60
proposed a paradigm for LV
remodeling wherein the increased systolic wall stress of pressure over-
load was transduced to generate new sarcomeres laid down in parallel
such that myocyte thickness and LV wall thickness increased. Increased
wall thickness in the denominator of the Laplace equation offsets the
increased pressure term in the numerator, keeping wall stress (after-
load) normal and facilitating LV ejection. However, the increased
diastolic stress from the sarcomere stretch of volume overload leads to
new sarcomeres being laid down in series, increasing myocyte length
and ventricular volume and allowing the ventricle to increase stroke
volume. In experimental acute pressure overload, a 35% increase in
contractile protein synthesis occurs within 6 hours of the onset of the
pressure overload.
61
Conversely, following the acute volume overload
of mitral regurgitation and during chronic mitral regurgitation, no
increase in protein synthesis has ever been detected.
62
Because increased
muscle mass can only accrue from either increased protein synthesis or
decreased protein degradation and because synthesis is not increased, it
has been suggested that the hypertrophy of mitral regurgitation devel-
ops from a process opposite of that of pressure overload (ie, decreased
protein degradation instead of increased protein synthesis). It might be
that older contractile proteins are less robust, a factor in part respon-
sible for the LV dysfunction that ultimately develops.
As noted earlier, if mitral regurgitation is corrected before LV dysfunc-
tion is long standing, ventricular function can recover dramatically both in
the experimental animal and in humans. Recovery is marked by restora-
tion of myocyte contractile elements and a reduction in adrenergic drive.
In summary, the pure volume overload of mitral regurgitation is
compensated by eccentric LV hypertrophy, which enables rapid LV dia-
stolic filling and an increase in stroke volume. However, this remodel-
ing eventually encumbers systolic emptying. This maladaptive geometry,
together with the adrenergic overactivation, results in contractile pro-
tein loss, abnormal calcium handling, and a decrease in contractility. If
mitral regurgitation is corrected in a timely fashion, this pathophysiol-
ogy can be reversed.
CLINICAL PRESENTATION
The typical symptoms of mitral regurgitation are those of LV failure and
include dyspnea on exertion, orthopnea, and paroxysmal nocturnal dys-
pnea. If pulmonary hypertension has developed, ascites and edema may
also occur. Debate continues as to whether or not there is a mitral valve
prolapse syndrome (ie, a group of symptoms associated with degenera-
tive mitral valve disease). These symptoms are thought to include palpi-
tation, fatigue, and chest pain, which are atypical of classic angina and
syncope or presyncope.
63,64
These symptoms are common in the general
population, and whether they occur more frequently in patients with
mitral valve prolapse continues to be a subject of controversy.
On physical examination, the reduced forward stroke volume tends
to reduce systolic blood pressure and pulse pressure, but this finding is
quite variable, and some patients are actually hypertensive. The apical
beat is displaced downward and to the left in chronic severe disease
due to LV dilatation. The typical murmur is holosystolic if the lesion
is chordal rupture and is heard best at the apex and radiates to the
axilla. There is a weak positive correlation between mitral regurgitation
severity and murmur intensity.
65
Severe mitral regurgitation is often
accompanied by an S
3
produced by the emptying of the large left atrial
volume under higher than normal pressure into the LV. The presence
of an S
3
is often evidence that the mitral regurgitation is severe, rather
than indicating that the patient is in heart failure.
Mitral valve prolapse in Barlow disease is sometimes referred to as
click-murmur syndrome, indicative of the typical findings on physical
examination of a mid-systolic click followed by a late systolic murmur.
The click is generated as the elongated chordae are stretched taut. The
valve leaflets then move past their coaptation point, and the murmur
ensues. Physical maneuvers that decrease LV volume, such as standing
or the Valsalva maneuver, cause the click and murmur to come ear-
lier in systole and consequently to increase in intensity (Table 772).
This occurs because a decrease in LV volume reduces tension on the
