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2. Regnase-1 overexpression as a therapeutic approach of Marfan syndrome

Author

Noormalal, Marie, Schmiedel, Nesrin, Bozoglu, Tarik, Matzen, Andrea, Hille, Susanne, Basha, Dima Ibrahim, Vijaya Shetty, Prithviraj Manohar, Wolf, Anja, Zaradzki, Marcin, Arif, Rawa, Pühler, Thomas, Lutter, Georg, Wagner, Andreas H., Kupatt, Christian, Frank, Derk, Frey, Norbert, Remes, Anca, and Müller, Oliver J.

Published
2024
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3. Is the outcome of elective vs non-elective patients undergoing transcatheter aortic valve implantation different? Results of a single-centre, observational assessment of outcomes at a large university clinic

Author

Wundram, Steffen, Seoudy, Hatim, Dümmler, Johannes C., Ritter, Lukas, Frank, Johanne, Puehler, Thomas, Lutter, Georg, Lutz, Matthias, Saad, Mohammed, Bramlage, Peter, Sathananthan, Janarthanan, Wood, David A., Lauck, Sandra B., Frey, Norbert, and Frank, Derk

Published
2023
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7. Hydrodynamic Assessment of Explanted Degenerated Transcatheter Aortic Valves

Author

Sathananthan, Janarthanan, primary, Nigade, Anish, additional, Meier, David, additional, Navarro, Dante, additional, Spencer, Julianne, additional, Lai, Althea, additional, Gill, Hacina, additional, Pirelli, Luigi, additional, Webb, John G., additional, Wood, David A., additional, Lutter, Georg, additional, Puehler, Thomas, additional, Tang, Gilbert H.L., additional, Fukuhara, Shinichi, additional, and Sellers, Stephanie L., additional

Published
2024
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10. Surgical Myocardial Revascularization with a Composite T-graft from the Left Internal Mammary Artery—Comparison of the Great Saphenous Vein with the Radial Artery.

Author

Eide, Arne, Jussli-Melchers, Jill, Friedrich, Christine, Haneya, Assad, Lutter, Georg, Cremer, Jochen, and Schoettler, Jan

Subjects
ARTERIAL grafts, INTERNAL thoracic artery, MYOCARDIAL revascularization, RADIAL artery, REVASCULARIZATION (Surgery), SAPHENOUS vein
Abstract

Background Composite T-grafts between left internal mammary artery (LIMA) and radial artery (RA) are a common concept in complete arterial myocardial revascularization. The aim of the present study was to investigate whether the use of the great saphenous vein (SV) instead of RA leads to comparably good results in terms of outcome in this context. Methods Patients who underwent myocardial revascularization with a T-graft using RA or a segment of SV to the right coronary artery or circumflex artery between the beginning of 2014 and the end of 2019 at the Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel were included. To minimize surgical variation, only patients were observed by a single senior surgeon in the department. Exclusion criteria were previous cardiac surgery, preoperative extracorporeal circulatory support, off-pump surgery, additional aortocoronary bypasses, and cardiac combination procedures. Results A total of 115 patients were studied. In 55 patients, the T-graft was placed between the LIMA and SV, and in 60 patients, the T-graft was placed between the LIMA and RA. Patients in the SV group were older (70.6 ± 7.8 vs. 58.5 ± 10.0 years; p < 0.001), suffered more frequently from non-ST elevation myocardial infarction (12.7 vs. 1.7%; p = 0.027), arterial hypertension (83.6 vs. 61.7%; p = 0.009), and atrial fibrillation (18.2 vs. 1.7%; p = 0.003). They were less likely to be active smokers (16.4 vs. 38.3%; p = 0.009) and less likely to have a history of variceal surgery (0 vs. 15.0%; p = 0.003). Calcification of the ascending aorta was also found more frequently in the saphenous group (18.2 vs. 3.3%, p = 0.009). Operative times and number of distal anastomoses did not differ significantly between the two groups. Postoperative deliriums (16.7 vs. 5.0%; p = 0.043) were observed more frequently in venous patients. Wound healing disorders of the leg (11.1 vs. 0%; p = 0.011) did only occur in SV group and wound infections of the arm only in the RA group. Complete follow-up was achieved in 74.8% of cases. Median follow-up was 60.3 (39.6; 73.2) months. Serious adverse cardiac–cerebral events (19.0 vs. 22.7%; p = 0.675) and mortality (14.5 vs. 6.7%; p = 0.167) did not differ significantly between the groups at follow-up. Myocardial infarction (0 vs. 2.5%; p = 1.000) and stroke (0 vs. 7.5%; p = 0.245) were observed exclusively in RA group. Percutaneous coronary intervention was required in single patients of RA group (0 vs. 15.0%; p = 0.028). No patient from either group underwent repeat coronary artery bypass grafting (CABG). The patients of SV group had angiographically competent grafts and open anastomoses. Graft failure was noted in a single patient in RA group, in which case both grafts and native coronary vessels were stented. Kaplan–Meier analysis revealed no significant survival disadvantage for SV group compared with RA group. Conclusion CABG with a composite T-graft between LIMA and a segment of SV may be comparable to bypass surgery with a composite T-graft between LIMA and RA. This might be true in terms of morbidity and mortality over an intermediate-term observation period. The results of our studies give rise to the hypothesis that the decision not to perform aortic bypass anastomosis may be more important than the choice of graft material. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Tricuspid Regurgitation and TAVR: Outcomes, Risk Factors and Biomarkers

