Transcatheter mitral valve repair

Transcatheter mitral annuloplasty

Mitral valve annuloplasty is routinely used during surgical mitral valve repair of degenerative or functional mitral regurgitation (MR). Annuloplasty techniques using percutaneous transcatheter approaches have been indirect or direct, based on their relation to the mitral annulus.

Indirect mitral annuloplasty

In functional MR, an important surgical approach is placement of a mitral annuloplasty ring to reduce the annular circumference and obtain better coaptation of the mitral leaflets. Transcatheter indirect mitral annuloplasty methods are based on the parallel relationship of the coronary sinus to the mitral annulus. The anatomical proximity of the coronary sinus to the posterior mitral annulus, coupled with ease of percutaneous access to this large vein, has been the basis for the development of catheter-based mitral annuloplasty devices. However, the distance between the mitral annulus and the coronary sinus is often increased in patients with heart failure.

The Carillon^TM Mitral Contour System (Cardiac Dimensions Inc., WA, USA), MONARC^TM coronary sinus device (Edwards Lifesciences, CA, USA), Viacor^TM Percutaneous Transvenous Mitral Annuloplasty device (Viacor Inc., MA, USA) and ARTO^TM system (MVRx Inc., CA, USA) have been used in humans. The Carillon^TM has received CE mark approval and the ARTO^TM system was studied in the MAVERIC CE Mark Trial.

Carillon^TM Mitral Contour System

The Carillon™ Mitral Contour System (Cardiac Dimensions Inc., WA, USA) is a transcatheter indirect mitral annuloplasty device which intends to improve mitral leaflet coaptation and reduce functional MR. The Carillon^TM System is CE-approved and is indicated for use in patients with functional MR who are symptomatic (NYHA ≥ grade 2) despite treatment with guidelines-directed medical therapy (GDMT) and who are presenting with annulus dilatation as primary contributor to the significant MR.

The Carillon™ Mitral Contour System consists of three components: the sizing catheter, the delivery system and the Carillon^TM implant. The sizing catheter is used to estimate the overall coronary sinus (CS)/great cardiac vein (GCV) dimensions so that an appropriately sized implant may be selected. Venous size estimates are determined using venograms captured with fluoroscopy. The delivery catheter facilitates percutaneous entry of the sizing catheter, delivery of the implant, engagement of the locking mechanism, and repositioning or recapture of the implant, if necessary. The Carillon^TM XE2 implant is made of nitinol and titanium and is manufactured in different lengths and with different anchor sizes to accommodate individual venous anatomy. The implant is composed of a distal anchor (positioned in the GCV), proximal anchor (positioned in the CS), ribbon connector (joining the anchors), proximal crimp tube, and distal crimp tube. The lock bump and arrowhead help secure their respective eyelets in the locked position ( Figure 1). The implant is designed to be deployed, tensioned, and secured in the coronary vein. The MR reduction is immediate and can be modulated during the procedure in the catheterisation laboratory. Combined or staged procedures with the MitraClip^TM system (Abbott, IL, USA) have also been described.

There are several limitations facing this coronary sinus approach [11. Choure AJ, Garcia MJ, Hesse B, Sevensma M, Maly G, Greenberg NL, Borzi L, Ellis S, Tuzcu EM, Kapadia SR. In vivo analysis of the anatomical relationship of coronary sinus to mitral annulus and left circumflex coronary artery using cardiac multidetector computed tomography: implications for percutaneous coronary sinus mitral annuloplasty. J Am Coll Cardiol. 2006;48:1938-45. , 22. Lansac E, Di Centa I, Al Attar N, Messika-Zeitoun D, Raffoul R, Vahanian A, Nataf P. Percutaneous mitral annuloplasty through the coronary sinus: an anatomic point of view. J Thorac Cardiovasc Surg. 2008;135:376-81. , 33. Maselli D, Guarracino F, Chiaramonti F, Mangia F, Borelli G, Minzioni G. Percutaneous mitral annuloplasty: an anatomic study of human coronary sinus and its relation with mitral valve annulus and coronary arteries. Circulation. 2006;114:377-80. , 44. Tops LF, Van de Veire NR, Schuijf JD, de Roos A, van der Wall EE, Schalij MJ, Bax JJ. Noninvasive evaluation of coronary sinus anatomy and its relation to the mitral valve annulus: implications for percutaneous mitral annuloplasty. Circulation. 2007;115:1426-32. ]. The relative position of the coronary sinus is approximately 1 cm away from the true mitral annulus, which may limit the therapeutic effectiveness. In addition, this distance is often increased in patients with heart failure. The branches of the left circumflex coronary artery frequently cross under the coronary sinus and have been compressed, with some cases of myocardial infarction in early human trials. Thus, careful screening is needed, and the circumflex coronary artery has to be monitored during device implantation – importantly, the device can be repositioned and/or retrieved to relieve coronary compression. Also, torsional forces in the CS resulted in device fractures in early human trials and necessitated repeated device re-designs. The Carillon^TM System is not recommended in patients with a CRT device or pacing lead in the coronary sinus.

Initial human experience demonstrated the ability to reduce MR by 1 or 2 grades with improvement in the 6-minute walk test and in quality of life and there was evidence of favorable LV remodeling at 12 months [55. Schofer J, Siminiak T, Haude M, Herrman JP, Vainer J, Wu JC, Levy WC, Mauri L, Feldman T, Kwong RY, Kaye DM, Duffy SJ, Tübler T, Degen H, Brandt MC, Van Bibber R, Goldberg S, Reuter DG, Hoppe UC. Percutaneous mitral annuloplasty for functional mitral regurgitation: results of the CARILLON Mitral Annuloplasty Device European Union Study. Circulation. 2009;120:326-33. ]. In the randomized, sham-controlled REDUCE FMR trial enrolling 120 patients, treatment with the Carillon^TM device was shown to significantly reduce mitral regurgitant volumes (-7.1 ml/beat vs. +3.3 ml/beat in the sham-control group) and left ventricular (LV) volumes in symptomatic patients with functional MR receiving optimal medical therapy [66. Witte KK, Lipiecki J, Siminiak T, Meredith IT, Malkin CJ, Goldberg SL, Stark MA, von Bardeleben RS, Cremer PC, Jaber WA, Celermajer DS, Kaye DM, Sievert H. The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation. JACC Heart Fail. 2019;7(11):945-955. ]. Recently published five-year follow-up data also indicate durable functional improvement and favorable five-year survival rates following treatment with the Carillon^TM Mitral Contour System [77. Lipiecki J, Kaye DM, Witte KK, Haude M, Kapadia S, Sievert H, Goldberg SL, Levy WC, Siminiak T. Long-Term Survival Following Transcatheter Mitral Valve Repair: Pooled Analysis of Prospective Trials with the Carillon Device. Cardiovasc Revasc Med. 2020;21(6):712-716. ].

