This document discusses mitral regurgitation (MR) and percutaneous approaches to mitral valve repair. It provides background on the anatomy of the mitral valve and the types of MR. Surgical repair or replacement is the standard treatment for MR but percutaneous options are being developed to provide less invasive alternatives for high-risk patients. The MitraClip procedure has been used successfully in humans and involves deploying a clip to grasp and oppose the mitral valve leaflets, reducing regurgitation. Indications, outcomes, limitations, and components of the MitraClip system are described.

2.  Mitral regurgitation (MR) is one of the most common heart valve
disorders .
 If left untreated it leads to progressive left ventricular dysfunction, heart
failure, and death.
 Surgical repair or replacement is the established treatment for degenerative
MR.
 patients with associated comorbidities or left ventricular dysfunction put
them at very high surgical risk.
 Need exists for less invasive, safer options for selected patients .

3.  The MV comprises two leaflets, annular
attachment at the atrioventricular junction,
tendinous chords and the papillary muscles
(PMs).
 mural leaflet has three scallops (segments) along
the elongated free edge.
 Carpentier’s nomenclature describes the most
lateral segment as P1, which lies adjacent to the
anterolateral commisure, P2 is central and most
medial is P3 segment, which lies adjacent to the
posteromedial commissure.
 aortic leaflet is also divided arbitrarily into three
regions A1, A2 and A3.

4. Type 1 exhibits normal leafl et mobility as with endocarditis.
Type 2 exhibits excessive leafl et mobility as in degenerative disease or mitral valve
prolapse.
Type 3a exhibits restricted leafl et motion due to chordal and leafl et thickening
from rheumatic heart disease.
Type 3b exhibits restricted leafl et motion due to ventricular wall motion
abnormality from dilated or ischemic cardiomyopathy

5.  The anatomic aetiologies of MR include degenerative or functional.
 Degenerative MR -- leaflets or chordae are structurally altered (fibroelastic
deficiency, leaflet prolapse and flail, or Barlow’s disease).
 Functional MR --is a direct consequence of underlying myocardial disease
affecting the valvular apparatus and is observed in patients with ischaemic
or dilated cardiomyopathy.

12.  The advantage of percutaneous valve repair technology is its promise to
reduce the morbidity and mortality associated with traditional invasive
surgical repair.
 Various percutaneous approaches to mitral valve repair are under
preclinical and clinical investigation.
 These approaches are predominantly based on established surgical
strategies.
 Selection of the appropriate technique for each individual patient ultimately
determine the success of these emerging technologies

13. Isolated MRIsolated MR
(n=877)(n=877)
Severe MRSevere MR
(n=546)(n=546)
No Severe MRNo Severe MR
(n=331)(n=331)
No SymptomsNo Symptoms
(n=144)(n=144)
SymptomsSymptoms
(n=396)(n=396)
No InterventionNo Intervention
(n=193) 49%(n=193) 49%
InterventionIntervention
(n=203) 51%(n=203) 51%
Mirabel et al, European Heart J 2007;28:1358-1365
2/3 of symptomatic
MR patients >70
are denied surgery

14. Percutaneous approaches to mitral repair can be broadly
divided into procedures that address the various components of
the mitral valve.
All are integral to the normal function of the mitral valve and
each is a potential avenue for repair.

15.  Approaches under investigation for transcatheter mitral valve repair or
replacement include the
 Edge-to-edge Clip
 Off-pump Adjustable Neochordal Implantation
 Indirect Annuloplasty (Generally Via Coronary Sinus Remodeling)
 Cinching Devices To Induce Annular Reduction
 External Compression
 Direct Annuloplasty (Transcatheter Surgical Rings Or Sutures).
 Energy mediated Annuloplasty (Collagen Shrinking) And
 Transcatheter Mitral Valve Replacement.

16. Current Status of Percutaneous Mitral Valve Repair Procedures

17. Leaflet Repair;
 The edge-to-edge is a surgical technique developed by Alfieri in the early 1990s.
 The technique is technically simple and used to treat both organic and functional MR.
 The surgical technique consists of the suture of the free edge of the leaflets at the site of
regurgitation, creating a valve with 2 orifices when the regurgitation originates from the middle
scallops.
 Its technical simplicity and versatility has been the foundation for the development of
transcatheter technologies.
 Two percutaneous leaflet repair procedures have been evaluated to date.
 The Mobius device procedure was complex and is not currently being pursued.

