INTRODUCTION

Significant mitral valve dysfunction, including both regurgitation (MR) and stenosis (MS), is associated with poor quality of life and prognosis. Surgical intervention is currently the gold standard for the treatment of significant degenerative MR and selected patients with secondary MR and MS with acceptable operative risk [1]. Mitral valve repair is the preferred method over valve replacement whenever it is feasible and when a durable result is expected. However, numerous patients require surgical prosthetic valve implantation. In recent years, an increasing number of mitral bioprosthetic valve implantations has been observed. Such a tendency is especially visible in the elderly and patients with significant comorbidities. The use of bioprosthetic versus mechanical mitral valves is associated with a lower rate of thrombotic and bleeding adverse events, but their clinical effectiveness may be restricted by limited durability. After years, some patients develop bioprosthetic valve deterioration that may lead in consequence to bioprosthesis valve failure (BVF). These individuals oftentimes require redo surgery, but as high surgical risk patients, are disqualified or not referred to the procedure. It is estimated that over a period of 10 years from surgical valve replacement, approximately 35% of individuals require reoperation [2]. Redo surgery is associated with an unfavorable prognosis with 30-day mortality reaching from 5% to 15% [3, 4]. An emerging treatment alternative is valve-in-vale transcatheter mitral valve implantation (ViV-TMVI). Based on the evidence on safety and efficacy of transcatheter aortic valve-in-valve implantation (ViV-TAVI), it is possible to perform this procedure with the use of devices dedicated to TAVI [5]. However, due to differences in anatomical conditions, transcatheter valve placement in the mitral position is usually more complex and challenging. Since the first ViV-TMVI in 2009, this method has been performed initially only through a transapical approach [6]. But later, to further decrease the invasiveness and avoid complications inherent in transapical access, the transfemoral route with transseptal puncture gained more attention with promising results coming from international registries [7]. Yet, there is a lack of available data about the Polish population other than case reports [8]. Therefore, this pilot study aimed to evaluate the early (30-day) safety and efficacy of transfemoral ViV-TMVI in Poland based on a nationwide registry.

METHODS

In order to collect reliable data from all Polish centers performing the procedure, the nationwide ViV-TMVI registry was initiated in 2021 (Polish Transcatheter Transfemoral Mitral Valve-in-Valve Implantation, ClinicalTrials.gov identifier NCT05625607). Inclusion criteria were mitral BVF demonstrating ≥moderate stenosis and/or ≥moderate regurgitation, referral for ViV-TMVI by the local Heart Team, and patient informed written consent. All patients undergoing transfemoral ViV-TMVI were eligible for the study.

Reported data consisted of patients’ baseline characteristics (sex, age, weight, height, New York Heart Association [NYHA] symptoms class, mechanism of BVF, time between surgical replacement and transcatheter reintervention, characteristics of failed surgical bioprosthetic valve, patients’ comorbidities, surgical risk presented by the Society of Thoracic Surgeons [STS] replacement score, and baseline echocardiographic characteristic), procedural characteristics (type of anesthesia, type and size of the implanted transcatheter prosthesis, the necessity of performing pre- and postdilatation), and 30-day follow-up (cerebrovascular events, major bleeding, major vascular complications, acute kidney injury stage 2 or 3, need for mitral surgery, echocardiographic characteristics, and all-cause death in follow-up).

The primary endpoint was all-cause mortality at 30 days. Secondary outcomes were technical, device, and procedural success according to the Mitral Valve Academic Research Consortium (MVARC) consensus document with device success modified according to the American Society of Echocardiography guidelines [9, 10]. Clinical endpoints were assessed based on the presence or absence of events defined in MVARC criteria. The safety and performance of the device included in the MVARC device success endpoint were assessed in echocardiography. Modified device success definition involved the acceptance of mean postprocedural transmitral pressure gradient <10 mm Hg, as the value reported in properly functioning bioprostheses. Technical success was assessed at the exit from the catheterization laboratory. Other endpoints were recorded at 30-day follow-up.

ViV-TMVI workup and procedure overview

Multi-slice computed tomography (CT) is an important imaging modality to plan the procedure to assess aorto-mitral angulation (preferably >120 degrees) and predict post-procedural left ventricular outflow tract (LVOT) area with superimposing the transcatheter valve that is intended to be placed (so-called neo-LVOT, minimum area of at least 200 mm2) to avoid LVOT obstruction (Figure 1).

