Anja Metzner

Percutaneous pulmonary valve replacement: autologous tissue-engineered valved stents

AIMS Percutaneous implantation has already been used clinically and is a great option for treating young patients. The use of autologous tissue-engineered valved stents might solve the problem of degeneration and limited durability of biological heart valves. METHODS AND RESULTS Porcine pulmonary heart valves and small intestinal submucosa were obtained from a slaughterhouse. The intestinal submucosa was used to cover the inside of the porcine pulmonary valved stents. Endothelial cells (ECs) and autologous myofibroblasts (MFs) were used from carotid artery segments of juvenile sheep. After MF seeding, constructs were placed in a dynamic bioreactor system and cultured for 16 days. After additional EC seeding, tissue-engineered valved stents were percutaneously deployed into the annulus of the pulmonary valve (n = 9). Angiography was performed at implantation and 4-week follow-up. Constructs were analysed radiographically, by post-mortem examination, and microscopically. In all but one case, orthotopic positioning of the stents (n = 6) at the time of implantation and explantation was observed angiographically, macroscopically, and by computer tomography scan and demonstrated normal valve function (n = 7). Gross morphology confirmed excellent opening and closure characteristics of all leaflets after 4 weeks (n = 7). Strong expression of α-smooth muscle actin in neo-interstitial cells and of von Willebrand factor and PECAM-1 in ECs was revealed by immunocytochemistry. CONCLUSION Good functioning and morphological characteristics were observed after percutaneous tissue-engineered valved stent implantation with autologous cells. This implantation of autologous tissue-engineered valved stents will become a valid future option in adolescents.

Off-pump transapical mitral valve replacement: evaluation after one month

OBJECTIVES The present study investigates outcomes one month after implanting pigs with a novel mitral valved stent. METHODS A novel nitinol stent custom designed for this study included a bovine pericardial valve. Six pigs received a valved stent into the mitral position by means of the transapical implantation technique. Afterwards, haemodynamic stability and valve function were assessed, immediately after implantation (n = 6), 4 weeks (n = 4) and 8 weeks (n = 1) thereafter using transoesophageal echocardiography (TEE), ventriculography and cardiac computed tomography (CT). Four of 6 surviving pigs were sacrificed at 4 weeks after implantation and one at 8 weeks thereafter. RESULTS Optimal deployment and positioning were obtained in all but one animal. This animal died of unrecognized imperfect valved stent positioning after 4 days. The average mean gradient across the new valves and the left ventricular outflow tract (LVOT) were small. Mild regurgitation developed after valved stent deployment in one of six animals just after 1 h, and in none thereafter. All animals exhibited normal haemodynamics after mitral valved stent implantation, and stability was maintained throughout the monitoring period. Migration, embolization and paravalvular leakage were not evident in the remaining animals after 4 and 8 weeks. Gross evaluation revealed that 50-70% of the atrial element was covered by tissue growth at 4 weeks/8 weeks. CONCLUSIONS This study demonstrates adequate deployment and anchorage of a unique, repositionable mitral valved stent. A good valve function was revealed in animals observed for 4 weeks and in one pig after 8 weeks.

Percutaneous tissue-engineered pulmonary valved stent implantation.

PURPOSE The purpose of this study was to evaluate the feasibility of percutaneously implanted tissue-engineered valved stents in the ovine pulmonary valve position. DESCRIPTION Porcine pulmonary heart valves and small intestinal submucosa were obtained from a slaughterhouse, and the intestinal submucosa used to cover the inside of the porcine pulmonary valved stents. Endothelial cells and autologous myofibroblasts were obtained from carotid artery segments of juvenile sheep. After myofibroblast seeding, constructs were placed in a dynamic bioreactor system and were cultured for 16 days. After Endothelial cell seeding, the tissue-engineered valved stents were deployed into the pulmonary valve annular site. Angiography was performed at implantation and explantation (4 weeks). Constructs were analyzed macroscopically and microscopically. EVALUATION Orthotopic positioning of the stents (n = 3) at the time of implantation and explantation, as well as normal valve function, was observed through angiography. Gross morphology confirmed excellent opening and closing of all leaflets. Strong expression of alpha-smooth muscle actin in neointerstitial cells and of von-Willebrand-Factor in endothelial cells was revealed by immunocytochemistry. CONCLUSIONS This study demonstrates successful merging of two novel technologies: (1) percutaneous valved stent implantation and (2) tissue engineering of autologous heart valves.