These results support the CARILLON randomized trial (ClinTrials.Gov: NCT03142152), which is ongoing at 75 sites in Europe and the United States, and is comparing the device to medical therapy in 352 patients with functional MR.

ARTO^TM system

The ARTO™ system (MVRx Inc., CA, USA) is a transcatheter indirect mitral annuloplasty device which aims to improve mitral leaflet coaptation and decrease functional MR via a ‘bridge suture’ that connects anchors placed in the great cardiac vein (GCV) and the atrial septum.

Using fluoroscopy, delivery of the ARTO^TM system is accomplished by venous access to the right atrium where two common procedures are performed: (1) the coronary sinus is cannulated from the right jugular vein and a T-bar implant is deployed in the lateral wall via the GCV; and (2) a septal implant is deployed through a transseptal puncture. A ‘bridge suture’ between these two anchors provides the means for inward displacement and subsequent reduction of the mitral annular antero-posterior diameter. The bridge length is adjusted to achieve optimal MR reduction. A step-by-step illustration of the ARTO^TM system implantation technique can be found in Figure 2.

Theoretical advantages of the ARTO^TM system are that it does not induce trauma to the native mitral leaflets or chords, it is reversible and/or removable during deployment, and it does not leave a residual atrial septum defect. In addition, accurate CT scan analysis of coronary arteries and coronary sinus anatomy, as well as intraprocedural coronarography, should prevent from damaging the left circumflex coronary artery.

Results of the prospective, non-randomized, pre-commercial MAVERIC trial (Mitral Valve Repair Clinical trial) using the ARTO^TM transcatheter mitral valve repair system in 45 patients with symptomatic heart failure and functional MR showed the ARTO^TM system to be safe and effective in decreasing functional MR up to one-year post-procedure. The median procedure time was 88 minutes and median hospitalization length two days. The primary safety composite endpoint (death, stroke, myocardial infarction, device related surgery, cardiac tamponade, renal failure) at 30-days and one-year was 4.4% and 17.8%, respectively. The mitral annular antero-posterior diameter decreased from 41.4 mm (baseline) to 36.0 and 35.3 mm at 30-days and one-year, respectively. Paired results for 36 patients demonstrated 24 (67%) had MR grade 3/4+ at baseline vs. only 5 (14%) and 3 (8%) patients with MR grade 3/4+ at 30-days and one-year post-procedure. Twenty-five patients (69%) had NYHA class III-IV symptoms at baseline, decreasing significantly to 9 (25%) and 8 (22%) patients at 30-days and one-year post-procedure, respectively [88. Rogers JH, Thomas M, Morice MC, Narbute I, Zabunova M, Hovasse T, Poupineau M, Rudzitis A, Kamzola G, Zvaigzne L, Greene S and Erglis A. Treatment of Heart Failure with Associated Functional Mitral Regurgitation Using the ARTO System: Initial Results of the First-in-Human MAVERIC Trial (Mitral Valve Repair Clinical Trial). JACC Cardiovasc Interv. 2015;8:1095-104. , 99. Erglis A, Thomas M, Morice MC, Narbute I, Zabunova M, Hovasse T, Poupineau M, Rudzitis A, Kamzola G, Zvaigzne L, Greene S, Rogers JH. The ARTO transcatheter mitral valve repair system. EuroIntervention. 2015;11:47-48. , 1010. Erglis A, Narbute I, Poupineau M, Hovasse T, Kamzola G, Zvaigzne L, Erglis M, Erglis K, Greene S, Rogers JH. Treatment of Secondary Mitral Regurgitation in Chronic Heart Failure. J Am Coll Cardiol. 2017;70(22):2834-5. , 1111. Worthley S, Redwood S, Hildick-Smith D, Rafter T, Whelan A, Demarco F, Horrigan M, Delacroix S, Gregson J, Erglis A. Transcatheter Reshaping of the Mitral Annulus in Patients with Functional Mitral Regurgitation: One-year Outcomes of the MAVERIC Trial. EuroIntervention 2020,doi:10. 4244/EIJ-D-20-00484. ]. Larger randomized controlled trials (RCTs) studying the safety and efficacy of the ARTO^TM system are needed.

Direct mitral annuloplasty

Direct mitral annuloplasty eliminates some of the limitations of the coronary sinus approach but requires transseptal access to the LA and represents a technically more challenging and complex procedural approach.

Two systems that come the closest to a surgical mitral annuloplasty and are expected to undergo robust clinical testing in the near future are the Cardioband^TM Mitral System (Edwards Lifesciences, CA, USA) and the Millipede^TM Transcatheter Mitral Annuloplasty System (Boston Scientific, MA, USA). Both systems use a transseptal approach with a steerable guide catheter. Few other percutaneous mitral annuloplasty devices or concepts have been designed or proposed; however, are currently not in further development.

The Mitralign system (Mitralign Inc, MA, USA) is another transcatheter direct mitral annuloplasty system, approaching the posterior mitral annulus through a retrograde LV access. Two pairs of pledgets are delivered at the P1 and P3 site of the annulus. The paired pledgets are pulled together to decrease the annulus circumference, and the achieved plication is locked in place. The Mitralign system has been used in several patients and gained CE mark for the treatment of functional MR in 2016 [1212. Nickenig G, Schueler R, Dager A, Martinez Clark P, Abizaid A, Siminiak T, Buszman P, Demkow M, Ebner A, Asch FM, Hammerstingl C. Treatment of Chronic Functional Mitral Valve Regurgitation with a Percutaneous Annuloplasty System. J Am Coll Cardiol. 2016;67(25):2927-36. , 1313. Schueler R, Nickenig G. The Mitralign: strategies for optimal patient selection and optimised results. EuroIntervention. 2016 Sep 18;12(Y):67-9. ]. In March 2019, Edwards Lifesciences announced it acquired certain assets of Mitralign, Inc. It is not known to the authors if further efforts are made to develop this device.

Cardioband^TM Mitral System

The Cardioband Mitral system is a transcatheter, transseptal adjustable direct mitral annuloplasty device which aims to reduce the annular circumference and improve mitral leaflet coaptation. The Cardioband implant consists of a polyester sleeve with radiopaque markers at every 8 mm; the sleeve covers the delivery system which deploys the screw anchors. Correct positioning of the first anchor is crucial and multiplanar TEE and 3D-TEE views are necessary to verify correct placement ( Figure 3). The first anchor is placed lateral and as anterior as possible in the mitral annulus; coronary angiography is performed to rule out damage to the left circumflex coronary artery. The anchors are repeatedly placed along the posterior side at the mitral annulus until the implant catheter tip reaches the last anchoring site at the medial side. A contraction wire following the same path as the sleeve is connected to an adjusting spool. Activating the spool cinches the Cardioband device, thereby reducing the mitral annular diameter. Adequate reduction of MR severity is assessed by TEE under beating heart conditions. The implant is available in different sizes.