18. Double-orifice surgical MVR with a
suture.
•Surgical repair of anterior leaflet prolapse
using an edge-to-edge technique by opposing
the middle scallops of the anterior and posterior
leaflets with stitches creating a so-called dual-
orifice or double-ori fice mitral valve.
•The clinical success and simplicity of this
technique prompted interest in development of a
catheter-based MitraClip technology.

19.  Morales et al. first described a device for beatingheart edge-to-edge repair
with a tissue grasper.
 Alfieri et al. reported the early animal experience with a suture based device
for double orifice repair with a beating-heart, direct transatrial approach.
 Mobius (Edwards Lifesciences, Irvine, California) proved safe and effective
in the animal experience.

20.  After the Milano II multicenter safety and feasibility trial, the program was
discontinued for evidence of limited efficacy and durability.
 The main limitation for the success of the Mobius was lack of adequate
image guidance (due to the poor echogenicity of the device).
 The limited durability was related to insufficient tissue penetration of the
suture and to asymmetric deployment of sutures.

22. • The development of the MitraClip dates back to 1998, when interventional
cardiologist Frederick St. Goar started experimenting with percutaneous techniques
for MVR.
• The feasibility of percutaneous MVR with the MitraClip device was first
demonstrated in a animal model.
• The first human implant of a MitraClip was performed in June 2003 by Dr. Jose
Condado in Caracas Venezuela in a 48-year-old woman with severe MR due to a
bileaflet flail.
• The procedure was performed without complications and after successful clip
deployment her MR decreased to <2+.

24. Reported clinical
benefit in selected
patients
Challenges
Lack of evidence,
particularlyfor FMR
Limited clinical
experience,
concentrated in high
volume centers
Limited applicability

25. In experienced centers, DMR is
treated with surgical repair at low risk,
long term durability of repair is
achieved in the majority of patients
 50% of Euro Heart Survey patients were
not referred to surgery (Mirabel EHJ 2007)
 Age and comorbidity increase the risk of
surgery (STS database, 2010)
 Surgery is not associated with improved
QoL in most elderly patients (Maisano et al
EJCTS 2009)

26. Surgical treatment of FMR is associated
with
 High hospital mortality
 High recurrence rate
 Long hospital stay
 Unproven survival benefit
Mitraclip for FMR
 Procedure more simple than for DMR
 Improvement of symptoms at low risk
 HRR suggests survival benefit
 Failure does not modify the surgical option

27.  The Mitraclip has been used in humans with success, due to the very
promising animal experience.
 main drivers for success of the therapy have been the precise and stable
delivery system, the solid and reliable tissue approximation, the good
visualization of the device, and its repositionability and retrievability.
 The main strength is feasibility of the procedure under beating heart
conditions, guided by the regurgitant jet position.
 main weakness is the limited applicability, according to strict anatomical
features.

28.  Indications and patient selection;
 applied to a wide spectrum of degenerative and functional mitral regurgitant
pathologies.
 However, considerable uncertainty still remains about indications and
ideally suitable patient populations for percutaneous MVR.
 Current patient selection criteria are based on the Endovascular Valve
Edge-to-Edge Repair Study (EVEREST) programme and include clinical
patient characteristics and anatomical features of the mitral valve.

29.  the main anatomical selection criterion appears to be the ability to properly
grasp both leaflets.
 Treating MR at the medial or lateral commissures is feasible, but requires
exceptional care as the ability to manoeuvre the device is limited and the
risk of entanglement in the commissural chordae high.
 In the majority of cases, transoesophageal echocardiography (TEE) will be
necessary to resolve relevant morphological features.

30.  several reports have documented high procedural success rates and good
short-term outcomes of percutaneous MVR in populations with severely
reduced LV function rendering it an attractive treatment modality for
symptomatic high-risk patients with poor LV function .
 Moreover, MitraClip treatment does not preclude the later use of other
device-based therapies that are often applied in patients with heart failure.

