trans catheter therapies for mitral and aortic valve replacement

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doi: 10.1136/hrt.2007.1211292009 95: 148-155 originally published online June 2, 2008Heart

R D Christofferson, S R Kapadia, V Rajagopal, et al.mitral diseaseEmerging transcatheter therapies for aortic and

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Emerging transcatheter therapies for aortic and mitraldisease

R D Christofferson, S R Kapadia, V Rajagopal, E M Tuzcu

Cleveland Clinic Foundation,Cleveland, USA

Correspondence to:Dr E M Tuzcu, Department ofCardiovascular Medicine,Cleveland Clinic, Desk F25, 9500Euclid Avenue, Cleveland, Ohio44195, USA; [email protected]

Accepted 22 April 2008Published Online First2 June 2008

Valvular heart disease is a common malady,affecting millions of people in the United Statesand world wide.1 The incidence of degenerative andfunctional valvular disease is rising with the ageingpopulation and the increase in patients withcongestive heart failure.2 Treatment requires sur-gery, as medical treatment has not providedsignificant advantages for these patients.

Although surgical valve repair or replacement hasbeen well established as a safe and effectivealternative,3 the procedure is invasive and stillcarries a significant morbidity and mortality risk,especially among patients with serious comorbid-ities or very elderly patients. The introduction of

transcatheter valve therapies is intended to reducethe morbidity and mortality of mechanical valveintervention for patients at higher risk. This reviewexamines the new and emerging transcathetertherapies for acquired aortic and mitral valvedisease.

The design and implementation of transcathetervalve therapies differ greatly based on the valveneeding treatment and the approach utilised. Thedominant design of valves developed for the aorticand pulmonic positions are stent-based biopros-thetic valves, advanced over a balloon andexpanded within the original valve, a conduit, ordeployed within a self-expanding stent device.

Approaches to the mitral position are more variedin terms of device designs, including direct leafletmodification (clip or suture), indirect annuloplasty using the coronary sinus, direct annuloplasty andventricular geometric modification.

HISTORY The use of a high-risk target population for thedevelopment of transcatheter technology began inthe 1980s with the use of percutaneous aorticballoon valvuloplasty (PABV) for high-risk surgicalpatients.4 5 Initial enthusiasm for PABV waned asits early haemodynamic benefits were attenuatedby subsequent restenosis. The momentum forpercutaneous treatment of high-risk patients andthe technical lessons learnt from PABV were notlost, however, as coincident with the refinement of balloon valvuloplasty techniques was the develop-ment of a stent-mounted, balloon-expanded bio-prosthetic valve by Andersen et al. This groupreported implantation of such a valve in pigs in1992.6

Human implementation of this technique had towait until 2000, when Bonhoeffer et al reported thefirst use of a stent-mounted bioprosthesis forplacement in a stenotic right ventricle to pulmon-

ary conduit with good immediate results.7

In the year 2002, Cribier and colleagues reported the first

percutaneous aortic valve replacement in humans,which consisted of a stainless steel, balloon-expandable stent, sewn to three pericardial leaflets(fig 1) and advanced by antegrade trans-septalapproach.8 A second self-expandable bovine peri-cardial valve-within-stent design (fig 2) wasintroduced in 2005,9 the earliest and most advancedcompetitor to the initial valve used by Cribier. A large number of companies and device designershave subsequently championed several new devicedesigns soon to be brought to clinical use. A subsequent hybrid surgical/transcatheter approachvia transapical sheath placement has also beendeveloped and is being clinically evaluated (fig 3).

