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From the Noninvasive Cardiac Laboratory, Massachusetts General Hospital,
Department of Medicine, Harvard Medical School, Boston, Mass (E.S., A.S.,
A.E.W., R.A.L.); the Cardiovascular Imaging Center of the Department of
Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio (S.N., H.M.L.,
J.D.T.); and the Cardiovascular Fluid Mechanics Laboratory, School of Chemical
Engineering, Georgia Institute of Technology, Atlanta, Ga (S.H., J.H.,
A.P.Y.).
Methods and Results—Different mitral geometries produced
surgically in porcine valves were studied in vitro. Comparable degrees
of SAM resulted in more severe mitral regurgitation for
geometries characterized by limited posterior leaflet excursion. Mitral
geometry was also analyzed in 23 patients with hypertrophic
cardiomyopathy by intraoperative
transesophageal echocardiography.
All had typical anterior leaflet SAM with significant outflow tract
gradients but considerably more variable mitral
regurgitation; therefore, regurgitation
did not correlate with obstruction. In contrast, mitral
regurgitation correlated inversely with the length over
which the leaflets coapted (r=-0.89), the most severe
regurgitation occurring with a visible gap.
Regurgitation increased with increasing mismatch of
anterior to posterior leaflet length (r=0.77) and
decreasing posterior leaflet mobility (r=-0.79).
Conclusions—SAM produces greater mitral
regurgitation if the posterior leaflet is limited in
its ability to move anteriorly, participate in SAM, and coapt
effectively. This can explain interindividual differences in
regurgitation for comparable degrees of SAM. Thus, the
spectrum of leaflet length and mobility that affects subaortic
obstruction also influences mitral regurgitation in
patients with SAM.
The degree of SAM, obstruction, and regurgitation are
closely related and have been shown to vary in parallel in the
individual case.16 Clinically, however, great
interindividual differences in the degree of mitral
regurgitation have been observed for comparable degrees
of SAM. Even in the classic article by Wigle et
al16 , who demonstrated the direct quantitative
relation of mitral regurgitation to outflow tract
obstruction in the individual patient, no significant correlation
between regurgitation and obstruction was found in the
overall patient group. This apparent discrepancy has not yet been
appropriately addressed.
Recent studies of mitral valve geometry in hypertrophic
cardiomyopathy by use of
transesophageal echocardiography
have demonstrated that the regurgitant jet arises from a gap between
the mitral leaflets. This gap results from severe systolic
anterior motion of the distal anterior leaflet.17
In many cases, both distal leaflets created a funnel, directing the
regurgitation through this gap.17
On the basis of these and similar clinical observations, we
hypothesized that variations in leaflet length (posterior/anterior
leaflet length mismatch) could restrict the ability of the posterior
leaflet to follow the anterior leaflet as it moves toward the septum
(participate in SAM) and to coapt effectively with it. Thus,
disproportionate degrees of anterior and posterior leaflet SAM, rather
than SAM of the anterior leaflet alone, would determine the degree of
mitral regurgitation. The purpose of the present
study was to test the proposed mechanism in vitro and then to
investigate its clinical relevance in a consecutive group of patients
with hypertrophic cardiomyopathy by use of
intraoperative transesophageal
echocardiography.