31. Clinical criteria;
•Moderate-to-severe (3+) and severe (4+) MR
•Class I indications for intervention
•MR aetiology: degenerative or functional
•Non-rheumatic or -endocarditic origin of MR
•High surgical risk by EuroSCORE or STS scores
Anatomical criteria;
•MR originating from the central 2⁄3 of the valve
•Mitral orifice area ≥4 cm2
Criteria for degenerative MR .
• Flail gap <10 mm
•Flail width <15 mm
Criteria for functional MR
•Coaptation depth ≤11 mm
•Coaptation length ≥2 mm

32. Components of
the MitraClip
system
The MitraClip System consists of
two parts:
1) the Clip Delivery System and
2) the Steerable Guide Catheter.
The Clip Delivery System consists
of three major components:
1) The Delivery Catheter
2) The Steerable Sleeve and
3) The MitraClip Device
•The guide cathetertapers down to 22
Fr at the point where it crosses the
atrial septum.
•A steering knob on the proximal end
of the guide catheter allows for flexion
and movement of the distal tip

33. The MitraClip.
•a ) The MitraClip device consists of a
percutaneously delivered MRI-compatible
cobalt-chromium implant with two arms
and two grippers which are used to grasp
the opposing edges of the mitral leaflets .
• The two arms have a span of approximately
2 cm when opened in the grasping position.
•On the inner portion of the clip are U-
shaped “grippers,”
•It is designed to hold up to 8 mm of leaflet
height ( vertically ) and 4 mm of width .
Leaflet tissue is secured between the arms
and each side of the gripper, and the clip is
then closed and locked to effect and
maintain coaptation of the two leaflets

34.  The procedure is generally performed under general anaesthesia with
fluoroscopic and transoesophageal echocardiographic guidance and
haemodynamic monitoring with a Swan-Ganz catheter in the pulmonary
artery.
 The device is delivered via transfemoral venous route.
 After transseptal puncture, the transseptal sheath is exchanged by a
steerable 24-F guide catheter (which tapers to 22-F at the interatrial septum)
through which the clip delivery system is advanced into the left atrium.
 Thereafter, the MitraClip device is manoeuvered under echocardiographic
guidance, aligned with the origin of the regurgitant jet, and pushed below
the level of the mitral leaflets into the left ventricle (LV)

35.  Careful consideration must be given to a perpendicular orientation of the
clip arms and the leaflet edges before closing the clip.
 After opening the two armsmof the clip, the device is retracted with
extended arms and both leaflets are grasped by closing the grippers.
 Once adequate leaflet insertion is ascertained with echocardiography, the
arms of the Mitra-Clip can be closed to approximate both scallops and
restore coaptation.
 MR is immediately assessed by transoesophageal echocardiography and
haemodynamic measurements, and if necessary, the device can be
repositioned by reopening the arms and releasing the leaflets.

36.  If the desired result is obtained, the MitraClip is deployed and released
from the delivery catheter
 Repeat clip insertion can be performed if MR reduction is suboptimal and
the result is expected to improve with more than one clip.
 The only limitation to the number o f clips implanted is the development of
significant mitral stenosis.

38.  The device was systematically evaluated in a series of prospective studies in
the United States , before being made commercially available in Europe in
2008.
 The device is commercially available in 40 countries.
 More than 10,000 patients have been treated throughout the world, with
1,200 patients having participated in clinical trials in the United States.
 The predominant usage in a commercial setting is high-surgical-risk
patients with functional MR.

39.  After the first-in-man experience, the EVEREST I feasibility study was
completed in 2006, enrolling 55 patients. Feldman et al. reported the pooled
data from EVEREST I and 52 “roll-in” EVEREST II patients (treated
before randomization as part of the training) demonstrating the safety of the
procedure as well as efficacy in selected patients.

40.  The EVEREST II RCT was a landmark trial, being the first randomized
trial to compare a percutaneous intervention for the reduction of MR to
mitral valve surgery.
 The intended population was patients with significant symptomatic mitral
regurgitation (MR ≥ 3+) of either FMR or DMR etiology that were non-
high risk candidates indicated for and who could undergo mitral valve
surgery.
 Patients were evaluated at baseline, discharge, 30 days, 6, 12, 18 and 24
months, and annually thereafter through 5 years.

44. Subgroup Analyses of Efficacy Endpoint at 4 Years

45.  patients treated with percutaneous therapy achieve less complete reduction in MR at
discharge and at 1 years as measured by echocardiography.
 after year 1, few patients in either treatment arm had recurrent MR or required a
repeat mitral valve procedure between years 1 and 4, and mortality rates were not
different between the treatment arms at 1 year or 4 years.
 For the overall trial population, benefits in terms of reduction in NYHA class were
sustained and comparable to surgery.