Although the development of percutaneoustechniques for pulmonary and aortic valve replace-ments occurred in parallel, with significant tech-nological cross-over between methods, thedevelopment of transcatheter mitral valve repairhas evolved independently, owing to anatomicaldifferences that limit application of techniquesapplied for semilunar valves. The earliest develop-ment in the field of mitral repair was theconception of an edge-to-edge mitral leaflet repairchampioned by Ottavio Alfieri, an Italian sur-geon.10 The surgical repair consisted of placementof a suture between the anterior and posterior

mitral leaflets, leading to enhanced leaflet coapta-tion and reduction in mitral regurgitation. Although a transcatheter device used to place asimilar suture was initially developed in a animalmodel by Alfieri himself,11 the first human applica-tion was developed by St Goar et al who created aclip device (fig 4) that was advanced antegradeacross the interatrial septum in a proprietary delivery catheter and delivered under echocardio-graphic and fluoroscopic guidance.12 The firsthuman series was reported in 2005 demonstratingsafe and effective use of the clip.13

The use of the coronary sinus to perform anindirect annuloplasty has been proposed mainly formitral regurgitation resulting from functionalabnormalities of the mitral valve due to ventriculardilatation or ischaemic papillary muscle andposterior wall dysfunction. The first implantationof such a device in an animal model was reportedin 2003.14 This device comprised anchor elementsplaced proximally and distally in the coronary sinus, with tension applied to cinch the sinus andmitral annulus (fig 5). Although these experimentsprovided some proof of concept, the initial humanapplication was reported for a different annulo-plasty device in 2006, and consisted of a coronary sinus implant with rods of varying shape and

curvature, used to reshape the coronary sinus.15

Several other device designs have subsequently

Technology and guidelines

148 Heart 2009;95:148–155. doi:10.1136/hrt.2007.121129











patients, with good valve function and a mean (SD) valve areaof 1.5 (0.3) cm2, with an average of 2+ aortic regurgitations.

A hybrid surgical/transcatheter approach has been developedfor high-risk surgical candidates, placing the Cribier–Edwardsvalve via the left ventricular apex (transapical) approach (fig 3).The procedure, performed on a beating heart with rapid pacing,using a full or partial sternotomy, may be of added benefit forpatients with groin access difficulties or aortic disease. The valve isdelivered through a sheath placed by apical puncture, in a similarfashion to the antegrade method. A swine feasibility model wasreported in early 2006, showing all valves to be successfully delivered to the target site, although device migration andparavalvular leak were noted.18 The first human case report was

published in May 2006, detailing successful implantation in a 75- year-old woman who had been deemed too high risk forconventional surgery.17 The procedure was successful, withappropriate prosthetic function and improvement of symptomsat 1-month follow-up. Six-month results have been published onthe initial seven patients undergoing this procedure, showing nointraprocedural mortality, and a 30-day mortality of 14% withgood valve function in the surviving patients.19

The results from a multicentre feasibility study of transfe-moral and transapical approach with the Cribier–Edwards valvein high-risk risk aortic stenosis, REVIVAL (PeRcutaneousEndoVascular Implantation of VALves trial) are not yetpublished. A second multicentre pivotal trial, PARTNER (Placement of AoRtic TraNscathER valves trial) will randomise

one cohort to surgery versus transcatheter valve replacement,and a second cohort to transcatheter replacement versus bestmedical treatment. This study is currently enrolling patientsand the results are eagerly awaited by the interventional andsurgical communities.

CoreValve (Paris, France)The CoreValve (Irvine, California, USA) aortic valve prosthesisconsists of a bioprosthetic porcine pericardial tissue valvesutured in a self-expanding nitinol stent. The stent is 50 mmlong and constructed with a lower section that has high radialforce to open the native valve leaflets, a middle sectioncontaining the valve with the nitinol stent constrained to avoid

the coronary ostia and an upper section that is flared to stabilisethe stent within the aorta and prevent prosthesis migration

(fig 2). The initial device iteration could only be implanted inpatients with an ascending aortic diameter of ,30 mm andrequired a 24 French sheath. Subsequent device iterations haveenabled device delivery by 21 French and lately 18 French sheaths,with an ascending aortic diameter up to 45 mm. Temporary support with extracorporeal membrane oxygenation or a percu-taneous ventricular assist device was used uniformly during

deployment in the earlier experience. With the 18 French system,implantations were carried out without cardiopulmonary supportor general anaesthesia (Ruiz C, personal communication) at theoperator’s discretion. As with the Cribier–Edwards valve,standard balloon valvuloplasty is performed under rapid pacingbefore device placement. The device is advanced across the nativevalve over a stiff wire in the left ventricle and deployed by retraction of the housing sheath. Standard methods are used toassess valve competence and function.

