Outcomes of Severe Mitral Stenosis With the Revised Severity Criteria: Mitral Valve Replacement vs Percutaneous Mitral Valvuloplasty

Clinical Research
Outcomes of Severe Mitral Stenosis With the Revised
Severity Criteria: Mitral Valve Replacement vs Percutaneous
Mitral Valvuloplasty
Dae-Young Kim, MD,a,z
Iksung Cho, MD, PhD,b,z
Kyu Kim, MD,b
Seo-Yeon Gwak, MD,b
Kyung Eun Ha, MD,b
Hee Jeong Lee, MD,b
Kyu-Yong Ko, MD,b
Chi Young Shim, MD, PhD,b
Jong-Won Ha, MD, PhD,b
William Dowon Kim, MD,b
In-Jai Kim, MD,c
Seonhwa Lee, MD,d
In-Cheol Kim, MD, PhD,d
Kang-Un Choi, MD, PhD,e
Hojeong Kim, MS, RDCS,f
Jang-Won Son, MD, PhD,e
and Geu-Ru Hong, MD, PhDb
a
Division of Cardiology, Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea
b
Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
c
Division of Cardiology, CHA Bundang Medical Center, CHA University School of Medicine, Pocheon, South Korea
d
Division of Cardiology, Department of Internal Medicine, Cardiovascular Center, Keimyung University Dongsan Hospital, Keimyung University School of Medicine,
Daegu, South Korea
e
Division of Cardiology, Department of Internal Medicine, Yeungnam University Medical Center, Gyeongsan, South Korea
f
Division of Physiology, Department of Biomedical Laboratory, Daegu Health College, Daegu, Korea
See editorial by Burns, pages 110-112 of this issue.
Canadian Journal of Cardiology 40 (2024) 100e109
https://doi.org/10.1016/j.cjca.2023.09.006
0828-282X/Ó 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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ABSTRACT
Background: This study aimed to compare the outcomes, according to
percutaneous mitral valvuloplasty (PMV) vs mitral valve replacement
(MVR), of severe mitral stenosis (MS) with the updated criteria (MVA
1.5 cm2
).
Methods: From the Multicenter Mitral Stenosis With Rheumatic Eti-
ology (MASTER) registry of 3140 patients, we included patients with
severe MS who underwent PMV or MVR between January 2000 and
December 2021 except for previous valvular surgery/intervention, at
least moderate other valvular dysfunction, and thrombus at the left
atrium/appendage. Moderately severe MS (MS-MS) and very severe
MS (VS-MS) were defined as 1.0 cm2
MVA 1.5 cm2
and MVA 1.0
cm2
, respectively. Primary outcomes were a composite of cardiovas-
cular (CV) death and heart failure (HF) hospitalization. Secondary
outcomes were a composite of primary outcomes and redo
intervention.
Results: Among 442 patients (mean 56.5 11.9 years, women
77.1%), the MVR group (n ¼ 260) was older, had more comorbidities,
higher echoscore, larger left chambers, and higher right ventricular
systolic pressure than the PMV group (n ¼ 182). During a mean follow-
up of 6.9 5.2 years with inverse probability-weighted matching,
primary outcomes did not differ, but the MVR group experienced fewer
secondary outcomes (P ¼ 0.010). In subgroup analysis of patients with
MS-MS and VS-MS, primary outcomes did not differ. However, the MVR
group in patients with VS-MS showed better secondary outcomes (P ¼
0.012).
Conclusions: PMV or MVR did not influence CV mortality or HF hos-
pitalization in both MS-MS and VS-MS. However, because of increased
early redo intervention in the PMV group in VS-MS, MVR would be the
preferable option without clear evidence of suitable morphology for
PMV.
RÉSUMÉ
Contexte : La pr
esente
etude visait à comparer les issues cliniques
li
ees à la valvuloplastie mitrale percutan
ee (VMP) à celles du
remplacement de la valve mitrale (RVM) pour corriger la st
enose
mitrale (SM) s
evère, selon les critères les plus r
ecents (surface val-
vulaire mitrale [SVM] 1,5 cm2
).
M
ethodologie : À partir des 3140 patients inscrits au registre multi-
centrique Mitral Stenosis With Rheumatic Etiology (MASTER), nous
avons inclus dans notre analyse les patients atteints d’une SM s
evère
ayant subi une VMP ou un RVM entre janvier 2000 et d
ecembre 2021,
à l’exclusion de ceux ayant auparavant subi une intervention ou une
chirurgie valvulaire, qui
etaient atteints d’une ou de plusieurs autres
dysfonctions valvulaires ou qui pr
esentaient une thrombose de l’atrium
ou de l’auricule gauche. La SM mod
er
ee à s
evère
etait d
efinie comme
une SVM 1,0 cm2
et 1,5 cm2
, alors que la SM très s
evère
etait
d
efinie comme une SVM 1,0 cm2
. Le critère d’
evaluation principal
composite comprenait le d
ecès d’origine cardiovasculaire (CV) et
l’hospitalisation pour insuffisance cardiaque. Le critère d’
evaluation
secondaire composite comprenait les
el
ements du critère principal et
la r
eintervention.
