Fig. 14.1
Close up of the MitraClip device
Beyond the MitraClip system, other percutaneous approaches to FMR include indirect and direct annuloplasty procedures. The indirect annuloplasty systems are in various stages of development, have no surgical equivalent and their efficacy needs to be proven. Conversely, percutaneous direct annuloplasty reproduces surgical techniques and can be achieved with annular plication or commissure-to-commissure implant.
Their clinical application is currently not comparable to the MitraClip therapy and for this reason most of this chapter will be focused on the percutaneous edge-to-edge mitral valve repair.
Technique
Percutaneous Edge-to-Edge Repair
The MitraClip delivery system is made up of a sophisticated tri-axial catheter system (steerable guide catheter and clip delivery system catheter) and an implantable clip, available in one single size. The clip delivery system, which can be steered in four directions, has the MitraClip device attached to its distal end. The guide catheter is 24 Fr at the level of the groin and 22 Fr at the atrial septum. The device is a cobalt-chromium implant with two arms and two “grippers” adjacent to each arm to independently secure the leaflets following grasping. The clip arms and grippers are covered with polyester to enhance healing (Fig. 14.1). The MitraClip is implanted under general anesthesia, guided by transesophageal echocardiography (TEE) and fluoroscopy. Currently, many procedures are performed under real-time 3D echocardiography with fusion imaging techniques, which makes them easier and more intuitive. After peripheral venous access at the groin, the atrial septum is crossed using diathermy in the mid-superior and posterior aspect of the fossa ovalis, to achieve proper alignment of the system. The location of the transseptal puncture is critical to reach the mitral valve leaflets with coaxial alignment to the long axis of the heart. Following trans-septal puncture, a steerable guide catheter is advanced into the left atrium. Afterwards, the clip delivery system is inserted and the MitraClip device is steered towards the mitral valve, at the origin of the regurgitant jet. The clip arms are opened and positioned perpendicularly to the line of coaptation; symmetric implantation is fundamental for an effective and durable repair (Fig. 14.2). The clip is advanced into the left ventricle and then retracted and partially closed to a “V” shape to engage the leaflets. Leaflets are grasped by gentle retraction of the clip toward the left atrium. To secure the leaflets into the device, the grippers are dropped and the clip is closed at approximately 60° to allow assessment of leaflet insertion. This step is still reversible and is used to assess symmetry and efficacy of the position. When the clip is closed, the final effect on MR reduction is evaluated using full-volume 3D color Doppler and, if the result of the implant is satisfactory, the clip is deployed (Fig. 14.3). However, if necessary, at this stage the clip can still be reopened, inverted to release the leaflets and repositioned. Alternatively, a second clip can be used, but it is rare for more than two clips to be used in order to avoid mitral valve stenosis. Once the procedure is completed, percutaneous vascular closure is performed, and the patient is weaned from general anesthesia.
Fig. 14.2
3D Transesophageal view of the MitraClip correctly oriented with the arms perpendicular to the line of coaptation
Fig. 14.3
3D Transesophageal view of a double-orifice mitral valve after MitraClip implantation
Percutaneous Annuloplasty
Undersized ring annuloplasty has been extensively used for the surgical treatment of FMR. On the basis of this surgical background, several trans-catheter percutaneous technologies have been developed to perform a percutaneous annuloplasty procedure. They can be essentially divided into direct and indirect annuloplasty systems.
Direct Annuloplasty
Percutaneous direct annuloplasty tries to reproduce surgical annuloplasty techniques:
Cardioband (Valtech Cardio Inc., Or Yehuda, Israel) is an adjustable, catheter-deliverable, sutureless Dacron band that is inserted percutaneously [10]. The insertion requires a steerable guide and device delivery system that is similar to the MitraClip system. Through a transseptal approach the band is anchored to the atrial side of the mitral annulus via multiple helical anchors, from trigone to trigone (Figs. 14.4 and 14.5). After delivery, the implant is tensioned to create posterior annuloplasty with septal-lateral dimension reductions of approximately 30 % and to achieve adequate leaflet coaptation and MR reduction. The first-in-human procedure was performed in 2013 in Milan, Italy, and a European multi-center CE Mark trial is underway.
Fig. 14.4
Implanted Cardioband in an animal model
Fig. 14.5
Angiographic image of Cardioband after implantation
The Mitralign Percutaneous Annuloplasty System (Mitralign Inc., Tewksbury, MA USA) is a suturing plicating system, originally designed to plicate the mitral annulus at P1 and P3 level from a retrograde ventricular approach with a guide catheter inserted across the aortic valve [11]. Two pledgeted anchors are inserted with the aid of a radiofrequency wire puncture of the annulus and then pulled together to shorten or plicate the annulus and fixed with a stainless steel lock. Two sets of paired anchors are placed at both commissures. In a phase 1 report, septal-lateral dimension was reduced up to 8 mm. Since the Mitralign is a true suturing system, multiple plicating pledgets can be implanted along the annulus and different applications may be speculated. A multicenter CE Mark trial in Germany, Poland, Brazil, and Colombia has completed enrollment.