The first patient receiving a CoreValve implant was a 73-year-old woman with severe symptomatic aortic stenosis who hadbeen refused surgery. The approach was via the common iliacartery, and cardiopulmonary bypass was employed during valveplacement. The valve performed well with reduction in meangradient from 45 mm Hg to 8 mm Hg. The patient wasdischarged home without event. In the Siegburg first-in-manstudy, Grube and colleagues reported their results from the first25 patients treated with the CoreValve prosthesis.20 The study reported that 80% of participants were women, with an averageage of 80 years. More than 90% of patients had NYHA class IIIsymptoms, and the median logistic EuroScore was 11%mortality. Vascular access was obtained by surgical cut-downof the subclavian artery in three patients, the common iliacartery in nine patients and the common femoral artery in 13patients (second-generation device). Extracorporeal bypass wasused in all patients during device deployment. Successful valveplacement occurred in 22/25 patients (88%). In one case the

device could not be advanced across the aortic valve and wassubsequently retrieved. However, this patient died 12 h later

Figure 3 The transpical approach for placement of the Cribier–Edwardsvalve, showing the transpical delivery catheter held in place as the valveis positioned before placement.

Figure 4 The endovascular cardiovascular valve repair system and theMitraClip, developed by Evalve (Menlo Park, California, USA) forpercutaneous mitral valve repair.


150 Heart 2009;95:148–155. doi:10.1136/hrt.2007.121129











from acute heart failure. In two patients, the device wasdeployed too high in the aorta, resulting in significantparavalvular regurgitation requiring surgical replacement.

In-hospital mortality was 20%, with one death fromhaemodynamic collapse, one death from disseminated intravas-cular coagulation and one death from sepsis. There was onecerebrovascular accident and major bleeding occurred in sixpatients (24%), although only one of 15 (6.7%) treated with a

second-generation device had major bleeding compared withfive of 10 (50%) treated with the first-generation device.

Although the in-hospital mortality and complication rate washigh, after discharge none of the 18 surviving patients (82%) hadhad a major adverse cardiac event by the 30-day follow-up. Themean (SD) peak aortic gradient had decreased from 69.90(22.96) mm Hg to 22.10 (3.61) mm Hg. Of note, no patientshad severe (3–4+) aortic regurgitation.

Mitral valveThere are four specific approaches to percutaneous repair, thebest-studied being edge-to-edge repair. A second approach placesa cinching device in the coronary sinus to effect favourablechanges in the geometry of the mitral annulus, improving leafletcoaptation. Left ventricular reshaping has also been studied toforce a reduction in septal-to-lateral diameter, which in turnimproves leaflet coaptation, and reduces mitral regurgitation.Finally, annuloplasty can be performed by a transventricular(direct) approach using a suture-based annular cinching device,or by radiofrequency ablation to shrink the annulus.

Edge-to-edge Alfieri pioneered a creative repair, initially developed for anteriorleaflet prolapse, where the free edge of the anterior and theposterior leaflets are sewn together in an attempt to increaseleaflet coaptation, and reduce regurgitation.10 The resultingdouble-orifice mitral valve does not generally cause stenosis, evenwhen combined with an annuloplasty ring. When successful, itappears that the percutaneous edge-to-edge procedure doesproduce the same double-orifice and fibrosing bridge segment asthe surgical procedure, without significant mitral stenosis.21 Twodevices have been developed in this class with significantpreclinical and clinical data to evaluate safety and efficacy. Onedevice, the MOBIUS system by Edwards Lifesciences, has beendiscontinued owing to less than optimal results in preliminary human studies, and will not be discussed here.

