Medical University of Silesia

DUBLIN--(BUSINESS WIRE)-- Favorable patient outcomes from the TANDEM I first-in-human clinical trial of the CroíValve DUO™ System for the percutaneous treatment of tricuspid regurgitation (TR) were presented today by Professor Wojciech Wojakowski at the New York Valves 2024 scientific conference. The DUO System is a novel transcatheter coaptation valve that works in tandem with the native tricuspid valve to restore valve function, using an anchor system which leaves the right heart and native valve apparatus untouched. This press release features multimedia. View the full release here: W. Wojakowski , New York Valves Jun 2024 (Photo: Business Wire) TR is a severe heart condition that occurs when the tricuspid valve, on the right side of the heart, fails to close properly. This results in blood being pumped backwards into the right atrium and venous system causing debilitating symptoms. It affects over 1.6 million people in the US and is associated with significant morbidity and reduced life expectancy. The TANDEM I trial is a prospective, non-randomized, multicenter study designed to evaluate the safety and performance of the DUO System in patients with severe symptomatic TR. The study reported on 10 patients enrolled, showing sustained positive outcomes. Following 30-day outcomes presented last year, the six-month results demonstrated significant TR reduction by an independent core lab assessment, with TR reduced to moderate or less in over 85% of patients, even with massive or torrential TR at baseline. Patients also experienced markedly improved functional and Quality of Life outcomes, with a notable significant increase in both KCCQ score and 6MWT over baseline. The trial reported a 100% survival rate at 6 months. No incidences of arrhythmia or conduction disorder requiring permanent pacing were reported, demonstrating the advantages of avoiding right heart contact. Additionally, this data shows stable long-term device positioning and function, while supporting natural reverse remodeling. The simplified procedural experience was highlighted by an average device time of 43 minutes, even with first use cases. "The six-month results with the DUO System are highly promising, not only for its clinical safety and efficacy, but also for the procedure's simplicity and the technology's broad applicability," stated Professor Wojtek Wojakowski, Chief, Division of Cardiology and Structural Heart Diseases at the Medical University of Silesia in Poland. “This system offers new hope for patients suffering from severe TR, providing a versatile and predictable treatment option that simplifies the procedural and imaging experience for operators." The DUO System is delivered using percutaneous techniques and is secured using a novel anchor system which leaves the right heart and native valve apparatus untouched. The implant procedure is straightforward, uses standard imaging and is suitable for a broad patient cohort as it is independent of annular diameter, coaptation gap, leaflet morphology and visibility. "We are encouraged by these data, which demonstrate the DUO's success in reducing TR and improving patients' Quality of Life," said Dr Martin Quinn, CMO of CroíValve. "Our goal is to expand the reach of treatment option for patients with tricuspid valve disease. We are committed to building strong evidence to support emerging therapies like the DUO System, with further clinical studies and patient follow-ups underway." About CroíValve CroíValve is a clinical stage medical device company focused the development of a novel transcatheter device for the treatment of tricuspid regurgitation, with R&D & Operations activities based in Ireland and Clinical & Regulatory based in the U.S. Caution: The DUO System is an investigational device and not for sale in any geography.

DUBLIN, Ireland--( BUSINESS WIRE )--CroíValve has announced the successful First in Human implants of its DUO Tricuspid Coaptation Valve technology for the treatment of Tricuspid Regurgitation as part of its TANDEM I study in Poland. The procedures were performed as part of an ongoing clinical trial at the National Institute of Cardiology, Warsaw by Prof Adam Witkowski and Dr Maciej Dąbrowski and the Medical University of Silesia in Katowice by Prof Wojciech Wojakowski. Tricuspid Regurgitation (TR) is a severe heart condition that occurs when the tricuspid valve, on the right side of the heart, fails to close properly. This results in blood being pumped backwards into the right atrium and venous system causing debilitating symptoms. The DUO System consists of a coaptation valve implant that works in tandem with the native tricuspid valve to restore valve function. The device is delivered using minimally invasive techniques and is secured using a novel anchor system which leaves the frail right heart chamber and native valve apparatus untouched. The implant procedure is straightforward, uses standard imaging and is suitable for a broad patient cohort, including those who are challenging to treat with other valve repair and replacement technologies. These early cases demonstrate that the DUO System is highly effective at treating TR and significantly improves patients’ symptoms. This is achieved with a straightforward, short procedure, that is easy for the patient to tolerate and for the physician to perform. “ The DUO System is unique in providing a solution that can effectively treat the dilated right heart anatomy that accompanies Tricuspid Regurgitation, while avoiding contact with the right heart to maintain normal cardiac motion ,” commented Prof Adam Witkowski. “ After 30 days, our patient has already experienced a transformative improvement in symptoms, highlighted by the KCCQ Quality of Life survey and a reduction from NYHA III to NYHA II and significant improvement in 6MWT. In addition, the device continues to exhibit excellent efficacy .” “ This early use of the DUO System shows it’s an easy to use, safe and effective device ” added Prof Wojciech Wojakowski. “ Even though it was our first use of the DUO System, the procedure was very straightforward, which is highlighted by the short procedure time. It is a stepwise, controlled approach using standard echo and fluoro imaging and allows us treat patients we would otherwise have no option for” . "This achievement is an important milestone on our journey to implement the DUO System as the gold standard approach for treating Tricuspid Regurgitation. We'd like to thank the Heart Teams at the National Institute of Cardiology, Warsaw and the Medical University of Silesia in Katowice. We are excited by this early clinical experience in demonstrating a transformative treatment option for these patients." said Lucy O’Keeffe, CroíValve’s CEO.

