Shinshu Med J, 72⑴：49～59, 2024

Short-term Clinical Outcomes of Transcatheter Edge-to-edge Repair
using MitraClip for Mitral Regurgitation : Experience from a Single Center
Hidetomo Nomi, Yasushi Ueki, Masatoshi Minamisawa, Daisuke Sunohara
Yukari Okuma, Yusuke Kanzaki, Tamon Kato, Soichiro Ebisawa
Hirohiko Motoki, Tatsuya Saigusa＊ and Koichiro Kuwahara
Department of Cardiovascular Medicine, Shinshu University School of Medicine

Background : As the first commercially available device to treat mitral regurgitation (MR) percutaneously, theMitraClip transcatheter edge-to-edge repair (TEER) system was approved for use in Japan in 2017.
Objective : We evaluated the efficacy and safety of MitraClip TEER during its first year of implementation at
our hospital in comparison with previous studies.
Methods : This retrospective study included 23 consecutive patients who underwent MitraClip TEER for MR
between October 2021 and September 2022 at Shinshu University Hospital. The primary outcome was MR
reduction ≤ 2＋ and New York Heart Association (NYHA) class improvement at 30 days.
Results : The majority of the 23 patients (91.2 ％) were NYHA class III or IV at baseline. A reduction in MR
grade to less than moderate was achieved in all patients at discharge and in 22 (95.7 ％) patients at 30 days.
NYHA class improvement was observed in 21 (91.2 ％) patients at the study end point. No procedural complica­
tions were encountered.
Conclusion : The MitraClip TEER procedure improved MR grade and symptoms without any major complications
in patients with moderate-to-severe or severe MR. These results corroborated those of earlier reports anddemonstrated the short-term efficacy and safety outcomes of the MitraClip at our institution. Shinshu Med J
72 : 49―59, 2024
(Received for publication August 24, 2023 ; accepted in revised form November 30, 2023)
Key words : mitral regurgitation, heart failure, structural heart disease

Ⅰ Introduction

let, functional MR (FMR) is related to leaflet tether­ing with left ventricular or annular dilatation in the

The global demographic shift towards an older

absence of leaflet organic disease. The treatment

population has resulted in a higher number of patients

strategy for MR depends on its etiology ; current in­with heart failure (HF). Affecting up to 20 ％ of HF

ternational guidelines recommend mitral valve sur­patients, mitral regurgitation (MR) is the most preva­

gery for DMR and optimal medical therapy for FMR2）.

lent valvular heart disease and is strongly associated

In daily practice, however, many patients with DMR

1）with poor outcomes . While degenerative MR (DMR)

do not undergo surgery due to high surgical risk, andis caused by organic disease of the mitral valve leaf­

FMR patients often remain symptomatic even after
optimal medical treatment. The benefit of surgical＊

Corresponding author : Tatsuya Saigusa
Department of Cardiovascular Medicine,
Shinshu University School of Medicine
3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
E-mail : tatsuwan@shinshu-u.ac.jp

No. 1, 2024

mitral valve repair on cardiovascular outcomes has
also not yet been demonstrated for FMR. Against
this background, there has been a clinical need for lessinvasive treatment for MR.
49

Nomi・Ueki・Minamisawa et al.

Fig. 1 The MitraClip system(a) The the MitraClip system. The two arms and grippers grasps the leaflets ofthe mitral valve. (b) Fluoroscopic image of the MitraClip during procedure.

As the first commercially available device to treat

guidance. (Fig. 1) The inter-atrial septum was crossed

MR percutaneously, the MitraClip TEER system wasusing standard techniques through a femoral venous

approved for use in Japan in 2017. The MitraClip

access. The MitraClip Steerable Guide Catheter was

grasps and reapproximates mitral valve leaflets toadvanced across the transseptal puncture, and the

reduce MR. This procedure was first introduced at

MitraClip Delivery Catheter was advanced into the

our institution in October 2021. The present study

left atrium. Then, the MitraClip device was advanced

analyzed the short-term efficacy and safety of theacross the mitral valve into the left ventricle and was

MitraClip TEER procedure in patients with MR

pulled back to grasp the leaflets. Transesophageal

during its first year at our hospital.

echocardiography (TEE) and color flow doppler were
employed to assess the position of MitraClip device

Ⅱ MethodsＡ

and any residual MR. If the MitraClip device was not
positioned properly or MR burden was not adequately

