Jessica Theodorie1, Ignė Urbonavičiūtė1*, Gintarė Martinkutė2, Eglė Ereminienė2
1Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
2Department of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Abstract
Background: The correlation between rheumatic mitral valve (MV) alterations and left ventricle (LV) geometry and function has been controversial.
Aim: The aim of this prospective study was to establish changes of LV using 2D echocardiography (2DE) and two dimensional speckle tracking imaging (2DSTI).
Methods: 2DE was performed in 22 patients with mitral stenosis and 23 controls. Clinical data (NYHA functional class, coexisting diseases, medical treatment) were collected. MV area, LV end-diastolic diameter, indices of LV end-diastolic and systolic volume, LV ejection fraction (EF), diameter of left atrium (LA), LA volume, pulmonary artery systolic pressure were evaluated. LV global longitudinal strain (GLS) was assessed by 2DSTI. Parameters were analyzed by SPSS software.
Results: Reduced LV EF and LV GLS was found in MS patients (p<0.001), while LV diastolic diameter and volume index did not differ between groups (p=0.6 and p=0.84). The correlation between MV area and LV GLS, LA volume and the velocity of TV regurgitation was revealed. The smaller MV area (<1,4 cm2) correlated with lower LV GLS (r=-0.436, p=0.042), lower LV EF (r=0.533, p=0.01), more dilated LA (p=0,025) and higher TV regurgitation velocity (r=-0,579, p=0,005). There was no significant correlation found between MV area and LV end diastolic diameters and volumes (p=0.2 and p=0.3), as well as RV diameter and RV longitudinal function parameters.
Conclusions: LV GLS and LV EF was lower in rheumatic MS group patients when compared to control group and was related to the severity of valve stenosis.
Keywords: rheumatic mitral stenosis; left ventricle function; two dimensional speckle tracking imaging; left ventricle global longitudinal strain;
Journal of Medical Sciences. March 23, 2020 - Volume 8 | Issue 13. Electronic-ISSN: 2345-0592
10
Medical Sciences 2020 Vol. 8 (13), p. 10-16
Changes of left ventricle function and mechanics in rheumatic
mitral stenosis patients
Jessica Theodorie
1
, Ignė Urbonavičiūtė
1
*, Gintarė Martinkutė
2
, Eglė Ereminienė
2
1
Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
2
Department of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Abstract
Background: The correlation between rheumatic mitral valve (MV) alterations and left ventricle (LV) geometry
and function has been controversial.
Aim: The aim of this prospective study was to establish changes of LV using 2D echocardiography (2DE) and two
dimensional speckle tracking imaging (2DSTI).
Methods: 2DE was performed in 22 patients with mitral stenosis and 23 controls. Clinical data (NYHA functional
class, coexisting diseases, medical treatment) were collected. MV area, LV end-diastolic diameter, indices of LV
end-diastolic and systolic volume, LV ejection fraction (EF), diameter of left atrium (LA), LA volume, pulmonary
artery systolic pressure were evaluated. LV global longitudinal strain (GLS) was assessed by 2DSTI. Parameters
were analyzed by SPSS software.
Results: Reduced LV EF and LV GLS was found in MS patients (p<0.001), while LV diastolic diameter and
volume index did not differ between groups (p=0.6 and p=0.84). The correlation between MV area and LV GLS,
LA volume and the velocity of TV regurgitation was revealed. The smaller MV area (<1,4 cm2) correlated with
lower LV GLS (r=-0.436, p=0.042), lower LV EF (r=0.533, p=0.01), more dilated LA (p=0,025) and higher TV
regurgitation velocity (r=-0,579, p=0,005). There was no significant correlation found between MV area and LV
end diastolic diameters and volumes (p=0.2 and p=0.3), as well as RV diameter and RV longitudinal function
parameters.
Conclusions: LV GLS and LV EF was lower in rheumatic MS group patients when compared to control group
and was related to the severity of valve stenosis.
Keywords: rheumatic mitral stenosis; left ventricle function; two dimensional speckle tracking imaging; left
ventricle global longitudinal strain;
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Journal of Medical Sciences. March 23, 2020 - Volume 8 | Issue 13. Electronic-ISSN: 2345-0592
11
Introduction
Pathogenetically MS hemodynamics has not been
related to LV volume or pressure overload [1].
