Current MitraClip experience, safety and feasibility in the Netherlands
Current MitraClip experience, safety and feasibility in the Netherlands
Z. Rahhab 0 1 2 3 4 5 6 7 8 9 10 11 12
F. A. Kortlandt 0 1 2 3 4 5 6 7 8 9 10 11 12
J. F. Velu 0 1 2 3 4 5 6 7 8 9 10 11 12
R. A. J. Schurer 0 1 2 3 4 5 6 7 8 9 10 11 12
V. Delgado 0 1 2 3 4 5 6 7 8 9 10 11 12
P. Tonino 0 1 2 3 4 5 6 7 8 9 10 11 12
A. J. Boven 0 1 2 3 4 5 6 7 8 9 10 11 12
B. J. L. Van den Branden 0 1 2 3 4 5 6 7 8 9 10 11 12
A. O. Kraaijeveld 0 1 2 3 4 5 6 7 8 9 10 11 12
M. Voskuil 0 1 2 3 4 5 6 7 8 9 10 11 12
J. Hoorntje 0 1 2 3 4 5 6 7 8 9 10 11 12
M. van Wely 0 1 2 3 4 5 6 7 8 9 10 11 12
K. van Houwelingen 0 1 2 3 4 5 6 7 8 9 10 11 12
G. B. Bleeker 0 1 2 3 4 5 6 7 8 9 10 11 12
B. Rensing 0 1 2 3 4 5 6 7 8 9 10 11 12
I. Kardys 0 1 2 3 4 5 6 7 8 9 10 11 12
J. Baan jr. 0 1 2 3 4 5 6 7 8 9 10 11 12
J. A. S. Van der Heyden 0 1 2 3 4 5 6 7 8 9 10 11 12
N. M. Van Mieghem 0 1 2 3 4 5 6 7 8 9 10 11 12
0 Department of Cardiology, St. Antonius Hospital , Nieuwegein , The Netherlands
1 Department of Cardiology, Radboud University Medical Center , Nijmegen , The Netherlands
2 Department of Cardiology, Thorax center, Erasmus Medical Center , Rotterdam , The Netherlands
3 Department of Cardiology, University Medical Center Maastricht , Maastricht , The Netherlands
4 Department of Cardiology, Haga Hospital , The Hague , The Netherlands
5 Department of Cardiology, Medisch Spectrum Twente , Twente , The Netherlands
6 Department of Cardiology, University Medical Center Utrecht , Utrecht , The Netherlands
7 Department of Cardiology, Amphia Hospital , Breda , The Netherlands
8 Department of Cardiology, Zorggroep Noorderbreedte , Leeuwarden , The Netherlands
9 Department of Cardiology, Catharina Hospital , Eindhoven , The Netherlands
10 Department of Cardiology, Leiden University Medical Center , Leiden , The Netherlands
11 Department of Cardiology, University Medical Center Groningen , Groningen , The Netherlands
12 Department of Cardiology, Academic Medical Center , Amsterdam , The Netherlands
Purpose Data on MitraClip procedural safety and efficacy in the Netherlands are scarce. We aim to provide an overview of the Dutch MitraClip experience. Methods We pooled anonymised demographic and procedural data of 1151 consecutive MitraClip patients, from 13 Dutch hospitals. Data was collected by product specialists in collaboration with local operators. Effect on mitral regurgitation was intra-procedurally assessed by transoesophageal echocardiography. Technical success and device success were defined according to modified definitions of the Mitral Valve Academic Research Consortium (MVARC). Results Median age was 76 (interquartile range 69-82) years and 59% were males. Patients presented with ≥moderate mitral regurgitation and a predominance of functional mitral regurgitation (72%). Overall, 611 (53%) patients were treated with one Clip, 486 (42%) with ≥2 Clips and 54 (5%) received no Clip. The number of patients with ≥2 Clips increased from 22% in 2009 to 52% in 2016.
Valvular heart disease; Mitral valve; Mitral valve therapies
Mitral regurgitation (MR) has a 2% prevalence in the
general population and is more frequent in the elderly [1, 2].
Surgical treatment is considered the ‘gold standard’ for
patients with symptomatic severe mitral regurgitation .
However, a significant proportion (49%) of eligible patients
are denied for surgery because of age, comorbidities or poor
left ventricular function .