Endovascular cardiovascular valve repair systemThe most advanced percutaneous mitral valve repair system hasbeen developed by Evalve Inc (Menlo Park, California, USA),entitled the endovascular cardiovascular valve repair system.This device is implanted by a trans-septal approach using a 24French steerable delivery catheter. A V-shaped clip (MitraClip)is affixed to the anterior and posterior mitral leaflets (fig 4). Theclip grasps the leaflets from beneath the valve, creating a double

Figure 5 Current transcatheter mitral valve designs for implantation inthe coronary sinus. (A) The CARILLON mitral annuloplasty device fromCardiac Dimensions (Kirkland, Washington, USA). (B) The MONARCannuloplasty system from Edwards Lifesciences (Irvine, California, USA).

(C) Schematic representation of the Viacor percutaneous transvenousmitral annuloplasty system (Wilmington, Massachusetts, USA).

Figure 6 The antegrade approach for placement of the Cribier–Edwards percutaneous aortic valve. (A) Fluoroscopic appearance during ballooninflation; (B) the corresponding transoesophageal echocardiographic image.


Heart 2009;95:148–155. doi:10.1136/hrt.2007.121129 151











orifice. Under transoesophageal echocardiographic and fluoro-scopic guidance, the clip is introduced via guide catheter into theleft atrium, and the arms are deployed while the clip is aligned

to the long axis of the heart. The clip arms are rotated untilperpendicular to the line of coaptation and the clip is advancedinto the left ventricle. It is then retracted during systole to graspthe middle scallops of the anterior and posterior valve leaflets.Positioning is confirmed by echo and the clip is locked intoposition. If necessary, the clip can be reopened and detachedfrom the leaflets, and the process can be repeated. Once properly placed, the clip is released from the delivery catheter, remainingattached to the valve leaflets.

Preclinical data from a porcine model was published in 2003. 12

Complete endothelialisation and encapsulation of the clip wasseen with no clip embolisation or thromboembolism. The phase Iprospective, multicentre safety and feasibility trial called

EVEREST (Endovascular Valve Edge-to-Edge Repair Study) wasreported in 2005, with short-term and 6-month results in the first27 patients.13 All patients enrolled were candidates for mitral valvesurgery and had regurgitation that was centred between A2 andP2, meeting prespecified parameters for flail dimensions or leaflettethering to ensure device capture of the leaflets. Most patientshad degenerative valve disease (93%). Successful deployment wasachieved in 24 patients (89%). No prolonged mechanical ventila-tion (.24 h) was required and there were no access sitecomplications requiring surgery. All patients were dischargedhome. Partial clip detachment occurred in three patients (13%), allwent on to elective repair. Two patients underwent elective repairfor severe residual mitral regurgitation (MR), making a total of eight patients (30%) who had successful elective repair orreplacement subsequent to enrolment. Now that the ability toplace two clips has been introduced, residual MR may become lesscommon (fig 7). Of the 27 initial patients, 13 patients (48%)received a clip successfully and continued to have MR severity (2+ at 6 months’ follow-up. One year follow-up on thesepatients shows a durable reduction in MR if initial proceduralsuccess is achieved.22

The primary safety end point of EVEREST I was freedomfrom death, myocardial infarction, cardiac tamponade, cardiacsurgery for failed clip, clip detachment, stroke or septicaemia. A prespecified event rate of 34.4% was expected based oncomparison with surgical event rates; however, only 15% of patients had a major adverse event (three clip detachments

and one permanent stroke). The pivotal phase II trial hasbeen initiated (EVEREST II), comparing the endovascular

percutaneous transvenous mitral annuloplasty approach withstandard cardiac surgery. The study design is a prospective,multicentre, randomised controlled trial with a 2:1 randomisa-

tion to study and control arms, respectively.

