On the Verge of Breakthrough: Domestic Pulsed Field Ablation Products Nearing Mass Regulatory Approvals

Pulsed Field Ablation (PFA) Technology

VCBeat previously reported inGlobal Scan of 36 PFA Products: Rapid Commercial Progress and 3 Emerging Product Iteration TrendsA review of the development status of 36 PFA products from 30 companies worldwide reveals that PFA has shown excellent performance in expanding indications, upgrading ablation catheters/mapping technologies/pulse technologies. In 2024, the approval, clinical progress, and commercialization of PFA products are proceeding rapidly.

An industry insider predicted, "A group of companies will obtain certifications in a concentrated manner by the end of the year or early next year." In such a fiercely competitive environment, companies' channel development capabilities, market access advantages, and commercialization efficiency will become key factors in determining whether they can stand out.

Ablation parameters are key to the competitiveness of each manufacturer's PFA products, and the market currently has no unified solution for the optimal ablation parameters. VCBeat, based on publicly available information and interviews with experts from industry-leading companies such as AccuPulse, Jianhu Medical Technology (Suzhou) Co., Ltd., ShineyoMedical, and other enterprises, attempts to identify the development trends of PFA for industry reference.

Atrial fibrillation (AF) is one of the primary indications for PFA. Approximately 90% of AF patients with normal cardiac structure have the main triggering foci in the pulmonary veins, which are mostly located 2-4 cm inside the pulmonary veins. The primary treatment method for PFA is pulmonary vein isolation (PVI), which involves creating confluent ablation lesions around the four pulmonary vein ostia to achieve electrical isolation between the left atrium and the pulmonary veins.

The "Electrophysiology Industry Series Report" released by Pacific Securities mentioned that the effect of PFA depends on the combined action of multiple factors, such as electric field intensity, pulse duration, pulse waveform, number of pulses, single or double electrodes, cell arrangement, electrode-tissue distance, electrode spacing and size, electrode-tissue pressure, etc.

Multiple interviewees stated that the electric field intensity and pulse parameters are key factors determining the efficacy of pulsed electric field ablation. These two factors are related to parameters such as pulse voltage, catheter electrode spacing, electrode size, pulse width, number of pulses, and frequency.

Electric field intensity represents the electric force experienced by a unit positive charge in an electric field, directly determining the effect of pulsed electric fields on biological tissues such as myocardial cells.The greater the electric field intensity, the greater the impact on the target tissue, but at the same time, the risk of heat generation also increases, which may lead to a shift in thermal effects.

Based on the tissue-selective characteristics of pulsed field ablation, different tissues have different ablation thresholds, which range approximately between 400-3000V/cm. To achieve the desired ablation effect, manufacturers consider various influencing factors to determine the electric field intensity. According to the responses from multiple interviewees, the majority of PFA electric field intensity settings fall within the range of 1000-2000V/cm.

After determining the electric field intensity, each manufacturer will then confirm pulse parameters closely related to the electric field intensity, such as pulse width, pulse quantity, pulse polarity waveform, etc. These parameters collectively determine the degree of electroporation's impact on myocardial cells, i.e., the ablation effect.

Taking pulse width (the duration of a single pulse) as an example, the wider the pulse width, the stronger the electroporation effect. The longer the pulse width, the lower the voltage required to maintain the same level of cell electroporation.

ShineyoMedical R&D Director Xue ZhixiaoFor example, some PFA products that achieve ablation at lower voltages (500 volts) do so by increasing the pulse width. This ensures sufficient electroporation effects while reducing damage to surrounding tissues. Some manufacturers also use high-voltage (thousands of volts) nanosecond pulses for ablation, leveraging the principle that a sharp increase in electric field strength under high voltage can achieve electroporation within an extremely short time, with very narrow pulse widths. Such products typically offer faster ablation speeds and higher ablation efficiency. However, it should be noted that different scheme choices come with varying potential safety risks, requiring manufacturers to consider multiple factors comprehensively.

Jianhu Medical Technology (Suzhou) Co., Ltd.Introduction: In tumor treatment, nanosecond pulses generate less heat and fewer microbubbles, thereby reducing stimulation to surrounding tissues such as muscle twitching, significantly alleviating patients' pain and discomfort. To achieve nanosecond-level pulses, fast switches are the core components, which must realize nanosecond-level rapid on-off transitions while withstanding tens of kilovolts or even hundreds of kilovolts of high voltage. Traditional switching devices have limited pressure resistance. With the development of modern power semiconductor technology, new semiconductor switching devices have greatly improved in switching speed and voltage endurance, bringing a new direction for nanosecond pulse power technology. Experiments have proven that nanosecond technology also has the same effect in cardiac applications.

It should be noted that the electrode is a key component in pulsed electric field ablation, responsible for delivering electrical energy to the target tissue to achieve the ablation effect.The number and configuration of electrodes are the core of PFA catheter design, directly affecting the distribution and intensity of the electric field, which in turn influences the precision and depth of ablation.

