Ischemic Mitral Regurgitation: Unusual Approachesfor Correction

Judy Hung

Published online: 1 September 2010# Springer Science+Business Media, LLC 2010

Abstract Ischemic mitral regurgitation (MR) results fromischemic left ventricular distortion with tethering of themitral leaflets. The standard surgical therapy for ischemicMR is mitral ring annuloplasty, often performed at the timeof coronary artery bypass surgery. However, ring annulo-plasty is associated with an up to 30% recurrence rate ofMR, as it does not directly address ventricular distortionand tethering of the mitral leaflets and there is often furtherventricular remodeling following bypass surgery. Thisarticle reviews the background and mechanism of ischemicMR and unusual approaches to this important yet difficultto treat valvular problem.

Keywords Mitral regurgitation . LV remodeling

Introduction

Ischemic mitral regurgitation (MR) is a common compli-cation of coronary artery disease that conveys adverseprognosis, more than doubling the risk of late death [1–3].It occurs in approximately 25% of patients followingmyocardial infarction and in up to 50% of patients withheart failure and cardiomyopathy [4–8]. This adverseprognosis is related to the degree of MR, with thedevelopment of just mild MR contributing to mortality [4,5]. MR is also frequent in patients with global left

ventricular (LV) dysfunction, and is a potent stimulus foradverse LV remodeling, which begets further MR. Themechanism of ischemic MR relates to remodeling anddistortion of the ischemic left ventricle following infarction[9, 10]. Ischemic LV distortion leads to thinning anddisplacement of the myocardium supporting the papillarymuscles (PMs) to which the mitral leaflets are anchored.Displacement of these muscles tethers the leaflets andrestricts leaflet closure, resulting in MR (Fig. 1) [11].

Although ischemic MR may be reduced with contractileimprovement due to coronary revascularization, thisrequires sufficient functional improvement to change LVdimensions and reduce tethering [12–18], which may notoccur in the chronically infarcted heart. Aklog et al. foundthat following revascularization alone, moderate or severeMR persisted in 77% of patients [19]. Standard surgicaltherapy for functional MR at the time of revascularizationinvolves placing an annuloplasty ring, designed to restorecoaptation by correcting posterior annular dilation.

While ring annuloplasty is effective in some patients,results are variable, with important (moderate or greater)persistent MR often recurring months postoperatively inapproximately 30% of patients [20–24]. Importantly,however, annuloplasty aims at a moving target: initiallyeffective annuloplasty may later fail as the left ventriclecontinues to remodel and tethering increases [25]. Ringinsertion also shifts the posterior annulus anteriorly, whilethe ischemic PM remains posterior, which restricts theanterior excursion of the posterior leaflet toward coaptationwith the anterior leaflet [26].

Disappointment with the benefits of annuloplasty alone,in view of the added risks of prolonging cardiopulmonarybypass and ischemic time and the relatively high mortality[27], led McGee et al. from the Cleveland Clinic toconclude that “the development of additional techniques is

J. Hung (*)Cardiac Ultrasound Laboratory, Massachusetts General Hospital,Boston, MA, USAe-mail: jhung@partners.org

J. HungHarvard Medical School,Boston, MA, USA

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necessary to achieve more secure repair of functionalischemic mitral regurgitation” [24].

Chordal Cutting

Uncertainties with efficacy of ring annuloplasty alonefor treating ischemic MR have led to exploration ofalternate approaches. One approach involves cutting of

the basal strut chords to the anterior leaflet [27]. Basalor strut chordae attach to the mid-body of the anteriorleaflet. With the development of ischemic LV distortionand PM displacement, the tethering of the leafletsoccurs via the basal chords. In Fig. 2, the anteriorleaflet has a “bend” present due to tethering by a basalchord. In an experimental ovine model of ischemicMR, Messas et al. [27] performed cutting of the basalchord to the anterior leaflet to relieve mitral leaflet

LV

LA

Normal

AO

Ischemic

MR

TetheringRestrictedclosure

Papillarymuscle

displacement

IschemicLV

distortion

Decreasedclosing force

Fig. 1 Schematic of mechanismof ischemic mitral regurgitation(MR). Normal mitral valvespatial relationship with leftventricle (LV) on left. On right,ischemic LV distortion leads topapillary muscle displacement,resulting in tethering of themitral leaflets and MR

Fig. 2 Experimental ovinemodel of ischemic mitral regur-gitation (MR). Left demonstratesbend of the anterior leafletcreated by tethering from a basalchord (top left) with MR(bottom left). On top right,reduced tethering with straight-ening of the anterior leafletfollowing cutting of the basalchord and resolution of MR(bottom right). (From Messas etal. [27]; with permission)

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tethering and demonstrated reduction in MR comparedto controls.

Borger et al. [28••] compared 49 patients with coronaryartery disease and MR who underwent standard therapywith coronary artery bypass graft and mitral valve annulo-plasty to 43 patients who also underwent chordal cutting ofthe basal chord. There was no difference in mortalitybetween the group that also had chordal cutting and thegroup that did not (Fig. 3). However, there was a significantdecrease in MR in the group that underwent chordal cutting(Fig. 4).