Patient population
Twenty-three consecutive patients with moderate-

reduced, repositioning and additional grasping wereto-severe or severe MR who underwent MitraClip

attempted. When placement was deemed acceptable,

TEER between October 2021 and September 2022 at

the MitraClip device was closed and deployed from

Shinshu University Hospital were analyzed in thisthe Delivery Catheter. A second MitraClip device wasretrospective study. All subjects were determined as

added in cases of significant residual MR if there wasappropriate candidates for the MitraClip procedureadequate mitral valve orifice area to accommodate

by a multidisciplinary heart team in accordance withthe second clip without causing mitral valve stenosis.

3）

Japanese Circulation Society guidelines . The indica­

Device time was defined as time between the inser­

tions for surgery were moderate-to-severe or severetion and removal of the Guide Catheter.

FMR follwing optimal medical therapy as well as se­Ｃvere DMR patients with high surgical risk.
Ｂ

Procedure

Echocardiographic analysis
All patients undergoing the MitraClip procedure

were considered suitable for TEER on the basis of

The MitraClip (Abbot Vascular, Santa Clara, CA,

pre-procedural transthoracic echocardiography (TTE)

USA) was used for the study cohort under generaland TEE to determine the precise mechanism andanesthesia with fluoroscopic and echocardiographic

severity of MR. TTE was also performed at discharge

50

Shinshu Med J

72

Transcatheter edge-to-edge repair for mitral regurgitation : Insights from a single centerand 30 days after procedure. All echocardiograms

pressed as the mean±standard deviation or medianwere obtained by certified echocardiographers andand interquartile range, which were compared withreviewed by several cardiologists to determine thethe paired t-test or Mann Whitney Wilcoxon test, as

initial severity and etiology of MR, the etiology of post-

appropriate. P-values were 2-tailed, with values ofprocedural residual MR, and the status of single leaflet＜0.05 considered statistically significant in all analy­

device attachment (SLDA). MR severity was deter­ses. All testing was performed using SPSS software

mined according to quantitative criteria adapted fromversion 28.0 (SPSS, Chicago, Illinois).

the American Society of Echocardiography and Mitral

Ⅲ

Valve Academic Research Consortium guidelines4）5）.
MR was categorized as 0 (none), 1＋ (mild), 2＋ (mod­Ａ

Results

Patient characteristics

erate), 3＋ (moderate to severe), or 4＋ (severe). Left

A total of 23 consecutive patients who underwent

ventricular quantitative volume measurements and

MitraClip TEER were analyzed. Their baseline de­ejection fraction were obtained by the disk method,

mographics are summarized in Table 1 and Table 2.

and left atrial volume was calculated by the biplaneMedian age was 83 years, and mean Society of Tho­area-length method. MR type was classified based on

racic Surgeons (STS) risk score for mitral valve re­the anatomical etiology of the mitral complex. Ven­

placement was 10.5±7.5 ％. Eighty-seven percent of

tricular FMR (VFMR) was defined as MR due to ven­patients had a history of acute HF admission within

tricular leaflet tethering with left ventricular remod­

the previous 1 year. The majority of patients (91.2 ％)eling. Atrial FMR (AFMR) was defined as MR stemmingwere severely symptomatic (NYHA III/IV). Five pa­

from annular and atrial dilatation, with preserved left

tients displayed NYHA class IV symptoms on intra­

ventricular ejection fraction. DMR was judged as MR

venous inotropes. MR etiologies were ventricular

due to prolapse or degeneration of the leaflet. Acutein 14 patients (60.9 ％), atrial in 4 patients (17.4 ％),procedural success was defined as MR ≤2＋ on post-

and degenerative in 5 patients (21.7 ％). Approximately

procedural TEE. The baseline severity of tricuspid

30 ％ of patients had non-ischemic cardiomyopathy.

regurgitation was determined on the basis of quanti­

MR grade 3＋ and 4＋ were detected in 7 (30.4 ％)tative and semi-quantitative criteria adapted fromand 16 (69.6 ％) patients, respectively. Mean effective

4）

the American Society of Echocardiography .

regurgitation orifice area was 0.43±0.17 cm2. PatientsＤwith VFMR displayed a higher surgical mortality

