Images and Case Reports in Interventional Cardiology
`
`First-in-Human Case of Transfemoral CardiAQ
`Mitral Valve Implantation
`Lars Søndergaard, MD, DMSc; Ole De Backer, MD, PhD; Olaf W. Franzen, MD;
`Susanne J. Holme, MD; Nikolaj Ihlemann, MD, PhD; Niels G. Vejlstrup, MD, DMSc;
`Peter B. Hansen, MD; Arshad Quadri, MD
`
`Major advancements have been made in transcatheter
`
`aortic and pulmonary valve implantation during the
`past decade. However, transcatheter mitral valve implantation
`(TMVI) poses different challenges because of the complex-
`ity of the mitral valve apparatus. Although several companies
`are attempting to develop transcatheter approaches for mitral
`valve repair, these technologies may have limited applicabil-
`ity because of the heterogeneous nature of the disease and,
`to date, this strategy has had a difficult time demonstrating
`the efficacy that is equivalent to surgical approaches. In this
`report, we describe the first-in-human percutaneous trans-
`femoral-TMVI, which was performed at Rigshospitalet in
`Copenhagen, Denmark on June 12, 2012 using a dedicated
`device.
`
`Case
`An 86-year-old male with symptomatic mitral regurgitation
`(MR) was referred for interventional treatment. Transesopha-
`geal echocardiography showed severe MR (grade, 3+ to 4)
`because of mitral annular dilatation and a severely restricted
`posterior mitral leaflet in a dilated left ventricle (LV) with
`ejection fraction 40%. The patient was declined for mitral
`valve surgery (Society of Thoracic Surgeons score, 31.9%)
`and for MitraClip treatment because of a too large systolic
`coaptation gap. An informed consent from the patient and
`approval from the Danish National Board of Health were
`obtained for this first-in-human TMVI procedure using the
`first-generation CardiAQ valve (CardiAQ Valve Technologies,
`Irvine, CA; Figure 1).
`The procedure was performed under general anesthesia.
`In the right groin, access was obtained in the femoral vein
`(2 access sites—the highest for transseptal puncture and the
`delivery system and the lowest for a steering snare) and in
`the femoral artery (2 access sites—one for a triloop snare and
`one for a pigtail for LV angiograms; Figure 2A). Through the
`lower venous access, a steering snare was placed around the
`wire from the higher venous access; this snare was later used
`to steer the delivery system in the left atrium (Figure 2B). After
`
`standard transseptal puncture, a HiWire (Cook, Bloomington,
`IL) was maneuvered through the mitral annulus and LV cavity
`to the descending aorta. By means of a triloop snare intro-
`duced into the femoral artery, this HiWire was then captured to
`establish an arteriovenous loop. To ensure that the HiWire was
`not caught in the mitral apparatus, a 14-mm inflated Tyshak
`balloon (NuMED Inc, Hopkinton, MA) was tracked on the
`wire from the left atrium to the LV outflow tract and back,
`the so-called Copenhagen manoeuvre (Figure 2D). Once con-
`firmed that the balloon could move freely, the HiWire was
`exchanged for a custom-made polytetrafluoroethylene-coated
`nitinol wire within a long 4-Fr catheter. The wire was snared
`and pulled out of the femoral arterial sheath to reestablish the
`arteriovenous loop.
`The venous introducer sheath (30 Fr) was placed after
`gradual dilation of the highest venous access site, and the
`steering snare was positioned at the middle of the nose cone
`of the delivery system (Figure 2E). After smoothly advanc-
`ing the delivery system through the atrial septum, pulling
`on the steering snare redirected the system toward the mitral
`valve. Once positioned into the LV (Figure 2F), the snare was
`released from the nose cone and pulled back to the shaft of the
`delivery system.
`The landing zone between the mitral plane and the tip of
`papillary muscles was determined by transesophageal echo-
`cardiography and a left ventriculogram. By manipulating
`the arteriovenous loop and the delivery system, the CardiAQ
`valve could be positioned perpendicular to the mitral annular
`plane. A staged deployment allowed exposure of the ventricu-
`lar anchors and careful positioning to capture the posterior
`mitral leaflet (Figure 2G). Finally, the anterior mitral leaf-
`let was captured by pulling on the arteriovenous loop from
`the arterial side, before complete release of the TMV device
`(Figures 2H and 3). After angiographic and transesophageal
`echocardiographic confirmation of a well-positioned and
`well-functioning prosthesis, the delivery system was retracted
`and the resultant atrial septal defect was closed by a 16-mm
`Amplatzer Septal Occluder (St Jude Medical, St Paul, MN).
`
`Received January 16, 2015; accepted June 22, 2015.
`From the Departments of Cardiology (L.S., O.D.B., O.W.F., N.I., N.G.V.), Cardiothoracic Surgery (S.J.H.), and Anaesthesiology (P.B.H.), Rigshospitalet,
`Copenhagen, Denmark; and CardiAQ Valve Technologies, Irvine, CA (A.Q.).
