European Heart Journal (2003) 24, 1244–1253

Sequential assessment of mitral valve area during

diastole using colour M-mode flow convergence
analysis: new insights into mitral stenosis
physiology
David Messika-Zeitoun a, Siu Fung Yiu a, Bertrand Cormier c,
Bernard Iung c, Christopher Scott b, Alec Vahanian c, A. Jamil Tajik a,
Maurice Enriquez-Sarano a*
a
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, MN,
Rochester, USA
b
Section of Biostatistics, Mayo Clinic and Mayo Foundation, MN, Rochester, USA
c
Cardiovascular Division, Hôpital Bichat, Paris, France
Received 16 October 2002; revised 18 February 2003; accepted 27 March 2003

KEYWORDS Aims In mitral stenosis (MS) transvalvular flow and velocity continually change through-
Blood flow; out diastole but for mitral valve area (MVA), flow-dependent variations (valve reserve)
Echocardiography; are unknown. These physiologic changes can be studied by the proximal isovelocity
Haemodynamics; surface area (PISA) method, using the high temporal resolution of colour M-mode,
Mitral valve; essential for simultaneous measurements of flow and velocity. Hence, we aimed to
PISA validate the colour M-mode PISA method for measurement of MVA in MS and to define
using this method the physiologic flow-dependent changes of MVA during diastole.
Methods and results In 50 patients with native MS, MVA was measured by planimetry
(MVA-2D), Doppler pressure half-time (MVA-PHT), and two-dimensional PISA (2D-
PISA). MVA measurement by colour M-mode PISA in early diastole (M-PISA) (1.27±
0.46 cm2) with rigorously timed flow and velocity measurements by continuous wave
Doppler did not differ and correlated well with MVA-2D (1.29±0.44 cm2, p=0.59;
r=0.85, p<0.001) and MVA-PHT (1.30±0.41 cm2, p=0.52; r=0.80, p<0.001). In contrast
a trend towards underestimation of MVA by 2D-PISA was observed (1.23±0.42 cm2;
p=0.10 and p=0.07). Timed analysis of transvalvular haemodynamics at early, mid,
mid-late, and late diastole showed marked changes in flow and velocities (both
p<0.0001) but not in MVA (respectively 1.27±0.46, 1.29±0.47, 1.28±0.51 and
1.27±0.49 cm2; ns).
Conclusions In MS, the high temporal resolution of colour M-mode PISA allows
accurate MVA measurements. It also allows for the first time, sequential MVA
assessment during diastole. Notwithstanding marked flow and velocities changes,
MVA remained unchanged throughout diastole underscoring the lack of flow-related
valvular reserve in MS.
© 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.

* Correspondence: Dr Maurice Enriquez-Sarano, M.D., Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic,
200 First Street S.W., Rochester, MN 55905
E-mail address: sarano.maurice@mayo.edu (M. Enriquez-Sarano).