The number of electrodes on PFA catheters that are currently certified or under research generally ranges from 5 to 35. However, Kardium's Globe mapping and ablation system stands out with its balloon catheter featuring up to 122 electrodes.

Far Mountains Medical introduced that the number of electrodes is related to the design of the product's electric field strength. Taking the Globe Mapping and Ablation System as an example, this catheter was originally an RF ablation product used for high-density mapping. After discovering the development potential of pulsed electric field ablation (PFA), Kardium decided to continue using this catheter design and apply it to PFA energy ablation. During the procedure, doctors can first use the catheter for modeling and mapping, then utilize a portion of the electrodes for ablation.

The catheter is equipped with a large number of electrodes to achieve high-resolution mapping, and each electrode requires wires to be connected to external power supplies and control equipment. Given the limited size of the catheter, in order to accommodate more electrodes and corresponding wires, the wires need to be extremely thin. However, this reduces the voltage resistance of the wires, limiting the output voltage (100-200V). To achieve effective ablation, the Globe catheter increases the electric field intensity by shortening the distance between electrodes. A shorter electrode spacing also means that the ablation area of a single electrode will be reduced accordingly. Therefore, the Globe catheter increases the number of electrodes to expand the ablation area.

ShineyoMedical Founder Shuguo ChenThree reference dimensions for electrode quantity settings are proposed: First, clarify the function of the electrodes. If the ablation catheter is to have mapping capabilities, the more electrodes it has, the better the mapping effect will be. Second, it depends on the electric field coverage and tissue contact conditions. The more electrodes there are, the larger the electric field coverage area, the more effective the transmission of contact force, and the greater the number of electrodes that can achieve good contact, resulting in a larger effective ablation area. Third, consider the complexity of electrode development processes, manufacturing difficulty, and cost. For example, the electrodes and catheters need a certain level of rigidity and tissue compliance to achieve better contact. As the number of electrodes increases, so does the complexity of the process. It was revealed that there was once a balloon catheter in overseas markets with high raw material BOM costs and complex production processes, leading to high product costs and complicated operation for doctors. Despite obtaining certification from overseas regulatory authorities and domestic innovative fast-track approval, its market promotion results were minimal.

AccuPulse R&D Director Zhang XiangmingFrom a design perspective, increasing the number of electrodes can enhance the continuity of ablation, ensure its effectiveness, and reduce the number of ablations and operations. However, more electrodes are not always better; they need to be optimized and matched with various parameters such as electrode shape, catheter form, and pulse settings.

Unlike the cryoablation/radiofrequency ablation mode, PFA's effect on tissues is proximal rather than contact-based. Although the requirement for catheter contact is not as stringent as that of radiofrequency and cryoablation,In practical clinical applications of pulsed ablation, to achieve the desired ablation effect, it is also important to ensure good catheter contact as much as possible.

Some PFA systems also adopt deformable catheter shapes to adapt to different pulmonary vein anatomical structures, ensuring good contact and ablation effects. For example, balloon-shaped catheters and petal/basket-shaped catheters can assess the degree of contact through deformation.

From the perspective of ablation safety, good contact can also reduce the risk of complications for patients.When the electrode discharges without contacting the tissue, it may generate bubbles in the blood, damage platelets, and lead to unnecessary blood injury and potential complications. Therefore, some manufacturers design contact-indication functions based on impedance detection technology or other technical methods to determine in real time whether the electrode is in good contact with the tissue.

Besides,Pulse polarity and waveform, tissue characteristics, fiber orientation, and heterogeneity in the local environment can all influence the ablation effectiveness of PFA.For example, the bipolar biphasic pulse wave currently adopted by most manufacturers can reduce muscle contraction and the patient's pain sensation while improving the efficiency and safety of ablation.

AccuPulse stated that, theoretically, these parameters will have a general guidance range. Manufacturers will determine and optimize the parameter range through extensive testing. Some manufacturers may also allow doctors to set parameters within a certain range.These parameters can be freely combined with different values, but a relatively standardized combination has not been determined yet."Deeper clinical research needs to be conducted for the application of PFA in the cardiac system."

PFA shows broad prospects in improving the success rate and efficiency of catheter ablation for atrial fibrillation. However, it also faces some development challenges.

ShineyoMedical mentioned,The small number of clinical trial cases and the short follow-up period are important factors limiting the development of pulsed electric field ablation."Since clinical data emerged in 2019, it has only been five years. Restricted by the quantity of evidence-based medical data, the health economics and clinical value of PFA have not yet been clearly demonstrated. It may take another two to three years of accumulating application cases before the market development of PFA becomes more apparent."

FarMountain MedicalIt was stated that the current market environment is complex and ever-changing, and some manufacturers' rush to launch products without sufficient沉淀与积累 may undermine the trust of both doctors and patients in pulse technology. To address this challenge, manufacturers must ensure product standardization in the future to gain more recognition and support from doctors. Meanwhile,Strengthening market education is equally indispensable, as it is crucial for enhancing public awareness and acceptance.