Author

Puehler, Thomas, primary, Pommert, Nina Sophie, additional, Freitag-Wolf, Sandra, additional, Seoudy, Hatim, additional, Ernst, Markus, additional, Haneya, Assad, additional, Sathananthan, Janarthanan, additional, Sellers, Stephanie L., additional, Meier, David, additional, Schöttler, Jan, additional, Müller, Oliver J., additional, Salehi Ravesh, Mona, additional, Saad, Mohammed, additional, Frank, Derk, additional, and Lutter, Georg, additional

Published
2024
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12. 4D Printing of Bioartificial, Small‐Diameter Vascular Grafts with Human‐Scale Characteristics and Functional Integrity

Author

Pfarr, Julian, primary, Zitta, Karina, additional, Hummitzsch, Lars, additional, Lutter, Georg, additional, Steinfath, Markus, additional, Jansen, Olav, additional, Tiwari, Sanjay, additional, Haj Mohamad, Farhad, additional, Knueppel, Philipp, additional, Lichte, Frank, additional, Mehdorn, Anne‐Sophie, additional, Kraas, Jana, additional, Hess, Katharina, additional, Faendrich, Fred, additional, Cremer, Jochen, additional, Rusch, René, additional, Grocholl, Jannek, additional, Albrecht, Martin, additional, and Berndt, Rouven, additional

Published
2024
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20. Producing and Testing Prototype Tissue-Engineered 3D Tri-Leaflet Valved Stents on Biodegradable Poly-ε-Caprolactone Scaffolds

Author

Lutter, Georg, primary, Pommert, Nina Sophie, additional, Zhang, Xiling, additional, Seiler, Jette, additional, Saeid Nia, Monireh, additional, Meier, David, additional, Sellers, Stephanie L., additional, Gorb, Stanislav N., additional, Hansen, Jan-Hinnerk, additional, Seoudy, Hatim, additional, Müller, Oliver J., additional, Saad, Mohammed, additional, Haneya, Assad, additional, Frank, Derk, additional, Puehler, Thomas, additional, and Sathananthan, Janarthanan, additional

Published
2023
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22. Redo-TAVI with SAPIEN 3 in SAPIEN XT or SAPIEN 3 &ndash; impact of pre- and post-dilatation on final THV expansion

Author

Meier, David, primary, Landes, Uri, additional, Sondergaard, Lars, additional, De Backer, Ole, additional, Lutter, Georg, additional, Puehler, Thomas, additional, Akodad, Mariama, additional, Tzimas, Georgios, additional, Blanke, Philipp, additional, Payne, Geoffrey W., additional, Lai, Althea, additional, Gill, Hacina, additional, Wood, David A., additional, Webb, John G., additional, Sellers, Stephanie L., additional, and Sathananthan, Janarthanan, additional

Published
2023
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23. Transcatheter Mitral Valve Replacement

Author

Pommert, Nina Sophie, primary, Puehler, Thomas, additional, Meier, David, additional, Seoudy, Hatim, additional, Sathananthan, Janarthanan, additional, Sellers, Stephanie L., additional, Both, Marcus, additional, Saad, Mohammed, additional, Frank, Derk, additional, and Lutter, Georg, additional

Published
2023
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27. Optimization of Enzymatic and Chemical Decellularization of Native Porcine Heart Valves for the Generation of Decellularized Xenografts.