mitral valve, in effect lengthening the valve apparatus. Maneuvers that
increase LV volume, such as squatting or lying down, may cause the
opposite effect or may cause the click and murmur to disappear all
together. In some patients, only the click or murmur is present, or
mitral valve prolapse may occur without any physical findings. As the
severity of mitral regurgitation worsens, the murmur becomes progres-
sively more holosystolic, and the click may disappear.
TABLE 772. Response of the Murmur Caused by Degenerative Mitral
Valve Disease to Physiologic Interventions
Position Timing Intensity
Standing
Recumbent or more
Squatting or more
Hand grip
Valsalva
Amyl nitrite
Laboratory Findings
The electrocardiogram (ECG) and chest
x-ray often demonstrate nonspecific abnor-
malities. The ECG may show evidence of
left atrial enlargement and LV hypertro-
phy, and T wave abnormalities have been
reported in the inferior leads in patients
with prolapse. Because atrial fibrillation is
common in patients with mitral regurgita-
tion, a baseline ECG is important to have
on file in case this arrhythmia occurs later.
The chest x-ray may show cardiac enlarge-
ment and pulmonary congestion if heart
failure has intervened.
Although the previously mentioned
studies are modestly useful in diagnos-
ing mitral regurgitation, the echocardio-
gram is indispensible
66-71
(Table 773).
Transthoracic images can demonstrate
the pathoanatomy or lesions responsi-
ble for mitral regurgitation, the degree
of severity of mitral regurgitation, and
the effect of mitral regurgitation on LV
remodeling and function and can help
clarify the likelihood of eventual valve repair.
72-74
Because the esophagus
virtually abuts the left atrium, transesophageal echocardiograms usu-
ally produce clear images of the mitral valve and the left atrium and
ventricle.
Echocardiographic Pathoanatomy
The typical echocardiography features of fibroelastic deficiency and
Barlow disease are demonstrated in Fig. 779. In patients with fibroelas-
tic deficiency, echocardiographic findings typically include an isolated
segmental prolapse with flail leaflet segment due to chordal rupture
leading to holosystolic mitral regurgitation. Conversely, echocardio-
graphic findings in patients with Barlow disease include mid-systolic
and frequently diffuse regurgitation with multiple jets consistent with
chordal elongation affecting grossly thickened myxomatous leaflets.
The posterior leaflet is often displaced toward the left atrium away from
the ventricular hinge, resulting in a cul-de-sac along the posterior por-
tion of the annulus, which potentially becomes a precipitating factor
for the development of annular fissures and calcification.
75
Real-time three-dimensional echocardiography is now available at
several centers. Its main advantage is that it replicates the surgical view,
the view of the mitral valve the surgeon will see upon opening the left
atrium.
72
Quantitative analysis using proprietary software also allows
precise determination of prolapsing or restricted segments within the
plane of the annulus.
76
As such, this imaging technique is useful in
identifying the leaflet segments involved with disease and planning the
surgical approach to repair the mitral valve.
Echocardiographic Severity Assessment
Multiple echocardiography clues are used to determine the severity of a
patients mitral regurgitation. All should be taken in the context of left
atrial and ventricular size; severe mitral regurgitation is associated with
chamber dilatation unless it is acute. If severe mitral regurgitation is
thought to be present in the face of normal-sized, left-sided chambers
or if severe chamber dilatation is present but the mitral regurgitation is
thought to be only mild, reassessment of the mitral regurgitation sever-
ity is warranted because severity and the expected changes in left atrial
and ventricular geometry are inconsistent with one another.
TABLE 773. American College of Cardiology/American Heart
Association Guidelines for Echocardiographic Evaluation and
Management of Asymptomatic Patients With Degenerative Mitral
Valve Disease
Class I
Echocardiography is indicated for the diagnosis of MVP and assessment
of MR, leaflet morphology, and ventricular compensation in asymptomatic
patients with physical signs of MVP. (Level of Evidence: B)
Class lla
Echocardiography can effectively exclude MVP in asymptomatic patients who