Clinical Studies
Intraoperative Transesophageal Echocardiography
Statistical Analysis
Clinical Studies
Leaflet contact length, posterior leaflet length, ratio of anterior to
posterior leaflet length, and posterior leaflet mobility (sum of
angles) were significant univariate predictors of mitral
regurgitation (Table 1
The results of the present study show that SAM of the anterior
leaflet produces greater mitral regurgitation if the
posterior leaflet is limited in its ability to move anteriorly and to
participate in SAM. This ability is determined both by the length of
the posterior leaflet and by the range of motion dictated by its
chordal and papillary muscle connections. Thus, a close inverse
correlation was found between the severity of mitral
regurgitation and the length of the posterior leaflet
and its mobility, expressed as the sum of the 2 angles that determine
its net range of motion in the anterior direction. In none of the
patients with significant mitral regurgitation was the
posterior leaflet actually shortened; it simply was not sufficiently
elongated to follow the anterior leaflet and to coapt effectively with
it, which created a relative mismatch with reduced contact length or
even a visible gap. Therefore, it is reasonable that the ratio of
leaflet lengths was actually a stronger predictor of mitral
regurgitation than posterior leaflet length itself,
surviving as an independent determinant in the
multivariate analysis. Anterior mitral leaflet
length alone did not correlate with mitral
regurgitation because once the anterior leaflet has
reached the septum in these patients with obstruction, the length of
effective coaptation depends primarily on posterior leaflet length and
mobility. Angulation was used to assess posterior leaflet mobility
because the restraining force of the subvalvular
apparatus cannot be measured noninvasively but is
ultimately reflected in this angular limitation (Figure 4
Integration With Previous Data
Although most patients typically have SAM involving at least the
anterior leaflet, Maron et al15 reported a subset
with isolated posterior leaflet SAM. Of 5 patients in that group for
whom an angiogram was available (4 patients with severe and 1 with
moderate posterior leaflet SAM), only 1 had mitral
regurgitation, which was mild. This is
consistent with the present study, demonstrating the least
regurgitation with the most posterior leaflet
elongation. In these cases, the outflow tract pressure gradient might
actually contribute to effective coaptation by pressing the leaflets
more tightly together. The present data are also in accordance with
the findings of Grigg et al17 that the distal
parts of both leaflets form a funnel directing the jet through a
visible regurgitant gap in patients with significant mitral
regurgitation. In the present study, this geometry
could be quantitatively related to restricted posterior leaflet
mobility and length.
The present study focused on SAM-induced mitral
regurgitation in hypertrophic
cardiomyopathy and hence excluded patients with
other possible causes of mitral regurgitation, such as
significant mitral valve prolapse. Nevertheless, the concepts resulting
from the present study can be extended to patients with
obstructive hypertrophic cardiomyopathy who also
have mitral valve prolapse (
Because the study patients were undergoing surgery and had significant
resting gradients, it is reasonable that gradient did not contribute to
models that explained the variation in mitral
regurgitation among individuals (Tables 1
Clinical Implications
Limitations
Intraoperative transesophageal
echocardiography provides high-quality
visualization and quantification of mitral valve geometry and mitral
regurgitation in a standardized fashion and is
particularly useful in obstructive hypertrophic
cardiomyopathy.17 Although
assessment of mitral regurgitation by color flow
mapping of regurgitant jets is routine in clinical practice, it is
influenced by its dependence on driving
pressure31 32 33 and instrument
settings.34 35 36 In this case, the impact of jet
orientation on the quantification of jet size becomes less of a problem
when only 1 etiology of mitral regurgitation is
studied, because jet orientation is generally uniform within 1 etiology
(in the present case, superiorly and toward the posterior portion
of the left atrium). Nevertheless, we also used the proximal jet width
or vena contracta width, which is a marker of regurgitant orifice size
that is relatively independent of flow variables and instrument
settings,21 22 23 and obtained similar results.
Conclusions
This study was supported in part by grants HL-38176 and 53702
from the NIH, Bethesda, Md. Dr Schwammenthal was supported by a grant
from the Deutsche Forschungsgemeinschaft. Dr Nakatani was supported by
a grant from the Uehara Foundation, Tokyo, Japan. Dr Levine is an
Established Investigator of the American Heart Association.
Received August 14, 1996;
revision received April 17, 1998;
accepted April 22, 1998.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Mechanism of Mitral Regurgitation in Hypertrophic Cardiomyopathy
Mismatch of Posterior to Anterior Leaflet Length and Mobility
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—In hypertrophic
cardiomyopathy, a spectrum of mitral leaflet
abnormalities has been related to the mechanism of mitral
systolic anterior motion (SAM), which causes both subaortic
obstruction and mitral regurgitation. In the individual
patient, SAM and regurgitation vary in parallel;
clinically, however, great interindividual differences in mitral
regurgitation can occur for comparable degrees of SAM.
