Myocardial viability is crucial for the success of coronary artery bypass grafting (CABG) in patients with postischemic heart failure. Adjunctive therapies, such as stem cell or gene therapy, have been studied but are complex and carry significant financial burdens and adverse effects. Shockwave therapy has been used for over 30 years to treat kidney stones and can also regenerate infarcted and chronic ischemic myocardium. It improves ventricular function, regional myocardial wall motion and clinical symptoms in patients with chronic ischemic myocardium. The CAST-HF Trial is studying the benefits of direct cardiac shockwave therapy in a prospective, randomized-controlled manner. Shockwave therapy works by releasing exosomes, which carry nucleic acids that target Toll-like receptor 3, leading to angiogenesis. Direct epicardial shock wave therapy has been shown in a pilot trial to be safe and feasible in a clinical setting and may develop as an adjunctive therapy to CABG surgery, especially in those patients with large myocardial infarcts or areas of non-reversible ischemia.
Wie ist es zu diesen Entwicklungen gekommen. Beschreibung an was geforscht wurde und was die Ergebnisse waren. Welche Zertifizierungen liegen bereits vor und wie wirkt sich das auf die nächsten Schritte aus. Wir können hier schon auf die Forschung verlinken und dem Nutzer mehr Informationen geben. CTA ist hier wichtig, falls sich jemand für mehr informationen interessiert.
Wie ist es zu diesen Entwicklungen gekommen. Beschreibung an was geforscht wurde und was die Ergebnisse waren. Welche Zertifizierungen liegen bereits vor und wie wirkt sich das auf die nächsten Schritte aus. Wir können hier schon auf die Forschung verlinken und dem Nutzer mehr Informationen geben. CTA ist hier wichtig, falls sich jemand für mehr Informationen interessiert.
The use of shock wave therapy as a regenerative tool for the treatment of ischemic heart failure has been explored. Through numerous publications, it has been demonstrated that shock wave therapy has a potent angiogenic effect, resulting in decreased myocardial scarring and improved left ventricular function in cell culture and small animal models1-3.
The molecular mechanisms by which the mechanical stimulus is translated into a biological response have also been uncovered. Specifically, shock wave therapy creates a physical stimulus that induces the release of specific extracellular vesicles containing angiogenic cargoes4. These angiogenic growth factors, partly bound to the extracellular matrix, are released and cause endothelial cell proliferation and tube formation, resulting in efficient angiogenesis and arteriogenesis in the border zone of ischaemic hearts1.
Moreover, the factors released upon shock wave therapy stimulate the innate immune receptor Toll-like receptor 3 (TLR3), leading to a modulation of the inflammatory response and further inducing the regeneration of the ischemic myocardium (Figure). In TLR3 knock-out mice, the effect of shock wave therapy is abolished5. To initiate translation and confirm the regeneration of ischemic myocardium with improvement of left ventricular function in a large animal model, the world’s smallest shock wave applicator was developed.
Building upon the results from preclinical trials, the goal of the researchers was to efficiently translate their findings into a clinical study. As such, they initiated the CAST-HF trial, which was the first investigator-initiated prospective, randomized, sham-controlled trial aimed at assessing the safety and efficacy of direct cardiac shockwave therapy in addition to CABG surgery in patients with ischemic heart failure.
The Team of CareLab has expanded the use of shock wave therapy (SWT) for tissue regeneration to the treatment of spinal cord ischemia caused by aortic dissection or surgery. They found that in a murine model of spinal cord injury, SWT led to increased neuronal sprouting, reduced degeneration, and improved motor function. This was due to an innate mechanism of regeneration involving inflammatory cytokines, angiogenesis, recruitment of progenitor cells, and limitation of secondary injury. In addition, SWT reduced oxidative stress and apoptosis through the induction of nuclear factor erythroid 2-related factor 2, an antioxidative factor.
The authors observed that the effectiveness of SWT was impaired when Toll-like receptor 3 (TLR3) was inhibited or deleted, but enhanced when TLR3 was stimulated. They then translated their preclinical findings into the clinical setting and treated five patients with spinal cord ischemia with SWT, which showed promising results for safety and feasibility. This new treatment option may offer a novel approach to alleviate oxidative damage, reduce secondary neuronal damage, and preserve spinal cord tissue and function. The authors aim to prove the efficacy of this approach in a prospective, randomized trial.
Our research team has extended the application of shock wave therapy beyond cardiovascular diseases and spinal cord injuries. We are actively investigating the potential of shock wave therapy in various fields, including orthopedics, dermatology, and urology. Our efforts have resulted in numerous publications that demonstrate the effectiveness of shock wave therapy in promoting tissue regeneration and reducing pain. These preclinical and clinical studies pave the way for further exploration of shock wave therapy as a promising non-invasive treatment option for a wide range of medical conditions.
Regeneration of infarcted heart muscle remained an unsolved clinical problem despite decades of research on (stem) cell and gene therapy.
Shockwave therapy induces tissue regeneration in infarcted heart muscle and thereby significantly improves heart function (left ventricular ejection fraction). Shockwave therapy is proven safe in millions of patients over more than 35 years in orthopedic indications. This distinguishes shockwave therapy clearly from all other regenerative therapy approaches.
The main achievement of Avenns Medical is to refine low-energy regenerative shockwave therapy for direct cardiac use. We developed a sterile applicator suitable for direct cardiac application during heart surgery.
Shockwaves at low energy levels exert regenerative effects rather than disintegration of stones or plaques such as with high energies in Lithotripsie.
Numerous small and large animal trials of our academic research partners helped us to elucidate the exact molecular working mechanism of the new technology. Safety and feasibility have been proven in a human pilot trial. Efficacy is allready proved at Medical University of Innsbruck in a prospective randomized-controlled trial with results are better than expected.
Research results of our academic partners have been published in high-ranked scientific journals (e.g. Cardiovascular Research, JAHA, JTCVS, PLoS One) and presented at major international meetings (e.g. ESC, AHA, EACTS).