The MitraClip (Abbott Vascular, Menlo Park, CA)
offers a completely percutaneous mitral valve edge-to-edge
repair. The efficacy and safety of the MitraClip device have
been demonstrated in the EVEREST I (Endovascular Valve
Edge-to-Edge Repair Study) trial . Subsequently, the
EVEREST II randomised controlled trial compared
conventional surgery with MitraClip in operable patients with
moderate-to-severe or severe, predominantly degenerative
MR . MitraClip was associated with superior safety and
similar improvements in clinical outcomes. However, it was
less effective in reducing MR . Based on these results,
the Food and Drug Administration approved MitraClip for
high-risk patients with symptomatic degenerative MR. In
European practice, the majority of patients treated with
MitraClip have functional MR [7, 8]. In this clinical setting,
MitraClip may improve survival and hospital readmissions
Data on the Dutch MitraClip experience are scarce. We
therefore aim to provide an informative overview of the
current MitraClip procedural safety and efficacy in the
This multicentre observational retrospective study collected
all patients (n = 1151) from 13 Dutch hospitals treated
with MitraClip between January 2009 and June 2016. All
patients were discussed in local multi-disciplinary heart
teams including interventional cardiologists, imaging
specialist and cardiac surgeons, and were considered
symptomatic and at high operative risk. All patients provided
written informed consent for the MitraClip procedure.
Procedural data were prospectively and anonymously
collected by product specialists in collaboration with local
operators and, after approval of the participating centres,
retrospectively analysed. Effect on MR was
intra-procedurally (onsite) assessed by transoesophageal
echocardiography. The Medical Ethics Committee of the Erasmus
Medical Center reviewed the study protocol and waived the need
for additional informed consent because of the
non-interventional character of this retrospective study
(MEC-2016423) using anonymous data collection. The investigation
conforms to the principles outlined in the Declaration of
The MitraClip device is a 4 mm wide, polyester-covered
cobalt chromium V-shaped clip with two movable arms and
grippers (Fig. 1a). All procedures are performed under
general anaesthesia, using fluoroscopic and transoesophageal
echocardiographic guidance. A 24-French guide catheter
is introduced in a femoral vein and delivered into the left
atrium after transseptal puncture (Fig. 1b). The clip
delivery system is advanced through the guide catheter into
the left atrium and positioned above the origin of the
regurgitation jet, perpendicular to the mitral coaptation line
(Fig. 1c). The arms of the Clip are opened and advanced
into the left ventricle. The Clip is then gradually pulled
back towards the left atrium in order to grasp both mitral
valve leaflets (Fig. 1d). The grippers are lowered, the clip
is closed (Fig. 1e) and the leaflets are approximated
resulting in a double mitral orifice (Fig. 1f). Before releasing the
Clip, the severity of MR is assessed and the transmitral
gradient is measured. If the result is satisfactory, the Clip can
be released. In case of inadequate MR reduction or a high
transmitral gradient, the Clip can be opened and
repositioned or removed. More than 1 Clip may be necessary for
significant MR reduction.
Study endpoints and definitions
The primary endpoints were procedural safety expressed
in ‘technical success’ and procedural efficacy expressed in
‘device success’, both were modified from the Mitral Valve
Research Consortium (MVARC) criteria .
● Technical success is defined as successful deployment of
the device with absence of procedural mortality and
freedom from emergency surgery.
● Device success is defined as proper placement of the
device without procedural mortality and with reduction in
post-procedural MR by ≥1 grade from baseline and to an
absolute level of moderate MR.
● Significant MR reduction: reduction in post-procedural
MR by ≥1 grade from baseline.
● Device time is defined as the time from guide catheter
insertion to guide catheter removal.
Categorical variables are presented as frequencies and
percentages, and compared with the use of the Pearson Chi
Square Test or the Fisher’s exact test, as appropriate.
Continuous variables are presented as means (± standard
deviFig. 1 a MitraClip device with two movable arms and grippers; b Guide catheter advanced into the left atrium after transseptal puncture; c
Positioning of the MitraClip above the regurgitation jet perpendicular to mitral coaptation line; d The MitraClip is pulled back in order to capture both
leaflets; e The grippers are lowered and the arms are closed approximating the leaflets; and f creating a double mitral orifice. Image courtesy of
ation – SD), in case of normal distribution, or medians
(interquartile range – IQR), in case of skewed distribution, and
compared with the use of the Student’s t-test or the
MannWhitney U test. Normality of the distributions was assessed
using the Shapiro-Wilk test. We used a two-sided alpha
level of 0.05 to indicate significance. Statistical analyses
were performed using SPSS software version 21.0 (SPSS
Inc., Chicago, Illinois, USA).
A total of 1151 patients underwent percutaneous mitral
valve edge to-edge repair with the MitraClip device.