Author

Saeid Nia, Monireh, Floder, Lena Maria, Seiler, Jette Anika, Puehler, Thomas, Pommert, Nina Sophie, Berndt, Rouven, Meier, David, Sellers, Stephanie L., Sathananthan, Janarthanan, Zhang, Xiling, Hasler, Mario, Gorb, Stanislav N., Warnecke, Gregor, and Lutter, Georg

Subjects
HEART valves, XENOGRAFTS, HEART valve diseases, TRITON X-100, IMMUNE response, TISSUE engineering
Abstract

One of the most important medical interventions for individuals with heart valvular disease is heart valve replacement, which is not without substantial challenges, particularly for pediatric patients. Due to their biological properties and biocompatibility, natural tissue-originated scaffolds derived from human or animal sources are one type of scaffold that is widely used in tissue engineering. However, they are known for their high potential for immunogenicity. Being free of cells and genetic material, decellularized xenografts, consequently, have low immunogenicity and, thus, are expected to be tolerated by the recipient's immune system. The scaffold ultrastructure and ECM composition can be affected by cell removal agents. Therefore, applying an appropriate method that preserves intact the structure of the ECM plays a critical role in the final result. So far, there has not been an effective decellularization technique that preserves the integrity of the heart valve's ultrastructure while securing the least amount of genetic material left. This study demonstrates a new protocol with untraceable cells and residual DNA, thereby maximally reducing any chance of immunogenicity. The mechanical and biochemical properties of the ECM resemble those of native heart valves. Results from this study strongly indicate that different critical factors, such as ionic detergent omission, the substitution of Triton X-100 with Tergitol, and using a lower concentration of trypsin and a higher concentration of DNase and RNase, play a significant role in maintaining intact the ultrastructure and function of the ECM. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Transcatheter Aortic Valve Implantation by Intercostal Access: Initial Experience with a No-Touch Technique

Author

Pommert, Nina Sophie, primary, Zhang, Xiling, additional, Puehler, Thomas, additional, Seoudy, Hatim, additional, Huenges, Katharina, additional, Schoettler, Jan, additional, Haneya, Assad, additional, Friedrich, Christine, additional, Sathananthan, Janarthanan, additional, Sellers, Stephanie L., additional, Meier, David, additional, Mueller, Oliver J., additional, Saad, Mohammed, additional, Frank, Derk, additional, and Lutter, Georg, additional

Published
2023
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29. Timing of bioprosthetic valve fracture in transcatheter valve-in-valve intervention:impact on valve durability and leaflet integrity

Author

Meier, David, Payne, Geoffrey W., Mostaço-Guidolin, Leila B., Bouchareb, Rihab, Rich, Courtney, Lai, Althea, Chatfield, Andrew G., Akodad, Mariama, Salcudean, Hannah, Lutter, Georg, Puehler, Thomas, Pibarot, Philippe, Allen, Keith B., Chhatriwalla, Adnan K., Sondergaard, Lars, Wood, David A., Webb, John G., Leipsic, Jonathon A., Sathananthan, Janarthanan, Sellers, Stephanie L., Meier, David, Payne, Geoffrey W., Mostaço-Guidolin, Leila B., Bouchareb, Rihab, Rich, Courtney, Lai, Althea, Chatfield, Andrew G., Akodad, Mariama, Salcudean, Hannah, Lutter, Georg, Puehler, Thomas, Pibarot, Philippe, Allen, Keith B., Chhatriwalla, Adnan K., Sondergaard, Lars, Wood, David A., Webb, John G., Leipsic, Jonathon A., Sathananthan, Janarthanan, and Sellers, Stephanie L.