Jianhu Medical Technology (Suzhou) Co., Ltd.Introduction: Currently, many pulsed ablation procedures still need to be performed under general anesthesia, which carries a high risk of anesthesia and longer operation time. Additionally, there is a shortage of anesthesiologists in China, which will limit the promotion of such procedures in grassroots healthcare and the broader market in the future. Therefore, some manufacturers are optimizing relevant parameters to achieve a technological breakthrough enabling pulsed ablation under local anesthesia while ensuring effective transmural ablation. At the same time, he emphasized that when high-voltage electric fields are applied to muscle tissue, it may cause muscle contractions. How to effectively suppress muscle twitching is a key issue that needs to be addressed for pulsed ablation surgery under local anesthesia.

AccuPulse pointed out that despite the rapid development of PFA (Pulsed Field Ablation) technology, such as the market share of PFA in atrial fibrillation treatment in the United States approaching 20%, Europe having completed nearly 100,000 surgeries, and an increasing number of clinicians beginning to adopt PFA ablation, it still faces some new challenges.Such as the patient's tolerance under local anesthesia and new complications not seen with RF (radiofrequency) ablation, such as hemolysis and coronary artery spasm.

Moreover, multiple interviewees indicated that PFA is mainly applicable to paroxysmal atrial fibrillation, and research on its application for persistent atrial fibrillation is ongoing.In the field of PFA ablation, catheter forms are diverse, and research on energy optimization and procedural techniques has yet to be standardized. Many clinicians look forward to having mature and stable procedural methods along with standardized energy definitions for specific indications, which still requires a process of exploration and refinement.。

The core goal of the development of pulsed electric field ablation technology is to achieve simpler and safer operations, and reduce recurrence rates and the incidence of complications. With the continuous maturation of ablation technology, some new trends in the research and development of pulsed electric field ablation are gradually emerging.

Green electrophysiology has become a hotspot and development trend in atrial fibrillation ablation.The combination of intracardiac echocardiography (ICE) and pulsed ablation offers new approaches for the treatment of cardiovascular diseases. ICE provides clear visualization of the internal anatomy of the heart, assisting doctors in accurately locating the target sites of abnormal rhythm tissues. Pulsed ablation utilizes electric field energy to precisely ablate these targets, enabling accurate treatment.

AccuPulse introduced that, in addition, the three-dimensional mapping technology, which uses magnetic and/or electric fields for positioning to construct a three-dimensional electroanatomical structure of the cardiac cavity, has completely replaced the two-dimensional approach. This can minimize the harm of X-rays to both patients and operators, aligning with the concept of "green electrophysiology." However, the field of three-dimensional mapping is monopolized by international giants. Therefore, some domestically produced manufacturers are also actively enhancing their independent research and development capabilities in an attempt to rewrite the situation of import monopolies.

Catheter Upgrade Integrating Mapping and Pulse Ablation.Some Chinese-produced enterprises have highly integrated pulse ablation and mapping functions. The entire process, including three-dimensional modeling of cardiac tissue, electrophysiological mapping, pulse ablation, and evaluation of ablation effects, can be achieved with one or more specially designed catheters. This integrated design improves the precision and safety of surgeries, enhances treatment outcomes, and shortens operation time.

Big data and AI technologies can further enhance surgical outcomes and safety.AI Technology Can Improve Modeling Efficiency, Optimize Preoperative Assessment, and Postoperative Evaluation in 3D Mapping Systems. In May this year, Johnson & Johnson released the 8th upgraded version "CARTO 3 V8", which uses AI for the first time to reconstruct the anatomy of the left atrium. Doctors no longer need to manually draw contours, improving the efficiency of the surgical workflow and the accuracy of the maps.

Jianhu Medical Technology (Suzhou) Co., Ltd. introduced that in the field of electrophysiology, with the continuous development of artificial intelligence technology, its applications in the electrophysiology field have become more extensive and in-depth. For example, artificial intelligence can perform data analysis, diagnosis, and surgical assistance, and can also work collaboratively with CS (Cardiac Electrophysiology Surgery Training Fellows).

Jianhu Medical Technology (Suzhou) Co., Ltd. added that, currentlyThe PFA ablation index (PF index) is also a hot topic in industry research.PFI refers to a key indicator for comprehensively evaluating the effects of pulsed field ablation, including assessments of the degree of electroporation, the effectiveness in terms of ablation range, safety evaluations regarding complication rates and damage to surrounding tissues, as well as efficacy measures such as arrhythmia recurrence rates and pulmonary vein isolation rates.

In addition, the respondents also mentioned development directions such as the combination of multimodal energy, the exploration of more indications for pulsed electric field ablation, and dual-energy in a single catheter.

Current Market R&D Status of Pulsed Electric Field Ablation Technology Focuses Mainly on Clinical Trials and Approval Stages