have been diagnosed without clinical evidence to support the diagnosis.
(Level of Evidence: C)
Echocardiography can be effective for risk stratification in asymptomatic
patients with physical signs of MVP or known MVP. (Level of Evidence: C)
Class III
Echocardiography is not indicated to exclude MVP in asymptomatic patients
with ill-defined symptoms in the absence of a constellation of clinical symp-
toms or physical findings suggestive of MVP or a positive family history.
(Level of Evidence: B)
Routine repetition of echocardiography is not indicated for the asymptomatic
patient who has MVP and no MR or MVP and mild MR with no changes in
clinical signs or symptoms. (Level of Evidence: C)
MR, mitral regurgitation; MVP, mitral valve prolapse.
Adapted from Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorpo-
rated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart
disease: a report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the man-
agement of patients with valvular heart disease). Endorsed by the Society of Cardiovascular
Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of
Thoracic Surgeons. J Am Coll Cardiol. 2008;52(13):e1-e1.
(A) (B) (C) (D)
(E) (F) (G) (H)
FIGURE 779. Transesophageal echocardiographic correlation of two-dimensional (2D) and three-dimensional (3D)
rendering in the differentiation of degenerative mitral disease. A. Fibroelastic deficiency with a ruptured chord to P2 (pos-
terior middle scallop). B. 3D volume rendering of the same valve. C. 3D rendering using quantitative analysis (red area
corresponds to prolapsing area). D. Surgical view. E. Barlow disease with multisegment prolapse and excess leaflet tissue.
F. 3D volume rendering of the same valve. G. 3D rendering using quantitative analysis (red areas correspond to prolapsing
areas). H. Surgical view. A, anterior; AL, anterolateral; Ao, aorta; P, posterior; PM, posteromedial.
In general, the severity of mitral regurgitation is graded using clues
from the color flow mitral regurgitation jet as characterized in Bonow
et al.
42
Jet size and depth are often used during visual inspection to
grade mitral regurgitation severity, but eyeball estimation of severity
can be misleading. Consequently, more quantitative measures, such as
vena contracta width, effective regurgitant orifice area, and regurgitant
fraction and flow, are often used to better establish the severity of mitral
regurgitation. Figure 7710 demonstrates the proximal isovelocity
surface area (PISA) method for calculating effective regurgitant orifice
area. This method uses two principles: (1) area = flow/velocity and
flow = area velocity; and (2) mitral flow converges into a hemisphere
as flow approaches the mitral valve from the LV. The velocity of flow
is known from the machine settings for velocity aliasing, and the area
of a hemisphere is A = 2pr
2
, where r is the distance from the valve
to the convergence zone. Estimation of mitral regurgitation severity
continues to be a vexing problem. It is clear that visual estimation by
itself may be inaccurate in many cases, and yet the more quantitative
approaches described earlier are not always applicable (eg, eccentric
mitral regurgitation jet) and not even agreed upon as helpful by experts
in the field. Thus, all available clues may be needed to estimate the true
severity of a patients mitral regurgitation, and severity should never be
judged casually.
Other Imaging Techniques
Exercise Testing As noted later, the onset of symptoms is a negative
prognostic occurrence if left untreated by mitral valve surgery. In
some cases, however, symptomatic status may be difficult to ascertain
because the patient either denies symptoms or does not recognize an
insidious decline in exercise tolerance. In such cases, a formal exercise
test can establish exercise tolerance and may reveal latent symptoms.
In some patients with exercise-induced symptoms in whom a resting
echocardiogram indicates less than severe mitral regurgitation, exercise
echocardiography may demonstrate worsening of mitral regurgitation
during exercise, explaining the patients symptomatic status.
77
Cardiac Catheterization Once the mainstay of evaluation, invasive
hemodynamic evaluation is now reserved for cases in which the diag-
nosis of the severity and impact of mitral regurgitation are uncertain.
Although the exact mechanisms of dyspnea are not entirely under-
stood, in cardiac disease, dyspnea correlates best with elevated left atrial