Indirect annuloplasty via coronary sinus

In patients without degenerative mitral valve disease, a surgicalannuloplasty alone may be adequate to eliminate MR.23 24 Froma device design perspective, the proximity of the coronary sinusto the mitral annulus may be exploited advantageously to createan indirect form of annuloplasty by cinching up the coronary sinus, favourably modifying the mitral valve annular geometry.This is important as the outward displacement of the annulusdue to ventricular or atrial dilatation is a dominant mechanismof MR. The patient group that may be served by this techniqueis large, consisting mainly of patients with congestive heart

failure with functional MR, for whom there are few satisfactory options.25 The challenges to such an approach are both technical(safe instrumentation of the coronary sinus) and anatomical(proper patient selection for each device).

VIACOR PERCUTANEOUS TRANSVENOUS MITRAL

ANNULOPLASTY

Developed by Viacor (Wilmington, Massachusetts, USA), thepercutaneous transvenous mitral annuloplasty system usescomposite nitinol and stainless steel rods coated with Teflonand plastic, implanted into the coronary sinus. The straight shapeof the distal portion of the rod brings the posterior annulustoward the anterior annulus, resulting in increased leaflet

coaptation and reduced regurgitation (fig 5). Up to threedevices can be implanted. The catheter is capped and implantedsubcutaneously, but can be reaccessed and modified if needed.

In a sheep model of ischaemic MR a single rod resulted inimmediate reduction of MR to 1–2+. No mitral stenosis wasinduced by the device, and left ventricular ejection fraction wasimproved.26 Human implantation has been performed inpatients undergoing open heart surgery for functional MR.27

The single lumen prototype device confirmed the expectedalterations in mitral annular geometry. In five patients who hadattempted implantation of the multi-lumen device, delivery wassuccessful in only four. The reduction in MR was by two gradesin two patients, no change in one patient, and in the final

patient the effect could not be assessed. Further long-termhuman data are pending.

Figure 7 Transoesophageal echocardiographic images of the mitral valve showing a successful percutaneous mitral valve repair, using two EvalveMitraClips. (A) The pre-clip image showing a severe (4+) central regurgitant jet, reduced to mild (trivial to 1+) after clip placement (B).


152 Heart 2009;95:148–155. doi:10.1136/hrt.2007.121129











CARILLON MITRAL CONTOUR SYSTEM

Cardiac Dimensions (Kirkland, Washington, USA) has devel-oped the CARILLON mitral contour system, a fixed-length,double-anchor device (fig 5) advanced by a delivery catheter intothe coronary sinus. After anchor deployment, tension is appliedto the device, resulting in tissue plication. This reduces themitral valve annular diameter and results in decreased MR.

Initial preclinical testing indicated that there are anatomical,

design and safety concerns with coronary sinus devices, as threeof 12 dogs had circumflex coronary ischaemia, causing fatality in two dogs.28 In the seven dogs with successful implantation, at4 weeks there was a reduction in mitral annular size comparedwith those with unsuccessful implant. Subsequent experimentswere done in an ovine model, demonstrating favourable acutehaemodynamic effects and no mortality.14

A multicentre human safety and feasibility study is currently underway in Europe entitled AMADEUS, enrolling patientswith 2–4+ functional MR and NYHA class II–IV. A phase Iinvestigational device exemption study called COMPETENTtargets a similar patient population in the USA and is designedto assess haemodynamics, quality of life and exercise tolerance.

MONARC PERCUTANEOUS TRANSVENOUS MITRALANNULOPLASTY SYSTEM

Although initially called the VIKING system (EdwardsLifesciences), the first version of this device consisted of proximaland distal self-expanding anchors connected by a spring-like‘‘bridge’’ segment. The initial bridge segment had shape-memory properties leading to shortening of the bridge at body tempera-ture. However, bridge element fracture in early human experi-ments15 led to a new design which takes advantage of in vivopolymer degradation within the bridge to create a ‘‘delayed-release’’ effect, allowing bridge shortening over the first 3–6 weeksafter device implantation. This shortening is intended to induce aconformational change in the coronary sinus, extending to themitral annulus, further reducing any post-procedural MR. Theredesigned device is called the MONARC system (fig 5).