Mitral valved stent implantation: An overview

Abstract 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.

Tricuspid valved stent implantation: novel stent with a self-expandable super-absorbent polymer

OBJECTIVE Trans-catheter aortic and pulmonary valve replacement procedures can result in favorable outcomes in selected patients. The aim of this study was to investigate the functioning of a novel self-expanding valved stent with super-absorbent polymer (SAP) for minimally invasive replacement of the tricuspid valve. METHODS A newly designed nitinol stent with SAP was specially designed for the tricuspid annulus. This device was composed of right atrial anchoring elements, a left ventricular tubular stent, and a trileaflet bovine pericardial valve. The stent was coated with a waterproof material, and a pouch containing SAP for minimizing paravalvular leakage was placed beneath the atrial element. Seven pigs underwent minimally invasive off-pump tricuspid valved stent implantation. This was performed through a lower ministernotomy using a transventricular approach under transesophageal echocardiographic guidance. After 1 and 6h, a complete echocardiographic evaluation and hemodynamics (Swan-Ganz catheter) were performed. RESULTS Six of seven pigs exhibited normal hemodynamics immediately after tricuspid valved stent implantation and maintained stability for the entire period of monitoring. In one pig, a part of the atrial stent elements was deployed into the right ventricle, leading to significant paravalvular leakage, and died very soon. All subsequent animals survived with good results in the observation period. Accurate positioning of the valved stent was documented in six of seven pigs. SAP expanded and filled the gap between the stent and the native annulus in all animals. Mild paravalvular leakage was found in two of the six animals. Nevertheless, the observed leakage decreased to trace levels 6h after implantation. In the additional four pigs, only trace tricuspid regurgitation was revealed. No right ventricular outflow tract obstruction was detected. CONCLUSIONS Trans-apical off-pump tricuspid valved stent implantation is feasible in an acute experimental setting, and SAP may help to reduce paravalvular leakages.

Percutaneous pulmonary polyurethane valved stent implantation

OBJECTIVES Transfemoral application of pulmonary heart valves has been studied for the past 10 years. Nevertheless, size restriction of percutaneous heart valved stents is still imminent. METHODS In this study we implanted percutaneously a novel, low-profile polyurethane valved stent. Percutaneous implantation in pulmonary position was evaluated in 7 sheep. The new valved stent fits into a 14F delivery device. The self-expanding nitinol stent was produced by using a dip-coating technique, and a modified commercially available endovascular stent graft system served as a delivery device. The valved stents were deployed directly over the native pulmonary valve under fluoroscopic control. Transthoracic echocardiography was performed after 4 weeks. At the time of explantation, the animals were reanalyzed and killed. Angiography was performed at implantation and at the end of the study. Explanted constructs were analyzed macroscopically and microscopically. RESULTS Angiography and echocardiography in all animals demonstrated orthotopic position of the stents at the time of implantation and after 4 weeks. During the deployment procedure, rhythm disturbances occurred in all animals. The peak-to-peak transvalvular gradient was 2.3 +/- 1.2 mm Hg initially and 4.1 +/- 2.4 mm Hg at follow-up. One-month follow-up confirmed competent neovalves without any paravalvular leakage. Gross morphology demonstrated good opening and closure characteristics. No calcification was seen macroscopically, and surrounding tissue was free of calcification. CONCLUSION In the present study we demonstrated successful merging of 2 novel technologies for percutaneous treatment of pulmonary valve diseases using polyurethane stent valve constructs.

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.

COMPARISON OF BONE-MARROW DERIVED CD133p-CELLS AND CELLS OBTAINED FROM CAROTID ARTERY AFTER PERCUTANEOUS TISSUE ENGINEERED PULMONARY VALVED STENT IMPLANTATION

Tissue engineering represents an enormous advantage for the treatment of Tetralogy of Fallot. In this study we compared the use of endothelial cells (EC) and smooth muscle cells (SMC) derived from the carotid artery (group 1/ n=5) with CD133p-cells derived from bone-marrow (group 2/ n=5).