`The Data Supplement is available at http://circinterventions.ahajournals.org/lookup/suppl/doi:10.1161/CIRCINTERVENTIONS.115.002135/-/DC1.
`Correspondence to Lars Søndergaard, MD, DMSc, Kardiologisk Klinik B 2011, Rigshospitalet University Hospital, Blegdamsvej 9, 2100 Copenhagen,
`Denmark. E-mail Lars.Soendergaard.01@regionh.dk
`(Circ Cardiovasc Interv. 2015;8:e002135. DOI: 10.1161/CIRCINTERVENTIONS.115.002135.)
`© 2015 American Heart Association, Inc.
`Circ Cardiovasc Interv is available at http://circinterventions.ahajournals.org
`
`DOI: 10.1161/CIRCINTERVENTIONS.115.002135
`
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` Transfemoral Mitral Valve Implantation
`
`As no previous experience with a TMVI procedure in
`man existed, extracorporeal circulation support was shortly
`used during valve deployment (15 minutes) to ensure hemo-
`dynamic stability. Considering the smooth valve deployment,
`this extracorporeal circulation support seemed post hoc not
`essential. Procedure and fluoroscopic times were 140 and 32
`minutes, respectively, and 145 mL of contrast dye was used.
`The patient made an uneventful recovery the first 24 to
`48 hours, and a well-functioning TMV prosthesis was con-
`firmed by echocardiography at 24 and 48 hours after TMVI
`(Figure 4). However, the patient died 68 hours post procedure
`because of a systemic inflammatory response syndrome, pos-
`sibly triggered by the use of the extracorporeal assist device.
`Importantly, autopsy did not show significant pathology or
`malfunction of the TMV prosthesis and excluded perforation
`of adjacent structures.
`
`Discussion
`TMVI revolutionized the management of valvular aortic ste-
`nosis by providing a safe and efficacious alternative to sur-
`gical valve replacement in higher-risk patients. Similarly, the
`risk and uncertain benefit of mitral valve surgery in high-risk
`patients with severe MR have driven the search for new trans-
`catheter mitral valve therapies.
`The structure and function of the mitral valve, however,
`are far more complex than the aortic valve. This complexity
`poses many challenges in the development of TMVI systems:
`a larger and D-shaped annulus, the lack of a fibrous/calcified
`annular structure, a complex subvalvular apparatus, as well
`as the proximity of the mitral valve to the LV outflow tract,
`circumflex coronary artery, and coronary sinus. Interestingly,
`these challenges have been addressed in different ways, for
`example, by introducing a D-shaped stent design, annular ver-
`sus apical anchoring, or a large inflow sealing area.1–4 Also the
`CardiAQ prosthesis has been optimized since its first implant,
`as described in this report. The second-generation CardiAQ
`valve is built on the company’s proprietary method for anchor-
`ing the implant through leaflet engagement, chordal preserva-
`tion, and annular attachment, while offering improved flow
`properties and a novel feature for the prevention of paraval-
`vular leaks. Moreover, the delivery system was optimized and
`made user-friendlier. In the first half of 2014, this second-
`generation CardiAQ valve has been successfully implanted at
`our center in 3 patients. In all cases, the TMVI procedures
`were performed by transapical approach (Figure I in the Data
`Supplement).1
`The transapical approach seems to be more straightfor-
`ward than the transfemoral approach as it demands less pro-
`cedural steps. Moreover, obtaining axial alignment with the
`delivery system is much easier in the transapical procedure
`when compared with the transfemoral procedure. However,
`with this first-ever transfemoral-TMVI case described in this
`report, we demonstrate that TMVI is feasible by true percu-
`taneous approach and with the use of standard interventional
`
`techniques. This approach could be of value when intending to
`treat even the frailest patients and could theoretically result in a
`shorter hospital length of stay. Moreover, this approach avoids
`inducement of further akinesia in LV wall function, which is a
`possible risk with a transapical approach, and avoids potential
`complications associated with the thin and friable tissue of the
`LV wall common among secondary MR patients with severely
`enlarged ventricles.
`In April 2015, CardiAQ Valve Technologies received
`a Food and Drug Administration Investigational Device
`Exemption approval to conduct an early feasibility study.
`This study will enroll ≤20 patients and will involve both the
`transfemoral (n=10) and TA (n=10) TMVI systems. Also
`Neovasc Inc (Tiara valve),2 Tendyne Inc (Tendyne valve),3 and
`Edwards LifeSciences (Fortis valve)4 performed their first-in-
`human TA-TMVI procedures in 2014 and recently received
`Food and Drug Administration approval for early feasibility
`trials, indicating that the TMVI technology has reached a new
`stage in its development.
`
`Conclusions
`Although major challenges remain before transforming TMVI
`into routine clinical practice, this procedure may become an
`important therapeutic alternative for patients with severe MR
`who are high-risk candidates for open mitral valve surgery. In
`this case report, we demonstrate that transfemoral-TMVI can
`be successfully achieved by the use of standard interventional
`techniques.