We hypothesized that these differences relate to variations in
posterior leaflet length and mobility, restricting its ability to
follow the anterior leaflet (participate in SAM) and coapt
effectively.
Key Words: mitral valve • echocardiography • regurgitation • cardiomyopathy
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Systolic anterior
motion of the mitral valve (SAM) causes subaortic obstruction and
mitral regurgitation.1 2 3 4 5 6 7 8 9 10 11 In
patients with hypertrophic cardiomyopathy, a
spectrum of morphological abnormalities of the mitral leaflets that has
implications for the pathophysiological mechanism
of subaortic obstruction by SAM has been
described.7 12 13 14 15 This naturally leads to the
question of whether these variations in the mitral leaflets also
influence the presence and degree of mitral
regurgitation.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
In Vitro Model
We used a modification of a previously developed left heart flow
model reproducing mitral valve motion in hypertrophic
cardiomyopathy.18 A
completely excised porcine mitral apparatus with intact
papillary muscles and chordae was mounted on an elliptical Plexiglas
annular ring (Figure 1
). The papillary
muscles were attached to small Plexiglas disks, which can pivot around
the end of metal rods, permitting the muscles to reach their
equilibrium position and to distribute tension evenly across the valve
leaflets. The mitral valve apparatus was incorporated into
a transparent Plexiglas model machined to produce an internal
ellipsoidal cavity similar to that of the left ventricle. A
silicone-covered clay insert molded to simulate moderate asymmetrical
septal hypertrophy was placed in the model (Figure 2). Thus, the typical shape and
dimensions of the left ventricle in hypertrophic
cardiomyopathy, as observed
echocardiographically at the time of onset of
SAM-related mitral regurgitation, could be reproduced.
The mitral annulus covered an atrial outlet that permitted mitral
regurgitation. The metal rods passed to the outside of
the model through tubes at its apical end, which allowed us to produce
anterior and inward displacement of the papillary muscles, as seen in
hypertrophic obstructive
cardiomyopathy.9 18 19 20 To
simulate the systolic apex-to-base flow, flow entered the
ventricle from the apex through a nonrestrictive tube and exited
through an aortic tilting disk prosthesis and through the
mitral regurgitant orifice into the atrial outlet. The aortic outflow
was angled relative to the mitral ring. The mitral valve was
observed directly and visualized echocardiographically
for quantitative assessment of leaflet geometry. The left heart model
was integrated into a steady-flow loop with a typical instantaneous
aortic output kept constant at 15 L/min. Mitral
regurgitation was measured as the rate of overflow from
the atrial reservoir by use of a graduated cylinder and stopwatch.
Three different geometries produced by surgical manipulation of the
leaflets were tested: (1) elongation of both mitral leaflets by
insertion of patches from another valve (anterior mitral leaflet length
3.4 cm; posterior mitral leaflet 2.9 cm); (2) elongation of the
anterior mitral leaflet alone (anterior mitral leaflet 3.4 cm;
posterior mitral leaflet 1.8 cm); and (3) geometry B plus shortening of
the posterior leaflet chordae. For each geometry, SAM was varied by
changing the degree of anterior and inward displacement of the
papillary muscles to position the leaflets into the outflow stream and
allow them to move anteriorly.18 19 20 In an
echocardiographic long-axis view of the model, the
extent of SAM (excursion of the anterior mitral leaflet) and the
leaflet contact length, ie, the distance over which both leaflets
visibly coapted or the gap between them (negative contact length), were
assessed with a calibrated computer (Figure 3). Each measurement was made 3 times;
these results were within 5% of one another, and their average was
used for subsequent analysis.