The Cardioband Mitral System gained CE mark for the treatment of functional MR in 2016. In a single-arm, multicenter prospective study, results obtained in 60 consecutive patients with moderate or severe functional MR treated with the Cardioband System were reported. There were two in-hospital deaths (none device-related), one stroke, two coronary artery complications, and one tamponade. Anchor disengagement, observed in 10 patients, resulted in device inefficacy in 5 patients and led to device modification half way through the study to mitigate this issue. Technical, device, and procedural successes were 97%, 72%, and 68%, respectively. At 1-year, overall survival, survival free of readmission for heart failure, and survival free of reintervention (performed in 7 patients) were 87%, 66%, and 78%, respectively. MR grade at 12 months was ≤ grade 2+ in 61% of the overall population and in 95% of the 39 patients who underwent a transthoracic echocardiography at 1-year; but worsened by at least one grade in 11 patients (22%). The latter suggests some recurrence of functional MR in this population. Functional status (79% vs. 14% in New York Heart Association Class I/II), quality of life, and exercise capacity (+58 m by 6MWT) improved significantly [77. Lipiecki J, Kaye DM, Witte KK, Haude M, Kapadia S, Sievert H, Goldberg SL, Levy WC, Siminiak T. Long-Term Survival Following Transcatheter Mitral Valve Repair: Pooled Analysis of Prospective Trials with the Carillon Device. Cardiovasc Revasc Med. 2020;21(6):712-716. ]. In summary, the Cardioband Mitral System demonstrated reasonable performance and safety; however, a larger randomized controlled trial is absolutely needed. In the ACTIVE trial, patients will be randomized 2:1 to receive either TMVr with the Cardioband Mitral System plus GDMT versus GDMT alone.

Millipede^TM Transcatheter Mitral Annuloplasty System

The Millipede^TM system (Boston Scientific, MA, USA) is a transcatheter direct mitral annuloplasty device currently still under development and investigation. The technology has demonstrated proof-of-concept in more than 20 human clinical procedures [1414. Rogers JH, Boyd WD, Smith TW, Bolling SF. Transcatheter Mitral Valve Direct Annuloplasty with the Millipede IRIS Ring. Interv Cardiol Clin. 2019;8(3):261-7. , 1515. Rogers JH, Boyd WD, Smith TW, Bolling SF. Early experience with Millipede IRIS transcatheter mitral annuloplasty. Ann Cardiothorac Surg. 2018;7(6):780-6. , 1616. Rogers JH, Boyd WD, Smith TW, Ebner AA, Grube E, Bolling SF. Transcatheter Annuloplasty for Mitral Regurgitation with an Adjustable Semi-Rigid Complete Ring: Initial Experience with the Millipede IRIS Device. Structural Heart. 2018;2:43-50. ] and is currently enrolling in a global feasibility study.

The Millipede^TM device has a complete semi-rigid ring design that conceptually follows the full-ring surgical predicates most commonly used as a stand-alone mitral valve repair for functional MR patients. It has a nitinol zig-zag stent frame that is circumferentially fixed to the annulus by eight helical anchors. The top of the frame has eight slider components that can be individually cinched to achieve tailored downsizing of the mitral annulus ( Figure 4). The delivery catheter is designed for the transvenous transseptal delivery route and has a 27 Fr profile.

A unique feature of the Millipede^TM technology is an integrated intracardiac echocardiography (ICE) catheter that is running through the central lumen of the delivery catheter, providing unobstructed near-field imaging of the mitral annular anatomy. This imaging modality is primarily utilized for control of device anchoring.

Transcatheter edge-to-edge mitral valve repair

Alfieri and colleagues first described the surgical repair of prolapse of the anterior mitral valve leaflet using an edge-to-edge technique by opposing the middle scallops of the anterior and posterior leaflets with a stitch, creating a so-called ‘double-orifice’ mitral valve [1717. Alfieri O, De Bonis M, Lapenna E, Regesta T, Maisano F, Torracca L, La Canna G. “Edge-to-edge” repair for anterior mitral leaflet prolapse. Semin Thorac Cardiovasc Surg. 2004;16:182-7. ]. The simplicity of this technique, also called ‘edge-to-edge’ repair, prompted interest in development of catheter-based technologies that might enable percutaneous endovascular valve repair in the cardiac catheterization laboratory.

A first attempt to mimic the Alfieri technique was the MOBIUS^TM device (Edwards Lifesciences, CA, USA) which coapted the leaflets with a percutaneously applied suture. It has been used to treat severe MR in humans in a pre-CE mark trial. Technical problems including suture dehiscence were reported; the manufacturer has since stopped the development of the device [1818. Naqvi TZ, Buchbinder M, Zarbatany D, Logan J, Molloy M, Balke G, Ainsworth R, Webb JG, Alfieri O, Maisano F. Beating-heart percutaneous mitral valve repair using a transcatheter endovascular suturing device in an animal model. Catheter Cardiovasc Interv. 2007;69:525-31. , 1919. Webb JG, Maisano F, Vahanian A, Munt B, Naqvi TZ, Bonan R, Zarbatany D, Buchbinder M. Percutaneous suture edge-to-edge repair of the mitral valve. EuroIntervention. 2009;5:86-9. ].