R
esultats : Parmi les 442 patients de l’analyse (âge moyen de 56,5
11,9 ans, dont 77,1 % de femmes), les personnes dans le groupe
ayant subi une VMP (n ¼ 260)
etaient plus âg
ees, pr
esentaient plus de
troubles concomitants et avaient des valeurs plus
elev
ees pour le score

echographique, la taille des cavit
es cardiaques gauches et la pression
ventriculaire systolique droite que les personnes du groupe ayant subi
un RVM (n ¼ 182). Au cours d’un suivi d’une dur
ee moyenne de 6,9
5,2 ans, l’analyse avec appariement et pond
eration selon la probabilit
e
inverse n’a montr
e aucune diff
erence entre les groupes pour le critère
principal d’
evaluation, mais la fr
equence du critère d’
evaluation
secondaire
etait plus faible dans le groupe ayant subi un RVM
(p ¼ 0,010). L’analyse par sous-groupes des patients pr
esentant une
SM mod
er
ee à s
evère ou très s
evère n’a r
ev
el
e aucune diff
erence
entre les groupes pour le critère d’
evaluation principal. Chez les
patients atteints d’une SM mod
er
ee à s
evère, le groupe ayant subi un
RVM a obtenu des r
esultats plus favorables pour le critère d’
evaluation
secondaire (p ¼ 0,012).
Conclusions : Le type d’intervention (VMP ou RVM) n’exerçait pas
d’influence sur la mortalit
e d’origine CV chez les patients atteints d’une
SM mod
er
ee à s
evère ou très s
evère. Toutefois, en raison du taux de
r
eintervention pr
ecoce plus
elev
e dans le groupe de patients atteints
d’une SM mod
er
ee à s
evère ayant subi une VMP, il semble que le RVM
soit pr
ef
erable en l’absence d’une morphologie pour laquelle la VMP
est manifestement adapt
ee.
Rheumatic mitral stenosis (MS) remains the most common
valvular heart disease worldwide, and despite its decreasing
global burden, the condition still has a high prevalence,
particularly in the poorest region of the world.1-3
For symp-
tomatic severe rheumatic MS, symptoms and prognosis are
expected to be improved with optimal surgical or percuta-
neous interventional treatment.4
In the current guideline, severe MS is defined as mitral valve
(MV) area (MVA) 1.5 cm2
.5-7
In the 2006 American Heart
Association guidelines for valvular heart disease, MS severity
was divided into moderate and severe, based on the MVA
threshold of 1.0 cm2
.8
However, the revised guidelines in 2014
lowered this MVA threshold of severe MS from 1.0 cm2
to 1.5
cm2
,9
and recently updated guidelines of valvular heart disease
still maintained this MS categorization. In the revised guide-
lines, identical treatment strategy is recommended for patients
with severe MS with MVA 1.0 cm2
and those with MVA of
1.0 to 1.5 cm2
. Without contraindications, percutaneous mitral
valvuloplasty (PMV) is recommended as the first-line treatment
Received for publication May 31, 2023. Accepted September 9, 2023.
z
These authors contributed equally to this manuscript.
Corresponding author: Dr Geu-Ru Hong, Division of Cardiology,
Severance Cardiovascular Hospital, Yonsei University College of Medicine,
Yonsei-ro 50-1, Seodaemun-gu, Seoul, Korea, 03722.
E-mail: grhong@yuhs.ac
See page 108 for disclosure information.
Kim et al. 101
Outcomes of Severe Mitral Stenosis

for severe MS, according to the guidelines. Surgical MV
replacement (MVR) is reserved for patients who are ineligible
for PMV or require other cardiac surgery. Although this
treatment strategy was based on the evidence from several
clinical outcome studies,10-13
these results were mostly based on
previous criteria of severe MS with MVA 1.0 cm2
, and there
are limited data on the clinical outcomes, according to PMV vs
MVR treatment strategy, in patients with severe MS, including
the moderately severe MS (MS-MS) group (MVA of 1.0 to 1.5
cm2
) that was recently integrated into the severe grade.
Therefore, the purpose of our investigation was to compare
the primary outcomesda composite of cardiovascular (CV)
death and heart failure (HF) hospitalizationdand the sec-
ondary outcomesda composite of primary outcomes and
redo interventiondin patients with severe MS undergoing
either PMV or MVR, using the updated criteria for the
subgroups categorized by MVA of 1.0 cm2
and 1.5 cm2
.