Relative contributions of the participating centres are
summarised in Fig. 2a. The overall cohort had a median age
of 76 (IQR 69–82) years and 59% were males. All patients
presented with ≥moderate MR at baseline, with a clear
dominance of functional MR (72%) (Table 1). Overall, 611
(53%) patients were treated with one Clip, 486 (42%) with
≥2 Clips and 54 (5%) received no Clip (Table 2). The
number of patients treated with ≥2 Clips increased from 22%
in 2009 to 52% in 2016 (Fig. 2). Significant MR reduction
(≥1 grade) was achieved in 94% of patients.
The overall device and technical success were 91 and
95%, respectively, and were consistent over the years
(Fig. 2b). Intra-procedural death and need for emergency
surgery occurred in 3 (0.3%) and 6 (0.5%) patients,
respectively (Table 2). The median device time declined from
145 (IQR 108–177) minutes in 2009 to 55 (IQR 34–86)
minutes in 2016 (Fig. 2b).
Degenerative vs. functional MR
Patients with degenerative MR were older (median age 82
[IQR 76–85] vs. 74 [IQR 67–79] years, p < 0.001), had
Table 1 Baseline characteristics of patients undergoing MitraClip
IQR interquartile range, MR mitral regurgitation, LVEF left ventricular
Table 2 Procedural characteristics of patients undergoing MitraClip
IQR interquartile range, MR mitral regurgitation
aDevice time: defined as the time from delivery system insertion to clip
delivery system removal
bDevice success: defined as proper placement of the device without
procedural mortality and with reduction in
post-procedural MR by ≥1 grade from baseline and to an absolute level
of moderate MR
cTechnical success: defined as successful deployment of the device
with absence of procedural mortality
and freedom from emergency surgery
more often severe MR at baseline (73% vs. 61%, p < 0.001)
and were more often treated with ≥2 Clips (50% vs. 39%,
p = 0.001) when compared to patients with functional MR.
Patients in the latter group had more often significant MR
reduction (95% vs. 91%, p = 0.025) (Fig. 3) and a shorter
device time (62 [IQR 40–99] minutes vs. 75 [IQR 49–110]
minutes, p < 0.001).
One vs. ≥two MitraClips
Patients treated with ≥2 Clips were more often males (68%
vs. 53%, p < 0.001) with degenerative MR (33% vs. 23%,
p < 0.001) and severe MR at baseline (81% vs. 53%, p <
0.001). Significant MR reduction was similar in both groups
(98% vs. 98%, p = 0.59) (Fig. 4) while median device time
was higher in ≥2 Clips group (86 [IQR 58–120] vs. 51 [IQR
35–75] minutes, p < 0.001).
To date, more than 1250 patients have undergone MitraClip
treatment in the Netherlands. We present the largest Dutch
multi-centre MitraClip study including 1151 patients. Key
findings are: 1) MitraClip was predominantly used to treat
functional MR; 2) MitraClip was successful in reducing MR
in 94% of patients; 3) MitraClip was slightly more effective
in patients with functional MR; 4) Over the years,
implantation of ≥2 Clips became more frequent; 5) With growing
experience, procedure time decreased with preserved device
success and technical success.
Patient demographics in our study were comparable with
large European registries (i. e. ACCESS-Europe A
TwoPhase Observational Study of the MitraClip System in
Europe (ACCESS-EU) and German Transcatheter
Mitral Valve Interventions Registry [TRAMI]) but different
from the EVEREST-II trial. The EVEREST trial was
conducted in the USA and included younger patients (67.3 ±
12.8 years) with preserved left ventricular ejection fraction
(60 ± 10.1). In Europe, MitraClip is more often applied in
functional MR, which contrasts with the clear dominance
(73%) of degenerative MR in the USA (Table 3; [6–8]).
In our study, MitraClip seemed slightly more effective
in functional MR than in degenerative MR (95% vs. 91%,
p = 0.025). Intra-procedural death and moderate MR after
Clip implantation were comparable with the ACCESS-EU
and TRAMI registry (0.3% vs. 0% vs. 0% and 92% vs. 91%
vs. 97%, respectively), confirming the safety and efficacy
of MitraClip (Table 3).