pressure. Thus, elevated left atrial or wedge pressure at rest or during
dynamic or handgrip exercise during heart catheterization can demon-
strate the hemodynamic underpinnings of a patients symptoms. The
presence of a large v wave (twice the mean left atrial pressure) in the
pulmonary capillary wedge or left atrial tracing may further indicate
severe mitral regurgitation. Remembering that left ventriculography
visualizes actual flow of blood from LV to left atrium, whereas color
flow Doppler only visualizes flow velocity, a well-performed ventricu-
logram can help clarify mitral regurgitation severity in some cases, pro-
vided a sufficient dye load is used.
Magnetic Resonance Imaging Magnetic resonance imaging can very
precisely measure regurgitant flow and left atrial and ventricular
volumes. However, it is not a valid alternative to echocardiography
because it does not visualize the mitral valve and its pathoanatomy
as well.
MEDICAL THERAPY
Infective Endocarditis Prophylaxis
The risk of infective endocarditis is significantly increased in patients
with mitral valve prolapse, especially in patients with thickened
redundant valves.
78
Because of this risk, antibiotic prophylaxis was
recommended prior to undergoing procedures that are known to
cause bacteremia such as teeth cleaning, scaling, and colonoscopy. This
recommendation was based on the theory (with little proof) that pro-
phylaxis was actually effective. Recently, amid controversy, the ACC/
AHA guidelines were changed and no longer make such prophylaxis
mandatory.
42
The change was based in part on the lack of proof of pro-
phylaxis effectiveness and in part on the fact that bacteremia is a daily
occurrence with eating and dental flossing but antibiotic prophylaxis
for these activities would be impossible.
Vasodilator Therapy
In acute severe mitral regurgitation, agents that reduce afterload, such
as vasodilators or even the intra-aortic balloon pump, are effective in
relieving heart failure.
79,80
Such therapy works by causing preferential
flow away from the left atrium and into the aorta as resistance to flow
into the aorta is reduced. Success of afterload reduction in acute mitral
regurgitation led to trials of vasodilators in patients with long-standing
mitral regurgitation. Although no large randomized trials have been
conducted, the small trials that have been performed have been
confusing but largely negative.
81-84
It is of interest then that although
these results have led the ACC/AHA to recommend against the use
of vasodilators in chronic mitral regurgitation, a recent survey shows
that a majority of practitioners use such agents, in the belief that they
may forestall the progression of the disease.
85
Although vasodilators
and other agents should be used to treat hypertension in patients with
mitral regurgitation, there is no evidence that they will delay the need
for eventual valve surgery.
b-Adrenergic Blockade
Adrenergic overstimulation appears to be a significant detriment in the
pathophysiology of mitral regurgitation, and there is evidence of ben-
efit with the use of -blockers in experimental mitral regurgitation.
86
A
recent small trial that randomized mitral regurgitation patients to
receive placebo or metoprolol found that the -blockers reduced LV
work as a possible mechanism by which -blockers might be benefi-
cial in treating the disease.
87
However, no trials exist to indicate that
-blockers are effective therapy in mitral regurgitation other than as
therapy for hypertension. Thus, the use of -blockers to treat mitral
regurgitation in normotensive subjects should be viewed as experi-
mental only.
R
V2
V1
LA
LV
V1
V2
Flow 2 = Flow 1 = 2 x R
2
x V1
ERO = Flow 1 / V2
FIGURE 7710. Principles of the proximal isovelocity surface area (PISA) method
of mitral regurgitation quantitation. The flow convergence is indicated by the large
open blue hemisphere. V1 is the velocity on the flow convergence hemisphere (white
arrows), whereas the jet velocity is V2. The formula indicates the calculation of regurgi-
tant flow (Flow 2) and effective regurgitant orifice area (ERO). The orange arrow (R) is
the radius of the hemisphere of flow convergence. LA, left atrium; LV, left ventricle.
SURGICAL THERAPY
Timing of Surgery
Severe mitral regurgitation is a mechanical problem with only a defini-
tive mechanical solution; at this time, the only definitive treatment is
surgery, either with mitral valve repair or mitral valve replacement.
42