However, LV systolic dysfunction has been reported
in MS [1-4]. Despite this fact, the impact of the
stenotic mitral valve on intrinsic LV myocardial
contractility remains an issue of debate for over 3
decades, especially due to evaluation of subclinical
LV dysfunction [5]. There is still controversy
whether LV dysfunction in this context is a result of
functional or myocardial factors. Evidence from
early studies suggested that impaired LV systolic
function may be due to rheumatic myocardial
fibrosis, especially of the basal LV segments or as a
consequence of scarring of subvalvular apparatus,
reduction of LV compliance, abnormal right-left
septal interaction, increased afterload and reduced
LV filling [6]. Nevertheless, other evidences reveal
that in patients with isolated MS, ventricular
contractility is normal [3,7].
Within the development of this progressive study,
we tried to assess changes of LV geometry, function
and mechanics as well as pulmonary artery pressure
in rheumatic MS, using 2D echocardiography
speckle tracking based LV global longitudinal strain,
in addition to evaluating the changes of LV
myocardial deformation parameters in this group of
patients.
Methods
This was a prospective study. A sample of 22
patients who underwent 2DE in the tertiary teaching
hospital, Department of cardiology, at the Lithuanian
University of Health Sciences, between the period of
May 2016 and December 2018, were enrolled. The
research was approved by LSMU bioethical center,
the ethics committee of the hospital, Nr. BECMF-
140. The control group consisted of 23 age and
gender matched persons with normal valvular
function. Ischaemic heart disease, history of
myocardial infarction, arrhythmia during the strain
analysis, insufficient tracking segments were
exclusion criteria. Clinical data including NYHA
functional classification, medical history (atrial
fibrillation, arterial hypertension, diabetes mellitus)
were reviewed attentively for all the selected
subjects. We analyzed MS group patients for the
impact of MV area on LV geometry, function and
mechanics. 8 patients had MV area >1,4 cm
2
, 14
patients - ≤1,4 cm
2
.
Echocardiographic evaluation was performed by a
single experienced cardiologist using commercially
available system (Vivid Seven, General Electric-
Vingmed Ultrasound AS, Horten, Norway), with a
3.5 MHz transducer, according recommendations of
the American Society of Echocardiography [8,9]. All
the patients were examined in the left lateral
decubitus position using TTE with two dimensional,
continuous wave doppler and speckle tracking
echocardiographic modalities. Many variables were
calculated including diameters of LV, LA, RA, RV,
indices of LV end diastolic and systolic volumes.
Parameters to determine global LV systolic function:
LV end systolic volume (LVESV), LV end diastolic
volumes (LVEDV) were determined from the four
and two chamber views using the modified
Simpson’s rule and LVEF was calculated using the
following formula: EF = (EDVESV)/EDV. To
compare between individuals with different body
size, chamber measurements were indexed to basal
surface area (BSA). Analysis of RV systolic function
included: fractional area change (FAC), DTI-derived
tricuspid lateral annular systolic velocity wave (S’),
tricuspid annular plane systolic excursion (TAPSE)
from apical 4 chamber view. Pulmonary artery
systolic pressure (sPAP) was derived from tricuspid
regurgitant jet velocity using Bernoulli equation.
Mean pulmonary artery (PA) pressure approximated
by the PA acceleration time (AT). Peak longitudinal
global LV strain using speckle tracking
echocardiography measured in three standard apical
views (2C, long axis view, 4C) and calculated as an
average of three apical views.
Mitral valve area was assessed directly through 2D
planimetry in parasternal short-axis view at the tip of
leaflet as well as by Doppler evaluation. Pressure
half time (P1/2t) was assessed - the time interval
between the maximum mitral gradient in early
diastole and the time point where the gradient
becomes half of the peak initial value, expressed in
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12
milliseconds. Valve area is inversely related to the
decline of the velocity of diastolic transmitral blood
flow. MVA was derived using an empirical formula:
MVA = 220/P1/2t cm2. P1/2t was derived by tracing
the slope of deceleration of E wave on Doppler
spectral display of transmitral flow, and the valve
area was calculated automatically by the software
[10,11].
All data were evaluated in Microsoft Excel and IBM
SPSS Statistics (SPSS Inc, Chicago, IL, USA). The
level of significance was accepted when the p value
was less than 0.05 (p < 0.05). Continuous variables
were expressed as mean ± SD. To compare control
group with study subjects, Mann-Whitney test was
used. Correlation between continuous variables were
tested by nonparametric Pearson correlation
analysis.
Results
The study examined 22 patients with mitral stenosis.
MV area was calculated as 1.22±0.2 cm2, with
medium gradient in diastole 10.3±0.7mmHg. High
proportion were females (95.5%) with mean age
63.5 [57.0-75.8]. The frequency of coexisting
diseases (diabetes mellitus, arterial hypertension,
dyslipidemia) did not differ between groups.