Figure 1. Basic pre-procedural computed tomography parameters (Hancock II 29 mm). A. Annulus size (24 mm) equal to the true internal diameter of the 29 mm Hancock II prosthesis. B. Aorto-mitral angle >120 degrees. C. Large predicted neo-LVOT area suggesting low risk of LVOT obstruction

Abbreviations: LVOT, left ventricular outflow tract

The correct valve size is usually based on CT and available sizing chart with respect to true internal diameters of surgical mitral devices — viv-mitral app (developed by Vinnie Bapat). Unlike in TAVI, the mitral valve is characterized by high closing pressures, thus the transcatheter device should be more oversized, and, ideally, a conical shape after deployment is desired to prevent immediate and late transcatheter prosthesis migration or embolization. In borderline measurements, BVF type may influence the correct size choice — larger in regurgitation and smaller in severe stenosis. Oversizing can be achieved by adding more balloon volume during valve inflation.

The procedure is performed under general anesthesia or conscious sedation depending on the standard protocol of the valve centers and starts with a right femoral venous puncture that can be secured with 2 Proglides. Then, to reach the left atrium under the guidance of transesophageal echocardiography (TEE), a septal puncture is performed typically in the low and inferior position in the fossa ovalis. Subsequently, using a steerable catheter (Agilis, Abbott Vascular, Chicago, IL, US), a surgical prosthesis is crossed with the pigtail catheter, and the stiff wire (e.g. Lunderquist or two Safari wires) is positioned with the pre-shaped tip facing downwards. Afterward, balloon septostomy (usually a 10–14 mm non-compliant balloon with prolonged low-pressure inflation) is performed to facilitate the crossing of the delivery system with the balloon-expandable valve. Predilatation of failed surgical valves is rarely needed as it also carries a risk of embolism or acute regurgitation but can be performed in selected borderline sizing situations. After achieving the optimal position of transcatheter prosthesis — importantly, it is mounted in the opposite direction in comparison to TAVI — with 10%–20% located in the left atrium and 80%–90% in the left ventricle, the valve is expanded during rapid ventricular pacing. In the case of suboptimal expansion or paravalvular leak, postdilatation may be performed by adding more volume to the balloon catheter to fully expand the valve. Respective angiographic steps and echocardiographic images of exemplary ViV-TMVI procedure are presented in Figures 2 and 3, respectively.

Figure 2. Step-by-step angiographic recordings of transfemoral ViV-TMVI in a failed Hancock II 29 mm prosthesis. All examples in deep RAO projection to align the mitral prosthesis. A. After securing right femoral venous access, TEE guided transseptal puncture (arrow). B. Placement of stiff the pre-shaped wire in the left ventricle (facing downwards) with the use of a deflectable Agilis catheter (arrow). C. Septostomy with a non-compliant 10–14 mm balloon (prolonged, low-pressure inflation) (arrow). D. Exchanging for the S3 delivery system (with the prosthesis mounted opposite to TAVI) and crossing the mitral prosthesis (arrow). E. Deployment of a 26 mm S3 valve during rapid pacing with intended 10–20% atrial positioning and 80%–90% ventricular positioning (arrow). F. Final result showing a good position with desired oversize and conical shape of S3 and no regurgitation

Abbreviations: RAO, right anterior oblique; TAVI, transcatheter aortic valve implantation; TEE, transesophageal echocardiography; ViV-TMVI, valve-in-valve transcatheter transfemoral mitral valve implantation

Figure 3. Transesophageal echocardiography during ViV-TMVI (26 mm S3 in 29 mm Hancock II prosthesis with predominant stenosis). A. Inferior and posterior transseptal puncture. B. Baseline regurgitation. C. Pre-procedural mitral valve area. D. Post-procedural mitral valve area. E. Absence of regurgitation post-implantation. F. S3 3D appearance inside Hancock II prosthesis

Abbreviations: see Figure 2

Fluoroscopic appearances of different surgical mitral valves are presented in Figure 4.

Figure 4. Fluoroscopic pre- and post-procedural (after S3 implantation) presentation of different surgical prostheses. A, B. Minimal visibility of Epic prosthesis ring (arrows). C, D. Radiopacity of prosthesis posts only in a Mosaic valve (arrows). E, F. Good visibility of both annulus and posts in a Perimount Magna prosthesis (arrows)

Statistical analysis

Continuous variables were presented as mean values with standard deviation (SD) or as medians with interquartile range (IQR). Qualitative variables were presented as numbers and percentages. Statistical analysis was performed in IBM SPSS Statistics 29.