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Figure 1. Diagram of completely excised porcine mitral
apparatus with intact papillary muscles and chordae,
mounted on an elliptical annular ring. The papillary muscles are
attached to small Plexiglas disks pivoting around the end of metal
rods, permitting the muscles to reach their equilibrium position.
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Figure 2. Diagram of transparent Plexiglas model, machined
to produce an internal ellipsoidal cavity with typical shape and
dimensions of left ventricle in hypertrophic
cardiomyopathy. Mitral annulus covers an atrial
outlet, which permits mitral regurgitation. Metal rods
pass to the outside of the model through tubes at its apical end,
allowing the papillary muscle position to be varied. Flow enters the
ventricle from the apex and exits through an aortic tilting disk
prosthesis or through a mitral regurgitant orifice into the
atrial outlet.
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Figure 3. Echocardiographic measurements
performed in the in vitro model. SAM-AML indicates extent of anterior
mitral leaflet motion with reference to line of coaptation; CL, contact
length (distance over which both leaflets visibly coapt or gap between
them); LA, model left atrium; and LV, model left ventricle.
Patients
Thirty-four patients with obstructive hypertrophic
cardiomyopathy consecutively undergoing surgery at
the Cleveland Clinic Foundation were initially considered for the
study. Two patients with significant mitral valve prolapse, 1 with a
flail mitral leaflet, and 8 with severe mitral annular calcification
were excluded. Thus, 23 patients with hypertrophic
cardiomyopathy but without associated structural
mitral valve disease were ultimately enrolled in the study. There were
12 women and 11 men. The mean age was 52±18 years (14 to 77 years).
All patients had significant outflow tract obstruction with a
systolic pressure gradient of 77±29 mm Hg (36 to
150 mm Hg) at the time of surgery.
The studies were performed with a 2-dimensional and color-coded
Doppler flow imaging system (Hewlett Packard Sonos 1500 and Acuson
128XP) and a 5-MHz phased-array transducer. The probe was passed after
induction of general anesthesia, and the study was
performed before the chest was opened. The following measurements were
made in the frontal long-axis transesophageal view,
which has been recommended for quantitative
echocardiographic assessment of SAM geometry and mitral
regurgitation17 (Figure 4): (1) maximal SAM-induced mitral
regurgitant jet area by planimetry,17 as well as
width of the proximal jet (vena contracta width) as the jet emerged
from between the leaflets21 22 23 ; (2) length of
the anterior and posterior mitral leaflets and their ratio, where the
length of each leaflet was measured in diastole from the
annulus to its chordal insertion, identified by a change in
echogenicity and thickness observed consistently during leaflet
motion throughout the cardiac cycle7 9 13 14 15 17 ;
(3) leaflet contact length, ie, the distance over which both leaflets
visibly coapted or the gap between them (negative contact length); (4)
sum of angle-
(between the posterior left ventricular
wall and the basal part of the posterior leaflet) and angle-ß
(between the basal and distal parts of the posterior leaflet) as a
measure of posterior leaflet mobility, with larger angles reflecting
greater mobility; and (5) systolic outflow tract pressure
gradient, calculated from the maximal outflow tract velocity as
measured by continuous-wave Doppler
echocardiography with a steerable beam. These
velocities corresponded well with preoperative and epicardial
measurements (within 0.3 m/s). As in the in vitro studies, each
measurement was made 3 times on a calibrated computer from an optimal
frame, and the average of these measurements was used for subsequent
analysis. Observer variability, assessed as the SD of the
differences in anterior and posterior leaflet length measurements made
by 2 independent observers in 20 patients, was 3.3% of the mean, and
intraobserver variability (1-month measurement interval) was 2.5%.
Interobserver variability for jet area was 4.2%, with an intraobserver
variability of 3.7%; for proximal jet width, the corresponding values
were 3.9% and 3.5%.