Abstract

BACKGROUND: Bioprosthetic valve fracture (BVF) can be used to improve transcatheter heart valve (THV) haemodynamics following a valve-in-valve (ViV) intervention. However, whether BVF should be performed before or after THV deployment and the implications on durability are unknown. Aims: We sought to assess the impact of BVF timing on long-term THV durability. METHODS: The impact of BVF timing was assessed using small ACURATE neo (ACn) or 23 mm SAPIEN 3 (S3) THV deployed in 21 mm Mitroflow valves compared to no-BVF controls. Valves underwent accelerated wear testing up to 200 million (M) cycles (equivalent to 5 years). At 200M cycles, THV were evaluated by hydrodynamic testing, second-harmonic generation (SHG) microscopy, scanning electron microscopy (SEM) and histology. RESULTS: At 200M cycles, the regurgitant fraction (RF) and effective orifice area (EOA) for the ACn were 8.03±0.30%/1.74±0.01 cm2 (no BVF), 12.48±0.70%/1.97±0.02 cm2 (BVF before ViV) and 9.29±0.38%/2.21±0.0 cm2 (BVF after ViV), respectively. For the S3 these values were 2.63±0.51%/1.26±0.01 cm2, 2.03±0.42%/1.65±0.01 cm2, and 1.62±0.38%/2.22±0.01 cm2, respectively. Further, SHG and SEM revealed a higher degree of superficial leaflet damage when BVF was performed after ViV for the ACn and S3. However, the histological analysis revealed significantly less damage, as determined by matrix density analysis, through the entire leaflet thickness when BVF was performed after ViV with the S3 and a similar but non-significant trend with the ACn. Conclusions: BVF performed after ViV appears to offer superior long-term EOA without increased RF. Ultrastructure leaflet analysis reveals that the timing of BVF can differentially impact leaflets, with more superficial damage but greater preservation of overall leaflet structure when BVF is performed after ViV.

Published
2023

32. Timing of bioprosthetic valve fracture in transcatheter valve-in-valve intervention: impact on valve durability and leaflet integrity

Author

Meier, David, primary, Payne, Geoffrey W., additional, Mostaço-Guidolin, Leila B., additional, Bouchareb, Rihab, additional, Rich, Courtney, additional, Lai, Althea, additional, Chatfield, Andrew G., additional, Akodad, Mariama, additional, Salcudean, Hannah, additional, Lutter, Georg, additional, Puehler, Thomas, additional, Pibarot, Philippe, additional, Allen, Keith B., additional, Chhatriwalla, Adnan K., additional, Sondergaard, Lars, additional, Wood, David A., additional, Webb, John G., additional, Leipsic, Jonathon A., additional, Sathananthan, Janarthanan, additional, and Sellers, Stephanie L., additional

Published
2023
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35. Multimodality Imaging to Assess Leaflet Height in Mitral Bioprosthetic Valves

Author

Akodad, Mariama, primary, Sathananthan, Janarthanan, additional, Tzimas, Georgios, additional, Salcudean, Hannah, additional, Hensey, Mark, additional, Gulsin, Gaurav S., additional, Meier, David, additional, (Anthony) Chuang, Ming-yu, additional, Chatfield, Andrew G., additional, Landes, Uri, additional, Blanke, Philipp, additional, Sondergaard, Lars, additional, Payne, Geoffrey W., additional, Lutter, Georg, additional, Puehler, Thomas, additional, Wood, David A., additional, Webb, John G., additional, Leipsic, Jonathon A., additional, and Sellers, Stephanie L., additional

Published
2022
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39. Coronary Access Following Redo TAVR

Author

Meier, David, primary, Akodad, Mariama, additional, Landes, Uri, additional, Barlow, Aaron M., additional, Chatfield, Andrew G., additional, Lai, Althea, additional, Tzimas, Georgios, additional, Tang, Gilbert H.L., additional, Puehler, Thomas, additional, Lutter, Georg, additional, Leipsic, Jonathon A., additional, Søndergaard, Lars, additional, Wood, David A., additional, Webb, John G., additional, Sellers, Stephanie L., additional, and Sathananthan, Janarthanan, additional

Published
2022
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40. TAVR for All? The Surgical Perspective