Material and Methods
Study population
We identified 3140 patients with at least moderate MS in
the Multicenter Mitral Stenosis With Rheumatic Etiology
(MASTER) registry in South Korea between January 2000
and December 2021. First, we screened patients with di-
agnoses of severe MS (n ¼ 2652), which was confirmed by
transthoracic echocardiography. Severe MS was defined as
MVA 1.5 cm2
by 2-dimensional (2D) planimetry according
to the latest guidelines for valvular heart disease.5,7
Among
them, we excluded patients with previous cardiac surgery or
PMV before the indexed echocardiography; combined sig-
nificant (at least moderate) mitral regurgitation or aortic ste-
nosis/regurgitation; and those with PMV contraindication,
including patients having visible thrombus at the left atrium
(LA) or LA appendage on transesophageal echocardiography
(TEE). After these exclusions, 1325 patients remained as
isolated severe MS cases.
Among them, 442 patients who experienced therapeutic
intervention for MS were finally included in this study
(Fig. 1). Treatment strategy was selected by the attending
special cardiologists, based on transthoracic echocardiography
and TEE, Wilkins echo score, and comorbidity of the patient.
All baseline characteristics, echocardiographic parameters, and
clinical outcomes of the patients were reviewed retrospec-
tively. Indexed echocardiographic data were collected within 3
months before PMV or MVR. The Wilkins score from
echocardiographic imaging for each patient was analyzed by
the expert cardiologist who was blinded to the clinical
outcome. This study was conducted in accordance with the
Declaration of Helsinki, and the protocol was approved by the
Institutional Review Board (IRB) of Yonsei University Health
System (IRB number: 4-2022-0214). They waived the need
for informed consent from patients because of the retrospec-
tive nature of this study.
Echocardiography
Standard 2D and Doppler evaluation were performed in all
patients with a standard ultrasound machine in accordance
with the guidelines of the American Society of
Echocardiography.14
Each cardiac chamber dimension and left
ventricular (LV) ejection fraction (EF) was measured by the
modified Simpson methods. MVA by 2D planimetry was
assessed at the leaflet tips at the mid-diastolic phase.6,15
MVA
by pressure half time (PHT) was calculated using the following
formula: 220/PHT. The mean diastolic pressure gradient
(MDPG) was measured from a continuous wave Doppler
signal at both MV leaflet tips. Right ventricular systolic pressure
(RVSP) was measured by summing the peak systolic pressure
from the maximal tricuspid regurgitation jet velocity, using the
modified Bernoulli equation and right atrial pressure, which
was estimated by measuring the inferior vena cava diameter.
Wilkins echo score was calculated by summing a score from 1
to 4, according to the severity of the mobility, thickness, sub-
valvular calcification, and calcification of the morphology of the
MV and its apparatus. Regarding the range of severe MS, MS-
MS, and very severe (VS)-MS were defined as 1.0 cm2
MVA
1.5 cm2
and MVA 1.0 cm2
, respectively.
Follow-up and clinical outcomes
After interventional treatment for severe MS, patients
regularly visited the outpatient clinic. During follow-up, pa-
tients were analyzed for repeated MV intervention, including
redo PMV or redo MVR. Basically, all patients were followed
up through each hospital’s medical records. For instances in
which patients could not be traced within these records, we
conducted telephone interviews to ascertain their survival
status. In addition, we supplemented our findings by cross-
referencing with national mortality data from the Korean
Ministry of the Interior and Safety. This allowed us to capture
out-of-hospital mortality events and thereby provide more
complete data of overall clinical events. Primary outcomes
were defined as a composite of cardiovascular death and HF
hospitalization. The main secondary outcomes were defined as
a composite of cardiovascular death, HF hospitalization, and
redo intervention (PMV or MVR). Other outcomes included
cardiovascular death, HF hospitalization, ischemic stroke, and
systemic embolism. HF hospitalization was defined when the
following conditions were met: dyspnea with a New York
Heart Association (NYHA) class of at least 3, receiving
medical treatment (including intravenous diuretics or vaso-
dilator), elevated N-terminal pro-B-type natriuretic peptide
(NT-proBNP), and pulmonary congestion or pleural effusion
on chest radiography. Ischemic stroke was defined as a focal
neurologic deficit of mainly vascular origin without primary
cerebral hemorrhage on initial imaging. Systemic embolism
was defined as arterial occlusion without evidence of signifi-
cant atherosclerosis of the affected artery, except for pulmo-
nary embolism and myocardial infarction. If a patient had
more than 1 clinical event during follow-up, the first event
was counted as the endpoint.
