Transapical Closure of Mitral Paravalvular Leaks With Use of Amplatzer Vascular Plug III

Abstract: Introduction. Paravalvular leak (PVL) may complicate cardiac valve replacement surgery. Radical treatment is required if a PVL produces heart failure (HF) symptoms or severe hemolysis. Even though transcatheter PVL closure (TPVLC) has become a valid alternative to reoperation, a number of anatomical conditions may prove technically challenging for transvascular access. We intended to verify the utility of transapical access in such settings. Methods. We report a prospective series of 7 patients with mitral PVLs who underwent transapical TPVLC. The Heart Team made the choice of treatment and Amplatzer Vascular Plug III devices were used off-label as occluders. Results. Transapical TPVLC enabled excellent sealing of mitral PVL in 6 cases. This resulted in HF symptom reduction and decreased NT-proBNP plasma concentration. No procedure-related complications occurred. Conclusions. Transapical access seems to be an efficient and safe alternative for transvascular approach for mitral TPVLC, but further technical development is still needed.

J INVASIVE CARDIOL 2013;25(10):497-501

Key words: paravalvular leak device closure, transapical approach, heart failure, mitral valve replacement

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Paravalvular leak (PVL) is a prosthetic valve dysfunction, which may exacerbate heart failure (HF) symptoms and trigger severe hemolysis. The prevalence of clinically significant PVL in patients after surgical mitral valve replacement is estimated at 1%-2%.^1,2 Even though a successful reoperation can improve prognosis in such cases,³ the perioperative risk is usually high. Transcatheter PVL closure (TPVLC) has been constantly developing over the past few years and seems to pose an efficient alternative today.^4,5 Still, the technical challenges that need to be overcome while accessing the PVL site and deploying the plugs can easily hinder the success.

In a patient with mitral PVL, thickened and stiffened interatrial septum along with grossly enlarged left atrium are often major obstacles. These can be circumvented with the alternative transapical approach. Left ventricle (LV) apical puncture was historically employed for imaging and hemodynamic measurements.⁶ Nowadays, it is frequently used for transcatheter aortic valve implantation (TAVI),^7,8 with lateral minithoracotomy typically performed as the initial step. It was our intention to evaluate the utility of this approach for TPVLC. 

Methods

The choice of transapical approach was in each case based on the collaborative judgment of the Heart Team. The patients were recruited prospectively from those in whom transvascular approach either previously failed due to technical impediments or was primarily considered unfeasible. Simultaneously, all patients were disqualified from surgical PVL correction based on prohibitive reoperation risk or known unfavorable local anatomical conditions. Before PVL was considered significant, prespecified clinical and echocardiographic criteria had to be met as follows. Despite optimal pharmacotherapy, the patients had to suffer from New York Heart Association (NYHA) class 3 or 4 HF, which, according to the opinion of the Heart Team, was attributed to mitral regurgitation. Concurrently, the presence of mitral PVL needed to be accompanied by two or more of the following indirect echocardiographic indicators of significant regurgitant flow: (1) systolic flow reversal in at least one of the pulmonary veins; (2) increased calculated pulmonary artery systolic pressure; (3) lack of left atrial (LA) size reduction after mitral valve replacement (MVR) or recurrent and progressive LA dilation at follow-up; and (4) forward transprosthetic flow velocity higher than expected with given prosthesis type and size, provided normal function of prosthetic leaflets. Indications for classical surgery, such as prosthetic valve instability or need for coronary artery bypass grafting, constituted the main exclusion criteria. Other exclusion criteria comprised severe scarring of the LV apical region, intracardiac thrombi, active systemic inflammatory conditions, and contraindications to general anesthesia. Among standard laboratory tests, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) plasma concentration was determined. Cephalosporin was administered preprocedurally and continued for a period of 2 days.