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Figure 4. Measurements obtained by
transesophageal echocardiography in
patients with hypertrophic cardiomyopathy. Left,
Anterior and posterior mitral leaflets visibly coapt over a relatively
long distance (contact length [C]). Right, Mitral leaflets fail to
coapt, resulting in a visible gap (G). Shaded area in left atrium
represents planimetered mitral regurgitant jet area. Ao
indicates aorta; LA, left atrium; LV, left ventricle; , angle
between posterior left ventricular wall and basal part of
posterior mitral leaflet; and ß, angle between basal and apical (more
distal) parts of posterior mitral leaflet.
The dependence of mitral regurgitation on
measures of mitral valve geometry and systolic outflow tract
pressure gradient was studied by use of linear or nonlinear regression
analysis as suggested by the data. In addition, we performed
stepwise multiple linear regression analysis to assess the
determinants of mitral regurgitation (regurgitant jet
area and proximal width), entering into the regression model contact
length, anterior and posterior leaflet lengths and their ratio,
posterior leaflet mobility (sum of bending angles), and
systolic pressure gradient. Because the likelihood of lack of
coaptation (gap between the leaflets) is inversely related to the total
available leaflet length, we also calculated the leaflet length ratio
(anterior/posterior) divided by total leaflet length. Stepwise multiple
linear regression analysis was also applied to assess the
contributions of anterior and posterior leaflet length, posterior
leaflet mobility, and pressure gradient to leaflet contact length. The
univariate correlation coefficients for these variables
were determined, and they were also entered into a
multivariate model for predicting mitral regurgitation
by use of the RS1 statistical package (Bolt, Beranek, and Newman, Inc,
1993). Forward stepping was used, with the F to enter and F to
remove any variable selected so that the corresponding significance
level (outer tail area) was <0.05. No variables were forced into
the model.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
In Vitro Model
Although mitral regurgitant flow rate increased with
increasing SAM for each individual mitral valve geometry, as expected,
there was no correlation between the extent of SAM of the anterior
mitral leaflet and mitral regurgitation over all the
configurations studied (P>0.25; Figure 5, left), because the increase in mitral
regurgitation with the induction of SAM varied with the
baseline valve geometry. Elongation of both leaflets caused mitral
regurgitation to increase slightly from 0.21 L/min with
mild SAM to 0.3 L/min with severe SAM. Elongation of the anterior
leaflet alone caused mitral regurgitation to increase
from 0.1 to 1.1 L/min. Chordal shortening to further limit posterior
leaflet excursion caused substantial mitral
regurgitation (2.3 L/min) even with mild SAM,
increasing to 9.0 L/min with severe SAM. In contrast to the lack of
correlation between SAM and mitral regurgitation in the
overall group, a close inverse correlation was found between the mitral
regurgitant flow rate and the contact length of the leaflets
(r=-0.91, P<0.005; Figure 5, right). Figure 6 demonstrates the impact of mitral
leaflet length on the resulting mitral regurgitant geometry. Elongation
of both leaflets permitted coaptation of the leaflets over a sufficient
length not only at baseline (baseline geometry A) but also with maximal
SAM of the anterior leaflet (SAM geometry A). Elongation of the
anterior leaflet alone resulted in a reduced contact length of the
leaflets with SAM (SAM geometry B). When the posterior leaflet was
further restricted in its mobility, a visible gap was observed (SAM
geometry C).
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Figure 5. Left, Lack of correlation between extent of SAM of
anterior mitral leaflet (AML) and mitral regurgitant flow rate (MR) for
all configurations studied in vitro. Right, Close inverse correlation
between contact length of leaflets (CL) and mitral regurgitant flow
rate (MR). Nonlinear regression models, as suggested by data, were used
in the analysis.
