General description of procedure, equipment, technique
Transcatheter repair of the mitral valve (MV) for severe mitral regurgitation (MR) with the MitraClip system (Abbott Vascular, Santa Clara, CA) is a novel, entirely percutaneous procedure requiring a transfemoral venous access (Figure 1). The system consists of a steerable guide catheter, which is inserted through a femoral access and across the intraatrial septum following a transseptal access. Through this, the clip delivery system (CDS) is advanced toward the MV.
At the tip of the CDS is the MitraClip, which is then carefully and accurately positioned where the MR is originating. Once closed, the clip opposes the free edges of the mitral leaflet, resulting in a permanent coaptation at that site. This procedure simulates the Alfieri surgical edge-to-edge mitral valve repair.
The unopposed free edges remain mobile, resulting in a double office MV. The clip is then released, and if MR reduction is inadequate, a second (or even third) clip could be used. The CDS is then simply exchanged for a second CDS.
Fluoroscopic and transesophageal guidance (TEE) is essential and thereby the procedure is performed with the patient under full general anaesthesia. Both 2D and 3D TEE is essential as it is used to guide the transseptal access, positioning and orientation of the CDS, assessment of MR, and mitral stenosis (MS) before, during, and after clip deployment, as well as for complications.
The MitraClip system can be applied to degenerative MR (DMR) and functional MR (FMR). DMR originates from organic disease of the MV leaflets and subvalvular apparatus. With FMR, the MV leaflets and subvalvular apparatus is preserved but deformation from an abnormal left ventricle and mitral annulus has led to MR.
Myxomatous degeneration with leaflet prolapse and flail are typical DMR cases, whereas posterior leaflet tethering and mitral annulus dilation with poor leaflet coaptation are typical FMR cases.
The MitraClip system is the only transcatheter device available for the treatment of mitral regurgitation. In the United States, it is commercially available for prohibitive surgical risk patients with DMR and as part of a clinical trial for FMR, whereas it is commercially available in Europe and in special access schemes in other countries.
Indications and patient selection
As MV surgery is still the preferred method of MV repair, a review of the American College of Cardiology/American Heart Association (ACC/AHA) 2014 guidelines for MV surgery or transcatheter repair in chronic severe DMR are as follows:
1. Symptomatic patients:
- Class I (B) – EF >30%Class IIb (LOE C) – EF <30%Class IIb (LOE B) – transcatheter repair in patients with NYHA class III/IV with reasonable life expectancy and are at prohibitive risk for surgery
2. Asymptomatic patients
- Class I (LOE B) – EF 30%-60% and/or ESD ≥ 40 mm
- Class IIa (LOE B) – EF >60% and ESD <40 mm, with >95% likelihood of successful repair without residual MR
- Class IIa (LOE B) – EF >60% and/or ESD <40 mm, with new onset atrial fibrillation or pulmonary hypertension (PASP >50 mm Hg at rest)
It is a Class I (LOE B) indication for the MV repair over MV replacement, and to be referred to surgical centers experienced in MV repair for DMR. For moderate DMR, it is a Class IIa (LOE C) for concomitant MR repair when the patient is undergoing cardiac surgery for other medical problems.
For chronic severe FMR, it is a Class IIb (LOE B) indication for MV surgery in symptomatic patients with NYHA class III/IV.
The following are appropriate indications for the consideration of repair with the MitraClip system based on recently published trials and ACC/AHA 2014 guidelines:
- Symptomatic patients.
- For DMR, prohibitive surgical risk patients with an estimated surgical MV replacement mortality rate ≥ 8% either from the Society of Thoracic Surgeon (STS) mortality score or as reviewed by a cardiothoracic surgeon. Due to on-going clinical trials, FMR patients maybe considered if they are not appropriate for MV surgery as determined by the local heart team.
- Moderately severe (3+) or severe (4+) MR on echocardiographic visualization. For DMR, at least a vena contracta width ≥ 7 mm (parasternal long axis view), a regurgitant volume ≥ 60 ml/beat, regurgitant fraction ≥ 50%, or an effective regurgitant orifice ≥ 40mm2 should be present. for FMR, at least a regurgitant volume ≥ 30 ml/beat, regurgitant fraction ≥ 50%, or an effective regurgitant orifice ≥ 20mm2 should be present.
- For DMR, the prolapsing or flail scallop should ideally be the middle anterior and/or posterior MV leaflets (A2 or P2 segments). Attempting the lateral or medial scallops is more challenging but are not necessarily an exclusion criteria.
The MitraClip procedure should be avoided in the following patients:
- Patients not able to undergo either TEE or general anesthesia.
- Patients requiring concomitant coronary artery bypass and other valvular surgery.
