Received: 12 July 2019 Revised: 14 September 2019 Accepted: 8 November 2019

DOI: 10.1002/jcu.22798

RESEARCH ARTICLE

Assessment of right ventricular dysfunction in patients

with mitral stenosis: A speckle tracking study

Kamuran Kalkan MD1 | Fikriye Kalkan MD2 | Emrah Aksakal MD1 |

Oktay Gulcu MD1 | Zakir Lazoglu MD3 | Ugur Aksu MD1
Selami Demirelli MD1
1
Department of Cardiology, University of
Health Sciences, Erzurum Education and
Research Hospital, Erzurum, Turkey
2
Department of Pulmonology, University of
Health Sciences, Erzurum Education and
Research Hospital, Erzurum, Turkey
3
Department of Cardiology, Kars State
Hospital, Kars, Turkey
Correspondence
Kamuran Kalkan, Department of Cardiology,
University of Health Sciences, Erzurum
Education and Research Hospital, Erzurum.
Turkey.
Email: kalkankamuran@yahoo.com.
| Ali Fuat Korkmaz MD1 |
Abstract
Purpose: Although it is affected at an early stage, there is a lack of studies investigat-
ing right ventricular (RV) function in patients with mitral stenosis (MS). We aimed to
investigate the correlation between conventional echocardiographic variables and tri-
cuspid annular plane systolic excursion (TAPSE), used as an indicator of RV
dysfunction.
Methods: We enrolled 59 consecutive patients with MS and assigned them in group
1 if TAPSE ≤16, or group 2 if: TAPSE >16.
Results: The mean age of the patients was 42.2 ± 8 years, and 74.6% were females.
In univariate analysis, maximal mitral valve gradient, mean mitral valve gradient, sys-
tolic pulmonary arterial pressure, RV strain, and RV strain rates were associated with
RV dysfunction. In multivariate analysis, both strain variables were found to be inde-
pendent predictors of RV dysfunction. Kaplan Maier survival analysis showed that
patients with lower RV strain had more rehospitalization rate during the one-year
follow-up period.
Conclusions: RV dysfunction is common in patients with MS and is associated with
higher rehospitalization rate and morbidity. Evaluation of RV strain and strain rate for
early detection of RV dysfunction and prediction of rehospitalization may be an
appropriate approach in mitral stenosis.

KEYWORDS
echocardiography, mitral stenosis, right ventricle, strain

1 | I N T RO D UC T I O N
Despite decreasing incidence of rheumatic fever, mitral stenosis
(MS) is still frequent in industrialized countries. It causes significant
morbidity and mortality throughout the world.1 MS severity can be
graded by echocardiography, but symptoms of heart failure do not
correlate with echocardiography variables.2
MS affects the entire heart, especially the left atrial functions.3
MS results in elevated left atrial pressure, leading to dilatation,
followed by increase in pulmonary venous and arterial pressure.
During the chronic stage of MS, right ventricular (RV) function and
structure are impaired and dilatation occurs due to pressure and vol-
ume overload.4 RV dysfunction is an as important cause of cardiovas-
cular mortality as left ventricle dysfunction.
RV function can be assessed by many echocardiography variables. Tri-
cuspid annular plane systolic excursion (TAPSE) reflects the RV function
and is also recommended by current guidelines to evaluate RV dysfunc-
tion.5 In our study, we aimed to investigate the relationship between RV
dysfunction (detected by TAPSE) and deformation, as well as the role of
deformation variables for predicting adverse events in patients with MS.

J Clin Ultrasound. 2019;1–6. wileyonlinelibrary.com/journal/jcu © 2019 Wiley Periodicals, Inc. 1

2 KALKAN ET AL.

2 | METHODS
We enrolled 76 consecutive patients who underwent echocardio-
graphic evaluation for MS. Patients with a history of severe chronic
obstructive pulmonary disease (n = 2), a history of atrial fibrillation
(n = 10), or who were unsuitable for echocardiography (n = 5), were
were obtained in the left lateral decubitus position using the same echo-
cardiography machine (Vivid 7, GE Healthcare, Horten, Norway). All
patients underwent the standard echocardiographic assessment includ-
ing two-dimensional (2D), pulsed-wave (PW) Doppler, color Doppler, M-
mode, and tissue Doppler imaging modes, and all images were recorded
for off-line analysis. Mitral valve area (MVA), systolic pulmonary arterial

excluded. Clinical and demographic characteristics of the patients pressure (sPAP), maximal mitral valve gradient (MMVG), and mean mitral