Statistical analysis
Continuous variables were expressed as mean standard
deviation. Categorical variables were expressed as numbers
and percentages. We conducted inverse probability-weighted
(IPW) analyses to control for known confounders between
the two groups undergoing PMV and MVR.16
Initially,
propensity scores were computed by using logistic regression
that predicts the probability of each treatment option based
102 Canadian Journal of Cardiology
Volume 40 2024

on observed covariates. Subsequently, weights were calculated
for each individual as 1/propensity score for the MVR group
and 1/ (1 e propensity score) for the PMV group. IPW score
was calculated using confounding variables, such as age, sex,
atrial fibrillation (AF), hypertension, diabetes mellitus (DM),
chronic kidney disease (CKD), MVA by 2D planimetry,
LVEF, LV mass index, LA volume index, MDPG, RVSP, and
echo score. Kaplan-Meier survival analyses were used to
compare the clinical outcomes between 2 treatment groups,
and comparison was performed using a log-rank test. For
handling of missing data, we used the multiple imputation
method to reduce the potential bias arising from each case
analysis in this cohort.17
After identifying variables with
missing data, multiple imputed datasets by generating plau-
sible values were created. Next, we performed the desired
analysis individually on each imputed dataset. Finally, the
combined results were made from the analyses. P value
0.05 was considered statistically significant. Statistical analyses
were performed using R packages (R Foundation for Statistical
Computing, Vienna, Austria) and SPSS 25.0 software (IBM
Corp, Armonk, New York).
Results
Baseline clinical characteristics and echocardiographic
data
A total of 442 patients (mean age: 56.5 11.9 years,
women: 77.1%) who underwent PMV or MVR were finally
included (MS-MS: n ¼ 256; VS-MS: n ¼ 186). Baseline
clinical and echocardiographic characteristics of MS patients
according to the treatment strategy (PMV: n ¼ 182; MVR:
n ¼ 260) were presented in Table 1. The MVR group was
older and had more comorbidities, such as DM, CKD, and
AF, than the PMV group. Another comparison of baseline
characteristics between patients with MS-MS and VS-MS is
shown in Supplemental Table S1. Compared with patients
with VS-MS, those with MS-MS were older, had a higher
prevalence of DM, and underwent PMV more frequently
(compared with MVR) as an initial MS intervention. Patients
with MS-MS had lower echo scores, MDPG, and RVSP, and
larger LV compared with those who had VS-MS.
Further analyses were also performed by comparing treat-
ment strategies of PMV and MVR in patients with MS-MS
and VS-MS (Table 2). In patients with MS-MS and VS-
MS, the MVR group was older and had a higher prevalence
of AF. Regarding echocardiographic findings, the MVR group
had higher echo scores and larger LA and LV chambers. In
patients with MS-MS, the MVR group had a significantly
higher prevalence of comorbiditiesdsuch as hypertension,
DM, and CKDdand higher MDPG and RVSP. However,
these features did not differ significantly between the PMV
and MVR groups in patients with VS-MS.
Clinical outcomes
During a mean follow-up of 6.9 5.2 years, 41 patients
experienced primary outcomes, such as cardiovascular death
and HF hospitalization, and 63 patients experienced second-
ary outcomes (primary outcome and redo intervention).
Detailed events are listed in Table 3. As described in
Supplemental Fig. S1 and Table 3, the PMV group experi-
enced significantly fewer primary outcomes than the MVR
group (log-rank, P ¼ 0.030). However, secondary outcomes
were not significantly different between 2 groups. Among
patients with MS-MS, the PMV group experienced signifi-
cantly fewer primary outcomes than the MVR group (log-
rank, P ¼ 0.008). However, secondary outcomes were not
significantly different between the 2 groups. Among patients
with VS-MS, the PMV and MVR groups of VS-MS patients
did not differ in their primary outcomes, (log-rank, P ¼
0.693), but the MVR group had significantly fewer secondary
outcomes, with a composite of cardiovascular death, HF
hospitalization, and redo intervention, primarily caused by
more frequent redo interventions in the PMV group (PMV vs
MVR: 10 vs 1). In comparing all-cause death, the outcome
Figure 1. Flowchart of the study, illustrating the selection from the Multicenter Mitral Stenosis With Rheumatic Etiology (MASTER) registry. A total
of 442 patients with isolated severe MS who underwent PMV or MVR between January 2000 and December 2021 were included. AS, aortic
stenosis; AR, aortic regurgitation; LA, left atrium; LAA, left atrial appendage; HF, heart failure; IPW, inverse probability weighting; MR, mitral
regurgitation; MS, mitral stenosis; MVA, mitral valve area; MVR, mitral valve replacement; PMV, percutaneous mitral valvuloplasty.
Kim et al. 103

was not significantly different between the 2 groups
(Supplemental Fig. S2).
