Over the past four years, the pulsed field ablation (PFA) arms race has become very heated. Once just a concept, PFA is nearly here as companies compete to be first to market in the U.S.
For over three decades, catheter ablation procedures have relied on radiofrequency (RF) electrocautery to destroy abnormal tissue in the heart, such as that which targets clinical tachycardia or frequent premature contractions. Worldwide, over 1 million of these minimally invasive catheter ablation procedures are performed each year, offering hope for tens of millions of patients.
However, the emergence of PFA is challenging that paradigm. Currently, U.S. and European cardiac guidelines identify RF catheter ablation as the most effective therapy available for treating many abnormal heart rhythm disorders. Traditional RF electrocautery – although frequently used – comes with a potential downside: the generation of significant heat that can damage healthy surrounding tissue in the heart.
Conversely, PFA is a non-thermal ablation technique that uses microbursts of low total energy but very high peak voltage pulses to disrupt cellular membranes. In RF ablation, temporary loss of cellular compartmentalization is common and has metabolic consequences that can lead to tissue death. However, cardiac muscle happens to be exquisitely sensitive to PFA, much more so than most other tissue in the body. The implication is that any given PFA treatment strong enough to ablate abnormal cardiac muscle is insufficient to ablate the healthy bystander tissues like nerves, blood vessels, and connective tissues.
In contrast to RF ablation and cryoablation techniques, PFA appears to prevent much of the collateral injury that limits the success of the treatment which is a significant breakthrough in cardiology.
To better understand the differences between PFA and RF ablation, Dr. Kars Neven, a leader in the field and head of electrophysiology at Alfred Krupp Hospital in Germany, compared the technologies to grilling a steak: “In our business, we want to have a well-done steak. However, nine out of 10 times, you can’t flip your steak because we can only ablate from one side. We have to cook our steak at a very low temperature, but we expect our steak to be well done, which is impossible. If we up-titrate our energy (temperature), we will have charring, burning, and side effects. This is always the big problem, but now for the first time, we can hit it with a lot of energy and not worry about the side effects.”
Improvement in safety versus previous catheter ablation technologies is one of the most critical factors driving interest in PFA among electrophysiologists. Most of the cardiac ablation procedures done today are to treat nuisance problems such as atrial fibrillation. Since these procedures are not life-threatening, they must be safe enough to justify their use.
“The difference between PFA and RF is the opening of a door to a whole new world,” says Dr. Neven. “When you do RF, it is always a tradeoff between power, efficacy, and safety. So, when you have more power and efficacy, you will have less safety. Same holds true for cryoablation because both are thermal ablations. Now for the first time, we don’t have to worry about the balance anymore because we know the safety aspect is out of the equation.”
The Next Frontier for PFA
As PFA has demonstrated significant improvements in safety, companies are now focusing on optimizing the effectiveness of the tools. Many companies in the catheter ablation space are repurposing conventional RF ablation catheters to deliver new energy designed for PFA, such as Medtronic’s PulseSelect system using an existing catheter marketed in Europe, or Biosense Webster’s THERMOCOOL SMARTTOUCH. Each PFA system has a different energy strategy, and much of the research and development has focused on optimizing waveform.
“We know that depending on the waveform, the effect on the tissue can be dramatically different. You can have greater or lesser tissue selectivity. You can have greater or lesser durable lesion formation, and you can have greater reversibility. There’s likely going to be significant differences between the waveforms,” says Dr. Vivek Reddy, director of cardiac arrhythmia services at Mount Sinai Hospital and Mount Sinai Health System. Thus, each system must prove its efficacy, safety, and feasibility.
Among the firms at the forefront of this arms race is FARAPULSE, a company I founded in 2012 (acquired by Boston Scientific in 2019) to commercialize PFA for atrial fibrillation. In 2019, FARAPULSE conducted a first-in-human clinical trial, called IMPULSE, to evaluate PFA for atrial fibrillation.
Following positive results from this trial, the entire catheter ablation industry quickly shifted product development away from thermal ablation to PFA. More recently, the much-anticipated ADVENT pivotal trial from FARAPULSE completes its follow-up phase paving the way for FDA approval. This will be the first prospective randomized study comparing PFA to current technologies in treating atrial fibrillation.
