Boston Scientific's FARAPULSE PFA System Gains NMPA Approval as China's First Imported Pulsed Field Ablation Platform for Atrial Fibrillation

· This is a new technology for treating atrial fibrillation. Pulsed field ablation is a non-thermal energy source that induces irreversible electroporation of the cell membrane by applying high-intensity, short-duration pulsed electric fields to cells, leading to cell death. It has tissue selectivity and can specifically target and ablate myocardial cells while avoiding damage to surrounding tissues.

On July 8, 2024, the pulsed field ablation system FARAPULSE PFA System of Boston Scientific (BSX.US), a multinational corporation in medical technology, was approved by the National Medical Products Administration of China for the treatment of drug-refractory, recurrent, symptomatic paroxysmal atrial fibrillation.

Reportedly, it is the world's first commercially available cardiac pulsed field ablation system. In January 2021, it received the EU CE certification (a mandatory certification mark and a required "passport" for products to enter the European market). It was launched in the United States in January 2024 as the second cardiac pulsed field ablation system approved by the U.S. Food and Drug Administration (FDA).

According to a Boston Scientific press release, the FARAPULSE PFA System is the most researched and utilized pulsed field ablation system globally, having been used to treat over 70,000 patients to date.

According to the "Chinese Guidelines for the Diagnosis and Treatment of Atrial Fibrillation 2023" formulated by the Cardiology Branch of the Chinese Medical Association and the Cardiac Rhythm Society of the Chinese Biomedical Engineering Society, atrial fibrillation (AF) is the most common type of rapid arrhythmia, significantly increasing the risk of death, stroke, heart failure (HF), cognitive dysfunction, and dementia. Based on epidemiological surveys and data from the seventh national census, China has approximately 12 million AF patients. However, since about one-third of patients are unaware that they have AF and thus go undiagnosed, the actual number should be higher.

"Chinese Guidelines for the Diagnosis and Treatment of Atrial Fibrillation 2023" mentioned that catheter ablation is gradually becoming a first-line treatment for rhythm control in atrial fibrillation. A popular science article published in 2018 by the electrophysiology team of the Cardiology Department at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, introduced that under normal circumstances, the heartbeat is controlled by the "sinus node" located in the right atrium through the transmission of electrical signals. If there are lesions in the heart emitting "abnormal signals," the normal "command system" will be disrupted. Catheter ablation is a minimally invasive surgery that involves puncturing the blood vessels in the groin to deliver a catheter into the heart. Energy is delivered at the junction of the atrium and pulmonary veins to block the conduction pathways of abnormal signals, preventing atrial fibrillation.

It is reported that the existing ablation solutions are mainly radiofrequency ablation and cryoablation. According to an article published in the March 2023 issue of the Chinese Journal of Practical Internal Medicine, both radiofrequency ablation and cryoablation cause coagulative necrosis of tissue through temperature changes, and they are non-selective for myocardial and adjacent tissues, potentially leading to complications such as pulmonary vein stenosis, esophageal injury, and phrenic nerve damage.

Pulsed Field Ablation (PFA) significantly reduces the aforementioned risks. According to an article published in the April 2024 issue of the *Chinese Journal of Practical Internal Medicine*, pulsed field ablation is a non-thermal energy source that induces irreversible electroporation of cell membranes by applying high-intensity, short-duration pulsed electric fields to cells, leading to cell death. It exhibits tissue selectivity and can specifically target and ablate myocardial cells while avoiding damage to surrounding tissues. As a rising star in the field of electrophysiology, the pulsed field ablation system has been gaining increasing attention in both domestic and international markets and is highly anticipated in clinical settings.

More precise and safer ablation therapy

A pivotal ADVENT clinical trial directly compared the FARAPULSE PFA System with conventional ablation energy (radiofrequency or cryotherapy) for the treatment of paroxysmal atrial fibrillation in terms of efficacy and safety. The study enrolled a total of 607 patients, with 305 patients assigned to receive pulsed field ablation and 302 patients receiving standard ablation.

One year later, the success rate of the pulsed electric field group was 73.3%, and the one-year success rate of the group receiving traditional ablation energy treatment was 71.3%. The probability of acute and chronic severe adverse events related to the device and operation within 7 days after surgery was low in both groups, with 2.1% (6 cases) in the PFA group and 1.5% (4 cases) in the thermal ablation group.

The results of the secondary safety endpoints of the study showed that the FARAPULSE PFA system demonstrated superiority, with the degree of pulmonary vein stenosis at 3 months post-ablation being significantly lower in the PFA group (0.9%) compared to the thermal ablation group (12%). In terms of ablation time, the FARAPULSE PFA system had a significantly shorter ablation time (29.2±14.3 minutes) compared to the thermal ablation group (50.0±24.6 minutes).

The relevant study was published online in The New England Journal of Medicine (NEJM) on August 27, 2023, local time. The research data showed that although the vast majority of doctors only had experience with thermal ablation, the final clinical outcomes of the FARAPULSE PFA System were non-inferior to standard ablation.

Reportedly, there is currently the largest real-world study on pulsed field ablation systems, which used a retrospective approach to analyze the outcomes of treating arrhythmias with the FARAPULSE PFA System. This large observational study, named MANIFEST-17K, collected data from 106 research centers, 413 operators, and a total of 17,642 patients. The results showed that the incidence of major adverse events was less than 1%, with no reports of atrial-esophageal fistula/esophageal dysfunction, pulmonary vein stenosis, or permanent phrenic nerve injury. The findings of this trial were presented in November 2023 at the American Heart Association Scientific Sessions (AHA).

