A Closer Look at Pulsed Field Ablation

Electrophysiologists at Penn Medicine Doylestown Health were among the first to treat patients with pulsed field ablation (PFA), participating in several clinical trials and now offering PulseSelect™, one of only two FDA-approved PFA delivery systems in the United States.

PFA is a novel, nonthermal approach to pulmonary vein isolation for the treatment of atrial fibrillation (AFib). By delivering very short energy pulses lasting nanoseconds to milliseconds, PFA preferentially targets heart tissue. Studies have demonstrated that with PFA, the risk of injury to the esophagus, phrenic nerve, and pulmonary veins is close to zero.

Atrial Fibrillation a growing health concern

AFib affects over 46 million individuals globally, with AFib prevalence in the US alone projected to increase to 12.1 million by 2030. While AFib is known to have increasing prevalence with advancing age, an increasing number of patients are aged under 65 years at presentation (10 to 15 percent). This younger group has substantial comorbidity burden, particularly obesity, heart failure, and hypertension with considerable long-term mortality (6.7 percent at less than 50 years; 13 percent between 50 and 65 years).

Earlier intervention leads to better outcomes

Greater AFib burden is associated with higher risks of stroke, mortality, and hospitalization for heart failure. Early rhythm control therapy for AFib, including treatment with antiarrhythmic drugs, lowers the risk of these adverse events.

Increasingly, there is role for catheter ablation (CA) over antiarrhythmic drug therapy for rhythm control. In the heart failure population in particular, CA compared to medical therapy is associated with greater maintenance of sinus rhythm, a decrease in all-cause mortality, and reduced risk of hospitalization for worsening heart failure.

Pulmonary vein isolation remains the cornerstone of CA for the treatment of AFib. Until recently, thermal technologies like cryoablation and radiofrequency ablation have dominated as energy sources. However, the downside of thermal ablation has been the risk of thermal injury to collateral structures such as the esophagus, phrenic nerve, and pulmonary veins which can result in very serious complications.

A novel nonthermal approach incorporating cardioselectivity is poised to dominate the field of ablation for atrial fibrillation

PFA is a novel nonthermal energy using high intensity ultrashort duration bursts of energy resulting in cell death via cell membrane electroporation, which results in rapid elimination of pulmonary vein potentials. Cellular sensitivity to this energy is highly tissue-specific with cardiac cells being ultrasensitive.

Thus, tissue specific ablation of myocardial cells can be effectively accomplished while minimizing and even avoiding the risk of injury to surrounding noncardiac cells. With PFA the risk of injury to the esophagus, phrenic nerve, and pulmonary veins is close to zero.

In addition to a favorable safety profile, early clinical trials have demonstrated excellent clinical results suggesting PFA could be a disruptive technology supplanting traditional energy forms as the “go to” ablation tool for AFib. The experience with PFA at Penn Medicine Doylestown Health suggests an improved patient experience with shorter procedure times, earlier discharge to home, and a lack of typical post ablation inflammatory symptoms such as chest pain.

Clinical trials demonstrate positive results

Penn Medicine Doylestown Health has participated in several pulsed field ablation clinical trials, including the two US pivotal trials, and finds this novel technology an exciting advance in the field of cardiac ablation.

The Pulsed AFib Pivotal Trial demonstrated a low rate of primary safety adverse events (0.7 percent). At 1 year, 70 percent of the paroxysmal-AFib group and 62 percent of the persistent-AFib group remained free of any recurrent atrial arrhythmia; 80 percent and 81 percent, respectively, met the clinical-success endpoint of freedom from symptomatic atrial arrhythmia recurrence. The results of this trial resulted in the FDA approval of the Medtronic PulseSelect™ PFA system in December of 2023.

Penn Medicine Doylestown Health also participated in the ADVENT Study of the Farapulse™ PFA system, the pivotal trial from Boston Scientific. ADVENT evaluated a system using a novel catheter design in 607 patients with symptomatic paroxysmal Afib. This trial demonstrated 12-month single procedure, off-drug success of 73.3 percent in the PFA arm and 71.3 percent in the thermal arm of the study.