Author

Zhang, Xiling, primary, Puehler, Thomas, additional, Frank, Derk, additional, Sathananthan, Janarthanan, additional, Sellers, Stephanie, additional, Meier, David, additional, Both, Marcus, additional, Blanke, Philipp, additional, Seoudy, Hatim, additional, Saad, Mohammed, additional, Müller, Oliver J., additional, Sondergaard, Lars, additional, and Lutter, Georg, additional

Published
2022
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42. TAVR for All? The Surgical Perspective

Author

Zhang, Xiling, Puehler, Thomas, Frank, Derk, Sathananthan, Janarthanan, Sellers, Stephanie, Meier, David, Both, Marcus, Blanke, Philipp, Seoudy, Hatim, Saad, Mohammed, Müller, Oliver J., Sondergaard, Lars, Lutter, Georg, Zhang, Xiling, Puehler, Thomas, Frank, Derk, Sathananthan, Janarthanan, Sellers, Stephanie, Meier, David, Both, Marcus, Blanke, Philipp, Seoudy, Hatim, Saad, Mohammed, Müller, Oliver J., Sondergaard, Lars, and Lutter, Georg

Abstract

In spite of the noninferiority of transcatheter aortic valve replacement (TAVR) in high- and intermediate-risk patients, there are still obstacles that need to be overcome before the procedure is further expanded and clinically integrated. The lack of evidence on the long-term durability of the bioprostheses used for TAVR remains of particular concern. In addition, surgery may be preferred over TAVR in patients with bicuspid aortic valve (BAV) or with concomitant pathologies such as other valve diseases (mitral regurgitation/tricuspid regurgitation), aortopathy, and coronary artery disease. In this review, we discuss and summarize relevant data from clinical trials, current trends, and remaining obstacles, and provide our perspective on the indications for the expansion of TAVR.

Published
2022

43. Comparison of Predicted and Confirmed Neo-Left Ventricular Outflow Tract After Transcatheter Mitral Valve Replacement

Author

Puehler, Thomas, Blanke, Philipp, Seoudy, Hatim, Sathananthan, Janarthanan, Sellers, Stephanie L., Meier, David, Both, Marcus, Saad, Mohammed, Frank, Derk, Søndergaard, Lars, Lutter, Georg, Puehler, Thomas, Blanke, Philipp, Seoudy, Hatim, Sathananthan, Janarthanan, Sellers, Stephanie L., Meier, David, Both, Marcus, Saad, Mohammed, Frank, Derk, Søndergaard, Lars, and Lutter, Georg

Published
2022

44. Coronary Access Following Redo TAVR:Impact of THV Design, Implant Technique, and Cell Misalignment

Author

Meier, David, Akodad, Mariama, Landes, Uri, Barlow, Aaron M., Chatfield, Andrew G., Lai, Althea, Tzimas, Georgios, Tang, Gilbert H.L., Puehler, Thomas, Lutter, Georg, Leipsic, Jonathon A., Søndergaard, Lars, Wood, David A., Webb, John G., Sellers, Stephanie L., Sathananthan, Janarthanan, Meier, David, Akodad, Mariama, Landes, Uri, Barlow, Aaron M., Chatfield, Andrew G., Lai, Althea, Tzimas, Georgios, Tang, Gilbert H.L., Puehler, Thomas, Lutter, Georg, Leipsic, Jonathon A., Søndergaard, Lars, Wood, David A., Webb, John G., Sellers, Stephanie L., and Sathananthan, Janarthanan

