Percutaneous mitral valve annuloplasty for functional mitral regurgitation: acute results of the first patient treated with the Viacor permanent device and future perspectives

Cardiovascular Revascularization Medicine 11 (2010) 265.e1–265.e8

Percutaneous mitral valve annuloplasty for functional mitral regurgitation:acute results of the first patient treated with the Viacor permanent device

and future perspectives☆

Olivier F. Bertranda,⁎, François Philippona, André St Pierreb, Can M. Nguyena, Éric Larosea,Sylvie Bilodeauc, François Dagenaisd, Éric Charbonneaud,

Josep Rodés-Cabaua, Mario Sénéchala

aDepartment of Cardiology, Quebec Heart and Lung Institute, Quebec City, CanadabDepartment of Anesthesiology, Quebec Heart and Lung Institute, Quebec City, Canada

cDepartment of Imaging, Quebec Heart and Lung Institute, Quebec City, CanadadDepartment of Cardiac Surgery, Quebec Heart and Lung Institute, Quebec City, Canada

Received 2 November 2009; accepted 9 November 2009

Abstract Background: There is a need to develop less invasive techniques to manage moderate or severe

☆ O.F. Bertrand aFoundation for Health

⁎ Correspondingtaire de Cardiologie eQuebec, Canada G1V6504544.

E-mail address: o

1553-8389/09/$ – seedoi:10.1016/j.carrev.2

functional mitral regurgitation in patients at high surgical risk.Objective: We report the acute results of the first patient treated with the permanent Viacorpercutaneous transvenous mitral annuloplasty (PTMA) device in North America, introduce thePTOLEMY-2 protocol, and briefly discuss the current status of transvenous mitral valve techniques.Case report: After several episodes of pulmonary edema, an 87-year-old woman was referred forhemodynamic evaluation. Angiography revealed normal coronary arteries and severe mitralregurgitation. Baseline echocardiography showed severe (4+) functional mitral regurgitation. Thecoronary sinus was cannulated with a 9.5-Fr introducer from a left subclavian approach. After distalpositioning of a coronary wire, the 7-Fr PTMA Viacor catheter was advanced to the anteriorinterventricular vein. Two 130 g/cm rods were then inserted resulting in an acute and dramaticreduction in mitral regurgitation as assessed by continuous transoesophageal echocardiography andwhich was associated with a sudden rise in arterial blood pressure. The next day, transthoracicechocardiogram showed a significant reduction in effective regurgitant orifice area (EROA) from 41to 10 mm2. The patient was discharged home the day following the procedure without complication.In accordance with the PTOLEMY-2 protocol, she will undergo 3-D transthoracic echocardiograms,quality of life assessments, and 6-min walk tests at regular intervals for the next 5 years.Conclusion: PTMA is a promising technique for the treatment of severe mitral regurgitation inselected patients. Further ongoing research will determine the predictors of success and long-termsafety and performance of this technique.© 2010 Elsevier Inc. All rights reserved.

Keywords: Percutaneous; Mitral valve annuloplasty; Mitral regurgitation; Device

nd E. Larose are research scholars from the QuebecResearch.author. Interventional Cardiology, Institut Universi-t de Pneumologie de Québec, 2725, chemin Ste Foy,

4G5. Tel.: +1 418 6503325x5947; fax: +1 418

[email protected] (O.F. Bertrand).

front matter © 2010 Elsevier Inc. All rights reserved.009.11.010

1. Introduction

Functional mitral regurgitation is frequently associatedwith heart failure and influences its long-term prognosis. InNorth America, 15–20% of patients suffering from heartfailure have moderate to severe mitral regurgitation. After

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265.e2 O.F. Bertrand et al. / Cardiovascular Revascularization Medicine 11 (2010) 265.e1–265.e8

myocardial infarction, up to 19% of patients have ischemicmitral regurgitation (IMR) [1]. The pathophysiology of IMRresides in the remodeling of the left ventricular geometry,papillary muscles displacement, mitral annulus dilatation,

Fig. 1. CT scan with three-dimensional reconstruction and colorization of native cdistance between coronary sinus and mitral annulus was measured at 20 mm.

and leaflet tethering [2]. These changes hamper normalleaflet coaptation.