During the past decade, the MitraClip^TM system (Abbott, IL, USA) has been increasingly adopted as a method of creating an edge-to-edge mitral valve repair using a percutaneous transseptal approach. The MitraClip^TM system received CE mark approval in 2008 [2020. Evalve, Inc. Announces CE Mark Approval of the World’s First Percutaneous Valve Repair System. March 2008. ] and has since then known a steady growth in its use [2121. Franzen O, Baldus S, Rudolph V, Meyer S, Knap M, Koschyk D, Treede H, Barmeyer A, Schofer J, Costard-Jäckle A, Schlüter M, Reichenspurner H, Meinertz T. Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: emphasis on adverse valve morphology and severe left ventricular dysfunction. Eur Heart J. 2010;31:1373-81. , 2222. Rogers JH, Franzen O. Percutaneous edge-to-edge MitraClip therapy in the management of mitral regurgitation. Eur Heart J. 2011;32:2350-7. , 2323. Franzen O, von Samson P, Dodge-Khatami A, Geffert G, Baldus S. Percutaneous edge-to-edge repair of tricuspid regurgitation in congenitally corrected transposition of the great arteries. Congenit Heart Dis. 2011;6:57-9. , 2424. Pleger ST, Mereles D, Schulz-Schönhagen M, Krumsdorf U, Chorianopoulos E, Rottbauer W, Katus HA, Bekeredjian R. Acute safety and 30-day outcome after percutaneous edge-to-edge repair of mitral regurgitation in very high-risk patients. Am J Cardiol. 2011;108:1478-82. , 2525. Rudolph V, Knap M, Franzen O, Schlüter M, de Vries T, Conradi L, Schirmer J, Treede H, Wegscheider K, Costard-Jäckle A, Meinertz T, Reichenspurner H, Baldus S. Echocardiographic and clinical outcomes of MitraClip therapy in patients not amenable to surgery. J Am Coll Cardiol. 2011;58:2190-5. , 2626. Van den Branden BJ, Post MC, Swaans MJ, Rensing BJ, Eefting FD, Plokker HW, Jaarsma W, Van der Heyden JA. Percutaneous mitral valve repair using the edge-to-edge technique in a high-risk population. Neth Heart J. 2010;18:437-43. , 2727. Maisano F, Godino C, Giacomini A, Denti P, Arendar I, Buzzatti N, Canna GL, Alfieri O, Colombo A. Clinical trial experience with the MitraClip catheter based mitral valve repair system. Int J Cardiovasc Imaging. 2011;27:1155-64. ]. The MitraClip^TM system also received FDA approval for degenerative and functional MR in 2013 and 2019, respectively [2828. Abbott Vascular. Press release. 25th October 2013. Abbott’s first-in-class MitraClip® device now available for U.S. Patients. , 2929. FDA news release. FDA approves new indication for valve repair device to treat certain heart failure patients with mitral regurgitation. March 2019. ]. It has been implanted in more than 100,000 patients in over 50 countries and is the only percutaneous mitral therapy to complete prospective trials comparing the device to conventional mitral valve surgery [3030. Feldman T, Foster E, Glower DD, Kar S, Rinaldi MJ, Fail PS, et al. Percutaneous Repair or Surgery for Mitral Regurgitation. N Engl J Med. 2011;364(15):1395-406. , 3131. Feldman T, Kar S, Elmariah S, Smart SC, Trento A, Siegel RJ, et al. Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation: 5-Year Results of EVEREST II. J Am Coll Cardiol. 2015;66(25):2844-54. , 3232. Feldman T. Final Results of the EVEREST II Randomized Controlled Trial of Percutaneous and Surgical Reduction of Mitral Regurgitation. Presented at ACC 2014, Washington DC, USA. 2014. ] and GDMT [3333. Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, et al. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018;379(24):2307-18. , 3434. Mack M, Abraham WT, Lindenfeld J, Stone GW. COAPT. Three-Year Outcomes from a Randomized Trial of Transcatheter Mitral Valve Leaflet Approximation in Patients with Heart Failure and Secondary Mitral Regurgitation. Presented at TCT 2019. San Francisco, CA. Sept 25–29 , 3535. Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, et al. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018;379(24):2297-306. , 3636. Iung B, Armoiry X, Vahanian A, Boutitie F, Mewton N, Trochu JN, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation: outcomes at 2 years. Eur J Heart Fail. 2019;21(12):1619-27. ]. The results are detailed later in this chapter.

The PASCAL^TM Transcatheter Valve Repair System (Edwards Lifesciences, CA, USA) received CE mark approval for the treatment of MR and was introduced in 2019 after showing acceptable safety and feasibility in the CLASP study in a patient population of functional, degenerative and mixed etiology [3737. Lim DS, Kar S, Spargias K, Kipperman RM, O’Neill WW, Ng MKC, Fam NP, Walters DL, Webb JG, Smith RL, Rinaldi MJ, Latib A, Cohen GN, Schäfer U, Marcoff L, Vandrangi P, Verta P, Feldman TE. Transcatheter Valve Repair for Patients with Mitral Regurgitation: 30-Day Results of the CLASP Study. JACC Cardiovasc Interv. 2019;12(14):1369-78. ]. The PASCAL^TM Transcatheter Valve Repair System and current generation MitraClip^TM System are being compared in both degenerative and functional MR patients within the CLASPIID/IIF Pivotal Clinical Trial (ClinTrials.Gov: NCT03706833).

MitraClip^TM system

The MitraClip™ system is a minimally invasive, transcatheter therapeutic option for patients with moderate-to-severe and severe degenerative, functional, or mixed MR who are not considered suitable candidates for conventional mitral valve surgery. The MitraClip^TM system consists of a steerable guide catheter and a clip delivery system (CDS), which includes the detachable clip ( Figure 5 A). The steerable guide and CDS allow maneuvering the clip in all different planes.

The clip consists of two arms that are opened and closed by control mechanisms on the CDS and two ‘grippers’ that match up to each arm and help stabilizing the leaflets from the atrial aspect as they are captured during closure of the clip arms. Leaflet tissue is secured between the arms and each side of the gripper, and the clip is then closed and locked to maintain leaflet coaptation.

MitraClip™ G4 is a fourth-generation device which comes with four enhancements and received CE approval in August 2020. A Controlled Gripper Actuation feature allows for simultaneous or independent leaflet grasping to facilitate or optimize leaflet grasping and insertion ( Figure 5 B). MitraClip^TM G4 also comes with the choice between four clip sizes (NT, XT, NTW, and XTW) offering more options for tailored mitral valve repair based on the patient’s mitral valve anatomy ( Figure 5 C). Integrated left atrial pressure monitoring enables real-time MR assessment. Finally, a simplified system preparation and deployment should further streamline the procedure.

Mitraclip^TM system implantation procedure

The MitraClip^TM procedure is performed under general anesthesia using fluoroscopy and TEE guidance. A good collaboration and communication between the interventional operator and the echocardiographer are an absolute necessity in order to perform a safe and successful Mitraclip^TM procedure [3838. Altiok E, Becker M, Hamada S, Reith S, Marx N, Hoffmann R. Optimized guidance of percutaneous edge-to edge repair of the mitral valve using real-time 3-D transesophageal echocardiography. Clin Res Cardiol. 2011;100:675-81. , 3939. Silvestry FE, Rodriguez LL, Herrmann HC, Rohatgi S, Weiss SJ, Stewart WJ, Homma S, Goyal N, Pulerwitz T, Zunamon A, Hamilton A, Merlino J, Martin R, Krabill K, Block PC, Whitlow P, Tuzcu EM, Kapadia S, Gray WA, Reisman M, Wasserman H, Schwartz A, Foster E, Feldman T, Wiegers SE. Echocardiographic guidance and assessment of percutaneous repair for mitral regurgitation with the Evalve MitraClip: lessons learned from EVEREST I. J Am Soc Echocardiogr. 2007;20:1131-40. , 4040. Ciobanu A, Bennett S, Azam M, Clark A, Vinereanu D. Incremental value of three-dimensional transoesophageal echocardiography for guiding double percutaneous MitraClip ® implantation in a “no option” patient. Eur J Echocardiogr. 2011;12:11. , 4141. Swaans MJ, Van den Branden BJ, Van der Heyden JA, Post MC, Rensing BJ, Eefting FD, Plokker HW, Jaarsma W. Three-dimensional transoesophageal echocardiography in a patient undergoing percutaneous mitral valve repair using the edge-to-edge clip technique. Eur J Echocardiogr. 2009;10:982-3. , 4242. Ryan LP, Salgo IS, Gorman RC, Gorman JH 3rd. The emerging role of three-dimensional echocardiography in mitral valve repair. Semin Thorac Cardiovasc Surg. 2006;18:126-34. ].

