Less AF recurrence with combination of catheter ablation and renal denervation
Effect of Renal Denervation and Catheter Ablation vs Catheter Ablation Alone on Atrial Fibrillation Recurrence Among Patients With Paroxysmal Atrial Fibrillation and Hypertension - The ERADICATE-AF Randomized Clinical Trial
Introduction and methods
Increased activity of the autonomic nervous system may result in increased risk of atrial fibrillation (AF) [1,2]. Renal denervation can be an approach to reduce blood pressure in those with resistant hypertension by ablating the renal sympathetic nerves that interact with the autonomic nervous system . The effectivity of renal denervation has been debated, as trials have shown conflicting results [4-7].
Catheter ablation via pulmonary vein isolation can be used in AF patients to reduce AF recurrence , but ablation has a failure rate of 20-50%, a common need for repeat procedures and a significant long-term AF recurrence rate even after initial success [9-11].
A pilot study showed significant reduction of AF recurrence with a combination of catheter ablation and renal denervation in patients with refractory AF and drug-resistant hypertension . Now, the Evaluate Renal Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation (ERADICATE-AF) trial examined the effect of renal denervation in addition to pulmonary vein isolation on long-term anti-arrhythmic efficacy compared to pulmonary vein isolation alone. The trial enrolled 302 patients with paroxysmal AF, plans for catheter ablation and hypertension despite antihypertensive medication in 5 centers from April 2013 to March 2018. Patients were randomized 1:1 to receive ablation alone or ablation with renal denervation. The primary endpoint of this trial was freedom from AF recurrence at 12 months and not taking antiarrhythmic drugs (not including the first 3 months after ablation). 7-day Holter recordings were performed at 3, 6, 9 and 12 months.
- The primary endpoint of freedom of AF, flutter or tachycardia at 12 months was seen in 56.5% in the ablation alone group and in 72.1% in the renal denervation group (HR: 0.57, 95%CI: 0.38-0.85, P=0.006).
- Mean SBP reduction after 12 months was 3 mmHg (95%CI: 0-5 mmHg) in the ablation alone group vs. 16 mmHg (95%CI:14-18 mmHg) in the renal denervation group, with a between-group difference of -13 mmHg (95%CI: -15 to -11 mmHg, P<0.001).
- Mean DBP reduction after 12 months was 2 mmHg (95%CI: 0-5 mmHg) in the ablation alone group vs. 11 mmHg (95%CI:10-13 mmHg) in the renal denervation group, with a between-group difference of -10 mmHg (95%CI: -11 to -8 mmHg, P<0.001).
- Seven patients in each group had a complication, which were all related to the ablation procedure.
- There were 10 fatal and nonfatal major adverse cardiac events in each group. Two patients died in each group during follow-up.
- In the ablation only group, 18 patients were hospitalized for CV causes and 8 patients in the renal denervation group (absolute risk reduction: 7.0%, 95%CI: 1.6-12.5%, P=0.03).
In patients with paroxysmal AF and hypertension, a combination of catheter ablation and renal denervation resulted in reduced risk of AF recurrence at 12 months compared to ablation alone. Addition of renal denervation also resulted in lowering of blood pressure, both SBP and DBP, and lesser need for CV hospitalization. A limitation of the study was that there was no sham control procedure in the renal denervation group.
In his editorial comment , the author emphasizes the importance of sham controlled studies for medical devices and interventions. Although renal denervation was first shown to be beneficial in initial trials, a large sham-controlled randomized trial of renal denervation in resistant hypertension patients showed no effect of blood pressure.
In the ERADICATE-AF study all patients underwent catheter ablation procedure under sedation and were therefore blinded to the presence or absence of renal denervation. But those who did not undergo renal denervation had no femoral artery puncture and renal angiography, as sham procedure in the SYMPLICITY HTN trial.
There are ethical concerns of exposing patients to sham procedures in clinical trials, but it is also important to realize there are considerable risks to patients undergoing clinical interventions not evaluated with sham procedures. Evidence of a placebo effect instead of a therapeutic effect helps protect future patients from exposure to ineffective procedures.
The author ends by saying that future evidence of sham-controlled studies with a broader patient population is needed before the combination of catheter ablation and renal denervation can be used in clinical practice to treat AF patients with hypertension.