Implantation is performed by internal jugular venous accesswith a large-diameter sheath. Initial results for the device inhumans with chronic ischaemic MR showed successful implan-tation in four of five patients, with one failure leading tocoronary sinus perforation. No significant changes in MR gradeor mitral annulus diameter were found at follow-up.15

With additional animal experience showing improved resultswith the new device design, a trial using the MONARC design hasstarted enrolling functional patients with MR. The EVOLUTIONtrial, a multicentre feasibility and safety study in Europe andCanada, has begun with a primary safety objective of procedural

success and 30-day safety, and a 90-day efficacy end point of reduction in MR by one grade. Preliminary results were presentedat Transcatheter Therapeutics (TCT) 2006, showing successfulimplantation in 32/36 patients (89%).29 Preliminary efficacy dataindicate that the efficacy end point (MR reduction by 1 grade at90 days) was met in 9/17 patients analysed (53%).

CLINICAL ROLE

Currently all percutaneous and endovascular mitral and aorticvalve repair devices are available only as investigational devices.This limits the clinical role of transcatheter techniques at present,as patients need to enrol in clinical studies at academic centres touse this technology. Assuming these devices can be shown to

be safe and effective, the dominant debate remains whethertranscatheter devices will play a complementary role or

competitive role to traditional surgery. At present, there remainsa significant difference between the early patient subsets used forinvestigation of transcatheter devices for aortic valve replacementand those used for mitral valve repair. Many patients enrolling inmitral repair studies are surgical candidates, as this technology isseen as less prohibitive of subsequent surgical intervention (the‘‘nothing to lose’’ principle). In addition, although surgery isfeasible for functional MR, the effectiveness of traditional surgical

mitral repair in this setting is not as clear as the effectiveness of traditional surgery for degenerative MR. In contradistinction,aortic valve replacement is the clear ‘‘gold standard’’ for goodsurgical candidates, and any device seeking to compete for thesepatients will have to meet a very high standard. For the foreseeablefuture, patients considered for aortic valve replacement viacatheter-based techniques must be of high surgical risk.However, as device design and delivery improves in both themitral and aortic arenas, the potential exists for early implementa-tion of transcatheter devices before progression to surgical disease,potentially delaying or eliminating the need for surgery. Thisapplication remains highly speculative but is provocative toconsider. There are currently insufficient data to include trans-catheter valve repair or replacement in current clinical guidelines.

CURRENT PROBLEMSThere are still major limitations to transcatheter aortic valvereplacement, the principle limitation being difficulty withvascular access. The initial Cribier antegrade trans-septalapproach was less problematic from an access perspective, asthe vein is more accommodating to a large sheath, but wasplagued by difficulty with device advancement across the mitralvalve, and damage to the mitral valve with resultant severe mitralregurgitation. As a consequence, the retrograde transaorticapproach was used, but this approach is hampered by the needto place a large arterial 24 French (8 mm) sheath, and advance-ment of a bulky device up the aorta and across a stenotic valve.

Although proprietary delivery catheters, longer sheath sizes andmodifications of technique have dealt with some of these issues,there remain a significant number of patients with concomitantvascular disease, preventing a transfemoral approach. A hybridsurgical approach has shown promise in dealing with thisproblem, with a chest incision and transpical access andplacement of a transcatheter valve. Adequate apical closure may be the most challenging aspect of this procedure. Vascular accessappears to be less problematic with the CoreValvedevice, which iscurrently placed via an 18 French introducer.

The Cribier–Edwards device was initially hindered by para-valvular regurgitation owing to poor stent apposition to thevalve annulus, found later to be in part due to device

undersizing. With the development of a larger 26 mm valveand improvement of valve implantation techniques, including asecond balloon inflation if necessary, the concern of paravalv-ular leak seems to be less significant. For both available valves,however, lack of long-term follow-up limits our ability to assessvalve durability, in particular in patients requiring a secondballoon inflation to eliminate paravalvular leak. Compromise of the coronary arteries has occurred by native valve leafletocclusion of the coronary ostium, leading to death if notimmediately recognised and treated. This problem can beminimised by early recognition of unfavourable anatomy, butis also being addressed by subsequent valve design character-istics. Device migration at the time of implantation has occurredin a very few patients but with improved procedural technique

and larger valve size, this is unlikely to remain a significantproblem.