were noted, and they were divided into two groups, using TAPSE
≤16 mm as an indicator of RV dysfunction (Group 1: TAPSE≤16,
Group 2: TAPSE>16). We assessed the relationship between RV dys-
function and echocardiographic variables.
3 | D E F I NI T I O N S
Hypertension was defined either as a history of chronic antihyperten-
sive medication use or a blood pressure level >140/90 mmHg in two
consecutive measurements. The patients whose fasting blood glucose
levels were >126 mg/dL or who were on oral antidiabetics or insulin,
valve gradient (MeMVG) were measured in all patients. MVA was calcu-
lated using the planimetric method. RV myocardial performance index
(MPI), and TAPSE were also calculated according to current guideline
recommendations.5
For RV-2D strain imaging, the patient's heart rhythm was moni-
tored with echocardiography, 2D video data were recorded from the
modified apical 4-chamber (A4C) view, and RV-focused images includ-
ing at least three cardiac cycles at a rate of 50 to 75 frames/s with
regular ECG signals were obtained in the tissue velocity imaging
mode. The off-line analysis of recorded image sequences and signals
was performed using the Echopack software (GE Healthcare, Horten,
Norway) on a computer workstation. After defining three reference

were accepted as patients with diabetes mellitus.
4 | E C H O C A R D I O G R A P H I C EV A L U A T I O N
The echocardiographic evaluations were performed by two experienced
cardiologists who were blinded to the study data. The measurements
landmarks (RV apex, medial and lateral tricuspid annulus), the software
automatically traced the endocardial and epicardial borders in the
modified A4C view. Tracking points were adjusted manually if neces-
sary, and 2D longitudinal strain and strain rate curves were obtained
for each myocardial segment. Peak negative longitudinal systolic strain
variables were derived from these curves. RV global longitudinal strain
(RVGLS), RV global longitudinal strain rate (RVGL-SR), and RV free-

Variables Group-1 (n = 23) Group-2 (n = 36) P-value

T A B L E 1 Baseline clinical and
echocardiographic characteristics of the
Sex, male 23.1% 26.1% .82
study population
Age (years) 39.5 ± 7.1 42.9 ± 8.8 .205
DM 2.3% 2.2% .39
HT 7.7% 17.4% .59
MVA (cm2) 1.34 ± 0.29 1.8 ± 0.45 .001
RV size (mm) 47 ± 5 43 ± 2.6 .09
LVEDD (mm) 46 ± 0.45 46 ± 0.37 .82
LVESD, mm 25 ± 0.42 27 ± 0.35 .21
LA (mm) 45 ± 6 43 ± 5.8 .15
sPAP (mm Hg) 44.2 ± 9.1 36 ± 7.3 .016
IVS (mm) 9.9 ± 0.8 10 ± 0.9 .69
MMVG (mm Hg) 18.8[14-23] 12.6[9-14] <.001
MeMVG (mm Hg) 9.1 ± 2.2 7.2 ± 1.3 <.001
LV-EF (%) 64.4 ± 5.4 64 ± 6.1 .95
RV global longitudinal strain, (%) 14.5 ± 3.7 18.2 ± 3.4 <.001
−1
RV global longitudinal strain rate (s ) 1.31[0.73-1.72] 1.68[0.8-1.7] <.001
RV free wall global longitudinal strain (%) 15.1 ± 4.3 18.6 ± 3.9 .003
RV free wall global longitudinal strain rate (s−1) 1.46[0.81-1.82] 1.73[0.85-1.91] .015
RVMPI 0.51 ± 0.09 0.56 ± 0.09 .37