Surgical details were additionally analyzed in a total of 260
patients with MVR. More patients had surgery by mechanical
valve (n ¼ 180, 69.2%). Most patients received warfarin after
MVR (n ¼ 249, 95.8%) than non-vitamin K antagonist oral
anticoagulant. In a type of AF, there were more patients of
persistent AF (n ¼ 188, 81.7%) (Supplemental Table S2).
There were a total of 23 stroke events among the surgical
patients. In the results of Kaplan-Meier analysis performed to
determine the relationship between valve type and stroke,
there was no relationship (P ¼ 0.174) (Supplemental Fig. S3).
Additional analysis with IPW methods
Given the significant differences in baseline characteristics
between the PMV and MVR groups, an IPW-matched sample
of the PMV (n ¼ 423.1) and MVR (n ¼ 430.8) groups was
generated. As described in Supplemental Table S3, there were
no significance differences in clinical and echocardiographic
parameters between the PMV and MVR groups of both pa-
tients with MS-MS and VS-MS after IPW matching.
Kaplan-Meier analyses for outcomes with IPW matching
are shown in Figure 2. In the results of all patients with severe
MS, there was no significant difference in primary outcomes
between the PMV and MVR groups (P ¼ 0.890). The MVR
group tended to have more primary outcomes in the early
follow-up period, but the PMV group tended to experience
late primary outcomes. When redo interventions were
included as secondary outcomes, the PMV group experienced
significantly more secondary outcomes than the MVR group
(log-rank, P ¼ 0.010). In addition, Kaplan-Meier analyses for
each outcome, such as all cause of death, redo intervention,
and stroke were also performed individually, and the results
are shown in Figure 3.
Among patients with MS-MS, there were no differences in
primary and secondary outcomes between the PMV and
MVR groups. Interestingly, the incidence of primary and
secondary outcomes in the PMV group rapidly increased after
80 months of follow-up (Fig. 2, B and E). Among patients
with VS-MS, there was no difference in primary outcomes
between the PMV and MVR groups. However, the MVR
group showed better secondary outcomes than the PMV
group (log-rank, P ¼ 0.012). Unlike patients with MS-MS,
secondary outcomes (mostly redo interventions) in the PMV
group of patients with VS-MS occurred from the very early
follow-up phase (Fig. 2F). These results implied that MVR
immediately after the initial PMV failure played an important
role in the poorer prognosis of the PMV group of patients
with VS-MS, and it was also confirmed through a separate
analysis of the outcome of redo intervention in this group
(Fig. 3C). There were no differences, regardless of MVA,
between PMV and MVR on the composite outcomes of CV
death, HF hospitalization, ischemic stroke, and systemic
embolism. In regard to stroke, the chosen treatment strat-
egydwhether PMV or MVRddid not influence the occur-
rence of outcome (Fig. 3, G-I).
Discussion
The primary findings of this investigation were as follows:
In all patients and each subgroup of patients with MS-MS or
VS-MS who underwent PMV or MVR, there was no signif-
icance difference in cardiovascular death or admission for HF
according to the initial treatment strategy (MVR vs PMV).
However, the PMV group experienced more frequent redo
interventions in the late (among patients with MS-MS) or
early (among patients with VS-MS) follow-up period
compared with the MVR group. Therefore, PMV would be
considered to be the preferred first-line therapy in patients
with MS-MS who have no PMV contraindications and would
benefit from deferring open-heart surgery, as suggested by
current recommendations. Meanwhile, given the significantly
higher rate of early redo interventions in the PMV group
compared with the MVR group, MVR would be considered
the primary treatment for patients with VS-MS, without clear
evidence of suitable morphology for PMV.
Previous clinical outcome evaluations of MS-MS and
VS-MS
Several studies have been undertaken to compare clinical
outcomes in patients with severe MS according to treatment
options. However, surgical treatment in most previous studies
was based on open mitral commissurotomy (OMC) rather
than MVR.18
In these studies, PMV and OMC had compa-
rable treatment efficacy and safety.10,19
Given the small size of
the study population and the low frequency of OMC at
present, therapeutic relevance of the outcomes of these in-
vestigations is limited. In a more recent study by Song et al.,
which included MVR in comparison with PMV, patients with
MVR had better outcomes than those with PMV.11
This
finding is partially consistent with our study results, as it
supports the presence of better long-term outcomes of surgical
treatment in patients with VS-MS compared with the
matched control group with PMV. However, this study used
the old criteria of severe MS (MVA 1.0 cm2
), and the
patients in the MVA range of 1.0 cm2
to 1.5 cm2
were not
included. Therefore, to our best knowledge, the current study
is the first large-scale registry comparison of clinical outcomes,
according to MVR and PMV treatment strategy, in patients
with severe MS, including those with MVA of 1.0 cm2
to 1.5
cm2
.
