Acutus Medical Inc. appears to have solved one of the more vexing problems in cardiology, the sheer persistence of persistent atrial fibrillation (AF) despite treatment. In a study recently published in Heart Rhythm, the Carlsbad, Calif.-based company demonstrated that 73% of patients undergoing ablation using the new pulmonary vein isolation (PVI) plus core-to-boundary guided approach experienced acute termination of AF after one procedure, compared to 10% of patients undergoing ablation with the traditional posterior wall isolation (PWI) approach.

The positive outcomes lasted at least two years. The authors reported that at 12 and 24 months, 87% and 68% of patients, respectively, remained free of atrial fibrillation without antiarrhythmic medications. The results matched the immediate responses and improved on the one-year results seen in Acutus's Uncover-AF study using its Acqmap system.

“Core-to-Boundary is really a follow-up to the landmark publication of the Uncover-AF trial, which was a multi-center, international study that showed us we can utilize the global charge density mapping technology from Acutus to guide individualized ablations to treat persistent atrial fibrillation,” study author Tom Wong and chair of arrhythmia service at Royal Brompton and Harefield National Health Service Foundation Trust told BioWorld. “What we found is at 24 months, the freedom from atrial fibrillation and atrial tachycardia in the study group, which all had individualized ablations guided by charge density mapping, was significantly higher than the propensity-matched control group.”

The Acutus Acqmap system creates high-definition maps based on information provided by its specialized Acqmap catheter that enable physicians to locate ablation targets outside the pulmonary veins and plan a personalize ablation strategy for each patient. The non-contact basket catheter uses 48 ultrasound transducers to replicate the heart’s three-dimensional anatomical geometry and a 48 engineered electrodes that display electrical activation patterns along the organ’s inner surface to guide navigation.

Core-to-boundary ablation targets the conduction pattern core with an extension to the nearest non-conducting boundary, while left posterior wall electrical isolation creates an entrance and exit block for electrical signals.

“Atrial fibrillation affects more than 37 million people worldwide, but the current voltage-based mapping technologies available are simply too limited in their capacity to help us better understand the complexities of AF, especially when associated with persistent atrial fibrillation,” explained Acutus Chief Technology Officer Derrick Chou. “The foundation of our Acqmap technology is charge source mapping, which enables the creation of whole chamber maps of the heart that show activation in real-time and with resolution up to four times sharper than voltage.”

The persistence problem

Persistent AF, in which the heart loses its ability to regulate its rhythm, accounts for nearly 50% of all cases of atrial fibrillation that require ablation. Typically patients first experience paroxysmal AF. Over time, it can progress to persistent AF which is associated with more damage to the atria and greater difficulty recovering a normal rhythm. Patients with AF may experience heart palpitations, racing heartbeat, dizziness, fatigue, general weakness and shortness of breath and face a significantly elevated risk of blood clots, myocardial infarction and stroke.

Pharmacotherapy forms the first-line treatment for paroxysmal atrial fibrillation, with beta blockers, calcium channel blockers, and digoxin to slow the heart rate as well as antiarrhythmic drugs and anticoagulants all playing key roles. Persistent AF seldom responds adequately to medication therapy and many patients will require some catheter ablation using radiofrequency, cryotherapy or pulsed frequency.

Current ablation procedures also often fail to relieve persistent AF, however. Pulmonary vein isolation (PVI) forms the cornerstone of ablation procedures and often enables individuals with paroxysmal AF to recover their normal rhythm, but frequently fails in patients with persistent AF.

“Pulmonary vein electrical isolation (PVI) alone delivers modest success in treating [persistent AF],” said the study authors. “Additional ablation beyond PVI has not improved clinical outcomes. A better understanding of [persistent AF] is sought through new mapping technologies, but these efforts have not yet established a consensus on the best ablation strategy.”

Acutus’s charge density mapping system shows the tissue-level distribution of the sources of the electric charges involved in persistent AF, which could allow for more targeted ablation and better outcomes for patients.

“Because of the complexity of an arrhythmia like persistent atrial fibrillation, there has never been a consensus on the most effective strategy for treating it,” added study co-author Tim Betts, clinical lead for cardiac electrophysiology, Oxford University Hospitals National Health Service Foundation Trust. “What Acutus Medical’s Acqmap technology offers, and the Core-to-Boundary study validates this, is the first real comprehensive solution for the guiding of precise, individualized ablation strategies that can eliminate complex atrial arrhythmias like persistent atrial fibrillation.”

The study

Forty patients with persistent AF were enrolled in the active arm of the Core-to-Boundary study and 80 in the control arm. All had presented with persistent AF for at least five months and six had presented with it for more than 18 months. Patients were all receiving their first radiofrequency catheter ablation at either the Royal Brompton Hospital in London or the John Radcliffe Hospital in Oxford, U.K., between 2016 and April 2018.

Follow up visits were scheduled at three, six, and 12 months post-procedure and every six months thereafter. Any occurrence of atrial fibrillation or atrial tachycardia of more than 30 seconds after a three-month blanking period after the procedure was considered an arrhythmia recurrence.

Eight patients in the intervention group achieved relief from AF after charge-density mapping-guided PVI alone. Another 21 had acute AF termination following core-to-boundary ablation. That compared to eight of 80 patients in the control group who experienced acute AF termination.