Mitral valved stent implantation: an overview.

To date, transcatheter valve implantation is limited to the replacement of pulmonary and aortic valves. The aim of this study was to analyze a valved stent for minimally invasive implantation in the mitral position. A self-expanding mitral valved stent was designed for transapical implantation. Thirty pigs underwent off-pump mitral valved stent implantation with follow-up times of 60 minutes (n = 17) and seven days (n = 13). Transesophageal echocardiography and computed tomography were used to evaluate stent function and positioning. After valved stent deployment, accurate adjustment of the intra-annular position reduced paravalvular leakage in all animals. Accurate positioning was established in all but five animals. The average mean transvalvular gradient across the mitral valve and the left ventricular outflow tract recorded immediately after deployment, six hours and one week were 1.85 ± 0.95 mmHg, 3.45 ± 1.65 mmHg, 4.15 ± 2.3 mmHg and 1.35 ± 1.35 mmHg, 1.45 ± 0.7 mmHg, 1.9 ± 0.65 mmHg, respectively. No valved stent migration, embolization, systolic anterior movement or left ventricular outflow tract obstruction was observed. The mitral valved stent can be deployed in a reproducible manner to achieve reliable stent stability, minimal gradients across the left ventricular outflow tract and adequate stent function in acute and short term experimental settings.

Novel stent design for transcatheter mitral valve implantation.

OBJECTIVES: In this study, results of a functional in vitro study of 2 newly developed valved stents for transcatheter mitral valve implantation are presented. METHODS: Two novel stent designs, an oval-shaped and a D-shaped stent with a strut fixation system were developed. The fixation force of the novel stents were tested in vitro in porcine hearts with a tensile test set-up. In further experiments, the stents were equipped with a circular valved stent, and the valve performances were investigated in a pulsatile heart valve tester. RESULTS: Sufficient mean stent fixation forces in the range of 24.2 ± 0.9 N to 28.6 ± 1.9 N were measured for the different stent models. The novel valved stents showed good performance in an in vitro pulsatile heart valve tester. A sufficient opening area and low opening pressures were measured for all tested mitral valved stents. Compared with an established reference valve, the D-shaped stent and the oval-shaped valved stent showed a lower systolic transvalvular pressure gradient, which indicates slightly greater extent of valvular leakage of the closed valved stents. However, the mitral nitinol valved stents demonstrated adequate durability. CONCLUSIONS: This study indicates a sufficient annular fixation force of the tested transcatheter mitral valve implantation valved stent prototypes. Therefore, these mitral valved stents demonstrate a new type of mitral valved stent design.

Transcatheter mitral valve implantation: supra-annular and subvalvular fixation techniques.

OBJECTIVES: Transcatheter mitral valved stent implantation provides an off-pump treatment option for mitral valve regurgitation, especially for secondary mitral valve regurgitation. The aim of this study was to evaluate novel fixation strategies: direct fixation (SUPRA) and subvalvular fixation (sub-VALV) to successfully implement alternative fixation methods at the mitral annulus and to reduce radial stent and apical tether forces. METHODS: Specific concepts were developed for the supra-annular hook-shaped fixation (SUPRA) and the subvalvular fixation (sub-VALV). These prototypes were compared with the sole apical tether fixation (AP) methods. Thirty-three pigs underwent mitral valved stent implantation accompanied by standardized transoesophageal echocardiographic and haemodynamic evaluation of heart function and the stent performance 1 h after implantation. Additionally, animals were followed up for 3 months. RESULTS: Secure deployment and correct positioning with low transvalvular gradients were achieved in all cases with mitral valved stent implantation. Nevertheless, 2 pigs died due to rhythm disturbances during dissection and pre-transcatheter mitral valve implantation. Paravalvular leakages were trace or less in prototypes with supra-annular fixation and sole apical fixation. In contrast, moderate paravalvular leakages were observed in the sub-VALV group (P < 0.001). In addition, the effect of a specific stent design on heart function was demonstrated: an increased rate of ischaemia and arrhythmia (P = 0.037) and a small left ventricular ejection fraction reduction (P < 0.05) were observed in the group with subvalvular fixation. In all but 1 case, gross evaluation demonstrated a good ingrowth of the valved stents of between 36% and 100% tissue coverage after a follow-up of 1 month or longer. CONCLUSIONS: The low degree of paravalvular leakages in the supra-annular and apical fixation groups and the normal longitudinal function highlight the good alignment of these new mitral valved stent designs within the native anatomy. The novel, hook-shaped, supra-annular fixation elements were well tolerated in the hearts resulting in excellent health of the animals at long-term follow-up times of up to 3 months.