Endpoints and follow-up
The primary efficacy endpoint was MR grade re­risk score, lower left ventricular ejection fraction, andduction to ≤2＋ and NYHA class improvement at 30

greater end-diastolic volume than did the other groups.

days. The secondary efficacy endpoints were changes

Left atrial volume was greater in the AFMR group.

in echocardiographic parameters, including left ven­

Moderate or severe tricuspid regurgitation was moretricular end-diastolic volume (LVEDV), left ventricu­

frequent in the AFMR (100 ％) and DMR (80 ％) groups

lar end-systolic volume (ESV), left atrial diameter,

compared with the VFMR group (28.6 ％).

and biomarkers including brain natriuretic protein

Ｂ

Procedural characteristics(BNP) and estimated glomerular filtration rate (eGFR)

The procedural characteristics of MitraClip TEER

between baseline and 30 days. Safety outcomes in­are presented in Table 3. Most patients (78.3 ％) werecluded major bleeding, stroke, vascular complications

treated with a single clip. A wide type clip was usedrequiring intervention, device embolization, cardiac

in 15 (53.6 ％) patients. Mean procedure time was 152

tamponade, and conversion to heart surgery.

min, and device time was 82.7 min. We observed noＥprocedural complications.

Statistical analysis
Categorical variables were presented as absolute

Ｃ

Procedural and clinical outcomesvalues and percentages, which were analyzed using

The changes in MR grade and clinical outcomes

Fisher’s exact test. Continuous variables were ex­

are summarized in Fig. 2 and Table 3. MR reduction

No. 1, 2024

51

Nomi・Ueki・Minamisawa et al.
Table 1Age(years)
80
83
86
91
77
87
53
85
81
89
57
83
88
83
86
68
81
83
74
67
78
78
90

Sex
F
M
M
M
M
F
M
M
M
M
M
F
F
M
F
M
F
F
M
M
M
M
M

BSA
(m2)
1.3
1.3
1.5
1.3
1.8
1.2
1.5
1.1
1.4
1.6
2
1.4
1.4
1.5
1.4
1.9
1.5
1.3
1.7
1.5
1.6
1.7
1.4

Baseline characteristics

Type of MR

Etiology of MR

FMR
FMR
FMR
DMR
FMR
FMR
FMR
FMR
FMR
DMR
FMR
FMR
FMR
DMR
FMR
FMR
DMR
FMR
FMR
FMR
FMR
DMR
FMR

Ventricular
VentricularAtrialP3 prolapse
Ventricular
Ventricular
Ventricular
Ventricular
Ventricular
A3 prolapse
VentricularAtrialAtrialA2 prolapse
Ventricular
VentricularP2 prolapse
AtrialVentricular
Ventricular
VentricularP2 prolapse
Ventricular

Type ofcardiomyopathy
DCM
ICM
Unclassified
Unclassified
ICM
DCM
DCM
DCM
ICM
Unclassified
ICM
ICM
Sarcoidosis
Unclassified
CTRCD
ICM
Unclassified
Unclassified
Sarcoidosis
AL-CA
ATTR-CA
Unclassified
ICM

CFS
4
3
3
3
3
5
3
5
5
3
2
3
4
3
5
2
3
3
3
5
2
4
3

NYHA

STS score

LVEF

class

(％)

(％)

3
3
3
3
2
4
4
4
3
3
3
3
3
3
4
3
2
3
3
4
3
3
3

14.2
8
15.1
10.5
7.9
8.7
2.9
9.2
33.2
12.3
29.3
4.8
9.1
13.2
11.1
9
4.6
4.8
4.2
7.2
4.1
2.6
17.1

34
33
63
62
42
28
26
32
34
46
33
87
50
47
26
22
78
73
38
35
35
60
40

Abbreviations : CA, cardiac amyloidosis ; CFS, clinical frailty scale ; CTRCD, cancer therapy-related cardiac dysfunction ; DMR,
degenerative mitral regurgitation ; DCM, dilated cardiomyopathy ; FMR, functional mitral regurgitation ; ICM, ischemic
cardiomyopathy ; NYHA, New York Heart Association ; STS, Society of Thoracic Surgeons.

to grade 1＋ or 2＋ was achieved in all patients during

Fig. 3. LVEDV and ESV did not change remarkably

the procedure and at discharge. MR recurrence at 30

in the VFMR and AFMR group, but were reduced indays was observed in 1 patient with DMR (P3 pro­the DMR group. Left atrial diameter decreased con­lapse). This patient had grade 2＋ MR at discharge,

siderably in VFMR and DMR groups. There was nowhich progressed to grade 3＋ at 30 days without

significant improvement in BNP level and eGFR be­

evidence of SLDA or leaflet tear. One patient withfore the procedure and after 30 days.