Although no randomized trials of mitral valve repair versus replace-
ment exist (and it is unlikely that such trials would be conducted), a
repair is favored over replacement in patients with degenerative mitral
valve disease for several reasons (Fig. 7711). These include lower
perioperative risk and improved event-free survival in the majority
of operated patients, the freedom from the various complications of
prosthetic heart valves (see Chap. 80), and better postoperative LV
function.
88-91
Although mitral valve repair rates have risen throughout
the last decade
92
and currently approach 70% in the Society of Thoracic
Surgery Database,
93
the application of mitral valve repair remains quite
variable, with some surgeons having repair rates of <30%, particularly
for more complex scenarios such as anterior or bileaflet prolapse,
94,95

whereas others have successful repair rates of 90%.
25,33,93,96,97
Less Than Severe Mitral Regurgitation Currently, there is no strong
indication to repair any degree of mitral regurgitation with a severity
of less than severe, except in symptomatic patients in whom there is a
high suspicion that the mitral regurgitation grade may be underesti-
mated. In such patients, exercise testing, as described earlier, is useful
to clarify the decision making.
98
Although there is the concern that
moderate mitral regurgitation will likely worsen over time, the major-
ity of patients should be treated with close observation until the mitral
regurgitation has progressed in severity.
42
Asymptomatic Severe Mitral Regurgitation With Preserved LV
Function The standard class I indications for mitral valve surgery are
the onset of symptoms and the onset of LV dysfunction.
42,99
However,
many experts (including those writing the ACC/AHA guidelines) would
offer early mitral valve repair for asymptomatic patients who have pre-
served LV function.
42,45,46,99-103
This strategy of early surgery is based on
two major tenets. The first is that in the patient being evaluated, mitral
valve repair will almost certainly be performed under at least a 90%
probability of repair (this number is likely to increase to 95% in the
next guidelines) based on preoperative evaluation of the valve anatomy
(Fig. 7712). If a mitral valve replacement with its higher operative
risk and more morbid postoperative outcome were performed, the
unwarranted risk of early surgery would not be justified. The second
tenet is that mitral regurgitation is a progressive disease and not as
well tolerated as was once thought. Recent studies indicate that within
5 years, a significant number of patients with severe mitral regurgita-
tion will develop a significant adverse event (eg, symptom onset, atrial
fibrillation, LV dysfunction)
8,46
(Fig. 7713). Thus, it can be argued
that early intervention with a low-risk procedure such as mitral valve
repair is preferable to waiting for complications to occur.
100,103
A recent
nonrandomized evaluation of this strategy suggested a survival benefit
to early surgery, providing additional support to the argument for
early but elective intervention
102
(Fig. 7714). Some patients in this
later study, however, refused surgery after symptoms occurred, which
may have compromised the outcomes in the conservatively managed
group. If a strategy of watchful waiting is pursued, then careful serial
echocardiographic assessment, ideally in a dedicated valve clinic, must
be performed, with strict adherence to guideline-directed intervention
for symptoms and/or changes in ventricular geometry or function.
Symptomatic Severe Mitral Regurgitation The occurrence of severe
New York Heart Association class III or IV preoperative symptoms
confers a poor prognosis for patients postoperatively, even if LV func-
tion is preserved
104-106
(Fig. 7715). Thus, it is important to correct
mitral regurgitation at the onset of even mild symptoms because wait-
ing for symptoms to progress appears dangerous. In fact, the onset of
symptoms represents a change in cardiac physiology because the mitral
regurgitation has begun to affect cardiac output and left atrial filling.
In addition, there may be a small risk of sudden death in patients who
have developed symptoms.
6,107
Thus, symptom onset is a clear indica-
tion for surgery, whether it be mitral repair or replacement.
Asymptomatic LV Dysfunction As LV dysfunction develops in mitral
regurgitation, many patients become symptomatic, but some do not.
However, if mitral regurgitation is not corrected at that time, LV func-
tion will worsen, and dysfunction may become permanent, leading
to a poor surgical outcome and eventually death. In patients lacking
symptoms, some other objective measure of LV function must be used
to determine the need for mitral valve surgery. Two accepted bench-
marks indicating the onset of LV dysfunction are an ejection fraction
of 60% or an end-systolic dimension 40 mm.
42,99
When these indica-
tors become evident on echocardiography, mitral surgery should be
undertaken. Recent studies from the Mayo Clinic have suggested supe-
rior survival if the end-systolic dimension is <40 mm
108
and superior
recovery of LV function if the ejection fraction is 65% at the time of
mitral surgery,
109
emphasizing the importance of timely identifica-
tion of changes in left ventricular function in asymptomatic patients
(Fig. 7716). Once a patient has been identified as having severe mitral
regurgitation, follow-up with history, physical examination, and serial
echocardiograms (or other imaging studies) should be conducted
every 6 to 12 months to ensure that the best time for intervention is
not overlooked. The previously mentioned measures of LV function,
although useful, are imprecise and reflect changes in the LV after the
negative impact of mitral regurgitation has already been realized. It is
likely that more sophisticated measures of LV function and the use of
biomarkers indicating an adverse myocardial response to mitral regur-
gitation will help to better determine the optimum timing of surgery
in the future. For example, high B-type natriuretic peptide levels have
been found to be associated with less favorable outcomes in chronic
mitral regurgitation compared with poor exercise tolerance test results
in asymptomatic patients.
98,110
Follow-up (y)
S
u
r
v
i
v
a
l