Abstract

Background: The implications and potential challenges of coronary access after redo transcatheter aortic valve replacement (TAVR) are unknown. Objectives: The authors sought to evaluate the impact of different transcatheter heart valve (THV) designs, neoskirt height, implant technique, and cell misalignment on coronary access after redo TAVR. Methods: Different THV designs (Sapien 3 [Edwards Lifesciences LLC], Evolut Pro [Medtronic], ACURATE neo [Boston Scientific Corporation], and Portico [Abbott Structural Heart]) and sizes were implanted inside Sapien XT (Edwards Lifesciences LLC) and Evolut R (Medtronic) THVs, which were modeled as the “failed” THVs, at different implant depths. Valve combinations underwent micro–computed tomography to determine the neoskirt height and dimensions of the lowest accessible cell for potential coronary access. This was compared with dimensions of 6-F/7-F/8-F coronary guiding catheters. Results: Redo TAVR combinations resulted in a wide range of neoskirt heights (15.4-31.6 mm) and a variable diameter of the lowest accessible cell (1.9-21.8 mm). An ACURATE neo implanted in a Sapien XT resulted in the largest accessible cells, whereas a Portico implanted in a Sapien XT resulted in the lowest neoskirt heights. The smallest accessible cell was observed in the Evolut Pro–in–Evolut R configuration with higher neoskirt heights. Redo TAVR in a tall frame valve with supra-annular leaflets caused a taller neoskirt height. In Evolut-in-Evolut combinations, misalignment of the cells of the 2 THVs reduced the cell area by 30% to 50% compared with an aligned configuration. Conclusions: This study demonstrates that different redo TAVR combinations are not equivalent in terms of future coronary access. Redo TAVR using a tall frame valve in a failed tall frame valve and misaligned cells may lead to potentially challenging coronary access.

Published
2022

45. Multimodality Imaging to Assess Leaflet Height in Mitral Bioprosthetic Valves:Implications for Mitral Valve-in-Valve Procedure

Author

Akodad, Mariama, Sathananthan, Janarthanan, Tzimas, Georgios, Salcudean, Hannah, Hensey, Mark, Gulsin, Gaurav S., Meier, David, (Anthony) Chuang, Ming yu, Chatfield, Andrew G., Landes, Uri, Blanke, Philipp, Sondergaard, Lars, Payne, Geoffrey W., Lutter, Georg, Puehler, Thomas, Wood, David A., Webb, John G., Leipsic, Jonathon A., Sellers, Stephanie L., Akodad, Mariama, Sathananthan, Janarthanan, Tzimas, Georgios, Salcudean, Hannah, Hensey, Mark, Gulsin, Gaurav S., Meier, David, (Anthony) Chuang, Ming yu, Chatfield, Andrew G., Landes, Uri, Blanke, Philipp, Sondergaard, Lars, Payne, Geoffrey W., Lutter, Georg, Puehler, Thomas, Wood, David A., Webb, John G., Leipsic, Jonathon A., and Sellers, Stephanie L.

Published
2022

46. Impact of Commissural Misalignment on Hydrodynamic Function Following Valve-in-Valve Intervention With the ACURATE neo

Author

Meier, David, Akodad, Mariama, Chatfield, Andrew G., Lutter, Georg, Puehler, Thomas, Søndergaard, Lars, Wood, David A., Webb, John G., Sellers, Stephanie L., Sathananthan, Janarthanan, Meier, David, Akodad, Mariama, Chatfield, Andrew G., Lutter, Georg, Puehler, Thomas, Søndergaard, Lars, Wood, David A., Webb, John G., Sellers, Stephanie L., and Sathananthan, Janarthanan

Abstract

Background: Limited evidence is available regarding valve-in-valve (VIV) intervention with the ACURATE neo transcatheter heart valve (THV). Low implantation has demonstrated leaflet interaction between the surgical bioprosthesis and the THV, leading to impaired hydrodynamic performance. It is unknown if commissural alignment (CA) can affect this phenomenon. Novel techniques have now been developed to achieve CA with the ACURATE neo THV. Objectives: The aim of this study was to assess the impact of commissural misalignment (CMA) on hydrodynamic function following VIV intervention with the ACURATE neo THV using a bench model. Methods: VIV intervention was performed with the ACURATE neo (a self-expanding THV with supra-annular leaflet position) implanted deep in the surgical bioprosthetic aortic valve (Mitroflow). Hydrodynamic function at CA (0°) and 3 different degrees of CMA (30°, 60°, and 90°) was tested. As per the International Organization for Standardization, a regurgitant fraction <20% is considered optimal. Results: Following VIV, the central THV regurgitant fraction at 0°, 30°, 60°, and 90° of CMA was 8.6% ± 2.0%, 30.3% ± 12.0%, 42.6% ± 11.9%, and 66.7% ± 25.4% (P < 0.0001), respectively. On high-speed video there was no evidence of leaflet interaction at CA, whereas at 30°, 60°, and 90° of CMA there was clear evidence of THV leaflet interaction with those of the surgical valve, leading to impaired leaflet closure and to severe central THV regurgitation. Conclusions: In VIV using the ACURATE neo THV at deep implantation, increasing degree of CMA was associated with THV leaflet interaction with those of the surgical valve and worsening regurgitant fraction. THV leaflet interaction was prevented when there was CA.