Distinct characteristics of MS-MS vs VS-MS
Although MS-MS is classified under current guidelines in
the same severity grade with VS-MS of MVA 1.0 cm2
, its
hemodynamic characteristics, as shown in the current study,
are different from features traditionally found in the severe
grade of MS. In the baseline echocardiography of our study
cohort, MDPG, RVSP, and echo score were lower in the MS-
MS group than in the VS-MS group. As rheumatic MS
progresses, LA pressure and MDPG increase to maintain LV
filling, which further triggers pulmonary arteriolar vasocon-
striction, leading to an increase in pulmonary artery pres-
sure.6,20
RVSP was also associated with severity of disease, and
progression of RVSP was associated with poor outcomes in
rheumatic patients with MS.21,22
In terms of anatomic fea-
tures, the echo score for patients with MS-MS was lower than
that for patients with VS-MS in the current study, suggesting
that the outcome of PMV would be worse in the VS-MS
group than the MS-MS group. Accordingly, MS-MS would
Volume 40 2024

be considered a distinct group from VS-MS, and a different
therapeutic approach could be employed.
Treatment strategy in severe MS
In our study, patients undergoing PMV were younger, had
fewer comorbidities, and showed lower echo scores compared
with those in the MVR group. We hypothesize that the PMV
group had fewer unfavourable morphologic characteristics,
rendering them more suitable candidates for the PMV pro-
cedure. In addition, PMV is not considered a definitive
treatment that replaces MVR. Because of its inherent limita-
tions, it serves primarily as a bridging treatment before surgical
intervention. This is why it tends to be chosen for less ris-
kydoften youngerdpatients. As such, it is likely our PMV
group predominantly consisted of younger and less risky
individuals.
In this study, there were no differences in primary and
secondary outcomes between the PMV and MVR groups of
patients with MS-MS. However, the late catch-up phenom-
enon caused by the increased prevalence of redointervention
in the PMV group was noticeable, particularly after 7 years.
This result suggested that PMV mainly serves as a bridging
treatment rather than a destination therapy in patients with
long life expectancies. Subsequently, PMV would only be
considered a destination therapy for very elderly patients who
are unable to undergo open-heart surgery or individuals with
limited life expectancies. PMV is a procedure that uses a
balloon to enlarge a constricted area, rather than replacing the
valve completely. It is more comparable with balloon aortic
valvuloplasty (BAV)da procedure designed to temporarily
widen the area before valve replacementdthan with trans-
catheter aortic valve replacement, which involves actual valve
Table 1. Baseline clinical and echocardiographic characteristics
Total (n ¼ 442) PMV (n ¼ 182) MVR (n ¼ 260) P value
Clinical variables
Age (year) 56.5 11.9 51.9 12.8 59.7 10.1 0.001
Female sex, n (%) 341 (77.1) 150 (82.4) 191 (73.5) 0.027
BMI, kg/m2
22.9 3.0 22.7 2.8 23.0 3.1 0.265
Hypertension, n (%) 184 (41.6) 66 (36.3) 118 (45.4) 0.056
Diabetes mellitus, n (%) 92 (20.8) 27 (14.8) 65 (25.0) 0.010
CKD, n (%) 20 (4.5) 3 (1.6) 17 (6.5) 0.015
Atrial fibrillation, n (%) 335 (75.8) 105 (57.7) 230 (88.5) 0.001
Follow up duration (y) 6.9 5.2 6.8 5.3 7.0 5.2 0.612
Echocardiography
Echoscore 7.7 1.4 7.1 1.3 8.1 1.4 0.001
MVA by 2D, cm2
1.02 0.2 1.05 0.2 1.00 0.2 0.038
LVEF, % 61.0 9.3 62.7 7.9 59.8 10.0 0.001
LA volume index, mL/m2
78.5 36.7 66.8 26.6 86.7 10.5 0.001
LV mass index, mL/m2
84.7 24.3 79.0 19.8 88.6 26.3 0.001
MDPG, mm Hg 8.5 4.3 8.6 3.9 8.4 4.6 0.549
RVSP, mm Hg 40.1 15.7 37.1 13.2 42.2 16.9 0.001
2D, 2-dimensional; BMI, body mass index; CKD, chronic kidney disease; LVEF, left ventricular ejection fraction; LA, left atrium; LV, left ventricle; MDPG,
mean diastolic pressure gradient of mitral valve; MVA, mitral valve area; MVR, mitral valve replacement; PMV, percutaneous mitral valvuloplasty; RVSP, right
ventricular systolic pressure.