The Accucinch device (Guided Delivery System Inc., Santa Clara, CA, USA) also uses a retrograde ventricular approach to implant a series of anchors beneath the mitral annulus in the basal ventricular myocardium and connect them with a nitinol wire that is then used to cinch the mitral annulus and the basal ventricular wall. The Accucinch is currently under clinical evaluation.
Other devices in this category remain preclinical including the BOA RF catheter (QuantumCor Inc, Bothell, WA) which uses radiofrequency energy delivered via a transseptal catheter to heat shrink the collagen within the mitral annulus to mimic surgical ring annuloplasty. In animals, a 20–25 % reduction in anterior-posterior dimension was achieved with 6-month durability. A first-in-human validation study during open heart surgery is planned.
Indirect Annuloplasty
The basic principle of indirect annuloplasty is to apply tension on the coronary sinus in order to indirectly reduce the mitral annulus dimension and improve leaflet coaptation. Unfortunately this approach has shown to have serious limitations. Early attempts led to a modest reduction in MR severity and a high incidence of adverse cardiovascular events, including early and late myocardial infarction as well as coronary sinus rupture [12, 13]. The limited efficacy is likely related to the variable distance between the coronary sinus and the mitral annulus and due to the high risk of coronary artery compression. For these reasons coronary sinus devices have gradually lost appeal in favour of direct annuloplasties. Nonetheless, it is possible that some super-responders may be identifiable on the basis of careful preprocedure imaging and could gain benefit from this technique.
Among the indirect annuloplasty devices which have been developed, only the Carillon (Cardiac Dimensions Inc., Kirkland, WA, USA) remains currently available for clinical use after having obtained CE mark (Fig. 14.6). This device has anchors placed permanently in the coronary sinus, which are then pulled toward each other with a cinching device to reduce the mitral annular circumference by traction. In the Amadeus feasibility study, the device was successfully implanted in 30 of 48 (62.5 %) patients with modest improvement of MR, a 15 % rate of coronary compromise and death in 1 patient [14]. A newer version of the device was evaluated in the Transcatheter Implantation of Carillon Mitral Annuloplasty Device (TITAN) trial [15]. Among 53 enrolled subjects with secondary (64 % ischemic) MR, the device was successfully implanted in 36 patients (68 %). At 6 and 12 months a significant improvement in the degree of MR, LV dimension, functional status, and quality of life was documented. Comparison was made with baseline and with the 17 patients who were enrolled in the trial but did not receive implants.
Fig. 14.6
Carillon indirect annuloplasty device
Results of Treatment
Although very promising, not enough data are available at the moment to judge the clinical value of the percutaneous annuloplasty devices. On the other hand, many studies have been published on the early and mid-term outcomes of the percutaneous edge-to-edge repair. When assessing the results of the MitraClip therapy, however, it is important to consider that this is also a relatively new technique with limited follow-up. In addition, most studies about the MitraClip have included mixed populations of patients with both degenerative and functional MR, making assessment of specific outcomes in different subgroups more complex.
For instance, in the randomized EVEREST II (Endovascular Valve Edge-to-Edge Repair of Mitral Regurgitation Study) trial, 184 patients were designated (2:1) to receive MitraClip therapy and 95 patients to undergo surgical repair or replacement [16]. However, most of the patients were low-risk patients with primary MR (FMR being present in only 27 % of the cases).
Major adverse events at 30 days were significantly less frequent with MitraClip therapy (9.6 % versus 57 % with surgery, P < 0.0001), although much of this difference was attributable to the greater need for blood transfusion with surgery. The primary end point of freedom from death, mitral valve surgery, and MR severity >2+ at 12 months in patients with initial clinical success was similar, but by intent to treat analysis was lower with MitraClip (55 %) as compared with surgery (73 %, P = 0.0007). At 4 years, overall mortality was similar in the 2 groups, mitral valve surgery was used more often after MitraClip (25 % versus 5 % after surgery), and moderate or severe MR was more common after transcatheter therapy. The primary combined end point of freedom from death, surgery, or 3+ or 4+ MR in the intention-to-treat population was lower (40 %) with percutaneous repair and 53 % with surgery (P = 0.070). However, patients with a good result after MitraClip had sustained improvement for 4 years [17]. For the reasons mentioned above, the EVEREST II trial does not provide the best evidence for high risk patients with mitral regurgitation secondary to LV remodelling and dysfunction. Nevertheless secondary MR represents currently the most common indication for percutaneous EE repair (65–75 % of patients) [18].
One of the studies suggesting a potential prognostic benefit in high-risk patients treated with the MitraClip in both the degenerative and functional MR has been the High-Risk Registry of the EVEREST II study. Patients treated with the MitraClip had a better survival rate at 1 year compared to a matched group managed with optimal medical treatment alone. In addition, the registry demonstrated a significant reduction in heart failure hospitalization by a factor of approximately 50 % as compared to the year before implantation, improvement in clinical symptoms, and significant LV reverse remodeling over 12 months in patients submitted to MitraClip therapy [19].
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