0195-668X/03/$ - see front matter © 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.
doi:10.1016/S0195-668X(03)00208-2
Colour M-mode PISA for mitral stenosis
Introduction
Measurement of mitral valve area (MVA) is the cor-
nerstone of mitral stenosis (MS) severity assessment.
As cardiac catheterization is mostly used to perform
balloon valvuloplasty,1 for clinical decision-making,
MVA is most often non-invasively measured by
Doppler echocardiography.2 However, all methods of
assessment of MVA are not always measurable and
each has specific limitations.3–6 Hence, to improve
consistency and reliability of MVA measurement,
combination of methods is often required and devel-
opment of new methods supports wide applicability
of Doppler echocardiography in clinical practice.
The proximal isovelocity surface area (PISA)
method7 provides accurate calculation of effective
orifice area in mitral,8,9 aortic10 and tricuspid re-
gurgitation.11 For MVA measurement in MS, the PISA
method is attractive because flow convergence im-
aging is highly feasible, and because it may be the
only method available in some patients.12–15 How-
ever, PISA measures instantaneous flow and in MS,
as mitral flow and velocity continually vary
throughout diastole, it is essential that these vari-
ables be measured simultaneously to allow accu-
rate calculation of MVA. Such requirement is
difficult to fulfil with two-dimensional (2D) colour
imaging due to relatively low frame rates. In con-
trast, colour M-mode PISA16–18 provides high sam-
pling rates and precise timing of measurements.
Thus, this method has great potential for MS assess-
ment but has not been validated yet.
Furthermore, in valve stenosis, flow-related
valve area change, or valve reserve, particularly
documented in aortic stenosis19,20 may play a role
in adaptation to haemodynamic stress.21 In MS the
concept of flow-related valve reserve remains
controversial4,22–26 mostly due to methodological
difficulties. Colour M-mode PISA with its high tem-
poral resolution is ideally suited to measure flow
and MVA changes throughout diastole and to fill
these gaps of knowledge regarding MS physiology.
Thus, this study was undertaken in patients with
MS (1) to analyse accuracy of colour M-mode PISA
compared to standard Doppler-echocardiographic
reference methods for MVA measurement, and (2) to
measure sequential variations of mitral flow and MVA
throughout diastole and determine the presence and
magnitude of flow-related valve reserve in MS.
Methods
Patients
Fifty patients with MS were prospectively enrolled
between 1994 and 1996 at Mayo Clinic, Rochester,
1245
MN, and Hôpital Bichat, Paris, France. Inclusion
criteria were (1) native mitral valve stenosis, (2)
overall quantitation of MVA by colour M-mode PISA,
(3) analysis of sequential transvalvular haemo-
dynamics changes throughout diastole by colour
M-mode PISA, and (4) simultaneous MVA quanti-
tation by at least two of the following reference
methods: two-dimensional planimetry (MVA-2D),
Doppler pressure half-time (MVA-PHT), and two-
dimensional PISA (2D-PISA). Exclusion criteria were
(1) colour M-mode images with fragmented borders
or inability to image through the centreline of the
flow convergence, (2) peak transmitral flow vel-
ocity of less than 119 cm/s at early diastole (defined
as three standard deviations superior boundary of
normal mitral inflow velocity in our laboratory), (3)
mitral transvalvular flow non-sustained throughout
diastole (not allowing visualization of flow conver-
gence throughout diastole) and (4) mitral (MR) or
aortic regurgitation (AR) more than moderate.
Doppler echocardiographic examination
All patients underwent complete two-dimensional
and Doppler echocardiographic examination. Data
for MVA-2D,27 MVA-PHT,28 2D-PISA, colour M-mode
flow convergence imaging, and other Doppler
echocardiographic measurements were collected
concurrently during the same examination. The
mitral score of valvular and subvalvular alteration
was calculated for each patient between 4 and
16.29
The PISA method of determining mitral
orifice area
The conceptual basis of the PISA method has been
described elsewhere.9 The method is based on flow
convergence analysis proximal to the stenotic
orifice by shifting the colour-flow scale baseline
upward to decrease the colour aliasing-velocity.
With hemispheric shape of the proximal isovelocity
surface, the diastolic flow rate is calculated as
Flowmitral (ml/s)⫽2πr2#
(angle
/180)#Valias (cm/s)
in which r (cm) is the maximal radius of the flow
convergence region in early diastole measured in
the centreline of the flow convergence region,
Valias is the aliasing velocity, and
/180 is the
correction factor accounting for mitral inflow con-
straint angle
.12–14 MVA is then determined by
dividing maximal diastolic flow rate (flowmitral [ml/
s]) by peak continuous wave Doppler velocity of
mitral inflow (Vmax [cm/s]).
1246 D. Messika-Zeitoun et al.

Fig. 1 Examples of measurement of mitral orifice area by the colour M-mode flow convergence method in mitral stenosis. The colour
M-mode tracing of the proximal flow convergence and continuous wave Doppler echocardiographic measurement at four phases of
diastole (early, mid, mid-late, and late) were matched at the same time intervals. The valve area at each phase was then calculated
by simply dividing the mitral flow rate by the corresponding inflow velocity.