VFMR had mean trans-mitral pressure gradient ＞5mmHg at 30 days. NYHA class improved in all cases

Ⅳ

Discussion

except for 1 patient with AL amyloidosis and VFMR,

The present study revealed several key findings

in whom the MitraClip successfully decreased MR

regarding the MitraClip TEER procedure for severe

grade from 4＋ to 2＋, although NYHA remained

MR. First, transcatheter mitral valve repair was con­class IV. No changes were noted in the grade of tri­

ducted predominantly for severely symptomatic pa­

cuspid regurgitation at 30 days, nor were any cases

tients at prohibitive surgical risk in our early experi­

of death, stroke/transient ischemic attack, myocardi­

ence. Second, the MitraClip TEER procedure could

al infarction, or reintervention of the mitral valves.

be performed successfully, with acute reduction of

Ｄ Echocardiographic parameters and biomarkers

MR to grade ≤2＋ and improvements in HF symp­

The changes in echocardiographic parameters andtoms in the vast majority of patients. Third, the pro­biomarkers from baseline to 30 days are presented in52

cedure was conducted without any safety issues.
Shinshu Med J

72

Transcatheter edge-to-edge repair for mitral regurgitation : Insights from a single center
Table 2

Baseline characteristics according to MR etiology

Characteristic
Age (years)
Male (％)
Hypertension (％)
Dyslipidemia (％)
Diabetes mellitus (％)
Previous myocardial infarction (％)
Previous PCI (％)
Previous CABG (％)
Previous stroke or TIA (％)
COPD (％)
History of atrial fibrillation (％)
Previous CRT (％)
HF hospitalization within previous 1 year (％)
NYHA class IV (％)
Cause of cardiomyopathy
Ischemic (％)
Non-ischemic (％)
Medication
Beta-blocker (％)
ACEI, ARB, or ARNI (％)
MRA (％)
SGLT2 inhibitor (％)
Diuretic (％)
Intravenous inotrope (％)
Anticoagulant (％)
Antiplatelet (％)
Hemoglobin (g/dL)
Albumin (g/dL)
2
eGFR (mL/min/m )BNP (pg/mL)
STS risk score (％)
Echocardiographic assessment
Severity of MR
3＋
4＋
Effective regurgitation orifice area (cm2)
Left ventricular end-diastolic dimension (mm)Left ventricular end-systolic dimension (mm)Left ventricular end-diastolic volume (mL)
Left ventricular end-diastolic volume index (mL/m2)
Left ventricular end-systolic volume (mL)
Left ventricular end-systolic volume index (mL/m2)
Left ventricular ejection fraction (％)
Left atrial dimension (mm)Left atrial volume index (mL/m2)
Moderate or severe tricuspid regurgitation (％)

Overall(N＝23)

Ventricular FMR(N＝14)

Atrial FMR
(N＝4)

DMR
(N＝5)

83 (78, 86)
16 (69.6)
12 (52.2)
10 (43.5)
6 (42.8)
6 (26.1)
7 (30.4)
3 (13.0)
2 (8.7)
3 (13.0)
14 (60.7)
2 (8.7)20 (87.0)
5 (21.7)

79 (70, 85)
11 (78.6)
6 (42.9)
7 (50.0)
3 (21.4)
5 (35.7)
7 (50.0)
1 (7.1)1 (7.1)0 (0.0)10 (71.4)
1 (7.1)13 (92.9)
5 (35.7)

85 (83, 86)
1 (25.0)
4 (100)2 (50.0)
2 (50.0)
1 (25.0)0 (0.0)0 (0.0)1 (25.0)
1 (25.0)
4 (100)0 (0.0)4 (100)0 (0.0)83 (81, 89)
4 (80.0)
2 (40.0)
1 (20.0)
1 (20.0)
1 (20.0)
1 (20.0)0 (0.0)0 (0.0)2 (40.0)
1 (20.0)
1 (20.0)
3 (60.0)0 (0.0)7 (30.4)
16 (69.6)

6 (42.9)
8 (57.1)