1. Vascular access

A 14-18 Fr sheath is placed in the right femoral vein for transseptal access. At a later stage of the procedure, the 24 Fr steerable guide catheter will replace it. After the transseptal puncture, an Activated Clotting Time (ACT) of 250-300 seconds should be maintained throughout the procedure.

2. Transseptal crossing and guide insertion

Following transseptal puncture, a stiff guide wire is placed in the left upper pulmonary vein and the steerable guide catheter and dilator are then carefully advanced into the left atrium over the stiff guide wire. Once the steerable guide catheter is in place and secured, the wire and dilator are removed, leaving the guide in the left atrium ( Figure 6 A). A steering knob on the proximal end of the guide catheter marked as (+/-) allows for flexion of the distal guide catheter tip (e.g., needed in case of a ‘aorta hugger’ position of the steerable guide).

3. Clip Delivery System (CDS) insertion and steering in the left atrium

To introduce the clip, the CDS is advanced through the steerable guide into the left atrium. A series of maneuvers and manipulations with the steerable guide and CDS are required to align the clip perpendicular to the mitral valve plane, and the clip arms perpendicular to the line of coaptation ( Figure 6 B) – this is done under TEE guidance.

4. Advancing into left ventricle and leaflet grasping

The mitral valve leaflets are grasped between the corresponding arm and gripper creating a ‘double orifice’ valve. MR is assessed throughout the entire procedure using real-time TEE to confirm optimal positioning and sufficient reduction in MR ( Figure 6 C-D). In case of insufficient MR reduction, the clip can be repositioned in order to optimize MR reduction and, if needed, even be retrieved.

5. Leaflet insertion assessment and hemodynamic measurements

Prior to clip closure and deployment, a leaflet insertion and hemodynamic assessment should be performed. Following MR reduction, pressure gradients are assessed to ensure there is no clip-induced mitral stenosis. Once the assessments are complete, the clip is fully closed and deployed. Where necessary, the physician may place (an) additional clip(s) to optimize MR reduction.

6. Deployment and system removal

The MitraClip^TM system is removed by releasing deflection on the catheter and slowly removing from the patient ( Figure 6 E-F). Groin management and continued medical therapy can be recommended per the institution’s guidelines.

Clinical value of Mitraclip™ therapy

MitraClip™ is supported by the largest body of evidence of all transcatheter mitral valve repair therapies. More than 30,000 patients have been treated in MitraClip™ clinical trials representing 16 years of clinical research published in more than 2,050 scientific papers. An overview of key MitraClip^TM studies can be found in Figure 7.

MitraClip™ therapy has repeatedly and consistently demonstrated a low rate of adverse events, as well as significant efficacy, confirming its status as a safe and effective option for selected patients with significant MR who are at high surgical risk.

MitraClip™ therapy is associated with a high rate of acute procedural success in case of proper patient selection ( Figure 6 G), defined as a reduction in MR grade to ≤2+ immediately following implantation. In the TRAMI registry, 97% of patients had a successful MitraClip™ procedure [4343. Kalbacher D, Schafer U, RS VB, Eggebrecht H, Sievert H, Nickenig G, et al. Long-term outcome, survival and predictors of mortality after MitraClip therapy: Results from the German Transcatheter Mitral Valve Interventions (TRAMI) registry. Int J Cardiol. 2019;277:35-41. ]. The same registry also demonstrated that 96% of patients had MR ≤2+ at discharge [4444. Schillinger W, Hunlich M, Baldus S, Ouarrak T, Boekstegers P, Hink U, et al. Acute outcomes after MitraClip therapy in highly aged patients: results from the German TRAnscatheter Mitral valve Interventions (TRAMI) Registry. EuroIntervention. 2013;9:84-90. ]. In the COAPT™ trial, 99% of MitraClip™ patients had MR ≤2+ at 2 years (compared with 43% of control patients) [4545. Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, et al. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018;379(24):2307-18. ]. Evidence from the EXPAND registry showed that 96% of patients achieved acute procedural success with MitraClip™ therapy; at 30 days post-procedure, 87% of degenerative MR patients and 90% of functional MR patients had MR ≤1+ [4646. Rottbauer W. Contemporary Clinical Outcomes with Mitraclip NTR/XTR System: Core-Lab Echo Results from Over 1000 Patients. Presented at PCR e-Course. June 25–27, 2020. ]. Multiple studies also demonstrate that MitraClip™ implantation is associated with reverse left ventricle remodelling [4646. Rottbauer W. Contemporary Clinical Outcomes with Mitraclip NTR/XTR System: Core-Lab Echo Results from Over 1000 Patients. Presented at PCR e-Course. June 25–27, 2020. , 4747. Feldman T, Foster E, Glower DD, Kar S, Rinaldi MJ, Fail PS, et al. Percutaneous Repair or Surgery for Mitral Regurgitation. N Engl J Med. 2011;364(15):1395-406. , 4848. Kar S, Feldman T, Qasim A, Trento A, Kapadia S, Pedersen W, et al. Five-year outcomes of transcatheter reduction of significant mitral regurgitation in high-surgical-risk patients. Heart. 2019;105(21):1622-8. , 4949. Kar S, Lim D, Smalling R, Whisenant B, Rammohan C, Fail P, et al. The EVEREST II REALISM continued access study: effectiveness of transcatheter reduction of significant mitral regurgitation in surgical candidates. Journal of the American College of Cardiology. 2013;61(10 Supplement):E1959. , 5050. Mack M, Abraham WT, Lindenfeld J, Stone GW. COAPT. Three-Year Outcomes from a Randomized Trial of Transcatheter Mitral Valve Leaflet Approximation in Patients with Heart Failure and Secondary Mitral Regurgitation. Presented at TCT 2019. San Francisco, CA. Sept 25–29 ].