In each colour flow image of the flow conver-
gence, flow constraint or interaction was examined
to determine the angle correction factor required
for the calculation of mitral diastolic flow rate.
Absence of flow constraint allowing full hemi-
spheric flow convergence was defined by contact of
less than one-third between the blue flow conver-
gence and the mitral leaflets, with red-orange
aliasing colour rim around the blue flow conver-
gence. An Angle correction factor of 1 (180/180)
was used in these situations for calculating flow
rate.
Colour M-mode PISA and analysis of phasic
haemodynamic variation
Under guidance of magnified two-dimensional
colour imaging, colour M-mode tracings were re-
corded by placing the M-mode cursor line through
the centre of the flow convergence. Colour-flow
imaging was carefully examined to ascertain that
transvalvular flow was maintained throughout dias-
tole. Geometric adequacy and flow constraint of
the flow convergence were predetermined by two-
dimensional colour flow imaging before the M-mode
technique. Diastole was divided into four phases
of equal duration: early, mid, mid-late, and late
diastole.
Peak radius of flow convergence was measured
during each phase to calculate mitral flow rate and
the specific timing of the measurement from the
beginning of diastole was noted. Each radius was
measured from the red–blue aliasing level to the
tip of the leaflet at the orifice.
Colour M-mode analysis was then paired with
continuous wave Doppler and cycles with identical
diastolic duration were used for both techniques.
Individual measurements of the radius of flow
convergence were then coupled with transmitral
velocity at the same matched time interval from
beginning of diastole. Three to five measurements
of each variable (on matched cycle for colour
M-mode and Doppler methods) were averaged,
depending on the patient's rhythm.
MVA was then calculated separately for each
phase of diastole simply by dividing the diastolic
flow rate by the corresponding matched continuous
wave Doppler velocity (Fig. 1).
Statistical analysis
All quantitative data were expressed as mean±
standard deviation.
The comparisons of mitral valve area obtained by
the different echocardiographic methods were
analysed by paired t-tests and linear regression. To
Colour M-mode PISA for mitral stenosis 1247