Surgical management of IMR involves most of the timerestrictive mitral annuloplasty with coronary artery bypass

oronary arteries, coronary sinus, and mitral annulus. In this case, maximum

265.e3O.F. Bertrand et al. / Cardiovascular Revascularization Medicine 11 (2010) 265.e1–265.e8

graft surgery [3]. However, surgery can be associated withsignificant risks of mortality and has not been shown topositively impact long-term follow-up [3]. These findingshave been correlated with the persistence or recurrence ofsignificant mitral regurgitation after the operation. Besidesthe increased risks of mortality, moderate or severe IMRsignificantly impairs the quality of life of patients and maylead to repeat hospitalizations for acute pulmonary edema.Hence, several percutaneous techniques have been recentlyproposed to reduce functional mitral regurgitation withfewer risks than conventional surgery. Among thesedevices, the Viacor percutaneous transvenous mitralannuloplasty (PTMA) permanent device consists of a 7-Frthee-lumen catheter which is advanced into the coronary

Fig. 2. Per-procedure transoesophageal echocardiogram before (A) and immediatelyof the left atrium due to the pressure exerted by the PTMA catheter.

sinus followed by the insertion of one to three nitinol rodswhich stiffen the catheter. Temporary use as a bridge tosurgery has been previously reported [4,5]. In this article,we describe patient selection, the procedure, and the earlyresults of the first permanent implantation in NorthAmerica of the PTMA catheter in a patient with severenonischemic mitral regurgitation.

2. Case report

An 87-year-old woman was initially referred to thecatheterization laboratory for diagnostic evaluation. Hercardiovascular history revealed that she had been hospital-

after (B) PTMA device implantation. Observe the bulging of the lateral wall


ized repeatedly over the previous year for pulmonary edema.Outside these acute episodes, she had remained in NYHAClass II heart classification. She had no cardiovascular riskfactors and her medical history was significant for a low-grade non-Hodgkin lymphoma treated by chemotherapy in1993. The patient was in sinus rhythm with normal QRSwidth. Diagnostic angiography showed normal coronaryarteries with a right dominant circulation. Left ventriculo-graphy showed mildly reduced ejection fraction withmoderate mitral regurgitation. Transthoracic echocardiogra-phy showed a dilated left atrium with a grade 4+ mitralregurgitation. The mechanisms of mitral regurgitation were

Fig. 3. Left cranial (A) and lateral (B) views showing the PTMA device withtwo rods. Observe the proximal marker at the ostium of the coronary sinusand the distal marker in the anterior interventricular vein.

Fig. 4. Left coronary angiography showing normal coronary flow in thecircumflex artery.

explained by annular dilatation at 40 mm (as measured in afour-chamber view) and restriction of both leaflets caused byleft ventricular dilatation (tenting area of 2.1 cm2, acoaptation distance of 8 mm, and a posterior leaflet angleof 20°) [6]. According to Carpentier's classification, themechanism of mitral regurgitation was of type I. Mitralregurgitation was graded 4+ with an effective regurgitantorifice area (EROA) of 41 mm2. The left atrium was severelydilated at 70 ml/m2, and systolic pulmonary artery pressurewas estimated at 50–55 mmHg. Considering a Euroscore of10.84%, she was considered for PTMA and written consentwas obtained for participation in the PTOLEMY-2 study.Multislice computed tomography (MSCT) was obtained toassess the anatomical relationships between the coronarysinus, the mitral apparatus, and the circumflex artery. Datawere sent to M2S (West Lebanon, NH, USA) for 3-Dreconstruction and color rendering (Fig. 1). Interestingly, thecoronary sinus was located significantly cranial to the mitralapparatus at a maximum distance close to 2 cm.

During the procedure, the patient was intubated andsedated under general anesthesia to allow real-timetransoesophageal echocardiography. The procedure wasperformed in a bi-plane angiography suite with one planemoved from left anterior oblique with caudal angulation toanterior–posterior and right anterior views, and the secondplane remained in lateral view. Left coronary angiographywas performed from the left radial artery. Venous accesswas obtained from the left subclavian approach; a 9.5-Frdelivery catheter was positioned at the origin of thecoronary sinus ostium using a standard electrophysiologydeflectable catheter. With the use of an inflatable balloon,contrast injection at low pressure was performed tovisualize the coronary venous system's detailed anatomy.A 0.035-inch hydrophilic wire (Magic wire, Boston