Results of two RCTs comparing MitraClip™ with GDMT – COAPT™ [4545. Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, et al. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018;379(24):2307-18. ] and MITRA-FR [5151. Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, et al. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018;379(24):2297-306. ] – in patients with functional MR became available in 2018, with two- and three-year follow-up data released in 2019 and 2020, respectively [5050. Mack M, Abraham WT, Lindenfeld J, Stone GW. COAPT. Three-Year Outcomes from a Randomized Trial of Transcatheter Mitral Valve Leaflet Approximation in Patients with Heart Failure and Secondary Mitral Regurgitation. Presented at TCT 2019. San Francisco, CA. Sept 25–29 , 5252. Hahn R. Impact of Tricuspid Regurgitation on Outcomes after MitraClip Treatment of Secondary Mitral Regurgitation: The COAPT Trial. Presented at ACC. 20/WCC Virtual. March 28–30, 2020. , 5353. Al-Azizi K. The COAPT Trial: Outcomes Of Transcatheter Mitral Valve Repair In Ischemic Versus Non-ischemic Cardiomyopathy. Presented at ACC. 20/WCC Virtual. March 28–30, 2020. , 5454. Lerakis S, Kini A, Kar S, Lim D, Mishell J, Whisenant B, et al. Outcomes of Transcatheter Mitral Valve Repair in Patients with Secondary Mitral Regurgitation According to the Severity of Left Ventricular Dysfunction: The COAPT Trial. Presented at ACC. 20/WCC Virtual. March 28–30, 2020. , 5555. Arnold SV. Short-Term Health Status Changes and Long-Term Outcomes in Patients With Heart Failure and Mitral Regurgitation: Results from the COAPT Trial. Presented at ACC. 20/WCC Virtual. March 28–30, 2020. ]. The RCT findings were conflicting, with the MITRA-FR study showing null results on the primary endpoint at 1 year (composite rate of deaths or first rehospitalization for heart failure) while the COAPT study showed positive results on the primary endpoint at 2 years (cumulative rate of rehospitalization for heart failure) as well as on all-cause mortality. These different outcomes observed in both RCTs may be explained by the following aspects: (1) COAPT enrolled a subset of patients who had more severe MR and less LV dilation compared with MITRA-FR patients; (2) the GDMT used in the two trials differed significantly. The rates of drug use and medication titration throughout the MITRA-FR trial course were not tracked, and although these were guideline directed, they may not have been guideline optimized; (3) technical success was different between the two trials. Residual MR class ≥3+ was higher post-MitraClip^TM in the MITRA-FR trial as compared to the COAPT trial, both acutely (9% versus 5%) and at 12 months (17% versus 5%) [4545. Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, et al. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018;379(24):2307-18. , 5151. Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, et al. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018;379(24):2297-306. ] Taken together, it can be concluded that MitraClip^TM therapy gives the best result for patients with severe MR and less advanced LV dilatation and in case a maximal MR reduction can be obtained. Under these conditions, the MitraClip™ system is the only transcatheter mitral valve device to show improved survival in heart failure patients with functional MR.

In conclusion, evidence for the safety and efficacy of MitraClip™ is drawn from multiple clinical trials and real-world studies, with data available up to 5 years post-procedure. A number of studies are ongoing – an overview of the most important studies can be found in Figure 7.

PASCAL^TM Transcatheter Valve Repair System

The PASCAL^TM Transcatheter Valve Repair System consists of a guide sheath, steerable sheath and implant catheter which includes the PASCAL^TM Ace implant. The PASCAL^TM implant is delivered through a 22 Fr guide sheath, with a steerable sheath to control implant positioning and trajectory and an implant catheter to control actuation, orientation and release of the implant. The ability to independently move these catheters allows maneuvering in three different planes.

The PASCAL^TM Ace implant consists of two paddles, two clasps and a central spacer. The two paddles promote leaflet approximation. The two clasps allow for staged leaflet capture and adjustment of leaflet insertion; the design of the retention elements on the clasps should prevent leaflet damage, while holding them tightly. The central spacer should reduce the tension over the leaflets and fill the regurgitant orifice area to minimize MR. A feature of the PASCAL^TM implant is its ability to elongate, which promotes safe retraction from the subvalvular apparatus, thereby reducing the risk of damaging the chords or the implant itself ( Figure 8).

The PASCAL^TM Transcatheter Valve Repair System received CE mark approval for the treatment of MR and was introduced in 2019 after showing acceptable safety and feasibility in the CLASP study in a patient population of functional, degenerative and mixed etiology [3737. Lim DS, Kar S, Spargias K, Kipperman RM, O’Neill WW, Ng MKC, Fam NP, Walters DL, Webb JG, Smith RL, Rinaldi MJ, Latib A, Cohen GN, Schäfer U, Marcoff L, Vandrangi P, Verta P, Feldman TE. Transcatheter Valve Repair for Patients with Mitral Regurgitation: 30-Day Results of the CLASP Study. JACC Cardiovasc Interv. 2019;12(14):1369-78. ].

PASCAL^TM Transcatheter Valve Repair System Implantation Procedure

The procedure is performed under general anesthesia with hemodynamic monitoring. Under the guidance of TEE and fluoroscopy, access to the left atrium is performed through a transseptal puncture, in which a guide sheath with an introducer is inserted over a previously inserted guide wire in the left atrium. The optimal puncture location for the PASCAL^TM procedure is at the posterior side of the fossa ovalis and 4.5 cm above the leaflets coaptation level. However, the PASCAL^TM delivery system provides the opportunity of having a successful procedure, even if the transseptal puncture happens lower or higher than the optimal location.

The implant is inserted within a loader through the proximal end of the guide sheath and the steerable catheter is advanced until the PASCAL^TM implant exits the loader. The steerable catheter is used to advance the implant system until the implant exits the guide sheath tip. With TEE guidance, the steerable catheter can be manipulated to adjust the trajectory and position until it is perpendicular to the plane of the mitral annulus and until over the MR jet. The unlocked steerable and guide sheath catheters help adjust the trajectory of the catheter perpendicular to the mitral valve annulus, both in an anterior-posterior and medial-lateral orientation.

The actuation knob on the implant catheter is rotated to open the paddles to ‘leaflet-capture ready’ position. The implant catheter can be rotated to orient the paddles as desired. The paddles should be oriented perpendicular to the line of coaptation. Before advancing the implant into the LV, the physician should independently check the clasps to identify the anterior versus posterior one, when independent leaflet grasping is needed. The implant catheter is advanced to lower the implant into the LV, and the implant catheter is retracted to capture the anterior and posterior leaflets. The clasps are lowered simultaneously or individually to retrain the leaflets within the paddles. Individual grasping makes it possible to optimize leaflet insertion. In addition, in patients with a large anterior-posterior gap, independent grasping may help to focus on one leaflet and grasp it, and then swing towards the opponent leaflet and capture the other one. The actuation knob is rotated to close the paddles and plicate the leaflets against the central spacer. Assessment of the residual MR and transvalvular gradient will allow confirmation of the implant position and leaflet capture. Before final deployment, the implant can be adjusted, if necessary, to obtain optimal outcomes [5656. Praz F, Windecker S, Kapadia S. PASCAL: A New Addition to the Armamentarium of Transcatheter Repair Systems for Mitral Leaflet Approximation. JACC Cardiovasc Interv. 2019;12(14):1379-81. , 5757. Praz F, Spargias K, Chrissoheris M, Büllesfeld L, Nickenig G, Deuschl F, Schueler R, Fam NP, Moss R, Makar M, Boone R, Edwards J, Moschovitis A, Kar S, Webb J, Schäfer U, Feldman T, Windecker S. Compassionate use of the PASCAL transcatheter mitral valve repair system for patients with severe mitral regurgitation: a multicentre, prospective, observational, first-in-man study. Lancet. 2017;390:773-80. , 5858. Webb JG, Hensey M, Szerlip M, Schäfer U, Cohen GN, Kar S, Makkar R, Kipperman RM, Spargias K, O’Neill WW, Ng MKC, Fam NP, Rinaldi MJ, Smith RL, Walters DL, Raffel CO, Levisay J, Latib A, Montorfano M, Marcoff L, Shrivastava M, Boone R, Gilmore S, Feldman TE, Lim DS. 1-Year Outcomes for Transcatheter Repair in Patients with Mitral Regurgitation from the CLASP Study. JACC Cardiovasc Interv. 2020;13(20):2344-57. ].

