LBS 07: New approaches to managing AFib
Combined linear ablation, radiofrequency ablation, metformin and aggressive risk factor management.
Investigators in four trials revealed surprising findings on novel approaches to atrial fibrillation (AFib) ablation during their Late-Breaking Science session on Monday. They found:
- Combined linear ablation strategy provides rhythm control in patients with persistent atrial fibrillation.
- Radiofrequency ablation did not offer a superior advantage to cryoballoon ablation.
- Metformin did not improve Afib burden or progression.
- Aggressive risk factor management may provide long-term relief from atrial fibrillation symptoms.
Combined linear ablation strategy for patients with persistent AFib may be considered
The disease burden of AFib is increasing globally. In the U.S. alone, the incidence is projected to double from 6 million to 12.1 million people by 2030. Rhythm control has shown potential to improve outcomes, but success rates of pulmonary vein isolation (PVI) alone have been modest for persistent AFib. Could linear ablation combined with ethanol infusion vein of Marshall (EIVOM), a treatment that involves injecting ethanol into the VOM (vein of Marshall) to eliminate AFib triggers, be superior to pulmonary vein isolation (PVI) alone?
That was the question asked in “Comparison of Linear Ablation Plus Pulmonary Vein Isolation Versus Pulmonary Vein Isolation Alone for Persistent Atrial Fibrillation: Results From the PROMPT-AF Randomized Trial.” In the investigator-initiated, multicenter, open label trial, 498 patients with persistent AFib over three months undergoing first-time AFib ablation were randomized 1:1 to pulmonary vein isolation alone or pulmonary vein isolation with linear ablation and EIVOM. EIVOM was performed first, followed by PVI and linear ablation of the left atrial roof, mitral isthmus and cavo tricuspid isthmus. Arrhythmia recurrence was monitored using wearable single-lead electrocardiogram (ECG) patches for 24 hours per week, along with any additional symptom-triggered ECGs and Holter monitoring. Among randomized patients, 495 were included in the primary analysis.
The primary endpoint, freedom from any documented atrial arrhythmias lasting >30 seconds without anti-arrhythmic drugs at 12 months post-procedure, was met in 174 patients (70.7%) in the PVI + lines + EIVOM group and 153 patients (61.5%) in the PVI alone group (HR 0.73, 95% CI: 0.54 to 0.99, p = 0.045).
“Our study demonstrates that linear ablation combined with ethanol infusion vein of Marshall in addition to pulmonary vein isolation can be an effective rhythm control strategy for patients with persistent atrial fibrillation,” said Cheyang Jiang, MD, a cardiologist with Sir Run Run Shaw Hospital and Zhejiang University School of Medicine in Hangzhou, China, the study’s co-principal investigator. Jiang noted that PROMPT-AF is the first randomized trial to investigate the benefit of linear ablation combined with EIVOM beyond PVI alone.
“Previous trials have failed to demonstrate a significant incremental benefit of linear ablation when added to PVI alone, primarily due to difficulties in achieving durable lesions,” Jiang said. “But our study provides direct evidence that ethanol EIVOM facilitating ablation at the mitral isthmus is an optimized linear ablation strategy.” The study was simultaneously published online in the Journal of the American Medical Association.
CRRF-PeAF shows cryoballoon ablation comparable to radiofrequency ablation in patients with persistent AFib
In catheter ablation of AFib, cryoballoon ablation demonstrated noninferiority to radiofrequency ablation, according to Cryoballoon Ablation Versus Radiofrequency Ablation in Patients With Persistent Atrial Fibrillation (CRRF-PeAF): A Prospective, Multicenter, Randomized, Noninferiority Clinical Trial.
The prospective, multicenter, randomized, parallel-group, open-label study randomized 500 patients with PeAF 1:1 to cryoballoon ablation or radiofrequency ablation across 12 sites in Japan between April 2021 and June 2023. Pulmonary vein isolation therapy was mandatory for all patients undergoing catheter ablation. Adjunctive ablation lesion sets targeting sites outside the pulmonary veins were performed at the physician’s direction.
One-channel electrocardiograms were recorded twice daily for one year after catheter ablation using an ambulatory electrogram recorder in addition to other scheduled examinations, including 12-lead ECGs and 24-hour Holter recordings at three and 12 months. All documented atrial tachyarrhythmias lasting ≥30 seconds occurring outside the 90-day blanking period were considered recurrences. The final analysis included 499 patients.
The primary endpoint, defined as the occurrence of atrial tachyarrhythmias at one year after the 90-day blanking period was observed in 22.5% of patients in the cryoballoon ablation group and 23.2% in the radiofrequency ablation group. Overall, cryoballoon ablation demonstrated non-inferiority to radiofrequency ablation for the occurrence of atrial tachyarrhythmias at one year after the 90-day blanking period in patients with persistent atrial fibrillation (PeAF), which met the primary endpoint (HR 0.99, 95% CI, 0.69-1.43; P=0.96). Cryoballoon ablation demonstrated less atrial structural change compared with radiofrequency ablation despite the similar recurrence rate and atrial fibrillation burden after ablation between the two groups.
“Until now, there hasn’t been a prospective randomized study conducted with sufficient sample size comparing the outcome of catheter ablation between cryoballoon ablation and radiofrequency ablation in patients with persistent atrial fibrillation,” said Kengo Kusano, MD, director of the division of arrhythmia and electrophysiology at the National Cerebral and Cardiovascular Center in Osaka, Japan. “Our study shows that in catheter ablation of persistent atrial fibrillation, cryoballoon ablation, which is a safer and shorter treatment compared to radiofrequency ablation, is something you may want to select for patients more often.”