Over the years, practice changed with a higher frequency
of implanting ≥2 Clips. Patients treated with ≥2 Clips were
more often males with degenerative MR and severe MR at
baseline. Patients with degenerative MR may have thicker
Overall p < 0.001
p = 0.025
p = 0.002
p = 0.12
p = 0.025
Fig. 3 Comparison of reduction of mitral regurgitation in patients
with degenerative mitral regurgitation versus functional mitral
regurgitation. MR mitral regurgitation, DMR degenerative mitral regurgitation,
FMR functional mitral regurgitation
and more mobile leaflets and had (in our cohort) more
often severe MR at baseline, which may explain why these
patients in particular are treated with ≥2 Clips. A previous
study identified anterior leaflet thickness (OR 1.7 per mm
[95% CI; 1.16–2.57], p = 0.007) and a greater regurgitation
volume at baseline (OR 1.21 per 10 ml [95% CI; 1.0–1.3],
p = 0.01) as echocardiographic predictors for the need for
more than 1 Clip . Another study showed that the vena
contracta (jet width) predicted need for >1 Clip (OR 2.5
Fig. 4 Comparison of mitral regurgitation reduction in patients
treated with 1 versus ≥2 MitraClips. MR mitral regurgitation
[95% CI; 1.2–5.3], p = 0.013) with 83% sensitivity and
90% specificity for a cut-off value of ≥7.5 mm . The
increased device time in degenerative MR may also be
explained by thicker and more mobile leaflets since this may
aggravate the grasping process. Another reason is simply
because of implantation of more Clips.
According to the latest European guidelines on valvular
heart disease, MitraClip may be considered in patients with
symptomatic severe primary and secondary MR, despite
optimal medical therapy, including cardiac
Overall p = 0.018
p = 0.59
p = 0.29
p = 0.59
Median device me
≥ 2 Clips implanted
p = 0.001
p = 0.012
1 Clip, n (%)
Table 3 Baseline and procedural characteristics of patients undergoing MitraClip implantation in different cohorts
MR mitral regurgitation, LVEF left ventricular ejection fraction, SD standard deviation
aDevice success: defined as proper placement of the device without procedural mortality and with reduction in post-procedural MR by ≥1 grade
from baseline and to an absolute level of moderate MR
bTechnical success: defined as successful deployment of the device with absence of procedural mortality and freedom from emergency surgery
tion therapy, who fulfil the echo criteria of eligibility, are
judged inoperable or at high surgical risk by a heart team,
and have a life expectancy greater than 1 year
(recommendation Class IIb, level of evidence C) . The American
guidelines consider transcatheter mitral valve repair only
for severely symptomatic patients with chronic severe
primary MR who have favourable anatomy for the repair
procedure and a reasonable life expectancy, but who have a
prohibitive surgical risk because of severe comorbidities and
remain severely symptomatic despite optimal
guideline-directed medical therapy for heart failure (recommendation
Class IIb, level of evidence B) . Yet, a wealth of recent
clinical data underscores procedural safety and efficacy of
MitraClip and a favourable longer-term outcome in selected
patients. MitraClip seems an excellent treatment strategy in
patients who are deemed at very high or prohibitive
operative risk by heart team consensus. Several studies have
shown significant MR reduction in the vast majority of
highrisk patients, resulting in positive left ventricular
remodelling and improvement of functional capacity [14, 15].
Also, heart failure patients who do not respond
effectively to cardiac resynchronisation therapy and have at least
moderate MR can improve with MitraClip. Auricchio et al.
showed that 73% of cardiac resynchronization therapy
nonresponders (with functional MR) improved in functional
class, and had increased left ventricular ejection fraction
and reduced ventricular volumes after MitraClip treatment
Ongoing randomised trials further elaborate on the value
of MitraClip in functional MR. The MATTERHORN
(Mitral vAlve reconsTrucTion for advancEd Insufficiency of
Functional or iscHaemic ORigiN) trial, is comparing
MitraClip with reconstructive mitral valve surgery in
highrisk patients with moderate-to-severe functional MR. The
Cardiovascular Outcomes Assessment of the MitraClip
Percutaneous Therapy for Heart Failure Patients with
Functional Mitral Regurgitation (COAPT) trial is investigating
the safety and efficacy of MitraClip versus optimal medical
treatment (OMT) in patients with moderate-to-severe or
severe functional MR who have been assessed as not eligible
for mitral valve surgery.
The Multicentre Study of Percutaneous Mitral Valve
Repair MitraClip Device in Patients With Severe Secondary
Mitral Regurgitation (MITRA-FR) is comparing the safety,
efficacy and the cost-effectiveness of OMT versus OMT
plus MitraClip in patients with severe secondary mitral
Expectedly, focused guidelines on valvular heart
disease will be updated in the foreseeable future and include
stronger recommendations for MitraClip. For now, our
study demonstrated substantial MitraClip experience in the
Netherlands with excellent procedural safety and efficacy.