Analyzing NYHA functional class in MS patients -
II NYHA functional class was diagnosed in 13
(61,9%), while III-IV functional class was found in
8 (38,1%) of the group patients. 68% of the MS
group patients had paroxysmal atrial fibrillation,
though during the echocardiographic investigation
all the patients were in sinus rhythm. The patients
reported taking cardiovascular agents, the used
agents were Beta blockers (82%), diuretics (77%),
anticoagulants (64%) and ACEi (55%). Clinical
characteristics parameters of patients group and
control group are detailed in Table 1.
Analyzing the echocardiographic parameters of LV
geometry and function we found that LV diastolic
diameters and volumes did not differ between
groups, but end systolic volume was higher and
LVEF was lower in MS group patients (Table 2) as
well as LV GLS (-14.9±3.34% in MS group vs -
24.7±1.69% in control group, p<0.001) (Figure 1a).
LA diameter as well as LA volume index was
increased when compared with control group data
(p<0.001) (Table 3). While analyzing right heart
geometry and function we concluded that though
indices of RV longitudinal function (TAPSE and s’)
as well as parameter of global RV function (FAC)
were within normal values, though they were
statistically significantly lower when compared with
control group data (Table 4). sPAP was higher in MS
group (Table 4).
The significant correlation between MV area and LV
function parameters, LA volumes and the velocity of
TV regurgitation (Figures 1b, 2) was revealed. The
smaller MV area correlated with lower LV global
longitudinal strain, lower LV EF, more dilated LA
and higher TV regurgitation velocity. There was no
significant correlation found between MV area and
LV end diastolic diameters and volumes (p=0.2 and
p=0.3), as well as RV diameter and RV longitudinal
function parameters.
Table 1. The clinical baseline characteristics of the patients
Variable
Total, n=45
MS group n=22
Control group
n=23
P value
Gender, n (%)
Men/Women
4(8,9)/41(91,1)
1(4,5)/21(95,5)
3 (13,0)/ 20 (87)
0,608
Age, Median [25-75%],
years
59,0 [55,0-65,5]
63,5 [57,0-75,8]
58 [54,0-59,0]
0,003
Body surface area [25-
75%], m
2
1,82 [1,76-1,92]
1,8 [1,74-1,89]
0,72
Diabetes mellitus, n (%)
4 (8,9)
1 (4,5)
3 (13,0)
0,608
Arterial hypertension, n
(%)
11 (24,4)
7 (31,8)
4 (17,4)
0,26
Dyslipidaemia, n (%)
15 (33,3)
6 (27)
9 (39,1)
0,399
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Table 2. LV geometry and function parameters between the groups
Variables
Groups
P value
MS group (n=22)
Control group (n=23)
Median [25-75%]
LV EDD (mm)
46,0 [43,0-50,3]
48,6 [42,8-50,3]
0,666
LV EDDi (mm/m
2
)
26,8 [24,5-29,2]
25,9 [24,6-27,5]
0,525
LV EDV (ml)
88,5 [72,5-115,5]
84,0 [74,0-100,0]
0,593
LV EDVi (ml/m
2
)
47,8 [39,9-59,6]
48,8 [41,6-56,2]
0,842
LV ESV (ml)
42,0 [38,0-57,0]
29,5 [24,8-36,0]
0,001
LV ESVi (ml/m
2
)
23,7 [21,0-30,7]
17,4 [14,0-20,4]
<0,001
LV EF (%)
51,5 [50,0-55,0]
64,0 [61,0-74,0]
<0,001
LV – left ventricle, EDD – end diastolic diameter, EDDI – end diastolic diameter index, EDV – end diastolic
volume, EDVi – end diastolic volume index, ESV – end systolic volume, ESVi – end systolic volume index, EF
– ejection fraction, p value – analyzed with non-parametric Mann-Whitney test for two independent sample
volumes
Table 3. Diameters and volumes of left and right atriums between the groups
Parameters
Groups
P value
MS group (n=22)
Control group (n=23)
Median [25-75%]
RA diameter (mm)
40,0 [38,0-44,5]
34,0 [30,0-38,0]
<0,001
LA diameter (mm)
48,5 [15,8-56,0]
32,6 [30,0 -36,4]
<0,001
LA volume (ml)
100,0 [91,0-142,5]
47,0 [40,0-58,0]
<0,001
LA volume index
(ml/m
2
)
56,0 [48,3-81,1]
26,2 [21,9-31,4]
<0,001
RA – right atrium, LA – left atrium
Table 4. RV size, hemodynamics and function parameters between study groups
Parameters
Groups
P value
MS group (n=22)
Control group (n=23)
Median [25-75%]
TAPSE (mm)
21,0 [17,0-26,0]
26,9 [23,0-28,6]
0,004
FAC (%)
36,5 [30,2-39,9]
55,9 [51,9-63,0]
<0,001
S’ (cm/s)
11,5 [9,5-14,7]
15,0 [14,0-17,0]
<0,001
RV diameter (mm)
34,0 [30,0-37,0]
31,3 [26,7-35,8]
0,047
TVR degree
2,0[1,4-2,5]
1,0 [0-1,0]
<0,001
PAS syst (mmHg)
50,0 [45,0-55,0]
28,0 [26,5-31,5]
<0,001
TAPSE – tricuspid annular systolic excursion, FAC – fractional area change, RV –right ventricle, S’ – tricuspid
lateral annular systolic velocity wave, TVR – tricuspid valve regurgitation, PAS syst – systolic pulmonary artery
pressure
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Figure 1. (a) Comparing LV global longitudinal strain between groups, (b) Correlation between MVA and LA
volume in MS patients.