RESULTS

Baseline clinical characteristics

Overall, up to May 2022, 27 procedures were performed in 8 Polish centers (26 valve-in-valve and 1 valve-in-ring). An increasing number of procedures was observed from 2020, comprising 85% of reported cases (n = 23). Women constituted 59.3% (n = 16) of the cohort. The mean (SD) age of the study population reached 73 (11.6) years. The mean (SD) time between surgical valve replacement and BVF requiring transcatheter treatment was 8.2 (3.2) years. At baseline, 70.4% (n = 19) of patients were in NYHA symptoms class III or IV. The median (IQR) STS replacement score reached 5.3% (4.3%–14.3%). (Table 1).

Surgical prostheses characteristics

Hancock II and Perimount Magna comprised the majority of dysfunctional bioprostheses. Others were Epic, Mosaic, Labcor, CE Standard, and Physio1 annuloplasty ring. The percentage of particular devices is shown in Figure 5.

Figure 5. Types and percentages of failed mitral bioprostheses

In more than half of the population, the label size of the failed prosthesis was 29 mm (55.5%), followed by 27 mm (25.9%). Three patients had a 31 mm valve and one 33 mm. The only failed ring was 34 mm.

Baseline echocardiographic assessment

The mechanisms of BVF were equally pure mitral regurgitation (37%, n = 10) and stenosis (37%, n = 10). In 7 (26%) patients, mixed dysfunction was diagnosed. Mean (SD) left ventricular ejection fraction before the transcatheter procedure was 48.8 (16%). Mean (SD) mitral transvalvular pressure gradient was 10.2 (4) mm Hg and mitral valve area 1.1 (0.6) cm2. More than 80% (n = 22) of patients demonstrated a mean transvalvular pressure gradient ≥5 mm Hg and more than one-third (n = 9) ≥10 mm Hg. Moderate or severe regurgitation was present in 17 patients (63%).

Transcatheter prostheses characteristics

All procedures were performed with transesophageal guidance. In 96.3% of patients, a balloon-expandable Sapien 3/Ultra bioprosthesis was used (Edwards Lifesciences, Irvine, CA, US) except for 1 Myval valve implantation (Meril Lifesciences, Gujarat, India). The majority of patients received a 29 mm size valve (59.2%), followed by 26 mm (37%), and 1 patient was implanted with a 23 mm prosthesis. In 4 (14.8%) cases, predilatation was done. Only 1 patient required postdilatation to fully expand the transcatheter prosthesis.

Outcomes

In all patients, the transcatheter prosthesis was successfully delivered into the mitral position. There were no periprocedural deaths, no cases of LVOT obstruction or need for conversion to surgery. The frequency of major vascular complications, major bleeding, and acute kidney injury was 3.7% (n = 1) for each complication. Technical success was achieved in 26 of 27 patients, which constituted 96.3% of all procedures. In the case when technical success was not achieved due to partial transcatheter prosthesis displacement towards the left ventricle, there was a need for a second valve for stabilizing and anchoring the first valve. After that, proper prosthesis function was achieved with a mean transvalvular gradient of 5 mm Hg, no evidence of LVOT obstruction, and the patient was discharged in good condition (Table 2).

Device success using strict MVARC criteria of mean transvalvular gradient less than 5 mm Hg was fulfilled only in 29.6% (n = 8), but modified device success according to the American Society of Echocardiography with a cut-off at less than 10 mm Hg that is more suitable for valve-in-valve procedures and previously adopted by others [11] was present in 92.6% (n = 25). Overall, mean (SD) transvalvular pressure gradient decreased to 6.7 (2.2) mm Hg, and mean (SD) effective orifice area (EOA) increased to 1.8 (0.4) cm2. Survi­val, freedom from stroke/transient ischemic attack or need for surgery at 30 days was 100% (Table 3).

Most of the patients were discharged on oral anticoagulation alone (n = 20, 74%); in 6 (22%) patients double therapy combining oral anticoagulation with a single antiplatelet agent was used, and in 1 case dual antiplatelet therapy was prescribed.