Clinical evidence of PASCAL^TM therapy

The PASCAL^TM Transcatheter Valve Repair System received CE mark approval for the treatment of MR after showing acceptable safety and feasibility in the CLASP study in a patient population of functional, degenerative and mixed etiology. In this study, the procedural success rate was 91.8% and the clinical success rate was 86.9%. The rate of major adverse events at 30 days was 6.5%, with an all-cause mortality rate of 1.6% and no incidents of stroke. There was reduction of MR grade 3+ or 4+ at baseline to MR grade < 2 in 98% of patients and to MR grade < 1 in 86% of patients at 30 days. In accordance, this study also proved clinically significant improvements in functional status with 85% of patients in NYHA functional class I/II, as well as improvements in exercise capacity, and quality of life [3737. Lim DS, Kar S, Spargias K, Kipperman RM, O’Neill WW, Ng MKC, Fam NP, Walters DL, Webb JG, Smith RL, Rinaldi MJ, Latib A, Cohen GN, Schäfer U, Marcoff L, Vandrangi P, Verta P, Feldman TE. Transcatheter Valve Repair for Patients with Mitral Regurgitation: 30-Day Results of the CLASP Study. JACC Cardiovasc Interv. 2019;12(14):1369-78. , 5656. Praz F, Windecker S, Kapadia S. PASCAL: A New Addition to the Armamentarium of Transcatheter Repair Systems for Mitral Leaflet Approximation. JACC Cardiovasc Interv. 2019;12(14):1379-81. ].

One-year outcomes of the CLASP study demonstrated a high survival rate of 92% for the overall population and 89% and 96% for the functional MR and degenerative MR populations, respectively. Freedom from heart failure hospitalizations was 88% for the overall population and 80% and 100% for the functional MR and degenerative MR populations, respectively. There was evidence of sustained MR reduction with 82% of patients having MR grade < 1 and 100% having MR grade < 2. In the functional MR population, 79% achieved MR grade < 1 and 100% MR grade < 2 and in the degenerative MR population, 86% of patients had MR grade < 1 and 100% MR grade < 2. Functional improvements were sustained at 1 year, with 88% of patients in NYHA functional class I/II. Improvement in exercise capacity and quality of life were also significant at 1 year [5858. Webb JG, Hensey M, Szerlip M, Schäfer U, Cohen GN, Kar S, Makkar R, Kipperman RM, Spargias K, O’Neill WW, Ng MKC, Fam NP, Rinaldi MJ, Smith RL, Walters DL, Raffel CO, Levisay J, Latib A, Montorfano M, Marcoff L, Shrivastava M, Boone R, Gilmore S, Feldman TE, Lim DS. 1-Year Outcomes for Transcatheter Repair in Patients with Mitral Regurgitation from the CLASP Study. JACC Cardiovasc Interv. 2020;13(20):2344-57. ].

Transcatheter mitral valve chordal repair

Transcatheter mitral valve chordal repair systems have been developed to treat severe degenerative MR due to a prolapse or flail posterior, anterior or both mitral valve leaflets. The two systems that are currently under investigation in FDA Pivotal and/or CE Mark Trials are the NeoChord^TM Artificial Chordae Delivery System (NeoChord, Inc., MN, USA) and the HARPOON^TM Beating Heart Mitral Valve Repair System (Edwards Lifesciences, CA, USA). Both systems are designed for transapical, beating heart, off-pump mitral valve repair and require a left lateral thoracotomy incision overlying the LV apex. Multiple chords are often implanted and TEE guidance is essential to assess the obtained leaflet coaptation and MR reduction.

NeoChord^TM

The NeoChord^TM Artificial Chordae Delivery System (NeoChord, Inc., MN, USA) is a transapical, beating heart, off-pump mitral valve repair system. NeoChord^TM implantation is currently indicated for severe degenerative MR due to a prolapse or flail posterior, anterior or both mitral valve leaflets. The mitral valve morphology is further sub-classified according to TEE assessment: type A: isolated central posterior leaflet prolapse/flail; type B: multi-segment posterior leaflet prolapse/flail; type C: anterior or bi-leaflet prolapse/flail; and type D: para-commissural prolapse/flail or any type of disease with the presence of significant leaflet/annular calcifications. Patients with type A and B morphology appear to be the better candidates for NeoChord^TM treatment; it should also be performed at an early stage of mitral valve pathology, before annular dilatation occurs [5959. Colli A, Manzan E, Zucchetta F, et al. Transapical off-pump mitral valve repair with NeoChord implantation: early clinical results. Int J Cardiol. 2016;204:23–28. ].

The procedure is performed under general anesthesia with intraprocedural TEE imaging guidance. Following a standard left lateral mini thoracotomy, the LV cannulation site should be confirmed by real-time 2D-TEE imaging using gentle ‘finger poking’ approx. 2 to 3 cm lateral from the true LV apex ( Figure 9 A-B). Correct localization of the ideal entry site allows the operator to navigate the device towards the mitral valve while maintaining a correct alignment between the papillary muscles without interfering with the sub-valvular mitral apparatus [6060. Colli A, Adams D, Fiocco A, et al. Transapical NeoChord mitral valve repair. Ann Cardiothorac Surg. 2018;7(6):812-820. ]. When an appropriate position of the device is reached, the jaws of the device are opened ( Figure 9 C), and the leaflet edge is grasped by withdrawing the device from the left atrium. Successful leaflet grasping is confirmed by observation of closure of the jaws of the device on the mitral leaflet and turning of all the four light indicators on the fiberoptic display monitor from red to white. A loop of the suture and a girth hitch knot can then be formed through the mitral leaflet ( Figure 9 D-E). The device can be reloaded with a new suture and the procedure can be repeated until enough neo-chordae have been implanted; usually 3 or 4 neo-chordae are implanted. The length of each neo-chordae can be adjusted to achieve maximal MR reduction under normal LV filling conditions as assessed by TEE ( Figure 9 F-G). Each of the neo-chordae can then be tied to the LV epicardial pledget ( Figure 9 H).