Heart 2009;95:148–155. doi:10.1136/hrt.2007.121129 153











The principal limitation with current mitral valve repairtechniques is the lack of true approximation to surgicalapproaches, upon which transcatheter approaches are based.Surgeon have at their disposal both leaflet repair andannuloplasty techniques when approaching a given valve lesion,but no transcatheter technique can perform both. It is stilldebated whether isolated surgical edge-to-edge repair is effective

and this technique has only been studied in a small number of patients. It remains to be seen if this will limit applicability of percutaneous mitral valve repair by edge-to-edge technique. Noclip embolisation with the MitraClip has been seen to date, butpartial clip detachment remains a limitation. The overall resultsof transcatheter edge-to-edge repair when compared withhistorical surgical controls may not be as effective, althoughthe surgical literature consists of single-centre series with noechocardiographic core-laboratory controls. Among patientswith good early results, the transcatheter edge-to-edge repairappears to be durable up to 2 years. More data are needed toconfirm the long-term durability of this technique.

One specific criticism of the edge-to-edge repair by Evalve isthe prolonged procedure time and steep learning curve for deviceimplantation, which may limit its widespread application.However, the investigators in the EVEREST I study havecountered by publishing, in abstract form, data that indicatethat individual operators have a much shorter implantationtimes on subsequent procedures (134 minutes) than with thefirst procedure (181 minutes).30 A second concern raised hasbeen whether the fibrosis accompanying the clip procedurewould eliminate subsequent surgical options. The early dataindicate that this is not the case, as all six patients undergoingmitral valve surgery after the clip was placed have been able tohave the clip removed uneventfully, with five valve repairs andone valve replacement.31

The indirect annuloplasty technique using the coronary sinus

has shown promise but also has significant anatomicallimitations. Choure et al demonstrated that the mitral annulus

is not always in close proximity to the coronary sinus,potentially limiting its usefulness in such patients.32 Thecoronary sinus covers about 50% of the mitral annulusperimeter and 80% of the posterior intertrigonal distance.33 Inaddition, the proximity of the coronary sinus to the leftcircumflex coronary artery has led to coronary compromise asthe left circumflex crosses below the coronary sinus in nearly half of cases.32 33 Compromise of the left circumflex coronary

artery can result in significant complications, making coronary angiography mandatory during implantation and potentially limiting global applicability. Imaging techniques includingcardiac CT, angiography and echocardiography may be helpfulin defining these relationships and matching the patient withthe proper approach. The long-term safety of instrumenting thecoronary sinus is unknown, including risk for thrombosis,perforation or device displacement, and it remains to be seen if these devices will interfere with the need for other devices in thecoronary sinus, such as biventricular pacing. One majormechanism of failure with surgical repair is progressive annulardilatation; it remains to be seen if this will also plague thetranscatheter repair devices.

For the remaining mitral strategies, including direct annulo-plasty or ventricular reshaping, insufficient clinical data arecurrently available to evaluate their device-specific limitations.

FUTURE DEVELOPMENT Additional aortic valve replacement device designs are underdevelopment (fig 8), with the major advance being retrievablevalves (AorTx, Redwood City, California, USA; Sadra Lotus

Valve, Sadra Medical, Campbell, California, USA) that willallow repositioning of the device if deployment is suboptimal.

Another device design uses an inflatable cuff to enable precisevalve placement, with infusion of cementing material into thevalve to replace the air once accurate deployment has beenobtained (Direct Flow Medical, Palo Alto, California, USA). In

addition, there are advances in prosthetic valve construction,including an all-metal prosthesis that is made of nitinol mesh,not requiring anticoagulation (PercValve technology), andpolymer-based leaflets to allow for smaller device size (Elast-Eon AorTech). These and other advances will lead topercutaneous aortic valves that are more deliverable, preciseand safe.