1 (25.0)
3 (75.0)0 (0.0)5 (100)21 (91.3)
17 (73.9)
15 (65.2)
15 (65.2)
21 (91.3)
5 (21.7)
14 (69.5)5 (21.7)
12.0±0.４
3.7±0.1
33 (22, 55)443 (129, 766)
10.5±7.5

14 (100)
10 (71.4)
9 (64.3)
12 (85.7)
12 (85.7)
5 (35.7)
10 (71.4)
5 (35.7)
11.9±1.9
3.5±0.6
27.5 (22, 43)472 (358, 836)11.7±8.9

4 (100)3 (75.0)
3 (75 ％)
1 (25.0)
4 (100)0 (0.0)4 (100)0 (0)12.5±1.9
3.7±0.5
51.5 (27.8, 61)
538±3378.5±4.9

3 (60.0)
4 (80.0)
3 (60.0)
2 (40.0)
5 (100)0 (0.0)2 (40)0 (0)12.2±2.2
4.0±0.2
33 (27.5, 64)
132 (88, 754)
8.4±4.5

7 (30.4)
16 (69.6)
0.43±0.1752.5±11.4
42.1±14.1
140.4±73.6
94.4±43.7
83.8±67.2
56.0±43.7
44.5±17.9
49.9±11.0
85.1±56.2
12 (52.1)

7 (50.0)
7 (50.0)0.42±0.19
55.0±13.2
49.1±12.2
155.3±88.0
104.0±57.5
109.8±74.1
73.4±47.7
32.7±5.647.9±5.673.5±22.9
4 (28.6)

0 (0.0)4 (100)0.38±0.04
48.2±11.1
29.1±10.7
109.3±55.5
75.0±34.2
34.8±26.8
23.7±17.4
68.3±15.761.9±20.5
144.7±119.5
4 (100.0)

0 (0.0)5 (100)0.50±0.13
48.6±3.3
32.3±5.9
123.6±13.7
83.1±14.950.1±16.3
33.2±10.1
58.6±13.1
45.9±8.1
69.9±25.2
4 (80.0)

Values are presented as the mean±standard deviation, median (interquartile range), or n (％).
Abbreviations : ACEI, angiotensin converting enzyme inhibitor ; ARB, angiotensin receptor blocker ; ARNI, angiotensin
receptor-neprilysin inhibitor ; BNP, brain natriuretic peptide ; CABG, coronary artery bypass grafting ; COPD, chronic
obstructive pulmonary disease ; CRT, cardiac resynchronization therapy ; DMR, degenerative mitral regurgitation ; eGFR,
estimated glomerular filtration rate ; FMR, functional mitral regurgitation ; PCI, percutaneous coronary intervention ; MRA,
mineralocorticoid receptor antagonist ; SGLT2, sodium-glucose cotransporter 2 ; STS, Society of Thoracic Surgeons ; TIA,
transient ischemic attack ; HF, heart failure.
No. 1, 2024

53

Nomi・Ueki・Minamisawa et al.

Fig. 2 Changes in MR grade and NYHA class from baseline to 30 days after
MitraClip transcatheter edge-to-edge repair
Abbreviations : MR, mitral regurgitation ; NYHA, New York Heart Association.

MR is strongly associated with a poor prognosis

been a clinical challenge since mitral valve surgery

and increased risk of HF and mortality. Given thehas not shown survival benefits. Two randomized

limited therapeutic options in patients at high surgicalcontrolled trials (RCTs) assessing the efficacy andrisk, transcatheter mitral valve repair represents ansafety of the MitraClip, Percutaneous Repair with theimportant advancement for this patient subset not

MitraClip Device for Severe Functional/Secondary

only to reduce MR burden and HF symptoms, but

Mitral Regurgitation (MITRA-FR)7） and COAPT6）,

also to improve mortality and HF admission rates, aswere published in 2018. Although they targeted the

supported by the growing body of evidence regarding

same patient population with the same disease using

the MitraClip. Our short-term clinical outcomes were

the same device, their findings were not consistent ;comparable to global landmark studies including thewhile COAPT showed a significant efficacy of the

Cardiovascular Outcomes Assessment of the MitraClip

MitraClip procedure, MITRA-FR demonstrated only

Percutaneous Therapy for Heart Failure Patients withneutral results. The possible explanations for this6）