- Unsuitable vascular access where both femoral veins are occluded or stenosed, or there is an inferior vena caval obstruction. An inferior vena cava (IVC) filter is not a contraindication.
- Echocardiographic assessment with MV orifice are <4.0 cm2, flail width ≥ 15 mm or flail gap ≥ 10 mm in DMR, coaptation depth >11 mm, and coaptation length is <2 mm in FMR (Figure 2).Mitral valve anatomical definitions: (A) Flail gap – greatest distance between ventricular side of flail segment and atrial side of opposing edge. (B) Flail width. (C) Coaptation length – vertical length of leaflets that is in contact.
- MR with multiple jets of significant severity should be excluded.
- Adverse leaflet morphology that makes grasping difficult includes severe calcification or nodules at leaflet tips, clefts at grasping sites or severe bileaflet prolapse, as well as rheumatic MV, which can lead to MS. Commissural MR is also not suitable.
- Previous MV leaflet surgery.
- Patients with active or a previous history of endocarditis.
Details of how the procedure is performed
Important preprocedure care includes:
- A transthoracic echocardiogram (TTE) and TEE confirming the indications and contraindications for the procedure.
- Warfarin is discontinued 3 days prior, aiming for an international normalized ratio ≤ 1.7.
- Aspirin and clopidogrel loading dose the night prior to the procedure.
- Lab work (basic profile), and group and hold blood.
Important procedure care includes:
- Patient is anesthetized and intubated in the catheterization laboratory, as fluoroscopy is required. A right internal jugular venous central line and radial artery line is obtained. These lines have dual usages, the venous line for fluids and drugs but also for right heart catheterization, the arterial line for pressure but also for left heart catheterization.
- TEE is performed to confirm severity and location of MR, preferably with a 3-D probe. Additional baseline information is noted, such as fluid in the pericardial space, ventricular function, intraatrial septum, and other valvular dysfunction.
- Intravenous antibiotic therapy at induction (such as cefazolin 1 g).
- Administration of heparin after the transseptal puncture, aiming for an activated clotting time (ACT) >250 seconds, which is checked every 30 minutes.
Important postprocedure care includes:
- Completion of intravenous antibiotic therapy
- Monitoring for any cardiovascular complications
- Ambulating about 4 hours after removal of femoral vein sheath (depends on closure technique or 6 hours following manual compression)
- Aspirin 325 mg daily for 6 months and clopidogrel 75 mg daily for 1 month
- Lab work morning following procedure (basic profile)
- Predischarge transthoracic echo, in particular, assessing residual MR
- Aiming for discharge by lunchtime
Follow-up is essential to assessing the patient’s response to the procedure, monitoring their symptoms, and adjusting medical treatment as appropriate; TTE assessment, in particular, the severity of MR and development of MS. Suggested follow-up intervals are 30 days, 6 months, 12 months, and yearly thereafter.
The MitraClip procedure in detail
Vascular access is performed under fluoroscopic guidance, over the femoral head, with a modified Seldinger technique with either a Cooks needle or a micropuncture kit. Preclosure can be performed at this stage.
Left and right heart catheterizations are performed via the radial arterial and internal jugular venous lines. The baseline hemodynamics and cardiac output are recorded and will be compared with those postprocedure.
Transseptal puncture is performed under TEE guidance to ensure that the optimal height above the MV coaptation is achieved. This height corresponds to the working length of the clip delivery system from its tip to the proximal steerable shaft, and is about 4 cm from the level of leaflet coaptation to the level of transseptal access.
In patients with DMR, the leaflet coaptation point is above the MV annulus, and the transseptal puncture is performed in a more superior and posterior position. In FMR, the leaflet coaptation is below the MV annulus, and the transseptal puncture is performed in a mid and inferior position. The position is assessed via the bicaval and short axis view (which can be simultaneously displayed using the X-plane view function on a 3-D probe), whereas the height is assessed in the four-chamber view (0° view).
The views are often used back and forth until the desired transseptal location is found. Although it may seem time-consuming, an optimal transseptal location will ensure a smoother MitraClip procedure.
Heparin is administered after transseptal puncture, aiming for an ACT >250 seconds and is checked every 30 minutes. A 16 Fr sheath is used to dilate the femoral vein prior to the introduction of the 24 Fr steerable guide catheter and dilator (of note the guide catheter tapers to a 22 Fr tip). Once it is across the septum, the dilator is removed, and the tip of the catheter is placed roughly 1 cm into the left atrium (visualized on TEE due to its echogenic tip) and deflected toward the MV.
The CDS consists of the MitraClip at its distal tip, which is preceded by the steerable sleeve and delivery catheter, and lastly the delivery catheter handle (Figure 1) (B). The MitraClip device (made from cobalt-chromium and covered in polyester) consists of the gripper, which when closed, sandwiches the mitral leaflets to the device arms (Figure 1) (C).
