AF Ablation, Renal Denervation a Promising Team in ERADICATE-AF

May 10, 2019

SAN FRANCISCO — Two catheter-ablation procedures during the same session could potentially be better than one ablation for reducing the burden of atrial fibrillation (AF) in patients with both paroxysmal AF and hypertension.

Pairing an AF ablation by pulmonary-vein isolation (PVI) with an ablative renal denervation (RDN) procedure was followed by a more than 40% decline in AF prevalence over 1 year, compared with a conventional solo AF ablation by PVI, in a single-blind randomized trial.

Also, systolic blood pressure (BP) dropped about 15 points and diastolic BP fell by about 11 points, on average, in patients receiving the double procedure compared with those getting only AF ablation.

Renal denervation was "remarkably safe" when combined with PVI ablation of AF and "is reasonable to employ to increase the success rate of AF ablation in patients with hypertension," said Jonathan S. Steinberg, MD, here at the Heart Rhythm Society 2019 Scientific Sessions.

Steinberg, from the University of Rochester School of Medicine and Dentistry, New York, is a coprincipal investigator on the trial, called Evaluate Renal Artery Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation (ERADICATE-AF).

The study, which some observers consider too preliminary and lacking sufficient follow-up to affect clinical practice now, entered 302 patients with symptomatic paroxysmal AF and a history of hypertension who were on at least one antihypertensive agent and referred for AF ablation.

They were randomized to undergo the procedure with a cryoablation catheter with RND using the same equipment or AF ablation plus sham RND.

Procedural complications, mostly vascular, occurred in 14 patients, with no significant difference between the two strategies. Procedure time averaged 190 minutes for PVI plus RDN and 167 minutes for PVI alone.

"Despite the added complexity of an extra procedural component, there appeared to be virtually no added risk" associated with PVI plus RDN, said Cara N. Pellegrini, MD, University of California, San Francisco and San Francisco Veterans Affairs Health System, as the invited discussant after Steinberg's presentation.

Based on ERADICATE-AF, she said, six patients would need to be treated with RDN to prevent AF from recurring for 1 year in one patient, "and I think that's pretty remarkable, actually, on top of the pulmonary vein isolation procedure already."

Catheter ablation for RDN saw its ups and downs when explored in trials as a treatment for hypertension. The randomized, sham-controlled SYMPLICITY HTN-3 trial showed no significant BP-lowering benefit from the procedure either at 6 months or 1 year. Later trials and meta-analyses were more hopeful that it could potentially find a role in select groups of patients with drug-resistant hypertension.

The hypertension trials had also shown provocative AF reductions in patients getting RDN, Steinberg pointed out; sympathetic activation can underlie both disorders.

He said the track record of RDN established in the hypertension trials bodes well for the safety of the combined RDN–AF ablation strategy. And although it's not a cardiac procedure, it can be reliably performed with success "in the skilled hands of electrophysiologists."

Still, Pellegrini offered some cautions about the RDN–AF ablation approach. It's noteworthy that AF recurrences were reduced significantly in patients treated with RDN, yet they still had a recurrence rate of about 30%. "So, this isn't a panacea."

Others had reservations about the study and the procedure. Attempting something as invasive as RDN for patients with hypertension would make more sense "if all other modalities are tried before it," Nora Goldschlager, MD, San Francisco General Hospital, who is not associated with the trial, told | Medscape Cardiology.

"You have other strategies that you can do first, ones we know more about, ablation and some drugs," and it's not known how renal denervation is going to fit in among them.

Further, RDN is not a reversible procedure, she noted, and ERADICATE-AF tracked patients only for a year. "They didn't follow them long enough. What are the long-term effects?"

Although it's provocative, "I don't think it's a practice-changing trial at all," Andrew D. Krahn, MD, also not associated with ERADICATE-AF, said in an interview.

Krahn, from the University of British Columbia, Vancouver, Canada, said he doubts that AF ablation with RDN is "the answer" for patients with hypertension and the arrhythmia, and that "they need medical optimization before we start doing invasive things."

The "obvious Achilles heel of the study," he said, is that there seemed to be "very suboptimal hypertension management" in the control group.

Pellegrini had also observed that the control patients in ERADICATE-AF were not medically managed to achieve guideline-recommended BP goals.

"How can you leave people with a blood pressure of 150/90 mm Hg in 2019? You just can't in a comparator arm," Krahn said. And that range was average, he noted; it means about half the patients had even higher blood pressures.

Systolic and Diastolic Blood Pressures by Treatment Group and Follow-up Time
Blood Pressure PVI Only, mm Hg
(n = 148)
PVI plus RDN, mm Hg (n = 154) P Value
At baseline      
Systolic 150 150 NS
Diastolic 90 89 NS
At 6 months      
Systolic 149 135 <.001
Diastolic 89 78 <.001
At 12 months      
Systolic 148 134 <.001
Diastolic 88 78 <.001
NS = not significant

Because both patient groups started the study with poorly managed blood pressure, Krahn said, it's questionable whether there would have been as striking a BP difference between them at 6 months and 1 year had the control group been optimally managed during the trial.

That's important, he said, because it's currently unknown how much of the observed RDN benefit seen in the trial is due to lowering of BP compared with a more direct antiarrhythmic effect.

Indeed, Steinberg said, "I think the most burning question that we all have is, is the effect of renal denervation essentially an antihypertensive effect or is it an antiarrhythmic effect, or perhaps both?"

Future RDN studies, he said, may include some that enrol patients with AF but without hypertension, "and I think that will finally answer the question of whether this is due to better blood pressure control or not."

In ERADICATE-AF, the patients were randomized, blinded to their treatment assignment of PVI with either RDN or a sham RDN. The 154 and 148 patients, respectively, came from five centers. The two groups had been similarly treated with cardiovascular meds. Women made up 40% of the study population.

The group receiving both PVI and RDN showed a significantly greater rate of freedom from AF recurrence over 12 months, the primary end point, excluding an initial 3-month blanking period. The rates were 72.1% for PVI plus RDN and 56.5% for PVI only, for a recurrence hazard ratio (HR) of 0.57 (95% CI, 0.38 - 0.85; P = .004), favoring the RDN group.

Addressing whether there was an adequate duration of follow-up, Steinberg told | Medscape Cardiology that the RDN studies in hypertension "have been around for quite a number of years and I am not aware of any long-term deleterious effects."

When interviewed, Pellegrini said her research in preparation for her discussant presentation on ERADICATE-AF did not turn up late outcomes data for RDN to clarify whether the procedure's safety holds up over the long term.

That information is needed, she said, because it's unknown whether "there might be other effects on renal function or something else that we haven't uncovered yet."

Steinberg discloses consulting for Medtronic, Biosense Webster, National Cardiac, Allergan, G Medical, Atricure, Corfigo, and Omron; having equity in National Cardiac, G Medical, and AliveCor; and receiving research support from the National Institutes of Health, Medtronic, AliveCor, and Biosense Webster. Goldschlager, Krahn, and Pellegrini report that they have no relevant disclosures.

Heart Rhythm Society (HRS) 2019 Scientific Sessions: Abstract S-LBCT01-03. Presented May 9, 2019.

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