Transcatheter Therapies for Mitral and Tricuspid Valvular Heart Disease

Mitral Balloon Valvuloplasty

Determining the morphology of the mitral valve and subvalvular apparatus is important in preprocedural planning for mitral balloon valvuloplasty (MBV). The suitability of a valve for MBV can be determined using a morphologic score; the most widely used is the system of Wilkins (see Classic References), which assigns a score of 1 to 4 for leaflet mobility, valve thickening, calcification, and subvalvular thickening (see Table 14.9). Recently, the incorporation of additional echocardiographic measures including commissural calcification and asymmetry and leaflet displacement have allowed refinement and improved accuracy for predicting outcome. The severity of concomitant MR is also a key determining factor for MBV, both as it relates to the final result, which may increase up to one grade, and to confirm that the patient’s symptoms are indeed caused by valvular obstruction and not concomitant regurgitation. In the latter case, surgical mitral valve replacement may be a better option for symptomatic relief. Transesophageal echocardiography (TEE) is a final step to assess further the severity of MR and valve morphology and to ensure the absence of left atrial (LA) thrombus before MBV. Some patients with severe calcification of the mitral annulus and leaflets, who are not candidates for balloon valvuloplasty, may be candidates for placement of a balloon-expandable transcatheter mitral valve replacement with a device initially approved for TAVR for AS. However, in a report of more than 100 such patients, the 30-day and 1-year mortality was high at 25% and 54%, respectively. For other patients with less calcification and a suboptimal balloon morphology or mixed stenosis and regurgitation, a dedicated transcatheter mitral valve replacement may be another alternative.

Indications

MBV is indicated in symptomatic MS patients who have at least moderate to severe MS, favorable valve morphology, absence of LA thrombus, and less than moderate to severe MR. In patients with rheumatic MS and calcified nonpliable valves who are at high risk or unsuitable for open surgery, MBV may be a reasonable alternative to provide palliative symptomatic relief. MBV may also be considered in asymptomatic patients with moderate to severe MS and new-onset atrial fibrillation after excluding LA thrombus (class IIb). In patients with symptoms and mild MS (mitral valve area [MVA] >1.5 cm ² ), MBV can be considered if there is evidence of significant MS with exercise testing (class IIb). The mechanism of benefit is separation of the fused commissures, which relieves the physical obstruction, thereby reducing the gradient and increasing MVA.

Procedure

The transvenous antegrade transseptal route is typically used to gain access to the left atrium to perform MBV. Inoue first used a self-positioning latex balloon wrapped with a nylon mesh to allow phased balloon expansion in 1982 and described the technique in 1984 (see Classic References). The double-balloon technique involves two peripheral arterial balloons tracked over separate guidewires placed in the left ventricle and simultaneously inflated.

The double-balloon technique was the first one used in the United States. Following transseptal catheterization and therapeutic anticoagulation, a balloon-tipped end-hole catheter is used to traverse the mitral valve via the transseptal puncture site. This catheter is navigated to the apex of the left ventricle, and once positioned, a 260-cm guidewire is then placed in the LV apex or looped across the aortic valve into the descending aorta. A second guidewire is placed using a similar technique or by using a dual-lumen catheter. Two 18- or 20-mm dilation balloons are tracked and positioned on the wires and inflated simultaneously to dilate the valve.

The Inoue technique has mostly replaced the double-balloon technique, in part because there is no risk of left ventricular (LV) perforation with the Inoue balloon ( Fig. 78.1 ). The initial size of the Inoue balloon is based on patient’s height. Once inserted over a guidewire into the left atrium, it can be steered across the mitral valve orifice with an internal stylet and then sequentially inflated multiple times over a 4-mm diameter range, with both hemodynamic and echocardiographic results assessed, to achieve the maximal dilation with the least increase in grade of MR. As such, it is important to evaluate carefully for severe commissural calcium preprocedurally. Calcium does not split with balloon inflation but does increase the potential for tearing the leaflets creating MR.

A reduction in mean mitral valve gradient by 50% or an increase in MVA greater than 1.5 cm ² is considered a successful result and can be achieved in more than 80% of appropriately selected patients. An increase in MR by more than one grade after balloon inflation should signal an end to the procedure despite a residual gradient. Event-free survival after MBV is influenced by valve morphology. In a large study of 879 North American patients with a mean follow-up of 4.2 ± 3.7 years, there was a greater immediate increase in MVA after MBV and improved long-term survival (82% versus 57%; P < 0.0001) in patients with a Wilkins score of 8 or less ( Fig. 78.2 ). Patients with higher echocardiographic scores have more events in the long term, including need for repeat MBV, need for mitral valve surgery, and death ( Fig. 78.2B ). In multivariate analysis, age, post-MBV MR grade of 3+ or higher, prior surgical commissurotomy, New York Heart Association (NYHA) Class IV symptoms, and elevated post-MBV pulmonary artery systolic pressure were all independently associated with worse outcome at follow-up.

