Adagio Medical, Inc., today announced successful pre-clinical results demonstrating their existing cryoablation catheter is also capable of ablating the tissue through pulsed-field ablation (PFA) delivered via the existing array of electrodes.
“Our goal is to lead the innovation and development of true continuous, transmural lesions anywhere in the heart. Our primary technologies under development have been ultra-low temperature cryo (ULTC) and electroporation (PFA),” said Olav Bergheim, President and CEO of Adagio Medical. He further says, “Therefore, our CE marked catheter and the catheter undergoing US IDE trials were designed to incorporate both technologies. The electrodes and the wiring in the catheters are currently activated for navigation and diagnostic purposes only. Software and hardware updates will be installed in the Adagio console to enable the PFA functionality once clinical and regulatory approvals are received.”
Dr. Alex Babkin, Ph.D., CTO of Adagio said, “In recent years, PFA and ULTC have become important alternatives in the field of AFib treatment. We believe that our ULTC technology, together with PFA, creates a new treatment and delivery option, the pulsed-field cryo ablation (PFCA) technology, that combines the best of both worlds.” As outlined below, our PFCA technology may overcome some disadvantages known to exist in each of these modalities. These two very different energy sources can also be used independently during one procedure depending on the treatment region in the heart.
While using our PFA technology, we had to overcome the following issues:
- Creation of bubbles in the atrium of the heart due to significant electrical current generated in the blood during a PFA treatment.
- Lesion depths are normally limited to 3-4 mm due to the nature of the electric field. Creating deeper lesions are more problematic as they would require applied voltage that may not be practical and/or safe to use.
- Musculoskeletal contractions associated with pulsed-field application.
- Ablation of adipose tissue. The most known safety benefit of PFA, tissue selectivity, can potentially become its “Achilles heel” in a situation when a myocardial tissue has inclusion of some other tissue e.g. adipose tissue.
While using our ULTC technology, we want to overcome the following issue:
- Risk of collateral damage to the esophagus and phrenic nerve
Dr. Babkin stated that “our pre-clinical trials have demonstrated that these issues can be controlled by combining the two platform technologies into one catheter.”
Avoiding bubbles and creating good tissue contact
The blood in the heart chamber has less electrical resistance than the myocardial tissue resulting in significant current density in the blood adjacent to the catheter. This current may result in the generation of microbubbles in the blood due to electrolysis. During our PFCA procedure, the catheter is placed by the stylet at the position of the targeted lesion followed by a short freezing cycle that covers the catheter with ice and isolates it from the blood, preventing bubbles to be formed by electrolysis. The frozen catheter makes it adhere to the tissue surface during the PFA treatment.
Lesion transmurality; adipose tissue
If only a shallow lesion of 2-4 mm depth is sufficient to complete an isolation, PFA alone can do the job with 400V/cm electric field strength between the electrodes. At a higher voltage, a deeper lesion may be made with PFA, but with a risk of creating an unsafe discharge or even a spark between the electrodes. This risk is significantly reduced when the catheter is isolated from the blood with ice, therefore, the PFCA catheter may be operated with higher voltage and the PFA modality will create a deeper lesion. The same opportunity to safely apply higher voltage may provide a better overlap of single ablation regions, creating a contiguous lesion. Furthermore, in any non-homogeneous tissue, a deeper lesion can be created with the cryoablation modality. Additionally, when created in low-temperature ice, the electric field created by PFA will be confined to the ice-ball, potentially creating an ability to directly visualize the ablation zone with traditional imaging technology such as ultrasound.
Due to the significantly reduced electrical conductivity of ice, PFCA requires a much lower value of associated current to create a lesion, therefore reducing or even eliminating contraction of the skeletal muscles. We could clearly see that effect in our pre-clinical studies.
During recent preclinical studies, Gregory K. Feld, MD, professor in the Department of Medicine at the University of California, San Diego School of Medicine and Director of the Cardiac Electrophysiology Program at UCSD Health System stated, “I was impressed with the versatility of the PFCA technology and was pleased to notice that we saw very limited muscle contractions during the procedure.”
“I am excited about adding another treatment multimodality to the same delivery system,” said Tom De Potter, MD, Associate Director and head of Electrophysiology at the Cardiovascular Center of the OLV Hospital, in Aalst, Belgium. “I am already familiar with the iCLAS cryo catheter delivery system after using it with great success on more than 70 patients. It can form multiple shapes that allow me to treat multiple targets in both atria without the need to remove the catheter from the heart. Having the option to tailor the energy source to a specific target using the same platform opens a completely new domain of possibilities.”
“ULTC and PFA ablations are relatively new additions to the field of EP and both are known to produce great clinical outcome,” said Prof. Michel Häissaguerre, MD, Professor at the Hôpital Cardiologique du Haut-Lévêque, Bordeaux-Pessac, and Director of the Electrophysiology and Heart Modeling Institute, LIRYC. “Combining both technologies in one treatment tool will allow us to achieve synergy between these modalities, therefore, overcoming certain shortcomings of both approaches. As a result, we could potentially create a very flexible, safe, and efficient instrument that will take advantage of both worlds. Patients can clearly benefit from this combination for atrial and ventricular applications!”
The Company is preparing for clinical trials with the PFCA combo catheter with the goal of extending the label claim to the dual-modality PFCA technology.
“We believe that all iCLAS™ users will enjoy the ability to expand the use of the same catheter to three modalities: ULTC, PFA, and PFCA,” says Mr. Bergheim.