46. Although left ventricular dimensions were reduced with either
therapy, the degree of reduction was greater for surgery.
 In the subset of patients with functional MR, who appeared to
have had comparable outcomes with the percutaneous
procedure compared with surgery at 1 year these results were
sustained, as measured by freedom from death, operation for
mitral valve dysfunction, or recurrent MR of grade 3+ or
higher

47.  Almost all of the MitraClip-treated patients who require an additional
procedure do so within the first 6 months after initial treatment
 After this, the rates of reopera-tion or additional MitraClip procedures are
no different between the 2 treatment groups.

48.  The stability of the results in MitraClip-treated patients up to 4 years is a
key finding of this report, with preserved left ventricular function, and
ventricular dimensions in follow-up, and few additional patients having
increased MR grade after the first year of follow-up.

49.  Conclusions
 At 4 years, surgery remains the standard of care for treatment of MR among eligible
patients.
 Percutaneous repair is associated with similar mortality and symptomatic improvement
but a higher rate of MR requiring repeat procedures, and less improvement in left
ventricular dimensions than surgery.
 Although percutaneous repair of the mitral valve to treat MR was associated with a
higher rate of residual MR at 1 year, there was no difference in later occurrence of MR or
mitral valve intervention between 1-year and 4-year follow-up.
 Further studies are necessary in patients with functional MR where percutaneous
treatment was most comparable to surgery in terms of late efficacy.

50. Overview of MitraClip US Clinical Trials

51. Safety is probably superior compared to surgery
Efficacy is probably inferior compared to surgery
High rate of pts with residual MR
clinical benefit yet to be demonstrated
Results will be influenced by
improvements in:
Learning curve
Indications
imaging
Addition of annuloplasty

52. CONTRAINDICATIONS
The MitraClip Clip Delivery System is contraindicated in
DMR patients with the following conditions:
• Patients who cannot tolerate procedural anticoagulation or
post procedural anti-platelet regimen
• Active endocarditis of the mitral valve
• Rheumatic mitral valve disease
• Evidence of intracardiac, inferior vena cava (IVC) or femoral
venous thrombus

53.  serious life-threatening or fatal complications related to the MitraClip
procedure are exceedingly rare.
 rates of major clinical complications such as stroke, myocardial infarction,
acute renal failure, and septicaemia are below 5%.
 Urgent surgery for persistent or aggravated MR varies across different
reports (0–8%).
 Among minor complications, the most common was access site bleeding or
groin haematoma

54. Clip-related complications are rare (<5%) but potentially
deleterious.
Complications from transseptal puncture may include
pericardial tamponade.
Clip-related chordal rupture may result from inadvertent
tangling of the device in the subvalvular apparatus and may
result in acute MR.

56. MitraClip therapy (Abbott Vascular) received U.S. FDA
approval on October 24, 2013.
MitraClip has been approved for patients with
significant symptomatic degenerative mitral
regurgitation (MR) who are at prohibitive risk for
mitral valve surgery.
Ongoing prospective, randomized trials — COAPT in
the United States and RESHAPE-HF in Europe — will
evaluate the impact of MitraClip treatment on the
progression of heart failure in patients with severe MR.
Both studies are currently enrolling patients.

58. Coronary Sinus Annuloplasty;
 Mitral annuloplasty using an undersized ring is a routine component of
surgical mitral valve repair.
 percutaneous devices have attempted to reproduce the beneficial effects of
surgical annuloplasty by taking advantage of the proximity of the coronary
sinus to the mitral annulus.
 The coronary sinus and its major tributary, the great cardiac vein, parallel
the annulus of the mitral valve along its posterior and lateral aspect .

59. Percutaneous approaches have generally used internal
jugular or subclavian access.
 Various remodeling devices can be introduced into
the coronary sinus, with the objective being to
displace the adjacent posterior mitral annulus toward
the anterior aspect of the annulus and thereby improve
coaptation of the mitral leaflets.