Scientific) was positioned distally in the anterior interven-tricular vein. Then, the 7-Fr PTMA catheter was advancedover the wire under fluoroscopic guidance until it reachedthe proximal part of the anterior interventricular vein. Two130 g/cm rods were introduced into the PTMA catheter andproduced immediate and dramatic reduction of the mitralregurgitation as assessed by transoesophageal echocardiog-raphy (Fig. 2A and B). At that time, systolic blood pressurerose suddenly from 120/60 to 180/80 mmHg and anitroglycerin intravenous drip and an intravenous furose-mide 40 mg were administered to control the bloodpressure. After verifying that the proximal marker of thePTMA catheter was positioned at the ostium of thecoronary sinus, the 9.5-Fr introducing catheter was slitand slowly removed under fluoroscopic guidance to avoidany displacement of the PTMA catheter (Fig. 3A and B).Final angiography confirmed no external compression ofthe circumflex artery (Fig. 4). The proximal part of the

Fig. 5. Apical views from transthoracic echocardiogram showing severegrade 4+ mitral regurgitation prior to PTMA procedure (A) and residualgrade 2+ mitral regurgitation 24 h after (B).

PTMA catheter was sutured to the pectoral muscle similarlyto a pacemaker pocket to prevent later dislodgment. Afterthe procedure, the patient was monitored in the recoveryroom for 2 h and was then transferred to the coronary carestepdown unit for overnight monitoring. The patientunderwent 24-h postprocedure control echocardiography,which showed grade 2+ moderate residual mitral regurgi-tation with an EROA reduction from 41 to 10 mm2; mitralgeometry was as follows: annular dilatation of 36 mm,tenting area of 1.5 cm2, coaptation distance of 5 mm, andposterior leaflet angle of 20°. The patient was dischargedhome the day following the procedure without

Fig. 6. Chest X-rays 24 h after PTMA procedure; (A) anterior–posterior and(B) lateral views.

Fig. 7. Thirtieth-day CT scan showing the PTMA catheter in the coronarysinus which is located above the mitral apparatus.


complication (Fig. 5A and B, Fig. 6). No ECG changes orrise in cardiac biomarkers was observed. At 30 days,MSCT was performed (Fig. 7). At 6-month follow-up, thepatient has remained in NYHA Class I with no furtherhospitalization for pulmonary edema.

3. Discussion

Despite current guidelines on valvular diseases, a significantnumber of patients with severe mitral regurgitation are deniedor simply not referred for surgery [7]. Reasons include the highincidence of comorbidities, older ages, and lower ejectionfraction frequently associated with mitral regurgitation.

Mitral valve function is highly complex and depends on theproper relationships between the valve leaflets, the mitralannulus, the subvalvular apparatus, the papillary muscles, andthe left ventricular geometry. Accordingly, percutaneoustechniques do not target severe organic mitral regurgitation inwhich the primary causes are due to intrinsic mitral valveabnormalities such as leaflet prolapse, chordal rupture, orfusion. Functional mitral regurgitation can be found most oftenwith ischemic or idiopathic cardiomyopathy. Although themitral apparatus may be anatomically normal, mitral regurgi-tation results from dilatation of the left ventricular cavity and ofthe mitral apparatus (Carpentier's mitral regurgitation type I)and tethering of the mitral leaflets (Carpentier's mitralregurgitation type IIIb). As a result of these abnormalities,mitral leaflets mal-coaptation and regurgitation occur. Althoughannular dilatation is common in ischemic and idiopathiccardiomyopathies, it seems that asymmetric tethering ispredominant in IMR. At this stage, it remains to be determinedwhether ischemic or nonischemic functional mitral regurgita-tion will be more amenable to PTMA. Furthermore, cardiacresynchronization therapy has also become an importanttherapeutic option and it has recently been proposed that both

techniques could be complementary in selected cases [8–10].Lastly, similarly to surgical repair, it will be required tocritically assess whether PTMA may affect survival or onlyaffect patient's quality of life and related issues.

Currently, two main percutaneous treatment strategies havebeen developed and have undergone clinical testing. Onetechnique, which is based on the Alfieri principle, aims tosuture directly the two leaflets' tips; hence structural andfunctional mitral regurgitation can be tackled [11,12]. Thisedge-to-edge repair of mitral leaflets creates a double orificemitral valve. Despite strict inclusion criteria, a first feasibilityand safety study (EVEREST I) has been completed in 107patients and mid-term follow-up results have been reported[11]. A total of 50 (66%) among 76 successfully treated patientswere free from death, mitral valve surgery, and mitralregurgitation grade N2+ at 12 months. A pivotal Phase IIItrial comparing the Evalve clip to mitral valve repair orreplacement is underway, and the REALISM registry iscontinuing in US sites. Several other systems combiningvarious forms of annuloplasty or aiming to reduce the lateral toseptal distance of the mitral annulus are undergoing intensepreclinical evaluation and will be soon tested in feasibilitystudies in humans.