Abbreviations: DM, diabetes mellitus; HT, hypertension; IVS, interventricular septum; LA, left atrium;
LVEDD, left ventricular end diastolic diameter; LVEF, left ventricular ejection fraction; LVESD, left
ventricular end systolic diameter; MeMVG, mean mitral valve gradient; MMVG, maximal mitral valve
gradient; MVA, mitral valve area; RV, right ventricle; RVMPI, right ventricular myocardial performance
index; sPAP, systolic pulmonary arterial pressure.
KALKAN ET AL.
wall global strain (RVFGS), and RV free-wall global strain rate (RVFG-
SR) values were measured according to the current guidelines.5
5 | STATISTICAL ANALYSIS
The distribution of continuous variables was assessed by Kolmogorov-
Smirnov test, and they were expressed as mean ± SD if normally distrib-
uted, or median [interquartile range] if not. Categorical variables were
expressed as percentages. Comparisons of continuous variables between
two groups were assessed with Student's t-test or Mann-Whitney U test
as appropriate. Categorical variables were compared with Chi-square test.
Logistic regression analysis was performed to determine indepen-
dent predictors of RV dysfunction. In the univariate analysis, the vari-
ables found to be significant (P value <.05) were included in logistic
regression analysis. During the one-year follow-up period in MS
patients, deformation variables, TAPSE, and MVA were evaluated, and
Cox regression analysis was performed for their predictive value of the
need for rehospitalization. Kaplan Meier survival curves were traced to
F I G U R E 1 Box-and-whiskers plot of right ventricular deformation variables. Group 1: TAPSE≤16; Group 2: TAPSE>16. TAPSE: Tricuspid
annular plane systolic excursion
3
display rehospitalization rate according to RVGLS, RVGL-SR, RVFGS,
and RVFG-SR. The log-rank test was used to compare the groups. A
two-sided P value of <.05 was considered to be significant. Data were
analyzed using SPSS 22.0 version (IBM, Armonk, New York).
6 | RESULTS
We enrolled 59 patients with MS (mean age 42.2 ± 8 years; 74.6% of
patients were female). Main characteristics of the study population
are summarized in Table 1.
In the univariate analysis, MVA (OR: 2.1, 95% CI: 2.6-4.5,
P = .004), sPAP (OR: 0.88, 95% CI: 0.81-0.97, P = .008), MMVG (OR:
0.77, 95% CI: 0.62-0.94, P = .013), MeMvG (OR: 0.86, 95% CI:
0.89-0.98, P = .042) RVGLS (OR: 0.81, 95% CI: 0.70-0.93, P = .004),
RVGL-SR (OR: 1.2, 95% CI: 1.01-1.8, P = .006), RVFGS (OR: 0.85,
95% CI: 0.73-0.92, and P = .007), and RVFG-SR (OR: 1.3, 95% CI:
1.03-1.7, P = .032) were associated with RV dysfunction (Figure 1).
4 KALKAN ET AL.

Correlation analysis showed that all strain variables were correlated
with TAPSE (Figure 2).
In the multivariate analysis, RVGLS (OR: 2.6, 95% CI: 1.6-3.9,
P = .031), RVGL-SR (OR: 2.3, 95% CI: 1.5-3.7, P = .037), RVFGS (OR:
2.1, 95% CI: 1.2-3.5, P = .041), and RVFG-SR (OR: 1.8, 95% CI:
1.1-2.2, P = .050) were independently associated with RV dysfunc-
tion (Table 2). In Cox regression analysis, RVGLS (OR: 2.7, 95% CI:
1.2-3.6, P = .017) and RVFGS (OR: 2.1, 95% CI: 1.1-3.2, P = .039)
were compared with TAPSE and the conventional Doppler variables
10.3% vs 4.8%, log rank P = .04) during the one-year follow-up period
(Figure 3). In Cox regression analysis, low RVGLS was associated with
a 2.6-fold increase in risk of rehospitalization, while low RVFGS was
associated with a 2.1-fold increase in risk.
7 | DISCUSSION
The main findings of this study were:

and proved predictive of rehospitalization (Table 3).

In Kaplan-Meier analysis, patients with lower RVGLS and RVFGS i. Right ventricular deformation variables were more strongly correlated
had a higher rehospitalization rate (12.1% vs 3.9%, log rank P = .01, with RV dysfunction than conventional echocardiographic variables.

F I G U R E 2 The correlation plots of tricuspid annular plane systolic excursion (TAPSE) and right ventricular deformation variables. RV, right
ventricular; RVGLS, right ventricle global longitudinal strain; RVFGL-SR, right ventricle global longitudinal strain rate; RVFGS, right ventricle free-
wall global strain; RVFG-SR, right ventricle free-wall global strain rate
KALKAN ET AL. 5

TABLE 2 Independent predictors of right ventricular dysfunction in multivariate regression analysis

Variables Univariate OR, 95 %CI Univariate P-value Multivariate OR, 95 %CI Multivariate P-value
MVA 2.1[2.6–4.5] .004 1.3[0.9-2] .090
sPAP 0.88[0.81-0.97] .008 0.86[0.71-1.2] .143
MMVG 0.77[0.62–0.94] .013 4.6[0.93-7.5] .186
MeMVG 0.86[0.89–0.98] .042 0.93[0.81-1.21] .872
RV global longitudinal strain 0.81[0.70–0.93] .004 2.6[1.6–3.9] .031
RV free wall global longitudinal strain 0.85[0.73–0.92] .007 2.1[1.2–3.5] .041
RV global longitudinal strain rate 1.2[1.01–1.8] .006 2.3[1.5–3.7] .037
RV free wall global longitudinal strain rate 1.3[1.03–1.7] .032 1.8[1.1–2.2] .050

Abbreviations: MeMVG, mean mitral valve gradient; MMVG, maximal mitral valve gradient; MVA, mitral valve area; RV, right ventricular; sPAP, systolic
pulmonary arterial pressure.