Table 2. Baseline characteristics of the subgroup according to the MVA difference
MS-MS (n ¼ 256) VS-MS (n ¼ 186)
PMV (n ¼ 118) MVR (n ¼ 138) P value PMV (n ¼ 64) MVR (n ¼ 122) P value
Clinical variables
Age (years) 54.3 12.7 61.5 9.0 0.001 47.4 11.8 57.7 11.0 0.001
Female sex, n (%) 95 (80.5) 108 (78.3) 0.774 55 (85.9) 83 (68.0) 0.013
BMI, kg/m2
23.1 2.9 23.6 3.0 0.195 21.9 2.5 22.4 3.0 0.289
Hypertension, n (%) 41 (34.7) 67 (48.6) 0.036 25 (39.1) 51 (41.8) 0.838
Diabetes mellitus, n (%) 21 (17.8) 44 (31.9) 0.015 6 (9.4) 21 (17.2) 0.221
CKD, n (%) 2 (1.7) 11 (8.0) 0.046 1 (1.6) 6 (4.9) 0.425
Atrial fibrillation, n (%) 72 (61.0) 125 (90.6) 0.001 33 (51.6) 105 (86.1) 0.001
NYHA over 3, n (%) 44 (37.3) 63 (45.7) 0.220 19 (29.7) 60 (49.2) 0.016
Follow-up duration (y) 6.8 5.1 6.6 4.9 0.829 6.8 5.8 7.5 5.5 0.419
Echocardiography
Echo score 6.9 1.2 7.8 1.4 0.001 7.4 1.2 8.5 1.3 0.001
MVA by 2D, cm2
1.18 0.1 1.19 0.1 0.587 0.81 0.1 0.79 0.2 0.400
LVEF, % 62.0 7.6 60.1 9.6 0.080 64.0 8.2 59.4 10.5 0.001
LA volume index, mL/m2
67.1 28.7 87.6 40.4 0.001 66.322.5 85.6 40.8 0.001
LV mass index, mL/m2
83.7 20.1 93.7 26.2 0.001 70.3 16.2 82.9 25.3 0.001
MDPG, mm Hg 7.2 2.8 6.4 2.8 0.015 11.2 4.3 10.7 5.1 0.422
RVSP, mm Hg 34.0 9.2 38.7 14.2 0.001 42.7 17.2 46.0 18.9 0.228
BMI, body mass index; CKD, chronic kidney disease; EF, ejection fraction; LA, left atrium; LV, left ventricle; MDPG, mean diastolic pressure gradient of mitral
valve; MS-MS, moderately severe mitral stenosis; MVA, mitral valve area; MVR, mitral valve replacement; NYHA, New York Heart Association; PMV, percu-
taneous mitral valvuloplasty; RVSP, right ventricular systolic pressure; VS-MS, very severe mitral stenosis.
Kim et al. 105

Table 3. Clinical outcomes of the subgroup according to the MVA difference
MS-MS (n ¼ 256) VS-MS (n ¼ 186)
Total
(n ¼ 256)
PMV
(n ¼ 118)
MVR
(n ¼ 138)
Log-rank
P value
Total
(n ¼ 186)
PMV
(n ¼ 64)
MVR
(n ¼ 122)
Log-rank
P value
Primary outcomes 30 7 23 0.008 11 3 8 0.693
Secondary outcomes
CV death þ HF þ redo
intervention
44 17 27 0.289 19 11 8 0.012
CV death þ HF þ stroke þ embolism 50 17 33 0.056 28 8 20 0.481
CV death 9 5 4 0.543 1 0 1 0.480
HF hospitalization 22 2 20 0.001 10 3 7 0.849
Redo intervention 17 13 4 0.009 11 10 1 0.001
Ischemic stroke 22 11 11 0.701 16 4 12 0.407
Systemic embolism 0 0 0 d* 1 1 0 0.166
CV, cardiovascular; HF, heart failure; MS-MS, moderately severe mitral stenosis; MVA, mitral valve area; MVR, mitral valve replacement; PMV, percutaneous
mitral valvuloplasty; VS-MS, very severe mitral stenosis.
* Statistical comparison could not be performed because the number of patients was small.
Figure 2. Kaplan-Meier analysis of freedom from outcomes based on IPW matching. The MVR group demonstrated superior secondary outcomes
(P ¼ 0.010), particularly among patients with VS-MS (P ¼ 0.012), compared with the PMV group. CV, cardiovascular; HF, heart failure. IPW, inverse
probability weighting; MVA, mitral valve area; MVR, mitral valve replacement; PMV, percutaneous mitral valvuloplasty; VS-MS, very severe mitral
stenosis.
Volume 40 2024

replacement.23
Both techniques share common challenges
such as limited long-term effectiveness, suboptimal valvular
function, durability issues, and an associated risk of
complications.