Farapulse™ resulted in statistically shorter ablation times (mean of 29.2 minutes vs. mean of 50.0 minutes) with an excellent safety profile. The system received FDA approval in January 2024.

More recently, early results from a conformable ‘single-shot’ PFA catheter (Sphere-360; Medtronic) evaluating optimizing energy deliveries demonstrated freedom from atrial arrhythmia recurrences through 1 year in 100 percent of patients treated using the most-optimized of three waveforms. A subset of these patients underwent remapping about 75 days after the procedure demonstrating remarkable durability of electrical isolation. On a per pulmonary vein basis, 82 percent of lesions were durable using the initial PULSE1 waveform, 88 percent with PULSE2, and 99 percent with PULSE3.

Looking ahead

Thermal ablation has been around for more than 25 years, but PFA is still in its infancy. While results are exciting and applicable to present day ablation strategies, continued refinement is expected to further improve results and broaden application beyond AF to both supraventricular and ventricular arrhythmias. There is certainly enthusiasm surrounding this novel technology, but there are areas for potential concern, as well.

Currently available systems employ first generation catheter designs which could prove challenging for some operators. As with any new technology, the learning curve can be an issue, particularly for those who may be unfamiliar with larger “single shot” technologies such as cryoballoon ablation or PFA.

Additionally, the MANIFEST 17K registry assessing real world European experience has revealed some very rare complications, such as hemolysis and coronary artery spasm, both of which can easily be managed. Unsurprisingly, PFA systems are considerably more expensive than RF and cryoablation systems. Higher cost is typical of new technologies and may initially limit the ability of some centers to acquire PFA. However, with the introduction of greater competition in the market, pricing is expected to become more competitive in the near future.

Regardless of some potential limitations, there can be no doubt that PFA is a major advance in the field of interventional electrophysiology and should open the door for ablation therapy to reach more patients in a timely fashion while improving both safety and efficacy compared to traditional thermal energies.

Key Points

• Pulsed Field Ablation (PFA) is a novel, nonthermal approach to pulmonary vein isolation for the treatment of atrial fibrillation (AF). By delivering very short energy pulses PFA preferentially targets heart tissue. Studies have shown, with PFA the risk of injury to the esophagus, phrenic nerve and pulmonary veins is close to zero.
• The Pulsed AF Pivotal Trial demonstrated a low rate of primary safety adverse events (0.7 percent). At 1 year, 70 percent of the paroxysmal-AF group and 62% of the persistent-AF group remained free of any recurrent atrial arrhythmia; 80% and 81 percent, respectively, met the clinical-success endpoint of freedom from symptomatic atrial arrhythmia recurrence.
• The U.S. FDA approved the Medtronic PulseSelect™ PFA system in December of 2023.
• The ADVENT Study of the Farapulse™ PFA system is the pivotal trial from Boston Scientific which led to U.S. FDA approval in Jan 2024.
• More recently, early results from a conformable ‘single-shot’ PFA catheter evaluating optimizing energy deliveries demonstrated freedom from atrial arrhythmia recurrences through 1 year in 100 percent of patients treated using the most-optimized of three waveforms.
• The MANIFEST 17K registry assessing real world European experience has revealed some very rare complications such as hemolysis and coronary artery spasm both of which can easily be managed.
• While results are exciting and applicable to present day ablation strategies, continued refinement is expected to further improve results and broaden application beyond AF.

Performing Pulsed Field Ablation at Penn Medicine Doylestown Health Cardiology

• John D. Harding, MD
• Irfan M. Khurram, MD
• Robert M. Sangrigoli, MD
• Philip C. Wiener, DO

Clinical consult and patient referral

To refer a patient for pulsed field ablation at Penn Medicine Doylestown Health, please call 877-937-7366, or refer a patient online.