Table 1 Clinical and haemodynamic baseline characteris- pared to MVA-2D or MVA-PHT, M-PISA showed no
tics of the patients* significant difference (signed difference: −0.02±
Age, years 56±16
0.25 p=0.59 and −0.026±0.28 p=0.52 respectively)
Female sex 41(82) but 2D-PISA showed a trend toward underesti-
NYHA class III or IV 24 (48) mation of MVA (signed difference: −0.07±0.28
Heart rate, beats/min 74±15 p=0.10 and −0.07±0.28 p=0.07 respectively). The
Atrial fibrillation 22 (44)
Mild to moderate mitral regurgitation 22 (44)
absolute value of the difference with MVA-2D was
Mild to moderate aortic regurgitation 24 (48) the lowest for MVA-PHT (0.15±0.15 cm2) and was
LVED dimension, mm 49±6 similarly low for M-PISA (0.17±0.16 cm2, p=0.41)
EF,% 56±12 while it was higher for 2D-PISA (0.21±0.19 cm2,
SPAP, mmHg 45±9
Mean gradient across mitral valve, mmHg 8±4
p=0.05). Quality control plots using the Altman and
Mitral score 8±2 Bland method with two-dimensional planimetry
Angle of mitral valve leaflet, degree 127±20 (Fig. 3A) and Doppler pressure half-time (Fig. 3B) as
Total diastole duration, ms 445±123 reference techniques showed that there was no
Mitral valve area (cm2)
overall underestimation or overestimation of the
Planimetry 1.29±0.44
Pressure half-time 1.30±0.41 mitral valve area estimates by the M-mode PISA
Two-dimensional PISA 1.23±0.42 technique. The mean signed difference between
M-mode PISA 1.27±0.46 M-PISA and MVA-2D and MVA-PHT was small (re-
spectively 0.02 cm2 and 0.03 cm2), and the slope
*Data presented are number of patients (%) or mean±SD.
NYHA=New York Heart Association functional class; LVED= and intercept for the regression of the difference
left ventricular end-diastolic; EF=ejection fraction; SPAP= onto the mean of the reference and colour M-mode
systolic pulmonary artery pressure. PISA valve areas were not different from zero,
emphasizing the absence of systemic bias in the
M-mode method. The M-PISA MVA showed signifi-
cant correlations with simultaneous peak and mean
assess for error and bias, Altman and Bland analysis gradient (both r=0.57, p<0.0001) but no significant
method30 was used. Stability of phasic measure- correlation to cardiac output.
ments of flow, velocity and MVA by colour M-mode Subgroup analysis was also performed (Table 2).
and Doppler method was analysed by ANOVA for In patients in sinus rhythm, all methods showed
repeated measurement. Statistical significance was similar results (1.35±0.49 cm2 for MVA-2D,
defined with p<0.05. 1.29±0.38 cm2 for MVA-PHT, 1.27±0.48 cm2 for 2D-
PISA and 1.35±0.51 cm2 for M-PISA, all p>0.09). In
the 22 patients in atrial fibrillation, MVA-PHT
Results (1.31±0.46 cm2) was significantly higher than that
obtained by other methods (1.22±0.36 cm2 for MVA-
Baseline characteristics
2D, p=0.07; 1.17±0.34 cm2 for 2D-PISA, p=0.03;
Of the 50 patients (age 56±16 years), 41 (82%) were 1.18±0.38 cm2 for M-PISA, p=0.02) but there was
female, 22 were in atrial fibrillation (AF), 22 had no significant difference between the last three
mild to moderate mitral regurgitation (MR) and methods (all p>0.29). However, correlations of
24 mild to moderate aortic regurgitation (AR). M-PISA with MVA-2D, MVA-PHT and 2D-PISA re-
Mitral valvular score was 8±2 (range 5 to 13) and mained significant and good despite the atrial
mean gradient 8±4 mmHg. Baseline clinical and fibrillation (respectively r=0.86, r=0.84 and r=0.83,
haemodynamic characteristics are presented in all p<0.0001). In patients with severe anatomic
Table 1. damages (defined as a mitral score ≥8), a trend
towards underestimation of the MVA compared to
Mitral valve area by colour M-mode PISA in MVA-2D and MVA-PHT was observed with 2D-PISA
early diastole but not with M-PISA. Similarly compared to these
two reference methods, 2D-PISA, but not M-PISA,
MVA-2D was 1.29±0.44 cm2, MVA-PHT 1.30± underestimated MVA in patients with mild to
0.41 cm2 and 2D-PISA 1.23±0.42 cm2. MVA obtained moderate MR.
by colour M-mode PISA in early diastole (M-PISA), In 10 patients M-mode colour measurements
with the same aliasing velocity than 2D-PISA were repeated by a second blinded observer. Inter-
(25±6 cm/s), was 1.27±0.46 cm2 (Table 1). Corre- observer variability calculated as the standard
lations between all the methods were significant error of the estimate of valve area (0.16 cm2) was
(all r> 0.75 and p< 0.0001) (Fig. 2). However, com- comparable to that of other methods.22
1248
Fig. 2 Comparison of mitral valve area (MVA) by the colour M-mode proximal isovelocity surface area (PISA) method with an aliasing
velocity of 25±6 cm/s with the standard reference echocardiographic techniques of two-dimensional (2D) planimetry (Graph A) and
Doppler pressure half-time (PHT) (Graph B).
Colour M-mode PISA and flow
haemodynamics throughout diastole
Colour M-mode PISA measurement of transvalvular
flow was matched with similarly timed (using mitral
valve opening as the time reference) continuous
wave Doppler trans-valvular velocity measure-
ments. The timing after mitral opening was ident-
ical for radius of flow convergence and velocity
measurements and was on average 67±15 ms
in early-diastole, 170±45 ms in mid-diastole,
276±83 ms in mid-late-diastole, and 368±113 ms in
late-diastole. The wider range of timing at end-
than early-diastole does not reflect discrepancies
in timing of flow and velocity measurements but
rather between-patient heart rate differences (95%
confidence interval of distribution=60 bpm) and
hence diastolic duration differences. These timed
measurements at each phase (Table 3) showed
marked variations in transvalvular flow and velo-
cities. From minimum to maximum, change in
transvalvular flow was 144±98% while that of vel-
ocity was 104±61%, or more than doubling for each
variable. However, no significant change in the MVA
measured with colour M-mode PISA was noted
(Table 3) with compared to early diastole a change
of −0.02±0.15 for mid diastole, −0.002±0.30 for
mid-late-diastole and 0.007±0.35 cm2 for late-
diastole (all p>0.39). This lack of flow-related MVA
D. Messika-Zeitoun et al.
change was similarly observed irrespective of
stratification based on severity of anatomic
damage (mitral score ≥ or <8) or on presence of mild
to moderate MR (Table 3, Fig. 4).
Discussion
This study shows that in patients with MS, MVA can
be simply and accurately calculated by the colour
M-mode flow convergence method. With precise
timing of flow and velocity measurements, this
method shows good agreement with MVA obtained
from reference echocardiographic techniques with
a strong trend toward a better accuracy compared
to the 2D-PISA method. Importantly, this method
allows for the first time instantaneous measure-
ment of MVA throughout diastole and thus allows
demonstration that despite marked flow and vel-
ocity changes during diastole, the MVA remains
unchanged. The lack of valve reserve, demon-
strated by MVA stability throughout diastole was
observed irrespective of the severity of mitral
anatomical alterations or of the presence of mitral
regurgitation. Therefore, the M-PISA method can
be used as a simple and accurate adjunct in the
comprehensive echocardiographic assessment of
MS in clinical practice and provides important
insight into MS physiology.
Colour M-mode PISA for mitral stenosis 1249