The operations were executed in a hybrid operating room under general anesthesia with continuous invasive blood pressure monitoring and fluoroscopy (monoplane system) along with real-time three-dimensional transesophageal echocardiography (RT-3D TEE) guidance. We started with performing a 5-7 cm-long anterolateral incision in the fifth intercostal space. Its exact location was first optimized using transthoracic echocardiography. After exposing the apex, two U-stitches with Teflon felt pledgets using 3-0 Prolene polypropylene (Ethicon, Inc) were placed to enable linear LV closure at the end of the procedure. Next, we punctured the LV and introduced a soft guidewire. A 23 cm soft sheath, of diameter (6-12 Fr; median, 9 Fr) determined by intended size and number of plugs, followed in direction of the mitral prosthesis (Figure 1). A 6 Fr multipurpose (MP) angiographic catheter was used to precisely locate the PVL site. The PVL channel was then crossed with 0.014˝ coronary or 0.032˝ hydrophilic guidewire. Thus, an MP catheter and then vascular sheath could be inserted into the LA to serve as a delivery device. At this point, unfractionated heparin was administered to achieve an activated clotting time >250. Amplatzer Vascular Plug III (AVP III; St Jude Medical) devices were used as occluders. They are three-module devices with a narrowing within the middle section. Contrary to the round shape found in the majority of other plugs, the oval-shaped cross-section of the AVP III better adapts to the usually elongated or crescent-shaped PVL channel. After quantifying the cross-section dimensions of the PVL channel by RT-3D TEE, the exact size and number of plugs were decided to achieve approximately 30% oversizing of their middle modules. This strategy, previously reported efficient,⁹ is based on the assumption that such dense filling of the PVL channel, preferably with 2-3 plugs, ensures proper sealing. Once the planned number of AVPs was introduced into the LA, they were retracted so that only the distal modules remained open. Subsequently, the whole system was drawn back until RT-3D TEE confirmed the complete apposition of distal modules against the LA-sided PVL channel ostium (Figure 2). Retracting the delivery sheath only completed the implantation, which resulted in deployment of the middle and proximal modules within the PVL channel and against the LV-sided ostium. Regurgitant flow reduction and lack of conflict with prosthetic valve were then verified. At this point, another occluder could still be added if residual regurgitation was considered more than trivial. After ensuring proper stability with a standard tug-test, the plugs were released and their position was reconfirmed on fluoroscopy and RT-3D TEE. Once a satisfactory effect was proven, the sheath was removed and the apex was closed with purse-string sutures. Finally, protamine was administered and the pericardium was partially closed with a left lateral chest tube inserted. Low-molecular-weight heparin was introduced 6 to 8 hours after the procedure, provided proper hemostasis.

Follow-up was scheduled at 1 month. We assessed clinical improvement by NYHA class, laboratory findings including NT-proBNP, and transthoracic echocardiography. Safety parameters, such as death, myocardial infarction, stroke, hemorrhage, and hemolysis markers, were also monitored.

Statistical analysis. Data are presented as median value and 95% confidence interval (CI) for the median (95% CI); the Wilcoxon test was applied for statistical testing. 

Results

Procedure. We enrolled seven patients (median age, 73; 95% CI, 63.9-76.0 years) according to inclusion and exclusion criteria. Demographic and clinical characteristics are presented in Table 1. In 2 cases, the transapical approach was chosen without prior transvascular attempt, which was considered problematic due to anatomical conditions (multiple PVL channels with at least one located at the postero-medial portion of the sewing ring). All patients required implantation of multiple plugs,^2-4 which were deployed simultaneously in each case. An excellent effect, with only a trace of residual leak and stable anchoring of the plugs, was achieved in 6 patients (Figure 3), in two of whom we had to use an additional plug besides those initially planned by RT-3D TEE. In the seventh patient, we noted significant reduction of paravalvular regurgitation (from grade 4 to 2) following the deployment of 4 AVPs, but more complete closure was impossible due to a particularly irregular PVL channel. Prosthetic disc impingement occurred at no time during the intervention or follow-up.

Median time from induction of general anesthesia to closing the thoracotomy incision was 115 minutes (95% CI, 72.4-130.0). The procedural details are presented in Table 2. No complications occurred, and all patients were discharged after removing skin stitches on day 6 or 7. 

30-day follow-up. On follow-up visits after 30 days, lasting excellent effect was recorded in 6 patients and residual moderate PVL was found in the seventh patient (in this case, the unchanged position of the occluders was also reconfirmed by fluoroscopy). Clinical benefit was noted in all cases and improvement of functional capacity correlated with the reduction of regurgitant flow as presented in Table 3.