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Figure 6. Impact of mitral leaflet length on resulting
mitral regurgitant geometry in vitro (left,
echocardiographic images; right, corresponding
schematic images). Elongation of both leaflets permitted their
coaptation over a sufficient length, not only at baseline (baseline
geometry A) but also with maximal SAM of anterior leaflet (SAM geometry
A). Elongation of anterior leaflet alone resulted in reduced contact
length of leaflets with SAM (SAM geometry B), with only the tip of the
posterior leaflet contacting the anterior. When the posterior leaflet
was further restricted in its mobility, a visible gap between leaflets
appeared (SAM geometry C).
All patients had significant obstruction but considerably more
variable degrees of mitral regurgitation;
therefore, there was no correlation between the outflow tract gradient
and mitral regurgitation, as anticipated
(P>0.25; Figure 7, left). In
contrast, as in the in vitro setting, a close inverse correlation
between the contact length of the leaflets and mitral
regurgitation was found (r=-0.89,
P<0.005; Figure 7, right). Mitral regurgitant jet area
increased with both decreased posterior leaflet mobility, as assessed
by the sum of the angles and ß (r=-0.79,
P<0.0001; Figure 8, left),
and decreased posterior leaflet length (r=-0.71,
P<0.005; Figure 8, center). Mitral regurgitant jet area
increased with the ratio of anterior to posterior leaflet length
(r=0.77, P<0.0001; Figure 8, right),
particularly when total leaflet area was taken into consideration
(ratio of leaflet lengths/total leaflet length available;
r=0.85, P=2x10-7).
Similar results were found when proximal jet width was used to evaluate
mitral regurgitation (r=-0.82 for posterior
leaflet mobility, r=-0.64 for posterior leaflet length,
r=0.67 for the ratio of anterior to posterior leaflet
length, and r=0.76 for that ratio/total available leaflet
length; P<0.001). Figure 9 illustrates the mechanism of the
variability of mitral regurgitation in vivo. In the
first case (Figure 9A and 9B), the anterior and posterior leaflets were
considerably elongated. The posterior leaflet could thus follow the
anterior leaflet even with maximal SAM, resulting in a relatively long
contact length with virtually no mitral regurgitation.
In the second case (Figure 9C and 9D), leaflet contact length was
shorter, resulting in mitral regurgitation. In the
third case (Figure 9E and 9F), the posterior leaflet was not
sufficiently elongated to follow the anterior leaflet, resulting in a
sizable gap with maximal SAM and associated severe mitral
regurgitation.
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Figure 7. Clinical results. Left, Lack of correlation
between mitral regurgitation (MR jet area) and left
ventricular outflow tract (LVOT) gradient in overall
patient group. Right, Close inverse correlation between contact length
of leaflets (CL) and mitral regurgitation (MR jet
area).
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Figure 8. Clinical results. Left, Inverse correlation
between mitral regurgitation (MR jet area) and
posterior leaflet mobility assessed by sum of the angles and ß
(Figure 4
). Center, Inverse correlation between mitral
regurgitation (MR jet area) and posterior mitral
leaflet length (PML). Right, Correlation between mitral
regurgitation (MR jet area) and ratio of anterior to
posterior mitral leaflet length (AML/PML).
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Figure 9. Clinical examples of different degrees of mitral
regurgitation in 3 patients with comparable degrees of
outflow tract obstruction. A, Two-dimensional
transesophageal long-axis
echocardiographic image (left atrium at top) depicting
systolic mitral valve geometry. Arrowheads a and p point at the
tips of anterior and posterior mitral leaflets, respectively. C
indicates contact length of mitral leaflets, which is long in this
patient, in whom both anterior and posterior mitral leaflets are
elongated. Posterior leaflet could thus follow anterior leaflet even
with maximal SAM, resulting in a relatively long contact length. As a
result, there was virtually no mitral regurgitation, as
seen in B, the corresponding color Doppler flow image in the same
view. There is a turbulent outflow tract jet between mitral leaflets
and interventricular septum but no mitral
regurgitation. C and D, In second patient, leaflet
contact length was shorter, resulting in mild mitral
regurgitation (jet within left atrium, coming toward
transducer at top of image). E and F, In third patient, posterior
leaflet was not sufficiently elongated and mobile to follow anterior
leaflet, resulting in a significant gap (G) with maximal SAM and,
consequently, severe mitral regurgitation, with a large
jet visibly emerging through gap between leaflets. ).
