Mitral regurgitation (MR) is the most prevalent form of moderate or severe valve disease in developed countries.¹ The etiology of MR can be divided into two categories. Primary or degenerative MR is caused by pathology of one or more of the components of the mitral valve (MV) leading to valve incompetence and subsequently to left ventricular (LV) remodeling and dysfunction. In contrast, secondary or functional MR is characterized by structurally normal valve leaflets and chordae in the setting of LV remodeling and dysfunction leading to an imbalance between closing and tethering forces on the valve.

Medical management does not alter the outcome of MR, and current guidelines recommend surgical intervention for patients with severe symptomatic primary MR or those with high-risk features. However, studies have estimated that up to 49% of patients with severe symptomatic MR are denied surgery based on their high-risk features.²

Transcatheter valve interventions have emerged as a viable alternative for patients who are at prohibitive risk for surgery. Multiple imaging modalities are utilized when planning for and guiding these interventions, with a special emphasis on three-dimensional (3D) transesophageal echocardiography (TEE). This article focuses on imaging for MV interventions to treat MR, specifically transcatheter MV repair (MitraClip [Abbott; Menlo Park, CA]), transcatheter mitral valve replacement (TMVR), and transcatheter mitral valve-in-valve (ViV) procedures.

MitraClip

The MitraClip system is a transcatheter version of Dr. Alfieri's edge-to-edge surgical technique for MV repair. Introduced in 1991, the Alfieri technique involves suturing the free edge of the MV leaflets at the site of regurgitation to create a double orifice MV. The edge-to-edge technique was initially criticized because it does not directly address the anatomical pathology of MR, and, additionally, there was fear that this would result in significant stenosis of the MV. However, long-term results have proven this to be highly effective and durable.^3-4 The MitraClip uses a transvenous/transseptal approach that mimics the Alfieri technique by grasping and approximating the A2-P2 regions using a nickel-titanium clip to create a "double orifice."⁵ In high-risk patients with a prohibitive surgical risk, transcatheter MV repair has been shown to significantly decrease the degree of MR, reduce hospitalizations, and improve functional class.⁶ The MitraClip was approved for use in the United States in October 2013 for patients with significant symptomatic primary (degenerative) MV disease with MR severity ≥3+ in patients who are determined to be at prohibitive surgical risk.⁷ Clinical trials such as the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial are currently investigating the use of the MitraClip in patients with secondary (functional) MR. Additionally, in experienced centers, the treatment of both lateral A1-P1 and medial A3-P3 degenerative MR using the MitraClip has been shown to be feasible with comparable outcomes to central MR.⁸

Preprocedural Imaging

Transthoracic echocardiography is valuable as a screening tool for patients being considered for the MitraClip and can identify the etiology and severity of the MR. In the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study II) trial, patients were also assessed with a preprocedural TEE to determine eligibility for the procedure. 3D TEE can be particularly useful here because it allows for advanced quantification of the leaflet and annular anatomy. To confirm eligibility, patients ideally should have a primary regurgitant jet originating from malcoaptation of the A2 and P2 scallops. Calcification or clefts in the grasping area on A2 or P2 should be noted because this may preclude clip implantation. Additional exclusion criteria are severe mitral annular calcification as well as mitral stenosis (MV area <4.0 cm²). For patients with a flail leaflet, the width of the flail segment must be <15 mm, and the flail gap must be <10 mm. Lastly, the LV ejection fraction must be >25%, and the LV end-systolic diameter must be ≤5.5 cm.⁹

Procedural Imaging

The initial and a very important step is supervision and guidance of the transseptal puncture (Figure 1A-B). The optimal site of crossing is the posterosuperior aspect of the fossa ovalis. There must be sufficient superior clearance above the mitral annular plane to allow for positioning of the system and clearance for grasping the valve leaflets. The ideal site for transseptal puncture should also be >4 cm above the mitral annulus for degenerative MR and 3-4 cm for functional MR. The additional height is necessary in degenerative MR to avoid the leaflets that may prolapse above the annular plane. 3D TEE permits visualization of the real anatomical aspect of tenting of the interatrial septum and can allow for direct measurement and proper positioning of the septal crossing site. Tenting is also well-visualized with a combination of the midesophageal aortic valve short-axis view and the bicaval view.¹⁰

After transseptal puncture, the steerable guide catheter is advanced into the left atrium (LA) over an exchange wire. The tip of the steerable guide catheter has a radiopaque ring easily seen on fluoroscopy and TEE and must be imaged at all times to avoid injury to the LA. The clip delivery system is advanced through the steerable guide catheter under fluoroscopy and with continuous TEE guidance until it is advanced beyond the steerable guide catheter into the LA.