DISCUSSION

The above-mentioned results suggest that in short-term follow-up transfemoral ViV-TMVI is a safe and effective treatment for failed surgical mitral bioprosthesis. In recent times, an increasing number of ViV-TMVI procedures has been observed, which might be correlated with longer patient survival time after cardiac surgery and general patients’ preference for a biological prosthesis. In the current study of the Polish population, the 30-day survival rate was 100%, and there were no or minimal major adverse clinical events, e.g. cerebrovascular, bleeding/vascular, or repeat surgery. Other larger international cohort studies reported 30-day mortality reaching up to 8% with other adverse events also more frequently occurring when describing outcomes of early experiences [12]. These promising clinical results coming from this first experience in Poland are probably attributable to the later adoption of this technique in Poland and thereby avoidance of most of the issues characteristic of early stages of ViV-TMVI (e.g. LVOT obstruction prevention by CT imaging simulation, proper transseptal puncture position, greater oversizing of the transcatheter prosthesis to avoid displacement or embolization, positioning of the stiff wire to avoid apical perforation, etc). Our experience also highlights the importance of precise preprocedural assessment by both CT and echocardiography to properly qualify patients and plan safe procedures.

A life-threatening complication, requiring special consideration during ViV-TMVI is LVOT obstruction created by displacement of surgical prosthesis leaflet into an open position and thus limiting blood flow through the aortic valve. A small area of neo-LVOT (estimated on the basis of computed tomography simulation), acute mitral aorta-outflow-angle (aortomitral angulation), high ejection fraction, and small cavity size are confirmed predictors of LVOT obstruction [13, 14]. Again, in our population none of the patients experienced this event due to routine pre-procedural CT planning and the use of established cut-offs; however, other studies reporting earlier experiences show its incidence ranging from 0.7 to 5% [7, 15, 16].

Postprocedural gradients/area in our cohort (mean [SD] transvalvular mitral gradient of 6.7 [2.2] mm Hg, 70.3% ≥5 mm Hg, 7.4% ≥10 mm Hg and mitral valve area of 1.8 [0.4] cm2) are in line with other previously reported data. The largest VIVID registry data showed a mean (SD) transmitral gradient of 5.6 (2.7) mm Hg with 60% of the population presenting values ≥5 mm Hg and 8.2% ≥10 mm Hg and mitral valve area of 2 (0.7 cm2) [7]. The mean (IQR) transvalvular gradient and mitral valve area presented in the TVT registry reached 6 (4–8) mm Hg with area of 1.9 (1.4–2.5) cm2 [15]. A smaller study by Eleid et al. [16] on 60 patients demonstrated mean (SD) gradient of 6.9 (1.8) mm Hg and area of 1.9 (0.7) cm2.

The presence of a radiologically translucent dysfunctional valve makes TMVR a more challenging procedure and increases the risk of suboptimal valve position or displacement. However, under precise 3D transesophageal echocardiographic guidance, it is possible to successfully implant new bioprosthesis into failed valves even in the absence of radiopaque markers [17].

It is worth noting that it is feasible to perform ViV-TMVI implantation also via surgical access [18, 19]. The field started with the transapical route, later also open transarterial deployment was sometimes implemented, both allowing for more direct transcatheter valve delivery and immediate intervention in case of major complications requiring surgical management. However, these surgical access sites by nature are more invasive in high-risk populations compared with transfemoral venous access with a transseptal puncture leading to the increasing adoption of the latter.

Limitations

This study presents several limitations that must be taken into consideration when interpreting the results. Firstly, our registry includes also retrospective data with all their inherent limitations. Secondly, due to still early experiences with ViV-TMVI procedures in Poland, the study cohort was limited, and that precluded any meaningful subanalysis or comparisons. Finally, the study includes echocardiographic data provided by respective reporting centers, which are physician-dependent and were not validated by the core laboratory.

CONCLUSIONS

The promising results of this pilot study suggest that transfemoral ViV-TMVI is a safe and efficient method for failed mitral bioprostheses treatment when performed in a selected group of high-risk patients. This intervention has emerged as an alternative to surgery redoes in significantly burdened populations. However, meticulous preprocedural assessment and proper patient qualification are crucial to avoid major complications. Further studies on larger cohorts and longer follow-up are required for more definite evaluation.

Article information

Conflict of interest: None declared.

Funding: None.

Open access: This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, which allows downloading and sharing articles with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. For commercial use, please contact the journal office at kardiologiapolska@ptkardio.pl.