In the mitral valve arena, several additional devices are in thepreclinical or early clinical stages of testing, and deservemention. Another coronary sinus annuloplasty device underdevelopment by St Jude Medical (St Paul, Minnesota, USA)performs an asymmetric coronary sinus annuloplasty specifi-cally for asymmetric MR around the P2 and P3 scallops of the

mitral valve. There are several preclinical devices intended toperform a transventricular (retrograde) direct annuloplasty—notably, the Mitralign Direct Annuloplasty System (Mitralign,Salem, New Hampshire, USA), the Guided Delivery Systems

AccuCinch annuloplasty system, and the QuantumCor radio-frequency system (Lake Forest, California, USA).

Another significant approach to reduction in MR involvesindirect modification of the mitral valve geometry by placementof a tethering chord on either side of the ventricle and reshapingthe left ventricle, thus reducing MR. The effect is termed septal-to-lateral cinching and creates a more favourable geometricalignment of the mitral leaflets by modifying the shape of theventricle. A surgical implant called Coapsys (Myocor, MapleGrove, Minnesota, USA) is already receiving clinical testing in

the surgical setting, with good results; a percutaneous version of the device is also under development. The Percutaneous Septal

Figure 8 Emerging transcatheter aortic valve designs. (A)The SadraLotus Valve (Sadra Medical, Campbell, California, USA), which has theadvantage of being repositionable. (B) The PercValve aortic technologyusing an all-metal prosthesis of nitinol mesh, requiring noanticoagulation. ( C) The Direct Flow Medical Valve which uses inflatablecuffs for precise positioning.


154 Heart 2009;95:148–155. doi:10.1136/hrt.2007.121129











Sinus Shortening (PS3) System, developed by Ample Medical(Foster City, California, USA) works under a similar principle,although it tethers the interatrial septum with the coronary sinus and cinches above the annulus as opposed to the Coapsysdevice that cinches the ventricle.

In addition to the treatments mentioned above for acquiredaortic and mitral valve disease, it may be useful to mention theemergence of transcatheter therapies for acquired tricuspid valve

disease, including the development of a semilunar valvereplacement, to date implanted only in an animal model.

CONCLUSION

Transcatheter valve intervention remains an exciting newprospect for treatment of valvular heart disease. There issignificant impetus from patients, doctors and industry forthe development and success of such techniques. Initialattempts at transcatheter aortic valve replacement have metwith considerable success in a highly selected populationtargeted for this treatment, although to date there have beenno randomised multicentre trials in comparison with traditional

surgery. Until such data are obtained, these treatments cannotbe routinely recommended. Although the current technologicallandscape of transcatheter aortic valve replacement is domi-nated by stent-based valves, an impressive expansion of technological approaches promises to improve device deliver-ability and patient outcomes, bringing into question the use of such devices in more routine-risk patients. The field of devicedesign of mitral valve repair is more wide open, perhaps becauseof the complex physiology of the mitral valve and the inability of current device designs to completely approximate surgicalrepair. The mitral valve devices appear to be less prohibitive of future surgical intervention, and as such are already underinvestigation in comparison with standard surgical techniques.

The early successes of transcatheter valve therapies areprovocative but remain to be shown effective before full clinicalimplementation. Lack of long-term clinical data, as well assignificant device design and delivery problems prevent currentapplication of these techniques. The learning curve for deviceimplantation remains steep and a true multidisciplinary approach including interventional cardiologists, cardiothoracicsurgeons, imaging experts and anaesthesiologists will benecessary for safe and effective use of these devices. However,it appears likely that percutaneous transcatheter valve deviceswill play a significant role in the future treatment of valvularheart disease.

Competing interests: None declared.

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trans catheter therapies for mitral and aortic valve replacement

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