These arms are 4 mm wide and 8 mm long. The steerable sheath is adjustable in both the anterior-posterior and medial-lateral directions via knobs at the hilt. The delivery catheter handle controls the opening and closing of the MitraClip device arms and grippers, and release via the arm positioner knob, gripper lever, and actuator knob, respectively. Both the steerable guide and CDS are mounted on a stabilizer, preventing accidental movement and ensuring precise translation of steering.
The CDS is introduced into the left atrium via the steerable guide and is angled away from the free wall toward the MV via the directional knobs (the MitraClip device is in the closed position). Once above the MV, the MitraClip is adjusted so that it splits the MR jet on TEE. The arms are then opened, and on the 3-D TEE surgical view of the MV, the arms are rotated so that they are perpendicular to the leaflet tips. With the arms in the closed position, the CDS is advanced across the MV (to prevent any leaflet damage) and once it is below the MV, the arms are opened and the orientation is rechecked.
To grasp the leaflets, the CDS is slowly pulled back, so that the leaflets come to rest on the arms (Figure 3). This is visualized on TEE using a bicommissural view and simultaneous left ventricular outflow tract view from the probe’s X-plane function. To capture the leaflets, the gripper level is dropped, allowing the grippers to sandwich the leaflets to the arms.
The amount of leaflet insertion is assessed and is important, as it reduces the likelihood of leaflet detachment. The arms are then closed and a full MR assessment is made. If there is significant residual MR, the location is noted and a second MitraClip could be attempted, so long as the MV gradient is not greater than 5 mm Hg. If the MitraClip is not in the correct position, the arm can be opened, and regrasping can be performed until a satisfactory positioned is obtained.
Prior to releasing the MitraClip, the arms are locked, the lock line and then the gripper line are removed, and finally, the release pin is removed and turning the actuator knob releases the device. The CDS is removed, and if a second MitraClip is required, the process is repeated with a second CDS.
Grasping the mitral leaflets with a second CDS is easier, as the first MitraClip would have partially approximated the leaflet tips. At the conclusion of the procedure, a final MR assessment and hemodynamics with cardiac outputs are performed. Once the femoral vein sheaths are removed, hemostasis can be achieved via manual compression, subcutaneous stitch, or by completing the preclosure stitches.
Interpretation of results
The MitraClip procedure is associated with improvements in patient’s symptoms, NYHA grade, and quality of life but has yet to show improvements in survival rates in a randomized trial. There are also significant improvements in left ventricular function, including left ventricular ejection fraction and end diastolic diameter.
A MV mean gradient ≤ 5 mm Hg at the conclusion of the procedure is acceptable and often does not lead to symptomatic mitral stenosis nor is the gradient likely to increase in future echocardiographic assessments. However, an MV mean gradient >5 mm Hg prior to release of the MitraClip device should be avoided as symptomatic mitral stenosis is likely, and the gradient is likely to increase at follow-up. In this instance, the MitraClip should not be deployed and the procedure is concluded.
Hemodynamics assessment preprocedure and postprocedure have demonstrated significant improvements in cardiac output (CO) and index (CI), stroke volume, systemic vascular resistance, and left ventricular end-diastolic pressure. Importantly, a low CO syndrome (inotropic support to maintain a systolic blood pressure >90 mm Hg and CI >2.2 L/min/m2 for at least 30 minutes in the intensive care unit), which is observed in about 7% of MV surgery patients and is a predictor of operative mortality, was not observed with the procedure.
Performance characteristics of the procedure (applies only to diagnostic procedures)
The advantage of the MitraClip procedure is that the patient avoids the need for a traditional MV surgery and its associated comorbidities. Access is via a femoral vein rather than through the chest, leading to a less painful and shorter recovery time and a hospital stay of less than 24 hours in most cases. The patient is often extubated in the catheterization lab and does not require a stay in the intensive care unit. The heart is not arrested during the procedure; hence only one cardiac anaesthetist is required.
The disadvantages of the MitraClip procedure are the CDS itself, the MitraClip device, and dependence on TEE. The CDS, although extremely sophisticated, relies heavily on a good transseptal puncture (in an appropriate location) to ensure adequate height for manoeuverability and shaft alignment. The MitraClip device is limited by its dimensions and hence two or more clips are required if the regurgitant orifice is large.
Also there is no unilateral control of one side of the grippers or arms, which means if only one leaflet is caught, there is no way to capture the other leaflet without starting over. The procedure relies heavily on TEE, and prolonged imaging can lead to deterioration of the image quality as the probe heats up.