Fig. 3 Quality control plots (using Altman and Bland analysis) for mitral valve area (MVA) estimates by the colour M-mode proximal
isovelocity surface area (PISA) method in early diastole with use of two-dimensional (2D) planimetry (Graph A) and Doppler pressure
half-time (PHT) (Graph B) as reference methods. Each scatter plot indicates on the y-axis the differences between the reference
method and colour M-mode PISA MVA versus the mean of these two methods on the x-axis.

Table 2 Mitral valve area by the four different methods according to the rhythm, the mitral score and the presence of mitral
regurgitation
MVA-2D MVA-PHT 2D-PISA M-mode PISA
Overall 1.29±0.44 1.30±0.41 1.23±0.42 1.27±0.46
Atrial fibrillation 1.22±0.36 1.31±0.46 1.17±0.34* 1.18±0.38*
Sinus rhythm 1.35±0.49 1.29±0.38 1.27±0.48 1.35±0.51
Score ≥8 1.15±0.44 1.20±0.46 1.08±0.41 1.12±0.45
Score <8 1.39±0.42 1.37±0.36 1.33±0.41 1.38±0.45
Mild to moderate MR 1.33±0.47 1.37±0.49 1.22±0.44* 1.30±0.53
No or trivial MR 1.26±0.42 1.24±0.33 1.23±0.42 1.25±0.41

*p<0.05 vs MVA-PHT. Values are mean±SD. MR: mitral regurgitation.

Colour M-mode flow convergence unreliable for post-valvotomy examinations.37

measurement of mitral valve area
All echographic methods of MVA measurement in
MS have potential intrinsic limitations. Two-
dimensional echocardiographic planimetry is not
always feasible3,27,31 and is dependent on locating
the true mitral orifice in the short-axis view and on
the use of the proper gain settings.32 The accuracy
of the PHT may be affected by associated
regurgitations,5,33–35 tachycardia, atrial fibrillation
as shown in the present study and increased left
ventricular end-diastolic pressure.36 Similarly,
acute chamber compliance changes render PHT
Although the continuity equation provides an
additional independent means for determining the
severity of MS, the frequently associated valvular
regurgitations and atrial fibrillation are important
limitations of this method.5,38 Even without these
pitfalls, the standard error of the estimate of the
correlations between these methods is relatively
wide, usually around 0.3 cm2 (0.22 cm2 in the
present study), indicating a notable variability
of all currently used methods. The intrinsic limi-
tations and measurement variability of the
methods of assessment of MVA result in a large
error component of the standard deviation of the
1250 D. Messika-Zeitoun et al.