Figure 2. Correlation between: (a) MVA and LVEF in MS patients, (b) MVA and LV global longitudinal strain
in MS patients, (c) MVA and TV regurgitation velocity in MS patients.
Discussion
According to controversial data about LV
dysfunction in MS, this study analyzed changes of
LV geometry, function and mechanics in rheumatic
MS patients and the relation of MV area on LV
systolic function, mechanics, the size of LA and
pulmonary artery pressures. The results have shown
that MV stenosis cause significant variations on the
cardiac parameters that were measured by 2D
echocardiography. One of the new
echocardiographic modalities used in this study was
2D speckle tracking. This method is angle
independent in the assessment of global ventricular
function. Meta-analysis showed that the prognostic
value of GLS has been evaluated as more accurate
than LV EF, therefore, subclinical LV function
impairment has been confirmed even with normal
EF [12,13,14]. The LV GLS measurements were
obtained and compared between MS patients and
healthy control group. The results indicated that
patients with MS had significantly decreased
measurement of LV GLS when compared with
control group (-14.9±3.34 vs -24.7±1.69, p<0.001).
Similar results were identified by E. Bilen et al. who
obtained depressed LV strain and strain rate values
in 72 mitral stenosis patients who were enrolled in
the study. However, the values did not vary among
patients within different group when considering the
severity of stenosis [3]. Current results support the
theory that subclinical LV dysfunction observed in
MS patients, would probably depend on myocardial
factors as well as hemodynamic factors – we found
moderately significant relation between MV area
and LV GLS (r=-0,436, p=0,042), though correlation
between LV GLS and MV area was not revealed in
patients with rheumatic MS [15]. Parameters
collected from conventional echocardiography
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(LVEDV, LVEDD, LVESV, LVEF) showed some
differences between compared groups. LV end
diastolic diameter and volume did not differ between
groups (p=0.2 and p=0.3), while LV ESV was higher
(p<0.001) and LVEF was lower in MS patients
(p<0.001) though the absolute numbers were in
normal value range. M. A. Sowdagar and Y. V.
Subba Reddy performed an observational study on
30 patients with severe mitral stenosis (MVA < 1.0
cm2), they observed the changes after successful
PMV which was described as (MVA > 1.5 cm2).
Results showed an increase in LVEDD and LVEF
with a decrease in LVESD after successful repair
[16]. This seemingly discloses increased left
ventricular filling after alleviation of the obstruction
which again validates the results of the study
conducted. However, their study included only
severe stenosis patients while ours has limited
sample size so the results are generalized upon all
MS patients. As anticipated, MS patients in
comparison to control group, have revealed an
increase in both LA diameter and volume; that can
be clarified from chronic inflow reduction through
the valve, which over time, causes gradual increase
in loading pressure in the LA. Furthermore, atrial
function can be altered in two ways, either from
chronic loading pressure as it may cause fibrosis or
from the potential chronic rheumatic inflammatory
changes on the myocardium or can be from both
[17]. Our data confirmed the significant correlation
between LA volume and MVA. As a result a buildup
of pulmonary artery systolic pressure develops
which was proved in our results [18].
Study limitations
Several limitations of the study were discussed.
First, a small sample size is a significant limitation.
Accordingly, these results need to be reanalyzed and
aggregated on a larger number of patients with MS.
Second, the prognostic impact of LV dysfunction on
MS surgery outcomes would be of great value.
Conclusions
1. LV global longitudinal strain and LV ejection
fraction was lower in rheumatic MS group patients
when compared to control group and was related to
the severity of valve stenosis.
2. There was no significant correlation found
between MV area and LV end diastolic diameter and
volume indices, as well as RV diameter and RV
longitudinal function parameters, but the relation
was found between MV area and LA volume and
velocity of tricuspid regurgitation.
Conflict of interest: None declared.
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