Using live 3D TEE guidance with an en face view of the MV, the clip delivery system is cautiously deflected until it is directed toward the MV. Additionally, the two-dimensional (2D) TEE midesophageal long-axis view provides guidance for anterior-posterior positioning while the midesophageal intercommissural view does so for medial-lateral positioning. A manipulation made in one plane must be repetitively assessed in the other plane to confirm correct positioning of the clip. The clip with its arms closed is centered over the origin of the MR jet. The en face view provided by 3D TEE offers a clear advantage compared with 2D TEE views.^11-12

Once the delivery system is positioned in the LA above the MV, the arms of the clip device are opened. 3D TEE is preferably used to guide rotation of the clip (Figure 1C) so that it is perpendicular to the line of coaptation.¹³ The clip delivery system is then advanced into the LV just below the mitral leaflet edges, paying special attention to deviation or rotation of the clip with movement. Care should be taken to avoid significant adjustments of the clip within the LV in order to prevent injury or entrapment within the subvalvular apparatus. The orientation of the clip should be confirmed by both 3D TEE and 2D TEE. In 3D TEE, the clip can be assessed from either a ventricular perspective or an atrial perspective in either diastole or by significantly lowering the gain to cause leaflet dropout.^11-12

Grasping of the leaflets is best guided by 2D TEE utilizing the midesophageal long-axis LV outflow tract (LVOT) view. 2D TEE is superior for visualization of this step because of its higher temporal and spatial resolution (Figure 1D). The clip arms are positioned at a 120° angle and pulled back until the leaflets are firmly captured. The clip is gradually closed, and the residual regurgitation is monitored by color Doppler. If significant regurgitation is still present, the leaflets can be released and the clip should be repositioned.¹⁴ Once the clip location, reduction in MR, and residual MV area are considered appropriate, the clip is released (Figure 1E). MR must be reassessed because prior to clip release, the clip delivery system holds the clip in a relatively fixed position.¹¹ The degree of residual MR has been demonstrated to be a predictor of long-term survival, and additional clips may be implanted as needed. However, the risk of significant iatrogenic mitral stenosis must be considered because a residual transmitral gradient >5 mm Hg has been shown to have a negative impact on long-term outcomes.^15-16

Prior to the conclusion of the procedure, a final evaluation of residual MR, the transmitral gradient, and an assessment for any iatrogenic atrial septal defect at the site of transseptal puncture should be performed.¹¹

Figure 1: MitraClip Procedure

Transcatheter Mitral Valve Replacement

At present, there are no TMVR devices approved for clinical use. Transcatheter aortic valve replacement has been in clinical practice for more than a decade, but TMVR is still in development because the anatomy of the MV is more complex than that of the aortic valve. Whereas transcatheter aortic valve replacement relies on native valve calcifications for anchoring, prosthesis stability in a mitral annulus, which is typically noncalcified and saddle-shaped, presents a special set of challenges. Furthermore, TMVR may cause LVOT obstruction, and planning must account for this possibility. There are two possible approaches to TMVR: transapical and transseptal. There are currently at least seven different TMVR devices undergoing clinical evaluation, each of which employs a different structural design and anchoring mechanism.¹⁷

Preprocedural Imaging

The mitral annulus is a saddle-shaped, non-planar structure that needs to be anatomically quantified when planning for TMVR. Cardiac gated computed tomography (CT) and 3D TEE are the typical modalities of choice for preprocedural planning, including calculating the cross-sectional area, perimeter, and diameters of the mitral annulus.¹⁸ Additionally, CT protocols allow for virtual placement of a TMVR and characterization of a post-procedural "neo-LVOT." Factors that may predict neo-LVOT obstruction are a more acute aortomitral angle, small LV cavity size, and basal septal hypertrophy. These factors must be viewed together when assessing feasibility of TMVR; however, exact cutoff values for minimal neo-LVOT area are yet to be determined.¹⁹

For transapical TMVR, access location can be determined on CT images by examining the trajectory of the mitral annulus beyond the epicardium and even beyond the chest to select the appropriate intercostal space for access. Other important information for procedure planning that can be obtained on CT include presence of annular calcification, leaflet anatomy, tenting height, and papillary muscle structure.¹⁹ For transseptal TMVR, evaluation of the interatrial septum and location of transseptal puncture are similar to MitraClip.

Procedural Imaging

To illustrate TMVR imaging, we use Intrepid TMVR (Medtronic; Minneapolis, MN) as an example of a transapical TMVR and Caisson TMVR (LivaNova; London, UK) as an example of a transseptal TMVR. Although the procedural details for each device differ, intra-procedural imaging is best performed using a combination of 3D TEE and fluoroscopy:

• Intrepid TMVR. Using continuous imaging guidance, transapical LV access is obtained using a trajectory that avoids the papillary muscles, septum, and right ventricular apex (Figure 2A). An en face 3D TEE view is used to position the delivery system at A2-P2 in the mitral orifice. 3D TEE is especially useful for determining rotational alignment of the device with the annulus. Contemporaneous fluoroscopic imaging guides the valve deployment (Figure 2B-C). Simultaneous 2D long-axis and commissural views can also be used here and provide complementary data to the 3D images. Immediately after device deployment, 2D and 3D TEE are used to confirm device position and function (Figure 2D). An assessment of the LVOT using the transgastric view should be performed at this time to ensure that there is no obstruction. Attention should also be paid to the degree and type of MR as well as the MV orifice area.¹⁹
• Caisson TMVR. Once transfemoral venous access is obtained, TEE imaging guidance is provided for transseptal puncture. The Caisson system consists of two separate pieces: a mitral anchor and a bioprosthesis. Continuous imaging with TEE and fluoroscopy guides the positioning of the anchor within the mitral annulus (Figure 3A). The anchor has four feet on the ventricular side (which are able to engage the sub-annular fibrous groove) as well three atrial fixation loops (Figure 3B). The valve is then delivered into the anchor (Figure 3C). After deployment, there should be an immediate assessment to confirm device position, function, and LVOT obstruction. This device is repositionable and retrievable should there be an unsatisfactory result.^17,20

Figure 2: Transapical Intrepid MV Replacement

Figure 3: Transseptal Caisson MV Replacement

Transcatheter Mitral ViV Implantation

Among patients undergoing surgical MV replacement, there has been a trend toward using bioprosthetic valves as opposed to mechanical valves.²¹ Given the high risk of re-do MV surgery when these surgical valves fail, transcatheter ViV implantation using transcatheter aortic valves inside a failed surgical mitral bioprosthesis has emerged as a promising therapy. The balloon-expandable SAPIEN XT and SAPIEN S3 valves (Edwards Lifescience; Irvine, CA) have been approved for implantation in the mitral position, and initial data have shown excellent short-term outcomes when these valves are successfully placed.²² ViV placement can be performed through either a transseptal or transapical approach.

Preprocedural Imaging

Multimodality preprocedural imaging is critical to performing ViV procedures. Prior to imaging, accurate information regarding the manufacturer and size of the prior surgical bioprosthesis should be reviewed, and the true internal diameter should be used as a reference. Cardiac CT is utilized to assess the actual internal diameter; however, caution should be used because it mainly visualizes the metal frame of the bioprosthesis and may overestimate this distance. 3D TEE allows for high-quality visualization of all structures within the sewing ring and can provide complementary data to CT to determine valve sizing. Additionally, LVOT obstruction post valve implantation is again a concern here. Once the transcatheter valve is deployed, the surgical bioprosthetic leaflets are displaced and form a covered stent that can cause this obstruction. The risk for obstruction can be predicted preprocedurally through both CT and 3D TEE analysis.^23-24

Procedural Imaging

The procedural details differ based on the approach used. If a transseptal approach is used, 3D TEE is used to guide the transseptal puncture. The height above the bioprosthetic valve is not as crucial here in contrast to the MitraClip procedure, and thus an inferoposterior puncture may be beneficial because it allows for a more direct path to the valve. Fluoroscopy (Figure 4A-C) and 3D TEE (Figure 4D-F) are used to guide valve positioning. The new prosthesis is oversized by approximately 10% to allow for a flared deployment on the ventricular side to prevent atrial migration. After the valve is deployed under rapid ventricular pacing, 3D TEE should be used to assess for leaflet opening and valve position and to evaluate for transvalvular and intervalvular regurgitation.^23-24

Figure 4: Mitral ViV Procedure

Conclusions

Although MR is highly prevalent, many patients are not offered treatment because they were previously thought to be at prohibitive surgical risk. Transcatheter interventions offer efficacious treatment options for these patients. Multimodality imaging is essential for planning and guiding these interventions. All procedures described are demonstrated in Video 1.

Video 1: 3D TEE Guidance of Various Percutaneous Mitral Interventions

References

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Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, CHD and Pediatrics and Quality Improvement, Statins, Acute Heart Failure, Interventions and Imaging, Interventions and Structural Heart Disease, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging, Mitral Regurgitation

Keywords: Diagnostic Imaging, Alloys, Antineoplastic Combined Chemotherapy Protocols, Aortic Valve, Atrial Fibrillation, Atrial Septum, Bioprosthesis, Constriction, Pathologic, Cross-Sectional Studies, Cytarabine, Diastole, Echocardiography, Echocardiography, Transesophageal, Fluoroscopy, Heart Atria, Heart Failure, Heart Septal Defects, Atrial, Heart Valve Diseases, Hospitalization, Hypertrophy, Iatrogenic Disease, Metals, Mitral Valve, Mitral Valve Stenosis, Mitral Valve Insufficiency, Outcome Assessment, Health Care, Papillary Muscles, Pectinidae, Pericardium, Prolapse, Punctures, Rotation, Surgical Instruments, Stroke Volume, Stents, Transcatheter Aortic Valve Replacement, Tomography, Tomography, X-Ray Computed

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