Given the retrospective observational character of this study
and the onsite assessment of MR (i. e. absence of echo core
lab), potential self-reporting bias may be introduced.
Specific echocardiographic (quantitative) parameters such as
regurgitation volume and jet width were not available. In
addition, data were limited to procedural outcome.
Followup data are needed to evaluate the durability of device
Long-term efficacy may reveal recurrence of MR
(grade 3 or 4) as shown by the EVEREST-II trial and
ACCESS-EU study with more than moderate MR recurrence
rates of 21% at 12 months in both studies. Furthermore,
we also acknowledge that complications such as stroke,
bleeding and vascular complications, although rare, may
occur during follow-up.
MitraClip experience in the Netherlands is growing with
excellent technical success and device success. Over the
years, the device time decreased and more patients were
treated with ≥2 Clips.
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1. Nkomo VT , Gardin JM , Skelton TN , Gottdiener JS , Scott CG , Enriquez-Sarano M. Burden of valvular heart diseases: a populationbased study . Lancet . 2006 ; 368 : 1005 - 11 .
2. Iung B , Vahanian A. Epidemiology of valvular heart disease in the adult . Nat Rev Cardiol . 2011 ; 8 : 162 - 72 .
3. Joint Task Force on the Management of Valvular Heart Disease of the European Society of C, European Association for Cardio-Thoracic S, Vahanian A , Alfieri O , Andreotti F , et al. Guidelines on the management of valvular heart disease (version 2012 ). Eur Heart J . 2012 ; 33 : 2451 - 96 .
4. Mirabel M , Iung B , Baron G , et al. What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery ? Eur Heart J . 2007 ; 28 : 1358 - 65 .
5. Feldman T , Wasserman HS , Herrmann HC , et al. Percutaneous mitral valve repair using the edge-to-edge technique: six-month results of the EVEREST Phase I Clinical Trial . J Am Coll Cardiol . 2005 ; 46 : 2134 - 40 .
6. Feldman T , Foster E , Glower DD , EVEREST II Investigators, et al. Percutaneous repair or surgery for mitral regurgitation . N Engl J Med . 2011 ; 364 : 1395 - 406 .
7. Maisano F , Franzen O , Baldus S , et al. Percutaneous mitral valve interventions in the real world: early and 1-year results from the ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe . J Am Coll Cardiol . 2013 ; 62 : 1052 - 61 .
8. Schillinger W , Hünlich M , Baldus S , et al. Acute outcomes after MitraClip therapy in highly aged patients: results from the German TRAnscatheter Mitral valve Interventions (TRAMI) Registry . EuroIntervention . 2013 ; 9 : 84 - 90 .
9. Giannini C , Fiorelli F , De Carlo M , et al. Comparison of percutaneous mitral valve repair versus conservative treatment in severe functional mitral regurgitation . Am J Cardiol . 2016 ; 117 : 271 - 7 .
10. Stone GW , Adams DH , Abraham WT , Mitral Valve Academic Research C, et al. Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions: a consensus document from the Mitral Valve Academic Research Consortium . Eur Heart J . 2015 ; 36 : 1878 - 91 .
11. Armstrong EJ , Rogers JH , Swan CH , et al. Echocardiographic predictors of single versus dual MitraClip device implantation and long-term reduction of mitral regurgitation after percutaneous repair . Catheter Cardiovasc Interv . 2013 ; 82 : 673 - 9 .
12. Alegria-Barrero E , Chan PH , Foin N , et al. Concept of the central clip: when to use one or two MitraClips(R) . EuroIntervention . 2014 ; 9 : 1217 - 24 .
13. Nishimura RA , Otto CM , Bonow RO , American College of Cardiology, American Heart Association , et al. 2014 AHA/ ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines . J Thorac Cardiovasc Surg . 2014 ; 148 : e1 - e132 .
14. Van den Branden BJ , Swaans MJ , Post MC , et al. Percutaneous edge-to-edge mitral valve repair in high-surgical-risk patients: do we hit the target ? JACC Cardiovasc Interv . 2012 ; 5 : 105 - 11 .
15. Whitlow PL , Feldman T , Pedersen WR , Investigators EI , et al. Acute and 12-month results with catheter-based mitral valve leaflet repair: the EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study . J Am Coll Cardiol . 2012 ; 59 : 130 - 9 .
16. Auricchio A , Schillinger W , Meyer S , Investigators P-C , et al. Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling . J Am Coll Cardiol . 2011 ; 58 : 2183 - 9 .