Heart disorders, which affect millions of lives worldwide, encompass a wide range of abnormalities related to the heart’s structure and function. Amongst the various types of heart disorders, the prevalence of cardiac arrythmias has grown considerably. This condition manifests as heart beating too fast (tachycardia), too slow (bradycardia) or irregularly. These irregularities in the heart’s rhythm, either originating in the upper chambers (atrial fibrillation) or lower chambers (ventricular fibrillation) can disrupt its ability to pump blood effectively, leading to various symptoms, such as palpitations, dizziness, shortness of breath and in some cases, cardiac arrest. According to a study published in 2022, atrial fibrillation (AF) surged by 111% in the last 30 years, reaching around 60 million cases worldwide. As the prevalence of arrythmias, specifically atrial fibrillation, continues to rise, the quest for more effective and safer treatment options becomes increasingly vital. Atrial fibrillation (AF) is strongly linked to various cardiovascular diseases like heart failure, coronary artery disease (CAD), and valvular heart disease. While numerous cardiovascular drug delivery devices and drug eluting stents are accessible for treating these conditions, treatment options for AF, including the anti-arrhythmic drugs, frequently prove ineffective. Pulsed field ablation (PFA), a groundbreaking technology, has recently entered the market, promising a new era in the treatment of cardiac arrhythmias. Pulsed field ablation is a non-thermal modality which involves the application of electric fields to the heart tissue, leading to precise and controlled cardiac ablation without causing excessive damage to the surrounding areas. By using electrical fields rather than thermal energy, pulsed field ablation aims to offer a safer and more effective alternative, minimizing the risk of complications and potentially reducing the need for repeat procedures. In fact, research studies in the Journal of Cardiovascular Electrophysiology and the Heart Rhythm Society’s scientific have shown that this non-thermal ablation technique has demonstrated success rates ranging from 85% to 95%. As more clinical studies are conducted and investigational devices get regulatory approval, pulsed field ablation, a burgeoning segment of the cardiac ablation market, is likely to revolutionize the treatment of cardiac arrhythmias.
Components of Pulsed Field Ablation Solutions
Pulsed field ablation is a non-thermal ablation technology, that destabilizes cell membrane by forming irreversible pores, consequentially leading to cell death. PFA ablation, also referred to as DC ablation, leads to the formation of irreversible pores in the target cells, rendering current delivered between two or more electrodes, which produces the electric field. While ablating tissues, pulsed field ablation spares the extracellular matrix, averting the disruption of tissue planes, which is a key characteristic of radio frequency damage. Several pulsed field ablation technologies are currently being evaluated for cardiac ablation given their potential for improved procedural efficiency as well as safety.
While each proprietary system has distinct properties that cannot be broadly applied to other systems, they all comprise the following components:
Ablation Catheter: It is a thin tube inserted through a blood vessel and navigated to the ablation zone (heart). The design of the catheter highly impacts the ablation efficacy. The contact of the catheter tip with the surface of the tissue is an important factor for the formation of lesion of sufficient size and thickness. Various types of catheters are clinically used for AF ablation, which include, standard tip catheters, large tip catheters, open-loop irrigated tip catheters and closed-loop irrigated tip catheters.
Ablation Generator: It is a device designed for creating and emitting proprietary electrical pulses for the ablation procedure. The pulses created by different devices may vary in their electrical polarity and waveforms.
Mapping Software: Cardiac mapping is an electrophysiology study to evaluate the cause of arrhythmia. Mapping the cardiac electrical activity is a crucial component for diagnosis and treatment of arrhythmias.
Pulsed Field Ablation Procedure
The following figure presents a pictorial representation of the procedures involved in achieving pulmonary vein isolation using pulsed field ablation in patients suffering from atrial fibrillation.
As can be observed in the figure, pulsed field ablation for the treatment of atrial fibrillation is a minimally invasive procedure that utilizes a catheter, an ablation generator and is often used in combination with a mapping system. Further, the catheter used for the procedure can either be an ablation catheter or ablation and mapping integrated catheter. The integrated catheters eliminate the need for catheter exchange. In addition, the catheter tip configuration can vary as per the need of the procedure. The majority of the recently developed catheters have flower and basket, spherical or linear configuration, which aids the catheter to ablate specific regions of the heart with ease. Another important parameter is the diameter of the catheter, which should preferably be less. A smaller catheter diameter would lead to the formation of a minute transseptal puncture, which can be healed quickly. It is worth highlighting that the lesions formed by the short bursts of electric current dissipated by the pulsed field ablation catheter tip create transmural lesions (completely penetrates the heart tissue), thereby increasing the efficacy of the procedure.