The most common complication from MBV, severe MR, occurs in 2% to 10% of patients, with no significant difference between the Inoue and double-balloon techniques. Overall procedural mortality is approximately 1%. Other, less common procedural complications include pericardial tamponade, embolic events, vascular complications, arrhythmias, bleeding, stroke, myocardial infarction, residual atrial septal defect, and LV perforation.

Echocardiography is essential for many aspects of MBV, including the transseptal puncture and assessment of postprocedural results and complications (see Chapter 14 ). TEE is considered the gold standard, and 3D TEE has been shown to be superior to TTE in reducing fluoroscopy time and the interval from first transseptal puncture to first balloon inflation. Intracardiac echocardiography can also be used, with the advantage of avoiding the endotracheal intubation and general anesthesia usually required for TEE.

Rationale for Transcatheter Therapy

Surgery improves survival in observational studies but is associated with mortality rates of 1% to 5% and additional morbidity rates of 10% to 20%, including stroke, reoperation, renal failure, and prolonged ventilation. The risks of surgery are particularly high in patients who are elderly or have LV dysfunction and secondary MR. In one study of more than 30,000 patients undergoing mitral valve replacement, mortality increased from 4.1% in those younger than 50 years to 17.0% in octogenarians, although these outcomes improved in a more recent report. The risks and morbidity of surgery coupled with patient preference have stimulated attempts to develop less invasive solutions.

When considering percutaneous or transcatheter approaches for mitral repair, it is useful to classify them according to the major structural abnormality that they address. Unlike the extensive toolbox available to the mitral surgeon, transcatheter approaches are much more limited and often able to address only a single major element of the dysfunctional valve that contributes to MR.

Table 78.1 lists some of the devices, their manufacturers, and current state of development.

Leaflet Repair with MitraClip Device

MitraClip (Abbott Vascular) was the first transcatheter mitral valve repair technology to receive CE (Conformité Européenne) Mark approval (European Union) and has now also received FDA approval for patients with primary (degenerative) MR and prohibitive surgical risk as well as for heart failure patients with left ventricular dysfunction (secondary MR) despite optimal medical therapy ( Fig. 78.3 ). This system replicates the Alfieri stitch operation, in which the middle scallops of the posterior and anterior leaflets (P2 and A2, respectively) are sutured together to create a double-orifice mitral valve. The operation, although usually performed with adjunctive ring annuloplasty, has proved effective and durable in a wide variety of pathologies as well as in select patients without annuloplasty.

Trials with MitraClip have confirmed its feasibility (e.g., Endovascular Valve Edge-to-Edge Repair Study [EVEREST] I), and its safety and efficacy were compared with those of surgical repair in a randomized trial (EVEREST II). The procedure is performed with standard catheterization techniques using a transseptal approach from the right femoral vein. The clip delivery system is introduced through a 24F sheath into the left atrium, where it can be guided by TEE using a series of turning knobs through the mitral valve into the left ventricle. A properly aligned and oriented clip can grasp the P2 and A2 segments of the leaflets from the ventricular side to create leaflet apposition. Once leaflet insertion is confirmed by echocardiography, the clip can be released. If a suboptimal grasp occurs, the leaflet can be released, allowing repositioning before a second grasp attempt. Additionally, a second or more clips can be placed as needed for optimal MR reduction.

In the randomized EVEREST II trial, 184 patients received MitraClip therapy and 95 underwent surgical repair or replacement. These patients were almost a decade older (mean age, 67 years) than in usual surgical series and had more comorbidities. 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 the difference could be attributed to the greater need for blood transfusions with surgery. The freedom from the combined outcome of death, mitral valve surgery, and MR severity greater than 2+ at 12 months was higher with surgery (73%) than with MitraClip therapy (55%; P = 0.0007). In patients with acute MitraClip therapy success, the result appears durable, with a very low rate of later mitral valve surgery.

Subsequent analyses of this study and additional registries have demonstrated persistent reductions in MR grade, improvement in NYHA functional class, and reduction in LV dimensions with MitraClip therapy. Other studies have shown a lack of MS, no effect of initial rhythm on results, and importantly, greater benefit than with surgery for higher-risk patients ( Fig. 78.4 ). Although the EVEREST II trial failed to demonstrate efficacy equivalent to that of surgery for a diverse group of patients with varied risk and etiology, the EVEREST High-Risk Registry and prohibitive-risk patient subset, combined with the experience outside the United States, indicate a more appropriate role in high-risk patients.