Functional Mitral Regurgitation (COAPT) , and pos­

discrepancy include the proportion of left ventricular

sibly even better considering the more symptomatic

size and MR severity as well as the optimization ofpatients in our cohort, indicating a successful intro­

medical therapy. COAPT enrolled a subset of pa­

duction of the MitraClip TEER procedure at our in­tients having more severe MR, less advanced left

stitution. In our study, approximately 20 ％ of patients

ventricular disease (dilatation/systolic dysfunction),

had NYHA class IV symptoms on intravenous ino­

and more optimized medical therapy as comparedtropes and most suffered from impaired renal func­

with the MITRA-FR patients. Thus, the COAPT-

tion, which limited medical treatment options. In

like profile might be suitable to maximize the advan­such circumstances, the MitraClip was effective fortages of the MitraClip, while patients with overly

any type of MR in terms of reducing regurgitation

severe left ventricular dilatation/systolic dysfunctionand HF symptoms. Moreover, the procedural out­

may not benefit from the procedure. This assump­

come was excellent and without major complications.

tion appears reasonable since VFMR is, by nature,

These results were comparable or even superior tothe consequence of a diseased left ventricle and not

those of other trials despite our older and more symp­

mitral valve leaflets.

tomatic population.
The management of VFMR in particular has long54

A comparison of the above RCTs and the Japan
post-marketing surveillance (PMS) study8） regarding
Shinshu Med J

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Transcatheter edge-to-edge repair for mitral regurgitation : Insights from a single center
Table 3

Procedural and clinical outcomes.
Overall

Procedural characteristics
Acute procedural success
Number of clips per patient1
2
Distribution of wide and narrow clips
Wide clip
Narrow clip
Procedure time (min)Total device time (min)Procedural complications
Single leaflet device attachment
Major bleeding
StrokeVascular complications resulting in surgical intervention
Device embolization
Cardiac tamponade
Conversion to heart surgery
MR grade
Post-procedure
1＋
2＋
3＋
4＋
Discharge
1＋
2＋
3＋
4＋
Day 301＋
2＋
3＋
4＋
Mean trans-mitral gradient (mmHg)
Post-procedure
Discharge
Day 30Mean trans-mitral gradient ＞5 mmHg
Post-procedure
Clinical outcomes at 30 days
Death
HF admission
Stroke/Transient ischemic attack
Myocardial infarction
Reintervention of the mitral valve
NYHA class at 30 days
Ｉ
Ⅱ
Ⅲ
Ⅳ

Atrial FMR

DMR(N＝23)

Ventricular
FMR(N＝14)

(N＝4)

(N＝5)

23 (100)

14 (100)

4 (100)5 (100)18 (78.3)
5 (21.7)

12 (85.7)
2 (14.2)

4 (100)0 (0.0)2 (40.0)
3 (60.0)

15 (53.6)
13 (46.4)
152.4±4282.7±28.7

7 (43.7)
9 (56.3)
144±40.3
76.3±33.0

3 (75.0)
1 (25.0)
151.5±31.1
83.3±24.2

5 (62.5)
3 (37.5)
176.8±44.4
96.2±23.4

0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)20 (87.0)
3 (13.0)0 (0.0)0 (0.0)13 (92.8)
1 (7.1)0 (0.0)0 (0.0)3 (75.0)
1 (25.0)0 (0.0)0 (0.0)4 (80.0)
1 (20.0)0 (0.0)0 (0.0)18 (78.2)
5 (21.7)
0 (0.0)0 (0.0)12 (85.7)
2 (14.2)
0 (0.0)0 (0.0)3 (75.0)
1 (25.0)0 (0.0)0 (0.0)3 (60.0)
2 (40.0)0 (0.0)0 (0.0)19 (82.6)
3 (13.0)
1 (4.3)0 (0.0)13 (92.8)
1 (7.1)0 (0.0)0 (0.0)3 (75.0)
1 (25.0)0 (0.0)0 (0.0)3 (60.0)
1 (20.0)
1 (20.0)0 (0.0)2.4±1.0
2.5±1.1
2.3±0.8

2.4±1.1
2.3±1.3
2.2±0.７

2.8±0.4
3.3±0.8
2.9±0.7

2.2±0.8
2.6±0.4
2.5±0.9

0 (0.0)1 (7.1)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)6 (26.1)
14 (60.9)
1 (4.3)2 (8.7)5 (35.7)
6 (42.8)
1 (7.1)2 (14.2)

0 (0.0)4 (100)0 (0.0)0 (0.0)1 (20.0)
4 (80.0)0 (0.0)0 (0.0)

Values are presented as the mean±standard deviation or n (％).
Abbreviations : DMR, degenerative mitral regurgitation ; FMR, functional mitral regurgitation. HF, heart failure ;MR, mitral regurgitation ; NYHA, New York Heart Association.