As exciting as it is to see the entire industry being revolutionized by moving beyond thermal ablation, this will just be an initial foothold into PFA devices. My new organization, Field Medical, is building the next-generation of PFA which will expand on the promise of this first-phase medical technology. Our mission is to provide the most extensive range of treatment options in the field, such as bringing hope to underserved patients with severe and deadly arrhythmias like ventricular tachycardia (VT).
“What Field Medical is exploring are qualitative differences in electrode design, not just simply a configuration design like most other technologies. The way the electrical field is being shaped is qualitatively different through their work,” says Dr. Reddy. Several notable industry leaders have already signed on as Scientific Advisory Board members for Field Medical, including Drs. Reddy and Nevin.
The Next Generation: Hyper-Targeted Energy
The proprietary approach behind Field Medical is called FieldBendingÔ, which is a technique that predictably focuses energy around the catheter and reduces the unwanted far field, thereby improving efficacy and safety. Ultimately, the hyper-targeted energy of FieldBending will allow for a more accurate, concentrated application of power to the target tissue but also with the range to reach deep into tissue when large areas of tissue need to be ablated. The FieldBending catheter is currently in clinical development, with human trials expected to begin in the first quarter of 2024.
Most of the PFA technologies being developed today are specialized tools for performing a single procedure known as pulmonary vein isolation (PVI). This comes as no surprise because the largest single segment of the $3.5 billion catheter ablation market is atrial fibrillation. Many of the first-generation PFA technologies hoping to compete with FARAPULSE follow a similar approach as a PVI tool. But a few companies are looking beyond PVI-centric technology. Ongoing trials of single-point technologies including the SPHERE Per-AF trial (Medtronic) and the SmartfIRE study (Biosense Webster) demonstrate that a more versatile technology may be gaining traction in the PFA revolution. Clearly, a universal tool will be needed to address the entire spectrum of arrhythmias that can be treated with catheter ablation.
When asked what type of ablation catheter platform or tool he would choose to treat his patients, Dr. Neven said, “I would have a versatile catheter, and that means a catheter that is suitable for multiple ablations. So, you want to have one tool that can do everything. The current systems are dedicated tools; you can only do one thing with them. You want to have a MacGyver approach.”
While PVI may be necessary for the treatment of atrial fibrillation, it is often insufficient on its own and requires the ablation of additional targets. Furthermore, only half of the catheter ablations performed today are for atrial fibrillation. The other half are for other atrial tachycardias and more severe and deadly arrhythmias such as VT.
The next-generation PFA technology we are developing will be a universal PFA technology for the catheter ablation industry. We are thinking beyond atrial fibrillation and are focused on bringing a universal tool that can replace single-point RF ablation with effective PFA. Specifically, we are optimizing our technology to work extremely well in the ventricles.
The patient need is significant. Guidelines estimate that over 7 million people have clinical ventricular arrhythmias like VT and frequent premature ventricular contractions. Field Medical recognizes VT as one of the most important unmet needs that currently exist in healthcare. First-line therapies like implantable cardiac defibrillators can save lives by shocking patients back into normal rhythm, but they do not actually prevent VT. Drugs are not an ideal solution either. Antiarrhythmic drugs are some of the most toxic medications prescribed to patients with a very narrow therapeutic window, often making life-threatening arrhythmias worse.
Technical challenges of ablating in the ventricle are substantial and can make current treatment ineffective or impractical. VT ablation procedures are challenging, risky, and take a long time, often over five hours. Despite the potential benefits shown in clinical trials, catheter ablation remains a second-line approach. Doctors need a new tool kit, and it is coming.
Dr. Steven Mickelsen is the CEO and Founder of Field Medical, in Cardiff-by-the-Sea, Calif., and a board-certified Clinical Cardiac Electrophysiologist and practicing physician at Scripps Memorial Hospital in the San Diego region. He is widely recognized as being responsible for ushering in the use of pulsed field ablation technology to treat cardiac patients.