Table 3 Area and haemodynamic changes throughout the four phases of diastole
Phases of diastole
Early Mid Mid-late Late
Diastolic timing, ms 67±15 170±45 276±83 368±113
Radius of flow convergence, cm* 1.42±0.27 1.11±0.22 1.00±0.22 1.07±0.34
Flow, ml/s* 226±70 178±54 147±59 178±103
Velocity, cm/s* 185±36 146±36 124±43 139±58
Mitral valve area, cm2
Overall 1.27±0.46 1.29±0.47 1.28±0.51 1.27±0.49
Mitral score ≥8 1.12±0.45 1.13±0.43 1.10±0.47 1.08±0.41
Mitral zcore <8 1.38±0.45 1.41±0.47 1.40±0.50 1.40±0.51
Mild to moderate MR 1.30±0.53 1.36±0.52 1.32±0.52 1.30±0.54
No or trivial MR 1.25±0.41 1.24±0.43 1.24±0.50 1.24±0.46

*Denotes significant differences between the four phases of diastole by ANOVA for repeated measures (p<0.0001). The timed
calculations at early, mid, mid-late and late diastole illustrated marked changes in flow and velocities without significant changes
in mitral valve area (p>0.39). Values are mean±SD. MR: mitral regurgitation.

Fig. 4 Phasic measurements of mitral valve area (MVA, y-axis) in early, mid, mid-late and late diastole (x-axis) according to the
presence of a Mitral score < or ≥8 (Graph A) and according to the presence or absence of mitral regurgitation (Graph B). No significant
MVA changes throughout the diastole were noted in any subgroup (all p>0.30).