Transesophageal Echocardiography in Swine: Establishment of a Baseline.

The porcine model is a commonly used animal model in cardiovascular research. Along with new innovative operative techniques, choice of the optimal imaging technique is crucial. Transesophageal echocardiography (TEE) is a reliable imaging tool is highly important in a large number of experimental evaluations. But so far, TEE data for swine are limited, and few standard values have been established for the porcine model. The experience and baseline results for TEE in 45 swine are presented in this study. A full TEE examination was conducted in 45 German landrace or German large white swine, with an average body weight of 49 ± 3 kg, before experimental off-pump mitral valved stent implantation. Additionally hemodynamic measurements were evaluated. The valve implantation procedure was guided solely by real-time 3-D TEE. Baseline values of standard echocardiographic parameters are provided and, where appropriate, compared with human reference values. TEE proved to be an adequate imaging technique in this experimental porcine animal model. The baseline TEE and hemodynamic parameters established for the widely used porcine model can serve as a reference in future studies.

Transcatheter mitral valve implantation: a percutaneous transapical system.

Objectives: Despite recent achievements, implantation of a transcatheter mitral valved stent remains challenging. In this study, we present a different approach for implantation of a percutaneous mitral valved stent. Methods: Percutaneous transapical access is combined with, respectively, a left-transatrial, right-transatrial/transseptal or transfemoral/transseptal approach for mitral valve stent implantation and secure fixation. The apical fixation and occlusion are ensured with an Amplatzer occluder. This novel approach was tested in 22 porcine hearts in an in vitro setting under the guidance of fluoroscopy ( n = 11) and endoscopy ( n = 11). The in vitro setup included continuous flushing at 37 °C. We determined the feasibility, time of implantation, stent deployment and stent fixation. Results: Percutaneous mitral valved stent implantation was successful in all cases. Good handling properties and precise positioning were achieved. Time of implantation was comparable in the fluoroscopic and endoscopic groups at 10:41 ± 3:18 and 10:09 ± 2:42 min, respectively. Apical fixation with the occluder was excellent in all 22 cases. Conclusions: The feasibility of percutaneous mitral valved stent implantation has been demonstrated in preliminary in vitro experiments. Subsequent studies are warranted to determine the efficacy of this minimally invasive catheter-based mitral valved stent implantation.

Off-pump mitral valved stent implantation: comparison of apical and subannular fixation techniques.