60. Device Positioning
Anchor Deployment
Final Confirmation

61. Anatomical relations with
the mitral annulus
• only posterior
• atrialization
Relation with the Cx
artery
 Potential risk of AMI

62.  The coronary sinus approach is appealing for many reasons; notably
procedural simplicity with transvenous access and fluoroscopic guidance
but is also subject to several potential limitations.
 anatomic relationship of the sinus to the mitral annulus is highly variable as
demonstrated by a number of postmortem, computed tomography, and MRI
studies.
 Despite these concerns, early data suggest that the apparent benefit of
coronary sinus annuloplasty is not predicted by imaging assessment of the
spatial relationship between the coronary and the mitral valve annulus.
 increasingly used in patients with heart failure and benefit in MR has been
suggested.

63.  The MONARC percutaneous transvenous annuloplasty device (Edwards
Lifesciences) consists of a stent-like anchor placed in the great cardiac vein, a
connecting bridge, and a second anchor located proximally at the coronary sinus
ostium.
 The compressed device can be introduced from the jugular vein using a long
sheath.
 Once positioned within the cardiac venous system, the sheath is withdrawn
allowing the selfexpanding nitinol alloy anchors to expand, providing fixation


64.  Tensioning the device before deployment of the proximal anchor allows
for acute shortening of the coronary sinus.
 In addition, the nitinol bridge segment is constructed like a spring with
biodegradable spacers.
 Over a few weeks the spacers dissolve and the bridge shortens, the anchors
are drawn together and the coronary sinus shortens further.

65.  Panel A shows the delivery catheter.
 Panel B is the device, with proximal (smaller) and distal (larger) anchoring elements, as wellas the bridge element, that
shortens over time post procedure.
 Panel C is a fl uoroscopic image of the measuring device used to size
 the device.
 Panel D is a schematic of the device within the coronary sinus.

66.  device was evaluated in the EVOLUTION I feasibility trial, which enrolled
72 symptomatic patients with grade 2 functional MR.
 Interim analysis found a reduction in MR severity and functional class in
the majority of patients (J. Harnek, MD, personal communication).
 The larger EVOLUTION II trial will soon evaluate the safety and efficacy
of the MONARC device in patients with grade 3 or 4 functional MR.

67.  CARILLON Mitral Contour System (Cardiac Dimensions, Inc, Kirkland,
Wash) uses 2 self-expanding nitinol anchors connected by a wire.
 The distal coronary sinus anchor is deployed, manual tension is applied to
the connecting wire, and then the proximal anchor is deployed.
 As shortening of the coronary sinus is immediate, the effect on MR and the
potential for coronary compression can be readily assessed by
echocardiography and angiography.
 If necessary, the amount of tension can be adjusted or the device can be
retrieved before final release.

68.  The modified CARILLON XE device was evaluated in the multicenter
AMADEUS trial in which permanent device implantation was achieved in
30 of 43 patients.
 In some cases, the device was removed before final release because of lack
of MR reduction or to avoid apparent arterial compression.

69. No differences in CS/GCV location relative to the
annulus between patients with or without efficacy
Neither MR reduction or lack of MR reduction is
explained by relative position of vein to annulus
Courtesy of J Harnek, MD

70.  The Percutaneous transvenous mitral annuloplasty device (VIACOR, Inc,
Wilmington, Mass) represents a third approach to coronary sinus
annuloplasty.
 A catheter is implanted in the coronary sinus using a subclavian cutdown.
 Metallic rods are placed within the catheter with the intention of deflecting
the coronary sinus and adjacent posterior annulus anteriorly.
 Temporary implants suggested efficacy, and the subsequent PTOLEMY
trial found a reduction of MR by at least 1 grade was achieved in 13 of 19
patients with limited follow-up suggesting durability.

71. MONARC
(Edwards
Lifesciences
LLC)
Two-anchor design
with chronic
reshaping (6weeks)
by a foreshortening
bridge
EVOLUTION
trial
(69 pts
enrolled)
CARILLON
(Cardiac
Dimensions
Inc)
Acute reshaping
device acting in
P2P3, repositionable,
retrievable
AMADEUS trial
(43 pts
enrolled )
PTMA
(Viacor Inc)
Tri-lumen catheter,
reshapable,
possibility of
multiple long term
adjustment
PTOLEMY
(24 pts
enrolled)

72. 6-min-walking test

73. Atrial Remodeling
 MONARC coronary sinus device does extend its distal anchor into the
anterior interventricular vein and consequently may have minor effect on
the left ventricle.
 Other groups have tried to combine an anchor in the coronary sinus with a
second anchor in the right atrium in the hopes of more reliably applying
force to the plane of the mitral annulus.