A new indication has recently emerged for MitraClip therapy in heart failure patients with secondary MR based on the results of the COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients) trial. This landmark trial compared the MitraClip device with medical therapy in patients with secondary MR in 614 patients after initial optimal medical therapy. After 24 months of follow-up, there was a close to 50% reduction in the annualized rate of all hospitalizations for heart failure and an approximately 40% reduction in all-cause mortality with a very low rate of device-related complications (4%) ( Fig. 78.5 ). In contrast, a similar French study failed to demonstrate a difference between heart failure patients treated with MitraClip and optimal medical management at 12 months of follow-up. There are a number of reasons why these two similar trials had conflicting results, including different inclusion and exclusions, primary endpoints, operator experience, and procedural results. An additional trial in this space (RESHAPE HF2) has not yet been reported and may add further clarity to who are the best candidates for MitraClip repair. Several other devices, designed to provide leaflet repair, including NeoChord, Mitra-Spacer, and MitraFlex, are in preclinical or phase I evaluation (see Table 78.1 ). The PASCAL edge-to-edge repair device has some similarities to MitraClip in that it is used to create a double orifice mitral valve, but has wider grasping elements and a central spacer. In an initial report of 62 patients treated with this device, 98% and 86% had MR grade ≤2+ and ≤1+, respectively at 30 days. A comparison of this device and MitraClip (The CLASP Study of Edwards PASCAL Transcatheter Mitral Valve Repair System Study; NCT03170349) is underway.

Indirect Annuloplasty

The venous anatomy of the heart is of particular interest for treating MR because of the ease of access (from the right internal jugular vein) and the location of the great cardiac vein in proximity to the posterior mitral annulus. Some of the first attempts to treat MR without surgery consisted of mimicking surgical ring annuloplasty through placement of devices in the coronary sinus, so-called indirect or percutaneous coronary sinus annuloplasty. The goal of this approach is to remodel the posterior annulus, cinching the great cardiac vein or pushing on the posterior annulus from the vein to improve leaflet coaptation.

The CARILLON XE2 Mitral Contour System (Cardiac Dimensions) has CE Mark and uses anchors placed in the coronary sinus that are pulled toward each other with a cinching device to reduce the mitral annular dimension by traction ( Fig. 78.6 ). Early evaluation in the Amadeus study demonstrated feasibility, with implantation in 30 of 48 patients and modest improvement in quantitative measures of MR with a small risk of coronary compromise (15%) and death (one patient). More recently, a redesigned device was tested in the TITAN (Transcatheter Implantation of Carillon Mitral Annuloplasty Device) trial. Among 65 patients with secondary MR (62% ischemic), the device was implanted successfully in 36 patients, with a mean age of 62 years, mean ejection fraction (EF) of 29%, predominantly NYHA Functional Class III symptoms, and 2+ (30%), 3+ (55%), or 4+ (15%) grade MR. Quantitative measures of MR were better at 6 and 12 months than in 17 patients who did not receive implants. In the most recent randomized, blinded, and sham-controlled evaluation of this device (REDUCE FMR, NCT02325830), a statistically significant modest difference in MR volume was observed at 1 year despite many missing echocardiograms.

In general, indirect annuloplasty devices may be able to provide modest MR reduction in select patients, but likely less than that achievable surgically with a complete ring placed directly on the annulus. The limited efficacy is related to the location of the coronary sinus relative to the annulus (up to 10 mm more cranial), great individual anatomic variability, and limited benefit of partial annular remodeling. Whether this level of efficacy will result in sufficient symptomatic improvement and LV remodeling to justify the procedure requires further study. Some “super-responders” may be identified on the basis of anatomic considerations before the procedure. The risks of this approach must also be considered. In addition to the risk for damage to the cardiac venous system, devices in this location can compress the left circumflex or diagonal coronary arteries, which traverse between the coronary sinus and the mitral annulus in most patients. ^,

In this regard, one novel indirect approach to reduce the septal-lateral dimension that deserves further consideration is the cerclage annuloplasty technique, which recently entered clinical evaluation. This approach attempts to create a more complete circumferential annuloplasty by placing a suture from the coronary sinus through a septal perforator vein into the right atrium or ventricle, where it is snared and tensioned with the proximal end from the right atrium to create a closed pursestring suture. The procedure is guided by cardiac MRI and also uses a novel rigid protection device to avoid coronary compression.

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