OBJECTIVES: A large cohort of patients suffering from severe mitral regurgitation does not meet the indications for conventional surgery and would greatly benefit from a transcatheter approach in the beating heart. Consequently, off-pump transcatheter mitral valve procedures have been the focus of recent research. The aim of this study was the in vivo evaluation and comparison of subannular versus apical fixation of mitral valved stents to show the feasibility of subannular anchorage. METHODS: Twenty-two pigs received a self-expanding valved stent in the mitral position in an off-pump procedure. The first design (design AP: n = 12) was anchored apically and served as the control group. The second design (design SA: n = 10) included additional sub-annular fixation elements. Echocardiographic and haemodynamic evaluations were conducted before and 1 h after stent implantation. RESULTS: Haemodynamic stability was achieved, and the capillary wedge pressure was within a normal range (AP: 11 ± 4 mmHg, SA: 9 ± 4 mmHg). Paravalvular leakages were trace or less in 19 of 20 cases. The mean gradients across the valved stent increased (P ≤ 0.014) but remained within a physiological range in both groups (AP: 1.2 ± 0.6 mmHg, SA: 2.6 ± 2.0 mmHg). The longitudinal heart function remained within a physiological normal range (AP: 0.95 ± 0.1 cm, SA: 0.95 ± 0.1 cm) but was reduced in group SA. The ejection fraction decreased after stent implantation (AP: 52 ± 10%, SA: 48 ± 4%). The mean survival time was higher in group AP compared with group SA. CONCLUSIONS: The proof-of-principle for the subannular fixation was shown with haemodynamic stability, low gradients and physiological longitudinal function. A decreased ejection fraction, survival time and fractures identify potential areas for improvement. With regard to the long-term outcome, the group with subannular fixation did not reach the results of the group with apical fixation in this study.

Transapical mitral valved stent implantation: computed tomographic evaluation of different prototype designs.

AIMS: The evaluation of in vivo shaping of mitral valved stent prototypes using cardiac computed tomography (CT) was the focus of this study. METHODS AND RESULTS: Twelve pigs received a self-expanding mitral valved stent, composed of an atrial element connected to a tubular ventricular body at a modified angle (45°, 90°, 110°) resulting in three designs. Cardiac CT was performed three weeks after implantation, with focus placed on stent design-related parameters: possible left ventricular outflow tract obstruction and stent shaping. CT was successfully conducted in 11/12 animals showing correct stent position within the mitral annulus and no obstruction of the left ventricular outflow tract in 9/11 animals. Minor radial deformations of the stent body were detected. At the atrioventricular junction, deformations of the stent structure were observed in all cases. Stents with a 45° angle exhibited the greatest deflection (≤56.4°±14.5°). CONCLUSIONS: The effectiveness of cardiac computed tomography in the development process of valved stents to provide essential information and quantitative data about the in vivo stent geometry was demonstrated. The in vivo mechanical deformations of the stent were quantified, identifying critical design areas: a larger preset angle leads to less deflection and improved alignment and hence reduces the mechanical load.

Off-pump tricuspid valved stent implantation: real-time three-dimensional transesophageal echocardiography for guidance and assessment.

In this case report, the value of real-time three-dimensional transesophageal echocardiography (TEE) for guidance and assessment of orthotopic tricuspid valved stent implantation in the beating heart is assessed in four pigs. A full two-dimensional TEE evaluation of standardized parameters was conducted. Three-dimensional TEE provided dependable imaging of anatomical structures of the right side of the heart, the delivery system, and the valved stent, allowing easier orientation and more accurate views for the surgical team. Although visualization of the tricuspid valve in the porcine model is challenging, it contributed highly to the successful implantation of the tricuspid valved stent.

Transapical mitral valved stent implantation: comparison between circular and D-shaped design.

AIMS: In this study two designs of a self-expanding valved stent were compared after off-pump implantation into the mitral valve to identify the superior one. METHODS AND RESULTS: Two designs of a mitral valved stent were tested. The first design is composed of a circular atrial element connected to a tube-shaped ventricular element. In the second design, the atrial element is D-shaped to achieve better anatomical alignment. Prior to in vivo testing, the area with the highest risk of PVL was identified in a hydrostatic in vitro set-up. Subsequently, eight pigs received stents (circular, n=5; D-shaped, n=3) via apical access in the beating heart. Positioning and haemodynamics were evaluated by TEE and invasive pressure measurement pre-implantation, after 1 hr, and at two and four weeks. In vitro testing showed less PVL in the anteromedial region in D-shaped design stents (p<0.001). All stents were successfully deployed in vivo and six animals maintained normal haemodynamics for two weeks or longer. Rotational reorientation of all stents with D-shaped elements was observed. Both groups indicated no clinically relevant gradients over the mitral valved stent. CONCLUSIONS: This study demonstrates that the circular design was superior to the D-shaped model after rotational reorientation of the latter occurred.