Laboratory tests showed significant reduction of NT-proBNP plasma concentration in all patients (2221 pg/mL [95% CI, 1037.2-3698.4 pg/mL] vs 882 pg/mL [95% CI, 514.2-1349.4 pg/mL] P=.016) (Figure 4). TPVLC did not enhance hemolysis as assessed by lactate dehydrogenase (514.0 IU/L [95% CI, 257.8-921.8 IU/L] vs 443.0 IU/L [95% CI, 296.3-831.6 IU/L]; P=NS), unconjugated bilirubin (0.78 mg% [95% CI, 0.68-1.09 mg%] vs 0.70 mg% [95% CI, 0.58-0.88 mg%]; P=NS), but significantly reduced reticulocyte number (9.9% [95% CI, 7.7%-14.9%] vs 8.1 [95% CI, 5.8%-10.9%]; P=.047). Further laboratory and echocardiography data are presented in Table 3.

Discussion

Despite becoming an increasingly recognized alternative to surgical correction of PVL, TPVLC still remains at an early stage of methodological development with no dedicated devices on the market. The use of a variety of different occluders originally designed for congenital defects (atrial and ventricular septal defects, patent ductus arteriosus) has been described, also via transapical access.¹⁰ The current literature most frequently points at the AVP III, an asymmetrical plug primarily intended for vascular embolization, which is even referred to by some authors as a TPVLC-specific device.¹¹ This opinion is highly congruent with our own experience, particularly in the event of multiple plug anchoring. A series of transapical TPVLCs with a single AVP III has been previously reported.¹² We believe that the presented multiple AVP III implantation approach allows for denser PVL channel filling. It also reduces overhanging of the occluders’ distal modules, which, in turn, prevents prosthetic disc impingement. Our record of over 40 TPVLC procedures (mostly via transvenous and transarterial access) shows no instance of conflict with prosthesis despite common use of multiple occluders.

Three ways of accessing a mitral PVL have been validated. Antegrade transseptal approach, most frequently used in our center, is particularly suitable for PVLs located at the anterior aspect of the sewing ring, opposite the interatrial septum. Those adjacent to interatrial septum can also be approached in antegrade manner, but we generally find them more demanding. According to our own experience, a triple-telescopic system may then often enable the PVL crossing. Nevertheless, particularly if use of a large sheath (10-12 Fr) is required, manipulation in the LA becomes tricky and generates substantial tension within the system. A retrograde, transaortic approach is also possible, but involves introduction of large-size catheters via peripheral arteries along with rather aggressive maneuvering within the LV. Therefore, when a retrograde alternative is needed, we prefer transapical access with lateral minithoracotomy, which eliminates some mentioned setbacks.¹³ Development of this particular method was recently stimulated because the same method was used for TAVI. Over 100 transapical procedures were described in the PARTNER study¹⁴ alone and several hundred have been described in other registries.^15,16 The accumulated experience shows that such access may increase the risk of hemorrhagic complications and contrast-induced nephropathy.¹⁷ Excellent hemostasis in our group can probably be attributed to the smaller size of introduced sheaths and their relatively stable position throughout the procedure once the PVL crossing was achieved.

A series of efficient transapical TPVLCs with direct LV puncture under integrated fluoroscopy and computed tomography guidance has also been described.^18,19 This fully percutaneous method requires closure of the access site with an additional occluder. No head-to-head comparison of minithoracotomy versus direct-puncture strategy has been executed. Better control of hemostasis seems to be the major advantage of the former approach, while less invasiveness is the benefit of the latter.

Precise criteria of TPVLC efficacy remain to be further elucidated. Echocardiography parameters, while most useful intraprocedurally, remain dependent on momentary hemodynamics. Additionally, the presence of prosthetic valves, delivery systems, and occluding devices may compromise the quality of ultrasound images. Therefore, optimization of the procedure strategy aimed at best possible PVL sealing, for instance, by means of multiple plug implantations, is of paramount importance.

Transapical access with lateral minithoracotomy seems to be an efficient and safe alternative for transvascular approach for mitral TPVLC. Dedicated delivery systems and occluders are still to be proposed. Lack of fabric inside the nitinol mesh of the AVP III necessitates the implantation of multiple plugs to achieve dense filling of the PVL channel and constitutes a major disadvantage of the otherwise applicable device. Further studies comparing different access sites for TPVLC are needed.

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