In patients with VS-MS, there were no differences in pri-
mary outcomes between the PMV and MVR groups. How-
ever, unlike patients with MS-MS, the MVR group of patients
with VS-MS had better secondary outcomes than the PMV
group, suggesting that differences in clinical outcomes among
patients with VS-MS were primarily attributable to the
increased incidence of redo interventions in the PMV group.
Redo intervention commonly showed a clear prevalence in the
immediate post-PMV period, not in the late phase, as
observed in the MS-MS group. This finding implied that redo
interventions mainly resulted from unsuccessful PMV or
complications of PMV.
In previous studies, the increased risk of restenosis and
immediate complication after PMV is a factor of important
consideration in patients with VS-MS.24-26
As demonstrated in
Supplemental Table S3 and Table 2, the VS-MS group had
significantly higher echo scores than the MS-MS group. The
unfavourable morphology for PMV, including more progressed
Figure 3. Kaplan-Meier analysis depicting freedom from specific outcomesddeath, redo intervention, and strokedbased on IPW matching. Among
these outcomes, the PMV group exhibited a higher incidence of redo intervention compared with the MVR group, irrespective of the MVA. IPW,
inverse probability weighting; MS, mitral stenosis; MVA, mitral valve area; MVR, mitral valve replacement; PMV, percutaneous mitral valvuloplasty.
Kim et al. 107

valvular and subvalvular thickening and commissural calcifica-
tion, would be a major contributor to the increased early
redointervention rate in the VS-MS group. Further, the
assessment system for PMV eligibility is outdated and inaccu-
rate for sophisticated MV morphology evaluation.27
Despite
the introduction of a few other assessment systems,28
MV
morphologic assessment, which determines PMV eligibility,
continues to rely primarily on the Wilkins score.29
However,
because this score was developed using a very small sample size
of only 22 people, it has limitations related to the lack of a
detailed location of calcification and leaflet thickening, partic-
ularly in the commissural area, which can influence the suc-
cessful percutaneous intervention.30
Its clinical applicability in
the modern era is quite constrained, and it is necessary to study
a model that predicts the possibility of successful percutaneous
intervention using other multimodality imaging.
Therefore, in patients with VS-MS, given the risk of early
redointervention, it is crucial to investigate thoroughly
whether there is morphology suitable for attempting PMV; it
would only be considered for patients with highly favourable
morphology for PMV. Meanwhile, in the current study, early
PMV treatment failure was not associated with an increase in
cardiovascular death or HF hospitalization (primary out-
comes) in the VS-MS group. Therefore, a strategy of an initial
PMV, followed by rescue MVR, for patients with PMV failure
may be a feasible option for patients with high risk of open
heart surgery or those with limited life expectancies. However,
as early PMV failure must be carefully considered, a cardiol-
ogy team discussion and rigourous morphologic study with
the use of multimodal imaging would be beneficial for
treatment-plan determination.
Study limitations
First, this study was retrospectively designed. The possi-
bility of differences in clinical outcomes because of the
inability to follow patients in the same period could not be
excluded. Also, because the patients were included from
multicentres based on retrospective nature, and treatment
time was quite different for each patient, the consistent
standard criteria could not be applied in selecting treatment
methods. Second, despite employing IPW matching to adjust
for known confounders, the choice of treatment might still be
influenced by factors such as patient preference, economic
constraints, or physical performance status. This inherent se-
lection bias could potentially affect the interpretation of the
results. Furthermore, there were still remaining imbalances of
both groups despite IPW matching: specifically, in the VS-MS
group with age, NYHA, and some echocardiographic vari-
ables. Third, we did not include the follow-up echocardio-
graphic data related to cardiac symptoms. Therefore,
hemodynamic changes of each patient after treatment could
not be followed and compared.
Conclusions
For patients with severe MS, including both MS-MS and
VS-MS subgroups, there was no significant difference in
cardiovascular mortality or admission for HF according to the
initial treatment strategy of PMV vs MVR. However, the
PMV group experienced more redo interventions than the
MVR group, particularly among patients with VS-MS.
Therefore, MVR would be the preferable treatment in pa-
tients with VS-MS without clear evidence of suitable
morphology for PMV.
Ethics Statement
The research reported in this manuscript adhered to the
institutional ethical guidelines pertaining to historical cohort
studies.
Patient Consent
The authors confirm that patient consent is not applicable
to this article. This is a retrospective study using deidentified
data; therefore, the IRB did not require consent from the
patients.
Funding Sources
No funding was provided for this paper.
Disclosures
The authors have no conflicts of interest to disclose.
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Supplementary Material
To access the supplementary material accompanying this
article, visit the online version of the Canadian Journal of
Cardiology at www.onlinecjc.ca and at https://doi.org/10.
1016/j.cjca.2023.09.006.
Kim et al. 109

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