In addition, Boston Scientific is advancing the FARAPULSE PFA System for patients with drug-refractory symptomatic persistent atrial fibrillation. A clinical trial is also underway to evaluate the system as a first-line treatment for persistent atrial fibrillation. The study simultaneously assesses the safety and efficacy of the FARAPOINT PFA Catheter in performing cavotricuspid isthmus (CTI) ablation for atrial fibrillation.

An industry insider told The Paper that, in terms of the pulsed field ablation (PFA) track, the ablation outcomes of different technical routes largely depend on design details. For instance, catheter design is one of the most crucial elements in PFA technology. Clinically, each individual’s anatomical structure varies. Whether a universal catheter can be designed to adapt to the different shapes and sizes of pulmonary veins in different patients determines the safety and efficacy differences in treatment outcomes.

It is reported that the uniqueness of FARAPULSE lies in that it was originally designed as a product specifically for pulsed field ablation, rather than an improvement of an existing product. Its design fully takes into account the unique clinical application of pulsed field ablation and adopts catheters with variable basket-shaped and petal-shaped designs, which can adapt to various pulmonary vein anatomical structures, significantly reducing the duration of the device's stay in the left atrium.

Moreover, the FARAPULSE PFA System takes into account multiple factors such as electrode design and pulse waveform during its development to ensure that the targeted pulsed field ablation affects cardiac tissues, which are particularly sensitive to the energy source, rather than adjacent non-cardiac tissues. This makes the ablation treatment more precise and safer. Through clinical experience, the FARAPULSE PFA System has also established a relatively mature operational procedure and parameter setting, simplifying the operator’s pulmonary vein isolation ablation process, allowing for easy tissue contact and achieving an efficient ablation workflow.

The Track is Hot

A report by Future Market Insights (FMI) shows that the global pulsed field ablation market experienced a compound annual growth rate of 48.6% from 2021 to 2022, reaching a market size of US$1.3 million by 2023. By 2033, the market size may exceed US$11.7 million.

The aforementioned industry insider introduced that in recent years, many clinical trials of cardiac electrophysiology ablation based on the principle of pulsed field ablation have been conducted by companies both in China and abroad. At the 45th Annual Scientific Sessions of the Heart Rhythm Society held in May 2024, six out of the 21 latest clinical trial results announced in the special session were studies in the field of pulsed field ablation, which sufficiently demonstrates the popularity of this field and also proves that everyone is optimistic about the application of this technology in the prevention and treatment of atrial fibrillation.

The aforementioned industry insider stated that after the FARAPULSE PFA system was launched in the United States, its safety features, simple operation, and the effectiveness and efficiency of ablation were praised by electrophysiologists.

Boston Scientific's Q1 2024 earnings report shows that global sales in its electrophysiology division grew by 70%, with an 85% increase in the U.S. market.

According to media reports, Medtronic (MDT.US) reported net sales of $5.835 billion in its Cardiac Rhythm and Heart Failure (CRHF) division for the fiscal year 2023, representing a 1% decrease compared to fiscal year 2022. In its financial report, Medtronic stated that one of the reasons for the decline was the competitive pressure faced by its cardiac ablation solutions in the Western European market.

It is reported that Johnson & Johnson's (JNJ.US) pulsed field ablation device, Varipulse, received approval for marketing from Japan's Ministry of Health, Labour and Welfare in January 2024, obtained the EU CE certification in February 2024, and has submitted an application for market approval to the FDA.

In the Chinese market, the "PulsedFA Single-Use Cardiac Pulsed Electric Field Ablation Catheter" and the "LEAD PFA Cardiac Pulsed Electric Field Ablation System," developed by Sichuan Jinjiang Electronic Medical Device Technology Co., Ltd. (established in 2002), were approved for marketing by the National Medical Products Administration of China in December 2023. These products are characterized by magnetic navigation-based technology and integrate three-dimensional modeling, mapping, and ablation functions. In March 2024, the National Medical Products Administration approved the registration application for the innovative product "Single-Use Cardiac Pulsed Electric Field Ablation Catheter" from Hangzhou Denovo Electrophysiology Medical Technology Co., Ltd., which can be used in conjunction with the company's "Cardiac Pulsed Electric Field Ablation System."

According to Frost & Sullivan, the market size of pulsed field ablation in China is expected to reach 1.3 billion RMB by 2025 and 16.3 billion RMB by 2032. The proportion of China's pulsed field ablation market size in the overall electrophysiology device market will also continue to increase, from 8.18% in 2025 to 38.87% in 2032.

It is reported that the pulsed field ablation systems of Medtronic and Johnson & Johnson have entered the special review process of the China National Medical Products Administration. Chinese companies that are also active in this field include Beixing Medical, Huitai Medical, Xuanyu Medical, Aikema Medical, Maiwei Medical, Xin Lvtong, Zhoulǐn Medical, Yuanshan Medical, and Xinhanglu Medicine, among others.

References:

1.https://mp.weixin.qq.com/s/EsHeyB2nJmg2I9q9acDfWQ

2.https://mp.weixin.qq.com/s/qEwIkw56p_WuYfg0rGX92A

3.https://mp.weixin.qq.com/s/hLmioGFcqOteIEPvr29dJw

4.https://www.massdevice.com/whats-next-boston-scientific-farapulses-fda-approval/

5.https://www.futuremarketinsights.com/reports/pulsed-field-ablation-market