An international study has identified a gene that plays an important role in the development of the human embryo. If it is altered, malformations of various organ systems can result. The gene emerged very early in evolution. It also exists in zebrafish, for example, and performs a similar function there. An international study led by the medical Faculty of the University of Bonn has identified a gene that plays an important role in the development of the human embryo. If it is altered, malformations of various organ systems can result. The gene emerged very early in evolution. It also exists in zebrafish, for example, and performs a similar function there. The results have now been published in the Journal of Medical Genetics. The researchers tracked down the gene when they studied two individuals with congenital malformations. "It was a man and his niece," explains Dr. Gabriel Dworschak. "Both had malformed kidneys, urinary tract and esophagus, and the man also had a malformed right arm and heart." The physician at the University Children's Hospital in Bonn conducts research on rare genetic diseases at the Institutes of Anatomy and Human Genetics. When the team looked at the genetic makeup of the family members, they came across an anomaly: A gene called SHROOM4 was altered in affected individuals compared to healthy individuals. SHROOM4 was already familiar from another context: It was known to play a key role in brain function. Mutations can result in intellectual impairment, epileptic seizures and behavioral abnormalities. "Our findings indicated though, that it may play a broader role in embryonic organ development," Dworschak explains. The team from Bonn searched internationally for other cases in which abnormalities in the SHROOM4 gene had also been found -- and succeeded: "Together with our cooperation partners, this led us to four more affected individuals from three families," says Prof. Dr. Heiko Reutter, who has since moved from the University Hospital Bonn to the University of Erlangen-Nuremberg. "All of them had the SHROOM4 gene altered, but not always in the same way." Zebrafish also needs SHROOM4 However, this did not necessarily clarify whether SHROOM4 variants were actually responsible for the malformations. But there is an animal that has a very similar gene: the zebrafish. It serves as a model organism in many genetic studies today -- and not only because it is easy to keep in a species-appropriate manner and to reproduce quickly: The skin of its larvae is almost transparent. This makes it easy to observe the animals' embryonic development under the light microscope. "Here at the University Hospital, we have the advantage that the research group led by Prof. Dr. Benjamin Odermatt from the Institute of Neuroanatomy works a lot with zebrafish," stresses Dr. Caroline Kolvenbach, who was also involved in the study of SHROOM4. "This expertise came in handy in our study." The researchers almost completely inactivated SHROOM4 in the larvae. The animals then showed malformations similar to those seen in the patients. If, on the other hand, larvae with SHROOM4 switched off were injected with the intact human genetic material, they developed almost normally. "This shows first that they absolutely need a functional SHROOM4 for healthy development; and second, that the human gene can still take over the function of the fish gene," Dworschak emphasizes. The team now wants to find out which part the gene plays in embryonic development. "We assume that it is needed for very basic processes in the cell," says Dworschak. "It's hard to explain otherwise why changes in the same gene cause such a variety of symptoms." Small piece in the mosaic of an extremely complex picture How a mouse, a dog or a human being develops from a fertilized ovum is still not fully understood. This is because the ovum has the ability to form any type of tissue in the organism, whether it is bone, skin, muscle or the brain. Its daughter cells are genetically identical to it; so in principle they should be able to do the same. But at a very early stage, certain programs are activated in their cells that irrevocably determine their developmental fate. This process must be coordinated down to the finest detail. Because only then it is ensured that the eyes form in the appropriate spot on the face, while other cells very close by differentiate into the nasal cartilage. Surprisingly, however, there is no conductor wielding the baton. It is as if a Lego spaceship were assembling itself -- only infinitely more complicated. "Our study is a small piece of the mosaic to this picture, which is still largely incomplete," Dworschak says. Participating institutions and funding: In addition to the University of Bonn and the University Hospital Bonn, the study involved Children's Mercy Hospital (USA), the Medical University of Silesia (Poland), the University of Zielona Góra (Poland), the University of Southern Denmark (Denmark), the University of Cologne, the University of Heidelberg, the University of Erlangen-Nuremberg, Medeor Hospital Lodz (Poland), and Goethe University Frankfurt. The work was supported by the German Research Foundation (DFG), the BONFOR program of the University Hospital Bonn, the Else Kröner-Fresenius Foundation, the Luise and Horst Köhler Foundation, and the National Institutes of Health (USA).