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Nomi・Ueki・Minamisawa et al.

Fig. 3 Changes in echocardiographic parameters and biomarkers from baseline to 30 days after MitraClip
transcatheter edge-to-edge repair to MR etiology
Values are presented as the respective means of the baseline and 30 days.
Abbreviations : AFMR, atrial functional mitral regurgitation ; BNP, brain natriuretic peptide ; DMR, degenerative
mitral regurgitation ; EDV, end-diastolic volume ; eGFR, estimated glomerular filtration rate ; ESV, end-systolicvolume ; VFMR, ventricular functional mitral regurgitation ; LAD, left atrial diameter.

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Transcatheter edge-to-edge repair for mitral regurgitation : Insights from a single center
Table 4Comparisons of key baseline characteristics across studies

Age
Male (％)
Body-mass index (kg/m2)
History of atrial fibrillation (％)
Previous CRT (％)
HF hospitalization within previous 1 year
NYHA class III
NYHA class IV
Cause of cardiomyopathy
Ischemic
Non-ischemic
Medication
Beta-blocker
ACEI, ARB, or ARNIMRA
SGLT2 inhibitor
Diuretic
Intra-venous inotrope
Creatinine clearance (mL/min/m2)
STS risk score (％)
Echocardiographic assessment
Effective regurgitation orifice area (cm2)
Left ventricular end-diastolic dimension (mm)Left ventricular end-systolic dimension (mm)Left ventricular end-diastolic volume (mL)
Left ventricular end-diastolic volume index (mL/m2)
Left ventricular end-systolic volume (mL)
Left ventricular end-systolic volume index (mL/m2)
Left ventricular ejection fraction (％)

Shinshu

COAPT

MITRA-FR

Japan PMS

University
Hospital(N＝14)

DeviceGroup(N＝302)

DeviceGroup(N＝152)

FMR group

76.1±11.4
11 (78.6)

71.8±11.8
201 (66.6)

70.1±10.1
120 (78.9)76.2±9.1
220 (61.5)

20.4±4.5
9 (64.3)
1 (7.1)13 (92.0)
4 (28.5)5 (35.7)27.0±5.8
173 (57.3)
109 (56.1)
175 (56.1)
154 (51.0)
18 (6.2)

NA
49 (35.5)
46 (30.5)NA82 (53.9)
15 (9.2)

21.1±3.3
NA
81 (22.7)
40 (11.3)
173 (50.3)
78 (22.7)

6 (42.9)
8 (57.1)

184 (60.9)
118 (39.1)

95 (62.5)
57 (37.5)

NANA

14 (100)
10 (71.4)
9 (64.3)
12 (85.7)
12 (85.7)
5 (35.7)

275 (91.1)
216 (71.5)
153 (50.7)NA270/302 (89.4)
NA

134 (88.2)
125 (82.2)
86 (56.6)
NA
151 (99.3)
NA265/347 (76.4)
217/347 (62.5)
153/347 (44.1)
NA
303/347 (87.3)NA33.4±14.4
11.7 ± 8.9

50.9±28.5
7.8±5.5NANANA
12.4±10.2

0.42±0.19
55.0±13.2
49.1±12.2
155.3±88.0

0.41±0.15
62.0±7.0
53.0±9.0
194±69.2

0.31±0.10NANA
252±67.0

0.36±0.21NANA
176.3±79.4

104.0±57.5
109.8±74.1

101.0±34.0
135.5±56.1

136.2±37.4
NANA111.7±66.1(N＝358)73.4±47.7

NA

NA

NA

32.7±5.631.3±9.1

33.3±6.5

39.8±11.5

Values are presented as the mean±standard deviation or n (％).
Abbreviations : ACEI, angiotensin converting enzyme inhibitor ; ARB, angiotensin receptor blocker ; ARNI, angiotensin
receptor-neprilysin inhibitor ; CRT, cardiac resynchronization therapy ; FMR, functional mitral regurgitation ; HF, heart
failure ; MRA, mineralocorticoid receptor antagonist ; NA, not available ; SGLT2, sodium-glucose cotransporter 2 ; STS,
Society of Thoracic Surgery ; PMS, post-marketing surveillance.