T A B L E 3 Independent predictors of rehospitalization in Cox Most cases of mitral stenosis are caused by rheumatic fever. The
regression analysis in patients with mitral stenosis time between the first rheumatic fever attack and the clinical discov-
Multivariate OR, Multivariate ery of mitral valve stenosis varies from a few years to 20 years. Mitral
Variables 95 %CI P value valve calcification and congenital heart disease are rare causes of
MVA 1.7[0.92-2.7] .12 mitral stenosis.6 Normal mitral valve area is 4 to 6 cm2.5 When the
TAPSE 3.1[0.83-1.09] .21 mitral valve area falls below 2 cm2, the mitral stenosis becomes signif-

MMVG 4.2[0.73-1.06] .12

icant and forms an obstacle to the flow of blood from the left atrium
to the left ventricle. Eventually, pulmonary arterial pressure increases
MeMVG 0.84[0.71-1.04] .67
and RV dysfunction develops.7
RV global longitudinal strain 2.7[1.2–3.6] .017
Although clinically important, the evaluation of the systolic and
RV free wall global 2.1[1.1–3.2] .039
diastolic function of the RV is more difficult than that of the left ven-
longitudinal strain
tricle.8 Because of the complex anatomical structure of the RV and
Abbreviations: MeMVG, mean mitral valve gradient; MMVG, maximal
due to volume or pressure overload, RV dysfunction may occur. In
mitral valve gradient; MVA, mitral valve area; RV, right ventricular; sPAP,
systolic pulmonary arterial pressure. recent years, methods that are independent of geometric assumptions
have been particularly helpful. TAPSE is a sensitive indicator of RV
ii. RV strain was a useful diagnostic tool for the prediction of longitudinal function and has been proven to be correlated with
rehospitalization in patients with MS. To the best of our knowl- radionuclide-derived RV ejection fraction and fractional area change
edge, this was the first study to show the relation between RV (FAC).9 TAPSE, FAC, and tissue Doppler imaging (TDI) reflect RV dys-
deformation variables and rehospitalization. function. A TAPSE value ≤16 mm is an indicator of right ventricular

F I G U R E 3 Kaplan-Meier survival analysis demonstrating the rehospitalization rates in the long-term follow-up. RVGLS, right ventricle global
longitudinal strain; RVFGS, right ventricle free-wall global strain
6 KALKAN ET AL.
dysfunction.5 However, in the presence of regional systolic dysfunc-
tion, global systolic function may not correctly reflect changes in ven-
tricular function.
TDI is a validated technique for quantitative evaluation of left ven-
tricular functions, but its measurements are angle dependent and are
affected by global heart movements, which is an important limitation10
While strain imaging shows the dimensional changes (deformations)
resulting from contraction and relaxation, strain rate shows the defor-
mation rate.11 Strain and strain rate echocardiography has been shown
to be superior to TDI in assessing myocardial function in many cardiac
diseases.12 In our study, RV strains and strain rates were found to be
independent predictors of RV dysfunction and rehospitalization.
Furthermore, Kumar et al. showed that RV strain might indicate RV
systolic dysfunction in patients with MS before clinical symptoms of sys-
temic venous congestion become apparent.13 Cameli et al. demonstrated
the usefulness of RV strain in analyzing RV function in patients with
heart failure.14 Vitarelli et al. showed that 2D and 3D strain echocardiog-
raphy provided more information about RV hemodynamics than conven-
tional echocardiography variables in patients with chronic pulmonary
hypertension.15 In our study, there was a significant correlation between
TAPSE and the RV strains-strain rates, which were superior to conven-
tional echocardiography variables. This also suggests that the RV strains-
strain rates can be used in clinical practice in addition to TAPSE for evalu-
ating RV dysfunction and adverse event prediction.
In this context, our study brings findings that are consistent with
the three aforementioned studies but adds the evaluation of RV dys-
function according to TAPSE, and its relationship with RV strain.
Unlike other studies, we established that RV strain was also able to
provide useful information for the prediction of rehospitalization.
8 | LIMITATIONS
We included a small number of patients and we did not perform
three-dimensional strain measurement. The cross-sectional design of
our study is another limitation.
9 | CO NC LUSIO NS
RV dysfunction is common in patients with MS and is associated with
rehospitalization and morbidity. Evaluation of RV strain and strain rate
for early detection of RV dysfunction and for prediction of
rehospitalization may be useful in patients with mitral stenosis.
CONF LICT S OF INTE R ES T
The authors declare no potential conflict of interest.
ORCID
Kamuran Kalkan https://orcid.org/0000-0002-1779-560X
Ugur Aksu https://orcid.org/0000-0003-0918-5032
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How to cite this article: Kalkan K, Kalkan F, Aksakal E, et al.
Assessment of right ventricular dysfunction in patients with
mitral stenosis: A speckle tracking study. J Clin Ultrasound.
2019;1–6. https://doi.org/10.1002/jcu.22798