Metformin and lifestyle changes did not reduce AFib burden compared to standard of care
Treatment with metformin, lifestyle changes, or a combination of both did not improve AFib burden or progression, with compared with the standard of care, according to Randomized Controlled Trial of Metformin and Lifestyle/Risk Factor Modification for Upstream Prevention of Atrial Fibrillation Progression: The Targeting Risk Interventions and Metformin for Atrial Fibrillation, the TRIM-AF Trial.
In the prospective, open-label, blinded endpoint, 2x2 factorial trial, 149 adults with paroxysmal AFib or persistent Afib with plans for conversion, with a permanent pacemaker or ICD (with or without cardiac resynchronization therapy) with an implanted atrial lead or electrode capable of providing AFib diagnostics and remote monitoring. With at least one device-recorded ³5 minute episode of AFib over 3-month pre-enrollment period) were randomized to one of four treatment groups: standard of care (educational pamphlets on healthy diet and exercise without individual counseling); metformin up to 750 mg BID; lifestyle/risk factor modification (LRFM), including referral to a preventive cardiology team for diet and nutrition counseling as well as exercise prescription and to address other CV risk factors; or both metformin and LRFM.
Patients’ implantable devices were capable of recording daily AFib burden and activity. Patients were not on diabetes medications, with no contraindications to metformin use. The mean age of patients was 73.7 years; 38.9% were female, 3.4% were non-White, 79.2% had hypertension, 8.7% had diabetes, 38.3% had coronary artery disease, 68.5% had a pacemaker, and 31.5% had an ICD. Mean LVEF was 55.0±11.2%; left atrial size 4.3±0.79 cm, and baseline AF average daily burden 16.7±27.4%. The primary endpoint was a composite change in AFib burden or death after one year of follow-up by intention-to-treat analysis. Participants were followed for up to two years.
After the one-year follow-up, AFib burden decreased over time in the standard of care group, the lifestyle/risk factor modification group, and the lifestyle/risk factor modification and metformin group, but there were no significant differences in AFib burden change between the four groups. At 9-12 months, median AFib burden was 0.67% (relative change -73.5%) in the standard of care group, 0.62% (relative change -48.9%) in the metformin group, 0.13% (relative change -85.9%) in the lifestyle/risk factor modification group and 0.90% (relative change -72.4%) in the combined lifestyle/risk factor modification and metformin group.
All three intervention groups experienced weight loss, an average of 2.4% of their starting body weight in the metformin group, 2.1% in the lifestyle/risk factor modification group and 4.4% (9.1 pounds) -in the combined lifestyle/risk factor modification and metformin group.
“Interventions, including weight loss, exercise and metformin act on AMP kinase, the master regulator of metabolic stress in cells, but metformin alone should not be recommended as an upstream therapy for AFib,” said Mina K. Chung, MD, FAHA, a cardiologist and professor of medicine at the Cleveland Clinic in Ohio, the lead study author. Still, don’t underestimate the motivational power of discussing lifestyle and risk factor modification with patients with AFib. “We were surprised by the decrease in AFib burden in the standard of care group,” Chung said. “It’s possible that the written literature on diet and exercise we distributed to the standard of care group could have had a greater effect on reducing AFib burden than we thought.”
Aggressive risk factor management improved outcomes in patients after AFib ablation
The rising incidence of AFib coincides with an increase of cardiac risk factors in the general population, including obesity, hypertension, diabetes and sleep apnea. Catheter ablation of AFib is an effective treatment strategy, but it shows attrition of success over time. Cardiac risk factors are associated with increased risk of recurrence post-ablation. Could aggressive risk factor management improve outcomes in patients after AFib ablation treatment? That was the question asked in Aggressive Risk factor REduction STudy for Atrial Fibrillation (ARREST-AF) implications for ablation outcomes: A Randomized Clinical Trial.
The study randomized 122 patients in Australia with BMI >27 and one additional cardiac risk factor, such as hypertension, obesity, diabetes or sleep apnea 1:1 to intensive risk factor modification (RFM) or usual care after de novo catheter ablation for paroxysmal or persistent AFib. Patients in the RFM group attended a physician-led clinic to reduce modifiable risk factors in accordance with American Heart Association guidelines every three months for one year. Both groups received guideline-directed care for management of AFib. Pulmonary vein isolation was undertaken in each patient with additional ablation considered at the discretion of the electrophysiologist.
The primary endpoint, the percentage of patients free from AFib beginning at 12 months after ablation, which included a three-month blanking period, was 61.3% in the RFM group and 40% in the usual care group (HR 0.53, 95% CI 0.32-0.89, p=0.03). An arrhythmia was defined as a 30-second episode. Secondary endpoints included atrial symptom severity, risk factor profile, exercise capacity and the need for additional ablation. The risk factor management group had a median weight loss of approximately 20 pounds and showed superior blood pressure control, fasting glucose, lipid profile and exercise capacity, compared to the usual care group.
“This is the first in human randomized control trial showing that risk factor management after catheter ablation for AFib is associated with a significant reduction in AFib recurrence, as seen on an implantable loop recorder and improvement in self-reported symptoms and cardiac metabolic risk factors, compared with the usual care,” said Rajeev Pathak, MBBS, PhD, FHRS, the study’s principal investigator and clinical academic and director of cardiac electrophysiology at The Australian National University and Canberra Heart Rhythm.
Pathak noted the RFM group participated in a highly structured program tailored to each patient’s particular risk profile. “This was not one size fits all. For aggressive risk factor medication to work, it’s important to identify exactly which cardiac risk factors patients have and come up with a lifestyle modification plan that also addresses each patient’s limitations and challenges,” he said.