Ventricular Approaches

Direct remodeling of the left ventricle by repositioning ofthe PMs is another approach that has been proposed as atherapeutic target to reduce ischemic MR. A number ofsurgical therapies (both experimentally and in patients)that reposition the PMs to reduce tethering of the mitralleaflets have been developed as adjunctive or alternateapproaches to standard mitral ring annuloplasty (Table 1)[29••, 30–33].

The Coapsys device (Myocor Inc.) was one of the firstdevice-based ventricular approaches designed to treatischemic MR [34]. This device consists of two epicardialpads that are connected through an internal cord (Fig. 5)[34]. It has the advantage over ring annuloplasty in that itcan be placed on a beating heart without cardiopulmonarybypass [35]. Follow-up of the first 11 patients with aCoapsys device and off-pump coronary artery bypass graftshowed an improvement in reoperative MR grade 2.9±0.5to grade 1.1±0.8 at 1 year (P<0.05) [35]. A phase 2 trialwas completed but has not been reported, and the companyis no longer active.

Although ventricular approaches more directly addressthe fundamental mechanism of ischemic MR, theyremain relatively invasive. Most recently, a polymer-based approach to ventricular remodeling has beenreported experimentally with efficacy in reducing MR(Fig. 6). A polymer-based approach has the potentialadvantage of being less invasive than the other surgicaltechniques. A biocompatible polymer, polyvinyl alcohol,was specially formulated to gel once injected into themyocardium [36••]. This polymer was injected into

Sur

viva

l, %

100

80

60

40

20

0

0 6 12 18Months postoperatively

24

4349

1031

18

Numbers at risk

Chordal-cuttingControlP = 0.8

Fig. 3 No difference in survival between the ring annuloplasty andchordal cutting group versus ring annuloplasty–only group. (Adaptedfrom Borger et al. [28••])

4+

2+

1+

0

4+

3+

2+

1+

0

4+

3+

2+

1+

0

4+

3+

2+

1+

0

Pre-op(3.0 ± 0.9)

Post-op(1.4 ± 1.3)

Pre-op(2.8 ± 0.8)

Post-op(0.9 ± 0.9)

Ring only Ring + chordal cutting

23

1

111

221

983

5331

211

1

478

3

74

3+

Fig. 4 Chordal cutting grouphad greater reduction inmitral regurgitation than ringannuloplasty–only group.(Adapted from Borger et al.[28••])

398 Curr Cardiovasc Imaging Rep (2010) 3:396–402

infarcted myocardium underlying the PM in an experi-mental ischemic MR model. This resulted in tissuebulking of the weakened myocardial wall and reverseremodeling with decrease in mitral leaflet tethering andreduction in ischemic MR.

Edge-to-Edge Repair

In addition to ventricular and chordal cutting approaches,edge-to-edge repair has been applied to ischemic MR.Edge-to-edge repair was developed by Ottavio Alfieri, inwhich the edges of the mitral leaflets are sewn together,creating a double orifice while reducing MR (Fig. 7) [37].The etiology of MR in these patients had degenerative

mitral valvular disease, although this surgical repair hasbeen applied to ischemic MR. More recently, edge-to-edgemitral valve repair has been applied percutaneously with aclip device (MitraClip; Evalve Inc.) [38]. EVEREST II wasa randomized trial of 279 patients with significant MR (3+to 4+) comparing the mitral clip device to surgical therapywith either mitral repair or replacement for MR [38]. Theresults were recently presented and showed that the novelMitraClip device may lead to fewer early adverse eventsthan traditional valve repair or replacement, with non-inferior efficacy out to 1 year. However, the surgical armdemonstrated greater efficacy in reducing MR [38]. It isimportant to note though that the majority of patients inEVEREST II had degenerative MR (73%), with a minorityhaving ischemic MR (27%), and results may not be

Table 1 Adjunctive or alternate approaches to standard mitral ring annuloplasty

Study Patients, n Technique Follow-up, mo

Kron et al. [40] 18 Surgical relocation of posteromedial papillary muscle 2

Hvass et al. [31] 10 Papillary muscle sling 3–24

Menicanti et al. [41] 46 Intraventricular papillary muscle imbrication 30

Rama et al. [33] 8 Papillary muscle approximation 7–14

Fig. 5 On left, Coapsys deviceconsists of two epicardial padsconnected by an internal chord.On right is schematic of place-ment of the Coapsys device.(From Mishra et al. [35], withpermission; Courtesy ofKiyotaka Fukamachi, MD)

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completely extrapolated to the ischemic MR population[39].

Conclusions

Ischemic MR relates to mitral leaflet tethering secondary toPM displacement from ischemic LV distortion. Ringannuloplasty has limitations as it does not directly addressthe fundamental mechanism of ischemic MR. A number ofalternate approaches to treating ischemic MR involvingchordal cutting, direct ventricular reverse remodeling, andedge-to-edge repair have demonstrated efficacy in reducingischemic MR, predominantly in small patient series or in

experimental work. Further work is needed to improveventricular-based approaches and in selecting patients whowould benefit from a particular alternate therapy. Inaddition, further follow-up is necessary to determine long-term efficacy.

Disclosure No potential conflict of interest relevant to this articlewas reported.

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