74.  Percutaneous Septal Shortening System (PS3, Ample Medical Inc, Foster City,
Calif) uses transvenous access to the right atrium to allow placement of an
anchor in the coronary sinus adjacent to the mitral P2 scallop .
 However, an atrial transeptal puncture allows implantation of the second anchor
in the interatrial septum.
 A magnetic catheter system facilitates placement of a wire connecting these 2
anchors.
 Tensioning this wire reduces the diameter of the mitral annulus.
 Ovine studies and temporary human implants have demonstrated a reduction in
antero-posterior annulus diameter and MR severity

75. Direct Annuloplasty;
 Direct modification of the mitral annulus is the most obvious means of
reproducing the effects of surgical annuloplasty.
 Annuloplasty rings that can be introduced through a catheter are one possible
approach;
 however, reliable methods of positioning and fixation have proved problematic.
 Direct modification of the mitral annulus using a radiofrequency catheter to
heat and shrink annular collagen has been proposed (QuantumCor Inc, Lake
Forest, Calif)

77.  The Mitralign Percutaneous Annuloplasty System (Mitralign Inc, Tewksbury,
Mass) uses a guide catheter passed between the 2 papillary muscles to access
subvalvular space in the region of the mitral P2 scallop .
 The Accucinch system (Guided Delivery Systems Inc, Santa Clara, Calif) uses a
guide catheter to access this same space, but enters medial or lateral to the
papillary muscles.
 In both systems several anchors are implanted in the subannular ventricular
myocardium that corresponds to the mitral valve annulus .
 Linking sutures can be tensioned like a belt shortening the posterior annulus.
 Human experience initiated with the Mitralign system and similar trials of the
Accucinch system are anticipated shortly.

78. Ventricular Remodeling
 The iCoapsys device designed to produce a reduction in MR by remodeling
the leftventricle .
 This percutaneous device is implanted using a subxiphoid pericardial access
sheath.
 2 fixation pads are placed on the surface of the left ventricle, 1 anterior and
1 posterior.
 Left ventricular puncture allows a cable to connect the 2 pads. Tensioning
the cable draws the 2 pads together.
 As the anteroposterior diameter of the left ventricle is reduced, the
anteroposterior dimension of the mitral annulus also reduces, hopefully
resulting in improved leaflet coaptation, reduced chordal tethering, and
improved left ventricular function.

79. The TRACE feasibility and the randomized RESTOR-MV
trials in patients with ischemic, functional MR undergoing
bypass surgery demonstrated a reduction in MR and left
ventricular volume as well as symptomatic benefit comparable
with mitral surgery.
Feasibility of the percutaneous iCoapsys procedure has been
demonstrated in an ovine model, and recently initial human
implants have been performed.

80. Myocor (Edwards) i-
Coapsys
Rogers et al, Circulation 2006;113:2329

81. Other Novel Approaches
Surgical mitral valve repair often incorporates chordal repair,
implantation, or removal.
Transcatheter and percutaneous chordal procedures are
currently under development, including chordal cutting and
chordal implantatation.

82. Valve Replacement
 Transcatheter implantation of a valved stent within a degenerated surgical
mitral bioprosthesis has been accomplished, at least to some degree
demonstrating the feasibility of this approach.
 However, implantation of a valved stent within a native mitral valve is
problematic due to the saddle shape of the native annulus, chordal
structures, limited fluoroscopic landmarks, and the need to avoid
obstruction to the left ventricular outflow tract.
 Nevertheless, a number of groups have pursued this goal, generally
combining a self-expanding valved stent with percutaneous transseptal,
direct left atrial, or transapical access to the mitral valve.
 Clinical trials are anticipated

83. Asymmetric anatomy
Interaction with the aortic
valve
LVOT obstruction
At least 10 companies are
working on t-MVR

84. Tailored approach – the best option
for the patient
today

85. Minimally invasive and
transcatheter approach
Image guidance and computer
aided decision making
Devices will be
etiology-specific
Adjustable off pump
Implantable with no or minimal
conventional suturing
Early treatment
Stepwise and combined strategies