Published
2022

47. Transcatheter Mitral Valve Repair or Replacement:Competitive or Complementary?

Author

Xiling, Zhang, Puehler, Thomas, Sondergaard, Lars, Frank, Derk, Seoudy, Hatim, Mohammad, Baland, Müller, Oliver J., Sellers, Stephanie, Meier, David, Sathananthan, Janarthanan, Lutter, Georg, Xiling, Zhang, Puehler, Thomas, Sondergaard, Lars, Frank, Derk, Seoudy, Hatim, Mohammad, Baland, Müller, Oliver J., Sellers, Stephanie, Meier, David, Sathananthan, Janarthanan, and Lutter, Georg

Abstract

Over the last two decades, transcatheter devices have been developed to repair or replace diseased mitral valves (MV). Transcatheter mitral valve repair (TMVr) devices have been proven to be efficient and safe, but many anatomical structures are not compatible with these technologies. The most significant advantage of transcatheter mitral valve replacement (TMVR) over transcatheter repair is the greater and more reliable reduction in mitral regurgitation. However, there are also potential disadvantages. This review introduces the newest TMVr and TMVR devices and presents clinical trial data to identify current challenges and directions for future research.

Published
2022

50. Biodegradable Poly-��-Caprolactone Scaffolds with ECFCs and iMSCs for Tissue-Engineered Heart Valves

Author

Lutter, Georg, Puehler, Thomas, Cyganek, Lukas, Seiler, Jette, Rogler, Anita, Herberth, Tanja, Knueppel, Philipp, Gorb, Stanislav N., Sathananthan, Janarthanan, Sellers, Stephanie, M��ller, Oliver J., Frank, Derk, and Haben, Irma

Subjects
technology, industry, and agriculture
Abstract

Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-��-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. Cell adhesion, proliferation, and distribution, as well as the effects of coating PCL nanofibers, were analyzed by fluorescence microscopy and SEM. Mechanical properties of seeded PCL scaffolds were investigated under uniaxial loading. iPSCs were used to differentiate into iMSCs via mesoderm. The obtained iMSCs exhibited a comparable phenotype and surface marker expression to adult human MSCs and were capable of multilineage differentiation. EFCFs and MSCs showed good adhesion and distribution on PCL fibers, forming a closed cell cover. Coating of the fibers resulted in an increased cell number only at an early time point; from day 7 of colonization, there was no difference between cell numbers on coated and uncoated PCL fibers. The mechanical properties of PCL scaffolds under uniaxial loading were compared with native porcine pulmonary valve leaflets. The Young���s modulus and mean elongation at Fmax of unseeded PCL scaffolds were comparable to those of native leaflets (p = ns.). Colonization of PCL scaffolds with human ECFCs or iMSCs did not alter these properties (p = ns.). However, the native heart valves exhibited a maximum tensile stress at a force of 1.2 �� 0.5 N, whereas it was lower in the unseeded PCL scaffolds (0.6 �� 0.0 N, p < 0.05). A closed cell layer on PCL tissues did not change the values of Fmax (ECFCs: 0.6 �� 0.1 N; iMSCs: 0.7 �� 0.1 N). Here, a successful two-phase protocol, based on the timed use of differentiation factors for efficient differentiation of human iPSCs into iMSCs, was developed. Furthermore, we demonstrated the successful colonization of a biodegradable PCL nanofiber matrix with human ECFCs and iMSCs suitable for the generation of tissue-engineered heart valves. A closed cell cover was already evident after 14 days for ECFCs and 21 days for MSCs. The PCL tissue did not show major mechanical differences compared to native heart valves, which was not altered by short-term surface colonization with human cells in the absence of an extracellular matrix.

Published
2022
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