VFMR is summarized in Table 4. The subjects in ourof Japanese patients with HF. Guideline-based medi­

study were more elderly and had higher STS replace­cal therapy for HF with reduced ejection fraction

ment scores relative to COAPT. Most of the patientswas even more optimal in our study. The proportion

had experienced HF admission within 1 year, andof MR severity (effective regurgitation orifice area)

one third were NYHA class IV requiring intravenous

and left ventricular chamber size (LVEDV) in the

inotropes before and after the procedure. Such co­cohort is presented in Fig. 4. Indeed, the subjects dis­morbidities as atrial fibrillation and renal failure wereplayed a COAPT-like profile with more severe MR

more frequent in our population as well. As with theand relatively less severe left ventricular remodeling.

Japan PMS study, the baseline characteristics of our

These factors may have contributed to the efficacy

subjects reflected the real-world clinical backgroundobserved in our study.

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Nomi・Ueki・Minamisawa et al.

Fig. 4 Relationships between EROA and LVEDV across studies
The black line indicates the hypothetical relationship between EROA and LVEDV when the degree of severe MR is
proportional to the LVEDV, assuming a LVEF of 30 ％ and regurgitant fraction of 50 ％. The orange area represents
severe MR that is disproportionate to left ventricular dilation. The green area represents non-severe MR. The whitearea represents a degree of uncertain proportion of MR to LVEDV. The averages of patients enrolled in the MITRAFR and COAPT trials based on the information made public to date are represented as dots.
Abbreviations : EROA, effective regurgitation orifice area ; LVEDV, left ventricular end-diastolic volume ; LVEF, left
ventricular ejection fraction, MR, mitral regurgitation ; RF, regurgitant fraction.

AFMR has been increasingly recognized as an en­

may be feasible in DMR patients with prohibitive

tity without leaflet pathology, for which atrial dilata­

surgical risk and anatomical eligibility. Further con­tion and annular remodeling are the main etiologies.

temporary RCTs using the latest MitraClip G4 sys­

Despite the high prevalence and frequent coexis­

tem for moderate surgical risk are required to assess

tence of atrial fibrillation and MR, little is known on

the efficacy of the MitraClip compared with surgery11）.

the clinical course and optimal management of AFMR,

Ａ

Limitations

and current guidelines do not define it as a separate

Several limitations should be considered in the cur­9）rent study. First, the sample size was small, and data

entity. Patients with AFMR tend to be more elderly

and are often treated with conservative strategies

from a single center may lack generalizability. Sec­

because of their high surgical risk, especially sinceond, retrospective data collection has the risk of bias,

medical treatment for HF patients with preserved

although consecutive patients were analyzed in thisejection fraction has limited benefit. Although data

study. Third, the control group (e.g. patients not un­

on TEER with the MitraClip for AFMR are lacking,dergoing MitraClip or surgical repair) was not avail­favorable results in terms of both symptoms and MRable in the current study, which may result in thegrade were observed in our cohort.

inadequate assessment of the efficacy of MitraClip.

Lastly, TEER using the MitraClip versus surgery
10）for DMR was studied in the EVEREST II trial

Fourth, since the follow-up duration was short at 30

pub­

days, extended observation is needed to confirm thelished in 2011. The RCT showed the superiority oflong-term efficacy and safety of the MitraClip TEER

surgery over TEER in terms of long-term MR reduc­procedure.

tion and freedom from reintervention. However, TEER
58

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Transcatheter edge-to-edge repair for mitral regurgitation : Insights from a single center

Ｖ

Conclusion

Acknowledgements

MitraClip TEER resulted in marked improvements

We would like to thank all of the participants andin MR grade and symptoms without any proceduralechocardiographers in this study.

complications at 30 days in patients with moderate-

Conflicts of interest

to-severe or severe MR. These results support the
short-term efficacy and safety of the MitraClip pro­

The authors declare no conflicts of interest regard­
ing this study.

cedure at our institution.

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（2023. 8. 24 received ; 2023. 11. 30 accepted）

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