The Trans-Apical Chordae Tendineae (TACT) trial showed satisfying immediate safety and efficacy of the NeoChord^TM system, leading to CE approval of the device [6161. Seeburger J, Rinaldi M, Nielsen SL, et al. Off-pump transapical implantation of artificial neo-chordae to correct mitral regurgitation: the TACT Trial (Transapical Artificial Chordae Tendinae) proof of concept. J Am Coll Cardiol. 2014;63:914–919. ]. Durability of the NeoChord^TM system was examined in few studies. Colli et al. reported one-year outcome data of a multi-center study [6262. Colli A, Manzan E, Aidietis A, et al. An early European experience with transapical off-pump mitral valve repair with NeoChord implantation. Eur J Cardiothorac Surg. 2018;54:460-6. ]. Acute procedural success (defined as the placement of at least 2 neo-chordae and MR ≤ mild at the end of the procedure) was achieved in 206 (96.7%) patients. At one-year follow-up, overall survival was 98%. The composite endpoint of procedural success and freedom from death, stroke, failure of the MR repair, unplanned intervention, cardiac-related rehospitalization or worsening NYHA class was achieved in 84% for the overall population and 94%, 83% and 64% in Type A, Type B and Type C patients, respectively. Kiefer et al. [6363. Kiefer P, Meier S, Noack T, et al. Good 5-Year Durability of Transapical Beating Heart Off-Pump Mitral Valve Repair with Neochordae. Ann Thorac Surg. 2018;106:440-5. ] reported 5-year follow-up data in 3 out of 6 patients treated with the NeoChord^TM System (one patient underwent intraoperative conversion to open MV replacement as a result of leaflet injury; two patients had to undergo reoperation for recurrent MR at 3 and 16 months post-NeoChord treatment). These patients were free of cardiac symptoms and echocardiography showed MR < moderate at 1-, 2-, and 5-year follow-up and a LV reverse remodeling effect. The ongoing AcChord Registry will provide more long-term outcome data in a post-market setting.

The ongoing RECHORD trial (ClinicalTrials.gov: NCT02803957) is a prospective, multicenter, randomized FDA pivotal trial intended to establish the safety and effectiveness of the device as an alternative to standard surgical mitral valve repair.

HARPOON^TM Mitral Valve Repair System

The HARPOON^TM Beating Heart Mitral Valve Repair System (MVRS; Edwards Lifesciences, CA, USA) is intended to reduce the degree of MR in patients with severe degenerative MR caused by posterior mitral leaflet prolapse by delivering and anchoring ePTFE chords to the prolapsed mitral valve leaflet in a beating heart.

The HARPOON^TM MVRS consists of two parts: a 12 Fr introducer with a hemostatic valve and a 9 Fr delivery system. The procedure is performed under general anesthesia maintaining the patient anticoagulated with an activated clotting time >350 s. Once a left lateral thoracotomy incision (4th-5th intercostal space) overlying the LV apex is performed, the target zone for insertion of the introducer is identified approx. 2 to 4 cm basal from the true LV apex just lateral to the LAD. A ‘finger test’ helps to verify proper location via TEE by X-plane in short and long axis views. Two concentric pledgeted purse string sutures are passed around the apical insertion site using 3-0 Prolene horizontal mattress sutures, then snared with tourniquets ( Figure 10 A).

The delivery system is inserted into the introducer at an approximate 30-degree angle and navigated to the desired location on the underside of the mitral valve leaflet using TEE guidance ( Figure 10 B). As soon as TEE confirms that the delivery system does not move and that the end effector stays in contact with the targeted site on the mitral leaflet, the plunger is released to deploy a double-helical knot through the free-edge of the leaflet ( Figure 10 C-D). Once the plunger has fully returned to the starting position, the suture-release mechanism is opened to fully disengage the ePTFE chord and the delivery system is slowly removed from the introducer ( Figure 10 E). The above steps are repeated until the desired number of ePTFE chords have been implanted on the mitral valve leaflet starting from a lateral to medial target location. Next, all ePTFE chords are passed through a stiff Teflon pledget and simultaneously tensioned under 3D -TEE view. While observing the cardiac cycles in X-plane 3D-TEE, the sutures are adjusted one at a time to obtain the desired leaflet coaptation. Once tensioning is complete and optimal chord length is determined, a rubber shod clamp is applied between the pledget and the tourniquet to slightly increase tension. Finally, the tourniquet is removed prior to tie each chord with at least 15 alternating over/underhand knots. The LV insertion site is closed by tying down the purse string sutures.

The Early Feasibility Study and CE Mark TRACER trial investigated the early feasibility and safety of treatment with the HARPOON^TM system in 13 and 52 patients, respectively; the procedures were often completed through a non–rib-spreading left anterior thoracotomy approach [6464. Gammie et al.Transapical beating-heart mitral valve repair with an expanded polytetrafluoroethylene chordal implantation device: initial clinical experience. Circulation. 2016;134:189–97. , 6565. Gammie et al. Beating-Heart Mitral Valve Repair Using a Novel ePTFE Cordal Implantation Device, J Am Coll Cardiol. 2018;71:25–36. , 6666. Gammie et al. Safety and performance of a novel transventricular beating heart mitral valve repair system: 1-year outcomes. European Journal of Cardio-Thoracic Surgery. 2020:1–8. ].

Of 65 patients enrolled across the two studies, 62 (95%) achieved technical success, 2 patients required conversion to open surgery and 1 procedure was terminated. The primary endpoint was met in 59/65 (91%) patients. Among the 62 treated patients, the mean procedural time was 126 minutes. Through discharge, there were no deaths, strokes or renal failure events [6565. Gammie et al. Beating-Heart Mitral Valve Repair Using a Novel ePTFE Cordal Implantation Device, J Am Coll Cardiol. 2018;71:25–36. ].

At 1 year of follow-up, 2 of the 62 patients died (3%) and 8 (13%) others required reoperations. 98% of the patients were in NYHA class I/II; mitral regurgitation was none/trace in 52% (n=27), mild in 23% (n=12), moderate in 23% (n=12) and severe in 2% (n=1). Favorable cardiac remodeling outcomes at 1 year included decreased end-diastolic left ventricular volume (153 ± 41 to 119 ± 28 ml) and diameter (53 ± 5 to 47 ± 6 mm), and the mean peak gradient was 1.4 ± 0.7 mmHg [6666. Gammie et al. Safety and performance of a novel transventricular beating heart mitral valve repair system: 1-year outcomes. European Journal of Cardio-Thoracic Surgery. 2020:1–8. ].

In Europe, Post-Market Clinical Follow-Up (PMCF) trials are currently underway and will collect additional safety and device performance data on the HARPOON MVRS in severe degenerative MR patients [6767. Treatment of Mitral Regurgitation Using a Minimally Invasive Approach with the HARPOON Device. (NCT04382612). , 6868. Observational Registry on the HARPOON Device (NCT04393779). ]. The RESTORE IDE pivotal trial is being initiated in the US and Canada to evaluate the safety and effectiveness of the HARPOON MVRS in severe degenerative MR patients presenting with mid-segment posterior mitral leaflet prolapse [6969. Beating Heart Mitral Valve Repair With the HARPOON™ System (NCT04375332). ].