Stepwise multiple linear regression analysis identified contact
length as the most powerful predictor (F=94.4,
r2=0.83,
P=3.2x10-9), with a weaker
contribution from the ratio of anterior to posterior leaflet length
(F=1.01, r2=0.06, P=0.047);
including both in the model gave an r2
value of 0.88 (P=6.7x10-10). Similar
results were obtained for proximal jet width, with the same significant
univariate predictors; independent predictors in the
multivariate analysis were coaptation length
and posterior leaflet mobility (r2=0.77).
Leaflet mobility and posterior leaflet length were both significant
univariate predictors of coaptation length (Table 2); only posterior leaflet mobility
contributed independently in the stepwise multiple linear regression
analysis (F=35.1, r2=0.62,
P=0.000007). In this population (patients with significant
obstruction and outflow tract gradients), there were no significant
correlations with systolic pressure gradient in these
models.
View this table:
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Table 1. Correlates of Mitral Regurgitant Jet Area
View this table:
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Table 2. Correlates of Coaptation Length
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
Failure of the mitral leaflets to coapt effectively results in the
creation of a regurgitant orifice. In the case of obstructive
hypertrophic cardiomyopathy, systolic
anterior motion of the anterior leaflet causes subaortic obstruction
and moves the anterior leaflet away from the posterior leaflet,
disrupting their normal coaptation. Therefore, in the individual case,
the degree of mitral regurgitation increases with
increasing SAM.2 16 17 However, failure to meet
and coapt effectively depends on the motion of both mitral leaflets, as
demonstrated in the present study both in the controlled in vitro
environment and in patients with hypertrophic
cardiomyopathy undergoing quantitative
analysis of mitral valve geometry by intraoperative
transesophageal
echocardiography. ). In patients
with severe regurgitation, a more acute angle between
the body of the posterior leaflet and its tip (pointing toward the
posterior wall) was visible, with both distal leaflets creating a
funnel leading to the regurgitant gap (Figure 4, right; Figure 9E and 9F). In patients with significant (moderate to severe)
regurgitation, the sum of angles and ß was
consistently <180° (representing, on average,
the sum of 2 acute angles), whereas the sum of these angles was
>180° in patients with mild mitral regurgitation,
with a sufficiently long and mobile posterior leaflet to follow the
anterior leaflet and coapt effectively.
Recent evidence supports the concept that primary structural
alterations of the mitral valve constitute an essential feature in many
patients with obstructive hypertrophic
cardiomyopathy, with leaflet elongation
demonstrated by transthoracic9 and
transesophageal
echocardiography17 as well as
pathological morphometry.12 13 14 Such
analysis has shown considerable variability in leaflet
elongation, including increased size of both anterior and posterior
leaflets or asymmetrical enlargement of either the anterior leaflet or
a posterior leaflet scallop,14 consistent
with the variability demonstrated in the current study. These
observations are of interest because they seem to describe a primary
abnormality of the mitral leaflets in a disease characterized by
mutations of muscle protein genes. The variable morphology of
leaflet length has been identified as an important determinant of
outflow tract obstruction14 ; the present
study has demonstrated its impact on the severity of mitral
regurgitation. Our findings are also consistent
with those of Klues et al,14 who found that no
patients with importantly elongated leaflets had severe
regurgitation. 