(
%
)
Mitral valve repair
Mitral valve replacement
P = .0001
0 5 10 15
0
20
40
60
80
100
FIGURE 7711. Probability of survival (death from any cause) among patients having
mitral valve repair versus replacement for isolated posterior leaflet prolapse. Adapted
from Suri RM, Schaff HV, Dearani JA, et al. Survival advantage and improved durability
of mitral repair for leaflet prolapse subsets in the current era. Ann Thorac Surg. Sep
2006;82(3):819-826.
Class I Class I
Class IIa
Chronic severe mitral regurgitation
Clinical evaluation + echo
Clinical symptoms?
Yes
LV function?
No
LV function?
Normal LV function
EF > 60%
ESD < 40 mm
LV dysfunction
EF 60% and/or
ESD 40 mm
EF > 30%
ESD 55 mm
EF < 30%
ESD > 55 mm
New-onset AFib?
Pulmonary HT?
Class IIa
Mitral valve repair, if not
possible, chordal sparing mitral
valve replacement
Reference mitral surgeon
Likelihood of repair 95%
Operative mortality 1%
Mitral valve repair
Follow-up (6 mo)
Yes
No
Yes
No
Class IIa
FIGURE 7712. Proposed algorithm for management of patients with chronic severe mitral regurgitation. AFib, atrial fibrillation; Echo, echocardiography; EF, ejection fraction;
ESD, end-systolic diameter; HT, hypertension; LV, left ventricle; mo months. Modified from Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated into
the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force
on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular
Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52(13):e1-e1.
Discordance With Guideline Management in Real-World
Practice
Several recent studies have suggested discordance with timely refer-
ral of patients with chronic mitral valve regurgitation for surgical
intervention despite the presence of one or more accepted guideline
indications for surgery. A substudy of the Euro Heart Survey found
that 49% of patients with symptomatic severe mitral regurgitation of
various etiologies were not referred for surgery and that clinicians were
placing too much emphasis on age and ejection fraction in their deci-
sion to not offer patients surgery.
111
Another recent study involving a
large number of Canadian cardiologists in either university-based or
community-based practice suggested that nearly half were unfamiliar
with even class I indications for surgical intervention in patients with
severe mitral regurgitation.
112
A separate recent study at the University
of Michigan similarly found that over one-third of patients with degen-
erative disease and a guideline indication for surgical intervention were
not referred for surgical evaluation, despite the fact that no high-risk
patients were turned down for surgery during the study period, and
surgical results in this subgroup were excellent.
113
Thus, it appears
that perceived risks of surgical intervention in real-world practice
are often overestimated, suggesting the need for continued education
of practicing clinicians regarding current guidelines and best practice
outcomes.
Surgical Access
Various approaches have been described to surgically access the mitral
valve. The gold standard and still most popular approach is through
a median sternotomy, and some groups have limited the incision to
a hemi-lower sternotomy.
96,97,114
The other approach that has seen
resurgence in popularity is the right thoracotomy approach.
115-117