measurement. Assuming that two independent
methods measure the same signal with statistically
independent and equal measurement errors, the
error component of the final results, the average of
those two methods, is reduced by a factor √2. There-
fore, palliating imperfect accuracy of methods of
measurement of MVA requires in routine practice
the averaging of several methods applicable in
all possible clinical contexts, underscoring the
importance of analysing the value of the recently
developed PISA method.
The PISA method is attractive for MVA determi-
nation in MS, as the proximal convergence region
can be easily visualized and as it may be the only
method available in some patients.13,14 However,
the low frame rate and temporal resolution of
2D-colour imaging, has the potential to reduce the
accuracy of the 2D-PISA method because mitral
inflow and velocity continuously vary throughout
diastole and for the calculation of MVA, it is essen-
tial to measure them simultaneously. The potential
errors in timing of measurements of 2D-PISA may
result in significant differences with 2D-MVA and
PHT-MVA. Avoiding this potential limitation re-
quires a tedious, time-consuming approach poorly
compatible with routine clinical practice.
Colour M-mode PISA for mitral stenosis
In contrast colour M-mode PISA is simple and
accurate for MVA determination. It provides proper
timing for measurements and thus palliates one of
the main limitations of the 2D PISA. Identically
timed measurements of the radius of the proximal
convergence region and of the transvalvular vel-
ocity can easily be obtained in routine practice. In
our study, MVA determined by this technique at the
early diastolic peak of flow and velocity did not
differ and correlated well with MVA determined by
independent reference echocardiographic methods
and a strong trend toward a better accuracy com-
pared with 2D-PISA was observed. The overall accu-
racy of the method was not affected by the rhythm,
the severity of anatomic damage and the presence
of a mild to moderate mitral regurgitation. Thus,
colour M-mode PISA provides satisfactory results
and allows analysing phasic haemodynamic changes
throughout diastole.
Phasic valve area of mitral stenosis
throughout diastole
Studies of valvular heart diseases have shown that
the effective flow orifice area may vary during the
cardiac cycle or under the influence of changes in
cardiac output or loading conditions. For example,
despite organic valve lesions the effective regur-
gitant orifice of mitral regurgitation may change
during systole dynamic.16,39 Even in valve stenosis
with fixed lesions, it has been observed that the
effective orifice of aortic stenosis may vary during
systole19 or under the influence of dobutamine
infusion.20 Conversely, for mitral stenosis, the fixed
or dynamic nature of the mitral orifice has not been
well defined, particularly because during exercise
or dobutamine infusion, MVA assessment by
Doppler echocardiography is technically arduous
and challenging.4,23–25 In contrast, colour M-mode
PISA offers the opportunity to evaluate with appro-
priate timing of measurement the effect of marked
variations of flow on MVA changes.
For the first time, using colour M-mode PISA,
temporal variations of flow, velocity and orifice
area during the normal cardiac cycle were exam-
ined in our study. The timed calculations at early,
mid, mid-late, and late diastole showed that
despite marked changes in flow and velocities
throughout diastole, there were no significant
changes in MVA showing that in MS there is no
flow-related valve reserve. These results may ap-
pear at odds with the data previously reported in
other valve diseases, but require careful examin-
ation of the mechanism of the lesions. Indeed, in
mitral regurgitation most variability has been
1251
observed with mitral valve prolapse,16,39 while
rheumatic lesions are much less variable.16 Also the
lack of variability in MS with high score contrasts
markedly with the variability of aortic valve area in
similarly calcified aortic stenosis.19,20
Therefore, the degree of calcification or valvular
alteration (as observed in the present study) is not a
critical factor in the variability of valve area. One
major difference between mitral and aortic sten-
osis is that despite the fact that leaflets may be
similarly thickened and calcified in both lesions the
commissural lesions are very different. In degen-
erative aortic stenosis there is no commissural
fusion and the stenosis is due to rigid calcified
leaflets, while in MS the stenosis is mainly related
to commissural fusion irrespective of the severity of
valve calcifications. The fixed fusion of the com-
missures is a major limit to MVA changes during
diastole as illustrated by the valve reserve observed
after commissural splitting but not before val-
votomy.40 However with extreme flow changes dur-
ing exercise or dobutamine infusion, some MVA
increase might occur22,24,25 but have limited physio-
logical significance.26 As with fixed orifices the
transvalvular gradient increases as a squared func-
tion of increases in flow, the absent or very limited
variability of the MVA of MS often translates into poor
clinical tolerance of marked transvalvular flow in-
crease, such as in pregnancy.41,42 This poor toler-
ance often forces to emergent interventions or
balloon valvuloplasty.41,42 Finally, since patients
with low transmitral velocity (gradient) were ex-
cluded from the present study, MS with low transval-
vular flow and gradient may exhibit valve reserve.
Therefore, the methodology used in the present
study provides important information to reconcile
discordant clinical data and new insights into MS
physiology. The M-PISA method provides the meth-
odological basis for future studies aiming at further
clarifying these issues.
Limitations
Technical issues are of importance. The colour
M-mode technique requires guidance with 2D-
colour imaging. The flow convergence should not
be grossly deformed and the aliasing velocity set
around 25 cm/s as in previous reports,13,14 may
require adaptation to avoid this pitfall. Also, we
ensured that flow convergence shape adequacy was
maintained throughout diastole by direct examin-
ation. The colour M-mode cursor should pass
through the valve orifice and the centre of the flow
convergence to record the maximal radius, a
condition also achieved by 2D-colour guidance. In
1252
patients with atrial fibrillation some RR intervals
may be extremely long with cessation of mitral
inflow well before end-diastole, leading to non-
sustained colour M-mode flow convergence tracing
in diastole. In our study, such extreme diastoles
were not used for analysis. With current tech-
nology, mitral continuous wave Doppler velocity
and colour flow imaging of the proximal flow con-
vergence cannot be recorded on the same beat.
Beat-to-beat variation was minimized by measuring
the matched colour M-mode and continuous wave
Doppler tracings with the same corresponding RR
intervals. Such measurements on different beats of
similar characteristics have not been a limitation to
the clinical application of the PISA method for
MS12–15 or for other valve diseases.8–11
Clinical implications
The present study shows that the colour M-mode
PISA method allows accurate measurement of MVA
in patients with MS. Its simplicity and improved
temporal resolution resulting in a better accuracy
than the 2D-PISA make it a useful clinical tool. As
no method of assessment of MS is perfect and
increased accuracy is based on combination and
averaging of different methods, this new approach
has the potential to be useful in routine clinical
practice.
Importantly, colour M-mode PISA also allows
analysis of instantaneous transvalvular haemo-
dynamics throughout diastole under changing flow
conditions. To our knowledge, this is the first study
to demonstrate MVA stability throughout diastole
despite widely changing flow, which provides
unique insights into MS physiology and lack of valve
reserve. Hence, colour M-mode PISA has the poten-
tial to assess MS physiological changes under situ-
ations such as percutaneous mitral valvuloplasty,
exercise or pharmacological testing and may have
important future clinical and research applications.
Acknowledgements
Dr Messika-Zeitoun was supported by a grant from
the Federation Française de Cardiologie.
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