`
`Disclosures
`Dr Søndergaard is proctor for Medtronic (Minneapolis, MN) and
`received a research grant from St Jude Medical (St Paul, MN). Dr
`Franzen is proctor for and received speaker honoraria from Abbott
`Vascular (United States). Dr Quadri is the founder and co-owner of
`CardiAQ Valve Technologies (Irvine, IL). The other authors report
`no conflicts.
`
`References
` 1. Søndergaard L, Brooks M, Ihlemann N, Jonsson A, Holme S, Tang M,
`Terp K, Quadri A. Transcatheter mitral valve implantation via transapical
`approach: an early experience [published online ahead of print February
`3, 2015]. Eur J Cardiothorac Surg.
` 2. Cheung A, Webb J, Verheye S, Moss R, Boone R, Leipsic J, Ree R, Banai
`S. Short-term results of transapical transcatheter mitral valve implanta-
`tion for mitral regurgitation. J Am Coll Cardiol. 2014;64:1814–1819.
`doi: 10.1016/j.jacc.2014.06.1208.
` 3. Lutter G, Lozonschi L, Ebner A, Gallo S, Marin y Kall C, Missov E,
`de Marchena E. First-in-human off-pump transcatheter mitral valve
`replacement. JACC Cardiovasc Interv. 2014;7:1077–1078. doi: 10.1016/j.
`jcin.2014.06.007.
` 4. Bapat V, Buellesfeld L, Peterson MD, Hancock J, Reineke D, Buller
`C, Carrel T, Praz F, Rajani R, Fam N, Kim H, Redwood S, Young C,
`Munns C, Windecker S, Thomas M. Transcatheter mitral valve implan-
`tation (TMVI) using the Edwards FORTIS device. EuroIntervention.
`2014;10(suppl U):U120–U128. doi: 10.4244/EIJV10SUA18.
`
`KEY WORDS: mitral valve ◼ mitral valve insufficiency ◼ transcatheter aortic
`valve implantation
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`Figure 1. CardiAQ prosthesis consists of a self-expanding nitinol
`frame, which has 3 leaflets of bovine pericardial tissue and is
`covered with a polytetrafluoroethylene membrane to minimize
`paravalvular leakage. The frame design features 2 sets of oppos-
`ing left ventricular anchors and allows for annular attachment
`without radial force. The frame engages and preserves the native
`subvalvular apparatus and features a 40-mm anchoring region
`and a 30-mm inflow region. A, First-generation device, as used in
`the first-in-human transfemoral CardiAQ case. B, Second-gener-
`ation device, which offers improved load distribution, optimized
`flow properties in the left atrium, and better paravalvular leak pre-
`vention. Reproduced with permission from CardiAQ Valve Tech-
`nologies. Copyright ©2015, CardiAQ Valve Technologies.
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`Figure 2. Essential steps of the transfemoral transcatheter mitral valve implantation procedure. A, Four accesses are obtained, 2 in the
`femoral artery and 2 in the femoral vein. B, Snaring technique in the iliofemoral vein. C, Standard transseptal puncture. D, Copenhagen
`manoeuvre with inflated 14-mm balloon to ensure that chordae are not caught. E, Positioning of the steering snare around the middle of
`the nose cone of the delivery system. F, Steering the delivery system toward the mitral valve by pulling the snare. G, Obtaining perpen-
`dicularity to the mitral annular plane by manipulating the arteriovenous (AV) loop and the delivery system. H, Final deployment of the Car-
`diAQ valve with engagement of both mitral valve leaflets.
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`Figure 4. Echocardiographic images. A and B, Preprocedural
`severe mitral regurgitation because of mitral annular dilatation
`and a severely restricted posterior mitral leaflet with a large sys-
`tolic coaptation gap. C and D, Evaluation 48 hours after trans-
`catheter mitral valve implantation (TMVI) showing an accurate
`and stable position of the CardiAQ valve with a mean transval-
`vular pressure gradient of 2 mm Hg and only a mild paravalvular
`leakage. The left ventricular outflow tract (LVOT) peak gradient
`was 12 mm Hg and, thus, excluded LVOT obstruction. E and
`F, Three-dimensional images showing the bioprosthesis during
`diastole and systole.
`
`Figure 3. Implantation sequence. A and B, Copenhagen
`manoeuvre: an inflated 14-mm balloon is tracked from the left
`atrium to the left ventricular (LV) outflow tract to ensure that the
`wire is not caught in the chordae of the mitral valve. If resistance
`is experienced, the arteriovenous (AV) loop is reestablished.
`C and D, Advancement of the delivery system across the mitral
`annulus with the help of a steering snare, which is positioned
`around the middle of the nose cone. E and F, Coaxial align-
`ment, which can be obtained by manipulating the AV loop and
`the delivery system, and opening of the LV anchors. G, Further
`staged deployment of the CardiAQ valve. H, Left ventriculogram
`showing good position of the CardiAQ valve and absence of sig-
`nificant mitral valve regurgitation.
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