A “Scalpel” for interventional electrophysiologists

The author first used cryosurgery to electively ablate the His bundle in patients with various types of refractory supraventricular tachyarrhythmias at Duke University in 1973 with Dr. Will Sealy, the first surgeon to ever perform a surgical procedure for a cardiac arrhythmia (WPW syndrome, May 2, 1968). Over the ensuing years, as we developed more definitive surgical procedures to treat specific cardiac arrhythmias, such as AV node reentry tachycardia, automatic atrial tachycardias, ischemic and nonischemic ventricular tachycardia, and atrial flutter/fibrillation, cryosurgery was an integral tool in every operation that we developed. At that time, the only cryosurgical devices available utilized internally expanding nitrous oxide as the cryogen, which cooled the cryoprobe to approximately −60°C. Some 30 years later, argon gas, capable of cooling the cryoprobe to approximately −160°C, was introduced as a cryogen that could be used in surgical instruments but not for catheter ablation. Even today, available cryocatheters and cryoballoons still use nitrous oxide as the cryogen, though surgeons can choose between commercially available nitrous oxide and argon surgical cryoprobes. The cryocatheter used in the clinical study reported by Klaver et al. was developed by Adagio Medical, Inc., which was founded in 2010 with one specific goal . to provide interventional electrophysiologists (EP's) with a tool that would allow them to perform catheter ablation for atrial fibrillation with the same flexibility and efficacy that surgeons have with surgical instruments. We theorized that if we could provide EP's with the equivalent of a surgical scalpel, they could potentially treat atrial fibrillation with the same results that we routinely attained with the open‐heart Maze procedure. Our guiding principle was “The heart doesn′t know how atrial lesions are created, it only knows if they are contiguous, uniformly transmural, and placed in the correct positions. ” At that time, we evaluated two new energy sources that could potentially be adapted to standard catheter ablation for this purpose, irreversible electroporation and an ultra‐low cryogen called “near‐critical nitrogen” that was being tested at the time in the laboratories of Professor John Baust in Binghamton, NY. After several visits to Baust's laboratory and a few experiments using irreversible electroporation (pulsed‐field ablation, or “PFA”) in Professor Boris Rubinsky's laboratory at the University of California, Berkley in the summer of 2010, we chose to pursue the adaptation of ultra‐low cryosurgery as the most promising new energy source for the catheter ablation of atrial fibrillation. About a year later, we were fortunate to recruit Dr. Alex Babkin, a former NASA engineer and an expert in cryothermia, as our chief engineer at Adagio Medical and over the next 10 years Dr. Babkin and his colleagues at Adagio Medical developed the ultra‐low cryocatheter that is described in the accompanying article by Klaver et al. After some 8 years of animal research and catheter development, we invited Dr. Tom de Potter and later, Dr. Lukas Boersma, to perform the first clinical cases using the Adagio ultra‐low cryocatheter. We chose to use it first to create simple cavo‐tricuspid isthmus lesions in patients with atrial flutter because of the simplicity of the abnormal electrophysiology and its interventional treatment. The accompanying paper reports the results of that clinical experience. Since that time, clinical trials have been extended to treat paroxysmal atrial fibrillation and persistent and long‐standing persistent atrial fibrillation, the results of which await future publications. It has long been known that the coldest cryogen in nature is liquid nitrogen, which is capable of reaching a temperature of −196°C. Unfortunately, liquid nitrogen delivery requires such large probes and tubing for delivery that it is not feasible as a clinical tool for cardiac cryosurgery and certainly not for catheter ablation. However, several years ago it became possible to suspend liquid nitrogen in a so‐called “near‐critical” phase between liquid and gas. This provided a cryogen with the viscosity of gas that can be delivered through extremely small tubes at a temperature of −196°C, making it feasible as a cryogen for use in ablation catheters. The clinical results reported by Klaver et al. in this issue of JCE confirm the promise of this new approach for the catheter treatment of atrial fibrillation. Recently, Adagio Medical has developed a novel technology in which PFA and ultralow cryosurgery ULTC are combined into one energy source called “pulse‐field cryoablation” or PFCA that can be delivered through this single ablation catheter. The preclinical and clinical studies using PFCA are being performed under the direction of Dr. Atul Verma.