Cardiopulmonary bypass is required to perform mitral valve sur-
gery and is accomplished via the right atrium and aorta in a sternal
approach and most commonly via femoral artery and vein cannula-
tion from a right thoracotomy approach. The mitral valve is accessed
through an incision directly into the left atrium or through an incision
through the atrial septum via the right atrium. Video assistance has
allowed smaller incisions via the right thoracotomy approach, with
comparable results to the sternotomy approach in selected series.
118,119

One potential issue with the right thoracotomy approach is an apparent
increased risk of stroke compared with the sternal approach.
120
Robotic
assistance through a right thoracotomy approach has been described
in a few centers in the United States with good results, although this
approach remains uncommon due to increased complexity and costs
and lack of data of apparent clinical benefits.
121,122
Repair Techniques
Carpentiers techniques are the foundation of mitral valve repair
strategies.
11,123,124
A lesion-specific approach addresses leaflet, chordal,
and annular pathology. Resection of abnormal leaflet segments and
correction of chordal pathology with resuspension of the margin of
prolapsing leaflet segments are common techniques; recently, less or
Follow-up (y)
E
v
e
n
t
-
f
r
e
e

s
u
r
v
i
v
a
l

(
%
)
Any event
Symptoms
0 1 2 3 4 5 6 7 8
0
20
40
60
80
100
Asymptomatic LVD
New-onset AF/PHT
FIGURE 7713. Red line shows survival free of any event to indicate surgery. Blue line
shows survival free of symptoms. Yellow line shows survival free of asymptomatic left
ventricular dysfunction. Green line shows survival free of asymptomatic development
of atrial fibrillation (AF) and/or pulmonary hypertension (PHT) to indicate surgery.
Adapted from Rosenhek R, Rader F, Klaar U, et al. Outcome of watchful waiting in
asymptomatic severe mitral regurgitation. Circulation. 2006;113(18):2238-2244.
Follow-up (y)
S
u
r
v
i
v
a
l

(
%
)
Mitral valve repair
Watchful waiting
P = .001
0 1 2 3 4 5 6 7
0
20
40
60
80
100
FIGURE 7714. Comparison of event-free survival rates between the operated and
conventional treatment groups in propensity-matched pairs. Adapted from Kang DH,
Kim JH, Rim JH, et al. Comparison of early surgery versus conventional treatment in
asymptomatic severe mitral regurgitation. Circulation. 2009;119(6):797-804.
Follow-up (y)
S
u
r
v
i
v
a
l

(
%
)
0
NYHA I-II
NYHA III-IV
P = .0001
1 2 3 4 5 6 7 8 9 10
0
20
40
60
80
100
(A)
(B)
Follow-up (y)
S
u
r
v
i
v
a
l

(
%
)
0
NYHA I-II
NYHA III-IV
P = .0003
1 2 3 4 5 6 7 8 9 10
0
20
40
60
80
100
FIGURE 7715. Overall survival compared for patients in New York Heart Association
(NYHA) class I/II and those in class III/IV who had a preoperative left ventricular ejection
fraction (A) 60% or (B) <60%. Adapted from Tribouilloy CM, Enriquez-Sarano M,
Schaff HV, et al. Impact of preoperative symptoms on survival after surgical correction
of organic mitral regurgitation: rationale for optimizing surgical indications. Circulation.
1999;99(3):400-405.
no leaflet resection and use of artificial neochordae to correct leaflet
prolapse have gained in popularity
125,126
(Fig. 7717). Regardless of the
leaflet and chordal approach, essentially all mitral valve repairs include
an annuloplasty ring, which reshapes the annulus and addresses poste-
rior annular dilatation, which is always present in long-standing severe
mitral valve regurgitation
18,22
(Fig. 7718).
Replacement Techniques
Mitral valve replacement should be uncommon in patients
with degenerative mitral disease if patients are appropri-
ately referred to surgeons experienced with mitral valve
repair.
33,90,91,96,97
Advanced Barlow disease with bileaflet
prolapse is probably the most commonly replaced valve
by less experienced surgeons. If valve mitral valve replace-
ment is necessary, a chordal sparring approach should
be used.
127
The posterior leaflet with chords and often
all or portions of the anterior leaflet with chords are
incorporated into the sutures used to secure the replace-
ment valve prosthesis. This technique preserves chordal-
ventricular-annular continuity, which is important to
preserve long-term ventricular shape and performance.
128

Although guidelines continue to recommend mechanical
valve replacement when necessary in patients under the
age of 70 years, in practice, more and more patients are
selecting bioprostheses regardless of age because of their
desire not to commit to a lifetime of warfarin therapy.
Surgical Centers of Excellence
The latest guidelines recommend that patients with
degenerative mitral valve disease be referred to refer-
ence centers with the skill and expertise in mitral valve
repair.
42
Many groups are now emphasizing the need to
concentrate volume in select centers
129
and to use specific
surgeons to optimize outcomes and to refer selected
patients with complex valve pathologies to super spe-
cialists in mitral valve reconstruction.
130-132
This is par-
ticularly true in asymptomatic patients with preserved
Follow-up (y)
S
u
r
v
i
v
a
l