3% of all patients and 9% of those
undergoing surgery).13 24 25 26 Bulging of the
basal portion of the posterior leaflet beyond the anterior leaflet into
the left atrium can reduce the amount of posterior leaflet area
effectively available to follow the anterior mitral leaflet toward the
septum (in a different direction) and meet with it. Thus, leaflet
contact length is smaller for any given posterior leaflet length
(Figure 10), which explains why mitral
regurgitation is usually significant when prolapse is
present in hypertrophic
cardiomyopathy.26
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Figure 10. Clinical example of patient with hypertrophic
cardiomyopathy, SAM, and prolapse of posterior
mitral leaflet. Significant basal portion of leaflet bulges superiorly
into left atrium, reducing amount of leaflet area available to follow
anterior mitral leaflet toward septum (in opposite direction) and to
coapt with it. Thus, despite posterior leaflet elongation, length of
contact with anterior leaflet was relatively reduced, a gap was
present (A), and important regurgitation occurred
(B). and 2). The
inclusion of patients without obstruction would likely have shown a
correlation between the gradient and mitral
regurgitation, consistent with the
literature1 16 ; however, the purpose of the
present study was to explain why there are differences in mitral
regurgitation even within a group of patients with
significant obstruction.
In the present study, we demonstrated the impact of mitral
valve geometry on the severity of regurgitation in
obstructive hypertrophic cardiomyopathy. The
consideration of mitral valve geometry could be particularly helpful in
predicting the reversibility of mitral regurgitation
with reduction of SAM by subvalvular myectomy. When mitral
regurgitation is severe in the presence of a relatively
short posterior leaflet, posterior realignment of the anterior leaflet
after myectomy can result in complete or almost complete abolishment of
mitral regurgitation; in fact, this was the case in
virtually all the patients with significant
regurgitation studied in this series, which focused on
SAM-induced mitral regurgitation. However, when mitral
regurgitation is significant despite a substantially
elongated posterior leaflet, other mechanisms (additional intrinsic
abnormalities of the mitral valve) are likely to be present, and
mitral regurgitation may remain significant despite
adequate relief of SAM; conversely, mitral
regurgitation has been shown to resolve when mitral
valve repair is combined with septal myectomy.27
In addition, because correction of mitral valve geometry by anterior
mitral leaflet plication or patching (to reduce mobility) has recently
been introduced to relieve persistent mitral
regurgitation, as well as outflow tract
obstruction,28 29 30 assessment of mitral leaflet
coaptation by transesophageal
echocardiography as performed in the present
study may help to identify patients suitable for these procedures.
The use of a rigid, steady-flow, in vitro model cannot necessarily
account for all features of the complex and dynamic in vivo situation,
which is why the clinical relevance of the mechanism was also
investigated in vivo after having been demonstrated in vitro. However,
the ability to keep experimental conditions such as chamber dimensions
and flow rate constant in vitro, with different mitral valve geometries
being the only variable, offered a unique opportunity to study the
proposed mechanistic hypothesis in terms of its physical soundness,
without confounding factors that might be present in the clinical
situation. The in vitro part of this study therefore provides important
complementary evidence as to the validity of the hypothesis,
particularly because its results concur completely with those of the
clinical part.
Variable leaflet length and mobility, which lead to a mismatch
in coaptation of the posterior and anterior leaflets, can explain why
interindividual differences in mitral regurgitation
occur for comparable degrees of SAM despite the close relation of
mitral regurgitation to SAM in the individual case. The
present study demonstrates that this apparent contradiction can be
reconciled by considering posterior leaflet motion, thus expanding the
initial concept of the mechanism of mitral
regurgitation in hypertrophic
cardiomyopathy. According to this unifying model,
variability in posterior leaflet length and mobility, rather than
anterior leaflet SAM alone, result in insufficient contact length of
the leaflets, which represents the final common pathway of
mitral incompetence. Thus, the spectrum of variable morphological
changes that affects subaortic obstruction also influences the degree
of mitral regurgitation in patients with SAM.
Footnotes
Reprint requests to Ehud Schwammenthal, MD, PhD, Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Vincent Burnham 5 (VBK 523), Boston, MA 02114.
References
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Abstract
Introduction
Methods
Results
Discussion
References
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