Off-pump tricuspid valved stent implantation: the next step.

OBJECTIVES: Off-pump transcatheter valved stent implantation could be a treatment option for patients suffering from symptomatic tricuspid regurgitation (TR) who are classified as inoperable. In this study, we present our recent short-term results of transventricular tricuspid valved stent implantation and compare different stent types for atrial anchorage. METHODS: Fifteen pigs received a self-expandable valved stent implantation off-pump via a transventricular access. Successfully implanted pigs were observed over a period of 6 h (n = 9), 48 h (n = 1) and 4 weeks (n = 1). Haemodynamic and full transoesophageal echocardiographic (TOE) evaluations were done before, 1 h, 3 h (n = 11; all successfully implanted pigs), and 6 h (n = 9; acute group) after implantation. Nine days postimplantation, one pig received additional angiography, computed tomography (CT) and transthoracic echocardiography (TTE). Post-mortem, gross examination was conducted to analyse the stent position and deformation. In two pigs (48 h and 4 weeks survival) histological staining and immunohistochemistry of surrounding myocardium was performed. RESULTS: The heart rate significantly increased in all pigs postimplantation from 66.8 ± 13.6 to 101.8 ± 24.6 bpm, whereas cardiac output and pressure levels remained unchanged. Orthotopic positioning was reproducibly achieved. TOE showed an efficient reduction of paravalvular leakages from a mean grade of 1.4 1 h postimplantation to a mean of 0.9 at 6 h postimplantation due to a special sealing pouch. The ratio early and late ventricular filling velocities remained constant and the valvular gradient across the valved stent stayed low during the observation period. Angiography, CT and TTE confirmed orthotopic positioning and mild grade of paravalvular leakage after 9 days (n = 1). Only mild TR was observed here. The ventricular part of the stent was deformed to an oval shape in 7 of 14 animals as shown via post-mortem examination. The surrounding tissue after 1 month (n = 1) showed normal morphology, without inflammation or calcification. CONCLUSION: This study shows the feasibility of catheter-based replacement of the tricuspid valve by a valved stent in an off-pump procedure. The successive enhancements in this tricuspid valved stent design lead to a prototype being ready for mid- to long-term evaluations.

Transapical mitral valved stent implantation: enhanced survival and decreased paravalvular leakages.

BACKGROUND/OBJECTIVES: This study presents the recent results of transapical implantation of a new design of a mitral valved stent with up to three months follow-up. METHODS: A self-expanding re-designed mitral valved stent was implanted via transapical approach into the beating heart of eight pigs. Echocardiographic- and hemodynamic parameters were assessed before (n=8), at 1h (n=8), at one month (n=6), at two months (n=2), and at three months (n=1) after implantation and a cardiac CT was conducted. RESULTS: The stent was successfully deployed in all animals. Two animals died within the first month due to incorrect fixation force. Echocardiographic evaluation showed low gradients (3.9 ± 1.4 mm Hg and 1.9 ± 0.8 mm Hg across the valved stent and aortic valve) and a normal mitral annular plane systolic excursion (1.1 ± 0.2 cm) after one month. No paravalvular leakages (PVL) were detected after 1h. The pulmonary artery pressure did not increase after valved stent implantation (p ≥ 0.106). The pulmonary capillary wedge pressure (PCWP) slightly increased to 16 ± 3 mm Hg after one month (p=0.033). The left ventricular end-diastolic pressure was mildly elevated (15.8 ± 8.6 mm Hg) after one month. CONCLUSIONS: Secure deployment and correct position of the valved stents were reproducibly achieved in the off-pump implantation procedure. No paravalvular leakages after 1h as well as low gradients, few stent fractures and a normal longitudinal function after one month were achieved with this newly developed and well-aligned prototype. However, a number of challenges have been identified during this study and potential for improvement has been identified.