(
%
)
LVESD > 40 mm
LVESD 40 mm
P = .019
0 1 2 3 4 5 6 7 8 9 10
0.4
0.5
0.6
0.7
0.8
0.9
1.0
FIGURE 7716. Adjusted postoperative overall survival according to left ventricular
end-systolic diameter (LVESD) in operated patients with mitral regurgitation. Adapted
from Tribouilloy C, Grigioni F, Avierinos JF, et al. Survival implication of left ventricular
end-systolic diameter in mitral regurgitation due to flail leaflets a long-term follow-up
multicenter study. J Am Coll Cardiol. 2009;54(21):1961-1968.
Quadrangular resection Triangular resection PTFE neochordoplasty
FIGURE 7717. Current most applied surgical approaches to posterior middle scallop (P2) prolapse.
Dashed lines represent the area of leaflet to be excised. PTFE, polytetrafluoroethylene.
(A) (B)
(C) (D)
FIGURE 7718. Annuloplasty ring implantation. A. Surgical view of the mitral valve
shows severe annular dilatation. B. Ring size selection is based on measurements of the
intercommissural distance and the height of the anterior leaflet. C. Sutures are placed
carefully around the annulus and through the ring. D. Final result after remodeling
annuloplasty (4:3 ratio). Modified from Carpentiers R econstructive Valve Surgery by
Carpentier AC, Adams DH, Filsoufi F (Saunders Elsevier, 2010).
Follow-up (y)
S
u
r
v
i
v
a
l

(
%
)
0 4 8 12
0
20
40
60
80
100
Anterior leaflet prolapse
Posterior leaflet prolapse
Bileaflet prolapse
P = .019
Anterior leaflet prolapse
Posterior leaflet prolapse
Bileaflet prolapse
P = .013
Follow-up (y)
S
u
r
v
i
v
a
l

(
%
)
0 4 8 12
0
20
40
60
80
100
No Yes
No Yes
Greater than mild MR on predischarge echo?
Progression of
native disease
Moderate to severe MR after valve repair
Residual MR
Compatible with
primary pathology
Recurrent MR
Optimal choice of annuloplasty?
Optimal repair techniques?
Echo or ndings
Unexplained by primary
pathology or surgery
Ring or suture
dehiscence
Indeterminate mechanism
or new disease
Technical
failure
Inadequate
repair
FIGURE 7719. Freedom from reoperation (A) and recurrent moderate or severe mitral regurgitation (B) in patients with anterior, posterior, and bileaflet prolapse. Adapted from
David TE, Ivanov J, Armstrong S, et al. A comparison of outcomes of mitral valve repair for degenerative disease with posterior, anterior, and bileaflet prolapse. J Thorac Cardiovasc
Surg. 2005;130(5):1242-1249.
FIGURE 7720. Algorithm for ascribing the cause of mitral regurgitation (MR) occurring after mitral valve repair. Echo, echocardiography; OR, operating room. Adapted from
Anyanwu AC, Adams DH. Why do mitral valve repairs fail? J Am Soc Echocardiogr. 2009;22(11):1265-1268.
left ventricular function, for whom guidelines only recommend early
surgery if mitral valve repair is a near certainty (see Fig. 7712).
Surgical Outcomes
Current data show extremely low mortality rates with surgical therapy
for mitral valve regurgitation.
33,90,91,109,129,132
The rate of very long-term
freedom from reoperation is high after mitral valve repair,
133
although
a return of moderate to severe mitral valve regurgitation has been
reported in recent series to occur at a rate of approximately 1% per year
over the first 10 years
134-137
(Fig. 7719). Failure to use an annuloplasty
ring, chordal shortening techniques (which are now uncommon), and
anterior leaflet pathology are all associated with higher repair failure
rates.
135-137
Although technical failures account for residual and some
early repair failures, progression of disease with new pathology is the
most common cause of long-term failure
138,139
(Fig. 7720).
Future Perspective
Earlier surgical intervention before changes in ventricular performance
or geometry will likely continue to gain in popularity, especially if sur-
gical results and mitral valve repair rates continue to improve. More
widespread use of functional testing and further characterization of
biomarkers and ventricular performance will also likely play a role in
selective earlier referral in the future. Percutaneous approaches that
target leaflet prolapse or annular dilatation remain in various stages of
development and may also one day play a role in the future care of very
selected patients with mitral valve regurgitation.
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1721 CHAPTER 77: Mitral Valve Regurgitation

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