PFA ablationMechanism of Action
Electric fields can generate accurate and selective ablation effects by influencing the cellular-scale electrical properties, when applied to tissues. Electroporation, also called electropermeabilization is one such effect, which has numerous therapeutic and diagnostic applications including cardiac ablation, tumor ablation and intercellular delivery of DNA, RNA, protein and other therapeutic agents. The figure below presents a pictorial representation of the steps of electroporation
The steps of electroporation have been briefly discussed below:
Induction: Application of external electric field results in an increase in the trans membrane potential (TMP) until it reaches its critical value (natural TMP is disturbed at the critical value). This step usually takes less than one microsecond.
Expansion: The continuous supply of external electric field causes an increase in the number and radius of the created nanopores while the TMP is maintained constantly above its threshold value.
Stabilization: After the external electric field and the TMP decreases to a subcritical level, the nanopores still exist in the cell membrane.
Resealing: When the external electric field is withdrawn, the resealing process of the cell membrane begins.
Memory: After resealing, some more irreversible changes usually remain in the cell membrane for hours.
Advantages of Pulsed Field Ablation Technology
Some of the advantages of PFA ablation are mentioned below:
Pulsed field ablation has a high tissue-selective functionality, which is particularly important for carrying out cardiac ablation. Due to this attribute of PFA, complications such as phrenic palsy and esophageal injury are remarkably reduced. Due to its non‐thermal nature and unique tissue‐specific injury characteristics, it may lead to a superior safety profile when compared to alternate energy sources.
This non thermal ablation technique appears to have the ability to ablate cells through mechanisms that do not alter stromal proteins, sparing sensitive structures to improve safety, without compromising cardiomyocyte ablation efficacy.
When Pulsed field ablation is directly applied on coronary arteries, luminal narrowing is usually not observed. Further, effective pulmonary vein isolation is achieved without pulmonary vein stenosis.
In this technique, cell death is caused through apoptosis, which is a natural mechanism of cell death and does not cause inflammation. Therefore, patients benefit from quicker post-procedure recovery.
This cardiac ablation technique has remarkably reduced the procedural time for ablation. Most of the procedures under development can be done within an hour.
Pulsed field ablation allows meaningful pre-planning of ablation procedure and control of energy delivery. This can be attributed to the lesser variable parameters of the electric field mediated mechanism of PFA.
Post radiofrequency ablation treatment of atrial fibrillation, recurrence of the disease is generally caused by reconnection of the isolated pulmonary veins. Catheter-based RF pulmonary vein isolation (PVI) is affiliated with a single procedure freedom from atrial fibrillation in approximately 70% of patients with paroxysmal atrial fibrillation. A major factor of AF recurrence is lack of durability of PVI, which is observed by acute pulmonary vein reconnection during the procedure and late pulmonary vein reconnection, post procedure.
The following figure presents the advantages of pulsed field ablation.
The Inevitable Pitfalls Within Every Promise
While a wide variety of pulsed field ablation systems have demonstrated the ability to achieve acute electrical isolation, however, there are few concerns that are to be considered for using PFA ablation. The primary concern is the necessity of general anesthesia and intubation at the time of therapy. In addition to the post-procedural pain, the main concern is skeletal muscle contraction, which can lead to issues regarding catheter stability. As a strategy to combat the above-mentioned drawback, a PFA delivery protocol , high-frequency irreversible electroporation (HFIRE) has been designed, which uses multiple short pulses at a high frequency in a bipolar fashion. This therapy delivery mechanism has been proposed to prevent muscle contractions and its associated side-effects. Further, optimal sedation protocols are required to be designed in order to reduce the pain felt by patients post the procedure.
It is worth highlighting that three pulsed field ablation devices have received the CE mark for the treatment for atrial fibrillation, over the past few years and a number of such devices are under clinical development. Currently, the pulsed field catheter ablation devices are not approved by the FDA for commercial use. The currently available instruments form the first generation of pulse field ablation devices, which are likely to undergo further modifications. For instance, second generation pulsed field cryoablation catheters are being developed, which are more tissue-specific and reduce the chances of skeletal muscle contraction, which is one of the major limitations of PFA. In order to achieve optimum transmural lesions, reduce the transseptal puncture size, shorten the procedure time and reduce cost, the pulsed field ablation market is likely to witness significant growth in the coming decade.