Outcomes (applies only to therapeutic procedures)
In the only randomized trial comparing the device to surgery (2:1 ratio) that involved 279 patients, the MitraClip procedure was safer (major adverse events was 15% vs. 48%, P <.001); however, it was less effective with lower freedom from a combined end point of death, surgery for MV dysfunction, and from grade 3+ or 4+ MR at 12 months (55% vs. 73%, P = .007) in an intention to treat analysis. In the treated population, the acute procedural success rate (postprocedure MR grade ≤ 2+) was 77% for the device group versus 100% for the surgical patients.
Refocusing the study population on only high-risk surgical patients (defined as an estimated operative mortality rate ≥ 12% as determined by a cardiothoracic surgeon or the Society of Thoracic Surgeons mortality score) in a nonrandomized cohort, the 30-day mortality of 7.7% was similar to a medically treated comparator group but with an improved 12-month survival rate of 76% vs. 55% (P = .047). Compared to baseline, there were significant improvements in NYHA grade, quality of life score, left ventricular volumes, and rate of hospitalizations.
Alternative and/or additional procedures to consider
Patients not at high-risk for MV surgery should be referred to a center with expertise in MV repair. Similarly, in patients where the MitraClip procedure has been unsuccessful (severe symptomatic MR recurrence, clip detachment, endocarditis, development of mitral stenosis), the patient should be referred to a center with expertise in MV repair after the MitraClip procedure.
A randomized trial comparing medical treatment versus the MitraClip procedure in high surgical risk patients with FMR is underway; however, optimal medical management at the moment is still the standard of care. Approved devices for heart failure, such as a biventricular pacemaker or defibrillator, should be used in eligible patients, either before or after the MitraClip procedure.
Complications and their management
The standard risks for left and right heart catheterization remain true for the MitraClip procedure with additional risks from general anesthesia and procedural TEE use. Specific risks for the MitraClip procedure are:
- Failure to adequately reduce the severity of MR, leading to the requirement for elective MV surgery is uncommon with experienced operators.
- Partial clip detachment of the MitraClip from one leaflet, endocarditis, physical damage to the leaflets and MV apparatus, development of severe symptomatic MS (with transmitral mean gradient >5 mm Hg) and device embolization are uncommon.
- An iatrogenic atria septal defect (ASD) is created, however only hemodynamically unstable patients with large ASD require closure.
- Vascular complications from 24 Fr venous access are uncommon and can be further reduced using a subcutaneous stitch or direct vessel stitch devices.
- Periprocedural death, myocardial infarctions, and strokes are uncommon.
- Patients with a STS operative mortality score ≥ 12% have worse outcomes compared to lower STS scores, which reflect the underlying severity of the patients’ comorbidities.
What’s the evidence? (Provide an Annotated Bibliography. Follow the style of The New England Journal of Medicine.)
Feldman, T, Foster, E, Glower, DD. “EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation”. N Engl J Med. vol. 364. 2011. pp. 1395-406. (The only randomized multicenter percutaneous transcatheter mitral valve repair system trial versus surgery to date. The MitraClip system demonstrated superior safety with similar improvements in left ventricular size, NYHA class, and quality of life measures. However, driven by higher surgical intervention for mitral valve dysfunction at 12 months (20% vs. 2%), the MitraClip system was less effective (overall combined end point of death, surgical intervention, and freedom from MR grade 3+ or 4+ was lower 55% vs. 73%, P = .007).
Whitlow, PL, Feldman, T, Pedersen, WR. “EVEREST II Investigators. Acute and 12-month results with catheter-based mitral valve leaflet repair: the EVEREST II High Risk Study”. J Am Coll Cardiol. vol. 59. 2012. pp. 130-9. (Nonrandomized, multicenter comparison of 114 patients deemed as high surgical risk (either by a Society of Thoracic Surgeon operative mortality score of ≥12% or a surgeon estimated mortality rate) comparing the MitraClip system to medical therapy. The 12-month survival rate was higher (76% vs. 55%, P = .047) and significant improvements in left ventricular volumes, NYHA, and quality-of-life. Also, 78% had a 12-month MR grade ≤ 2+.
Siegel, RJ, Biner, S, Rafique, AM. “EVEREST Investigators. The acute hemodynamic effects of MitraClip therapy”. J Am Coll Cardiol. vol. 57. 2011. pp. 1658-65. (Multicenter hemodynamic results of 107 patients following the MitraClip procedure. There were significant improvements in forward stroke volume, cardiac output, and left ventricular end diastolic pressure.)
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- General description of procedure, equipment, technique
- Indications and patient selection
- Details of how the procedure is performed
- Interpretation of results
- Performance characteristics of the procedure (applies only to diagnostic procedures)
- Outcomes (applies only to therapeutic procedures)
- Alternative and/or additional procedures to consider
- Complications and their management
- What’s the evidence? (Provide an Annotated Bibliography. Follow the style of The New England Journal of Medicine.)