Introduction
CA has been well established for two decades and is superior to antiarrhythmic drug therapy in drug-refractory paroxysmal AF.¹ Despite continual advancement in ablation technologies and subsequent lesion delivery, the outcomes for persistent—and in particular long-standing persistent—AF remain suboptimal with patients, who often need repeat procedures. Replicating the previous success of the open heart Cox Maze III surgical AF ablation procedure, standalone thoracoscopic surgical ablation techniques have shown promising efficacy in patients with both paroxysmal and persistent AF but have not yet been tested in long-standing persistent AF.^2,3

The CASA-AF (Catheter Ablation Versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation) multicentre randomised controlled trial sought to compare thoracoscopic surgical ablation to CA as the first-line treatment strategy in patients with drug-resistant, symptomatic, de-novo long-standing persistent AF.^4,5 Instead of conventional intermittent holter monitoring methods to assess for arrythmia recurrence, implantable loop recorders (IRLs) were inserted, allowing for continuous cardiac monitoring and arrythmia burden assessment. In order to provide a holistic answer, the investigators also evaluated the change in patients' symptoms and quality of life and performed an in-trial health economic assessment.

Methods
A total of 120 patients long-standing persistent AF was randomised from 4 high-volume UK centres in a 1:1 ratio to surgical ablation or CA with pre-determined lesion sets. All patients had an ILR implanted with ILR data reviewed monthly by a blinded physiologist. In person follow-up visits were at 3, 6, 9, and 12 months. The primary outcome was freedom from AF/AT ≥30 seconds after a single procedure without anti-arrhythmic drugs at 1 year, excluding the 3-month blanking period. Secondary outcomes included serious adverse events within 30 days of the intervention, clinical success (≥75% reduction in AF/AT burden), assessment of quality of life, and cost-effectiveness. Complete cases were analysed as per intention to treat.

Results
Study treatment was received by 115 patients (55 surgical ablation, 60 CA; 5 withdrew consent after randomisation). AF/AT burden reduction was evaluated in 112 patients due to compliance with ILR downloads, with 110 patients completing all study follow-ups. Patients were 62.3 ± 9.6 years old, predominantly male (74%), with left atrial diameter 44.7 (±6) mm, and in continuous AF for 22 (16-31) months.

The primary endpoint was seen in 26% (14/54) of patients after surgical ablation and 28% (17/60) after CA following a single procedure and without anti-arrhythmic drugs (odds ratio [OR] 1.128; 95% confidence interval [CI], 0.46-2.82; p = 0.84) (Figure 1). The results for single procedure clinical success were far more encouraging, with 66% (36/54) of patients in the surgical ablation arm achieving this endpoint versus 77% (46/60) in the CA arm (OR 1.64; 95% CI, 0.67-4.84; p = 0.3) (Figure 2). Of those who did not achieve clinical success, 10/54 (18%) in the surgical ablation arm and 9/60 (15%) in the CA arm had redo CA procedures (OR 1.29; 95% CI, 0.48-3.46; p = 0.31).

Figure 1

Figure 2

In terms of serious adverse event rates within 30 days, this was seen in 15% (8/55) of patients in the surgical ablation arm compared to 10% (6/60) in the CA arm (p = 0.46). Over the 12-month follow-up period, serious adverse event rates were recorded in 18% (10/55) of participants after surgical ablation, compared to 15% (9/60) after CA (p = 0.65). However, the rate of all adverse events over the entire follow-up period attributable to the study intervention was significantly greater in the surgical ablation arm compared to the CA arm: 40% (22/55) versus 15% (9/60) (OR 3.78; 95% CI, 1.55-9.21; p = 0.003). Furthermore, 1 death occurred in the surgical ablation arm 3 weeks post-procedure due to sepsis complicated by multiorgan failure.

Improvements in patient-reported symptom and quality-of-life measures were seen from the first 3 months after ablation and sustained to the end of follow-up in both groups. However, the differences in mean European Heart Rhythm Association, Atrial Fibrillation Effect on Quality-of-Life, and EuroQol 5 Dimension 5 Level scores at 12 months were significantly worse for surgical ablation than CA: 0.916 (p = 0.02), ‑6.74 (p = 0.05), and ‑0.079 (p = 0.02), respectively. Over the 12-month follow-up, surgical ablation was associated with significantly lower quality-adjusted life-years than CA (0.78 vs. 0.85; p = 0.02) and higher costs, which translated to an incremental net benefit of £4,918 (95% CI, £1,101-8,735) for CA versus surgical ablation at a conservative cost-effectiveness threshold of £20,000 per quality-adjusted life-year.

Conclusion and Interpretation
This was the first multicentre randomised trial to assess outcomes in patients with long-standing persistent AF using continuous cardiac monitoring. The study showed that standalone thoracoscopic surgical ablation was not superior to CA in achieving freedom from atrial arrhythmia and reduction in AF burden. The adverse event rate was also greater for surgical ablation. CA patients experienced greater improvements in symptoms and quality of life compared with those treated by surgical ablation.

Patients with long-standing persistent AF are the hardest subset of patients with AF to treat, and the primary endpoint was extremely stringent as evidenced by the outcomes in both groups. It is important to appreciate that AF ablation is conducted for patients to relieve their symptomatic burden. Indeed, patients may derive significant symptomatic relief from AF burden reduction and be deemed a clinical success but fail the primary endpoint. The clinical improvement, measured as ≥75% reduction of AF/AT burden, with just 1 procedure and without anti-arrhythmic drugs, was very encouraging for both procedures at around 70%. Given that these patients were highly symptomatic and in continuous AF for 2 years, this reduction in AF burden provided significant clinical benefit as demonstrated by the improvement from baseline in quality-of-life measures. AF burden reduction may be a better indicator of positive clinical outcomes and is clinically very relevant from the patient perspective. Therefore, the use of continuous cardiac monitoring to accurately assess the burden of arrhythmia pre- and post-ablation is an important consideration for future clinical trials in AF.

Ultimately, CA fared better than surgery for symptoms, quality-of-life improvements in symptoms, and cost-effectiveness. Therefore, from our perspective, surgical ablation is not ready to be used as a mainstream therapeutic option yet, and we would still recommend CA as the first line intervention for symptomatic patients with long-standing persistent AF.

Figure 3

References

1. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-962.
2. Pearman CM, Poon SS, Bonnett LJ, et al. Minimally Invasive Epicardial Surgical Ablation Alone Versus Hybrid Ablation for Atrial Fibrillation: A Systematic Review and Meta-Analysis. Arrhythm Electrophysiol Rev 2017;6:202-9.
3. Haldar SK, Jones DG, Bahrami T, et al. Catheter ablation vs electrophysiologically guided thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: The CASA-AF Study. Heart Rhythm 2017;14:1596-603.
4. Khan HR, Kralj-Hans I, Haldar S, et al. Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised controlled trial. Trials 2018;19:117.
5. Haldar S, Khan HR, Boyalla V, et al. Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial. Eur Heart J 2020;Aug 29:[Epub ahead of print].

Clinical Topics: Arrhythmias and Clinical EP, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Atrial Fibrillation, Anti-Arrhythmia Agents, Electrocardiography, Ambulatory, Quality-Adjusted Life Years, Furylfuramide, Follow-Up Studies, Cost-Benefit Analysis, Quality of Life, Odds Ratio, Confidence Intervals, Intention to Treat Analysis, Catheter Ablation, Atrial Appendage

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