There are presently three different systems that insertpermanent implants in the coronary sinus in order to modifythe shape of the mitral annulus. The Edwards Monarc systemis based on a distal and a proximal stent-like anchor which areconnected by a shortening spring-like nitinol bridge. Thepostprocedure reduction in the distance between the distaland proximal anchors leads to an anterior displacement of theposterior part of the annulus, hence reducing the septal–lateral distance of the mitral annulus. Limited experience hasbeen reported so far, and technical modifications of thedevice have been required after initial human experience [13].The Evolution I study has been completed in 55 patients, andthe Evolution II study designed as a nonrandomizedmulticenter prospective registry is in planning. The Carillonmitral contour system also uses two nitinol-based anchorsdesigned as double helices connected by a curved nitinolbridge. Traction on the bridge creates a reduction in septal–lateral mitral annulus dimensions, leading to a reduction inmitral regurgitation. In contrast to the Monarc device, thesystem can be completely removed if traction on the bridgecreates coronary compression or if the anchors remainunstable. After completion of the AMADEUS and TITANfeasibility and safety studies in Europe, the system hasrecently received CE market approval [14,15].

The Viacor PTMA device includes a three-lumen 7-Frcatheter with a soft silicone distal tip to be advanced to theproximal part of the anterior interventricular vein. Up tothree rods with different stiffness can then be inserted intothe delivery catheter. Stiffening of the catheter produces asignificant pressure, which is maximal on the posterolateralpart of the mitral annulus [16]. This results in a reduction inthe anterior–posterior diameter of the mitral annulus, henceincreasing leaflet coaptation. In an IMR animal model, the


device has demonstrated a significant reduction in septal–lateral diameter, in mitral valve tenting area, and in mitralregurgitation [17]. Recently, prior to planned surgery, thedevice was temporarily implanted in three patients withsuccess. After implantation, the EROA was reduced from25±6 to 7±3 mm2, the regurgitant volume from 45±24 to13±7 ml, and the anterior–posterior diameter from themitral annulus from 41±4 to 35±2 mm [4]. Since 2002, thedevice has undergone several technical improvements priorto its current design [5]. Initial feasibility and safety resultsfrom PTOLEMY-1 have been recently reported [5]. FromApril 2006 to November 2007, PTMA procedures wereattempted in 27 patients. Temporary PTMA implants weresuccessful in 19 of 27 patients with a reduction in mitralregurgitation from grade 3.2±0.6 to 2.0±1.0. Afterpermanent implantation in nine patients, four deviceswere later removed for device migration and/or lack ofsignificant effect on mitral regurgitation.

PTOLEMY-2 is being performed in selected sites inEurope and Canada. The study will include 60 patients N50years of age in NYHA Class II to IV with functional mitralregurgitation (EROA≥20 mm2, regurgitant volume≥30 ml/beat, or regurgitant fraction ≥30%) and left ventriculardysfunction (25%bLVEFb50%). The primary safety endpoint will be the 30-day freedom from device-related or majoradverse events including death, myocardial infarction,emergency cardiac surgery, and stroke. The primary efficacyend point is the quantitative mitral regurgitation reduction at12 months as assessed by an independent echocardiographycore laboratory (Duke University: Dr. P. Douglas). A mitralregurgitation improvement score will be defined as EROAreduction of ≥10 mm2 from baseline or ≥15 ml regurgitantstroke volume or ≥10% regurgitant fraction. Each of theseparameters will be counted as a 1.0-point improvement scoreinmitral regurgitation severity. Efficacy success of the PTMAdevice will be defined as a 1.0-point minimum improvementscore in 50% of implanted patients at 12 months.

Although PTMA procedures are intended to fill atherapeutic gap in patients with moderate or severefunctional mitral regurgitation not amenable for surgicalvalve replacement or repair, the challenges to develop safeand effective techniques remain numerous. All existingtechnologies have their potential benefits and limitations,and, therefore, it is becoming increasingly suggested thatcombined techniques may be required in carefully selectedpatients. While percutaneous aortic valve techniques re-quired a decade to develop and have already become widelyused, PTMA techniques to reduce mitral regurgitation arestill at the early stages of development.

Acknowledgments

We are thankful to L. Bilodeau, M.D., and to the seniorscientists from Viacor for technical expertise in performingthis PTMA procedure.

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Percutaneous mitral valve annuloplasty for functional mitral regurgitation: acute results of the first patient treated with the Viacor permanent device and future perspectives