Small Study Lends Further Support to the Antiarrhythmic Potential of Renal Denervation

PARIS, France—In patients with hypertensive cardiovascular disease, renal denervation may be an alternative to catheter-based pulmonary vein isolation (PVI) for reducing the incidence of subclinical A-fib, early data from a single-center, sham-controlled study suggest.

The findings are in line with those of the ERADICATE-AF trial, which was recently presented at the Heart Rhythm Society 2019 Scientific Sessions. In that trial, patients with symptomatic paroxysmal A-fib, significant hypertension, and a referral for A-fib ablation were randomized to renal denervation added to PVI or PVI alone. At 1 year, patients in the renal denervation/PVI group were significantly more likely to be free of recurrent A-fib than those in the PVI-only group.

In an interview with TCTMD, Marshall Heradien, MD (Stellenbosch University, South Africa), said the new data, presented here at EuroPCR 2019, extend the findings of ERADICATE-AF and suggest that renal denervation on its own may prevent A-fib.

“I think there's light at the end of the tunnel,” he observed. “This might be a new treatment for patients who get paroxysmal AF as an alternative to PVI.” Although PVI is fairly effective, he noted that it is not without complications and is not curative.

In his presentation, Heradien showed that after an average follow-up of 3 years, patients in the sham renal-denervation group (n = 38) were more likely than those in the treatment group (n = 42) to experience an occurrence of subclinical A-fib lasting at least 6 minutes, the primary endpoint (47% vs 19%; P = 0.011), equating to a relative risk reduction of 60%. The number needed to treat to prevent one occurrence was 3.5. The two groups diverged fairly early on in the months after the procedure.

While the median age at first presentation of subclinical A-fib and the median ventricular rate were no different between groups, the sham group had a greater prevalence of fast A-fib, defined as > 100 bpm, than the denervation group (P = 0.002). Heradien said this finding suggests that decreased sympathetic tone after denervation was likely responsibly for the clinical improvement.

Some patients came to me and said, 'Doc, can I stop my medications because my blood pressure is good?' I think the real answer is we don't know. Marshall Heradien

Although blood pressure was significantly lower at 6 months in the intervention group compared with baseline (P = 0.03), the sham group also experienced a drop in blood pressure from baseline (P = 0.06), similar to what was observed in the SYMPLICITY HTN-3 trial. Heradien speculated that the observation may be due to the Hawthorne effect.

The data also hinted at the potential for a reduction in mortality, with fewer cardiovascular deaths among the renal denervation patients (six in the sham group vs one in the renal-denervation group; P = 0.04). To TCTMD, Heradien called the mortality signal “reassuring" but acknowledged that the sample size is too small to draw firm conclusions.

Elucidating Denervation’s Effects

Patients in the trial had a diagnosis of hypertensive heart disease (left ventricular hypertrophy and/or left atrial dilation on echocardiogram), were taking three or more antihypertensive drugs, including a diuretic, and had an indication for angiography. Procedures in both the intervention and the sham arms were performed radially. For the sham procedure, Heradien said patients heard a recording of the renal denervation device during their angiography.

In the renal-denervation group, the average number of ablations per patient was 24 (12 per artery), with a goal of denervating both kidneys as completely as possible. Most patients were discharged the same day, and all were implanted with loop recorders to catch the first instance of subclinical A-fib. The researchers scanned the implantable loop recorder every 6 months.

According to Heradien, none of the patients required additional denervation procedures after the initial treatment. Antihypertensive drugs were not changed and blood and urine testing was not conducted, he noted, so there is no way to know if patients were fully medication-compliant prior to their procedures.

"At the end of the study when we unblinded them, some patients came to me and said, 'Doc, can I stop my medications because my blood pressure is good?' I think the real answer is we don't know,” Heradien told TCTMD. “This was a group of patients taking three or more antihypertensive drugs. [If] they stop everything, we don't know what's going to happen and who is going to accept the responsibility if something happens?"

Going forward, he said, one possibility might be to incorporate a gradual decrease in medication and home monitoring of blood pressure.

The A-fib reduction at that level, especially documented with loop recorders, is impressive. Juan Granada

Juan Granada, MD (Cardiovascular Research Foundation, New York, NY), who co-chaired the session, was intrigued by the results, despite the small size of the study.

“I’m not impressed with the cardiovascular results, to be honest, because [the study] is small and not powered for that,” he said. “But the A-fib reduction at that level, especially documented with loop recorders, is impressive.”

But Granada’s co-chair Felix Mahfoud, MD (Saarland University Medical Center, Homburg, Germany), said he had reservations about the conclusions due to “mixing too many things at once.” Undergoing angioplasty, being on a high load of antihypertensives and having renal denervation can all confuse the issue as to which of those things, or some combination of them, could be responsible for the decrease in A-fib, he noted.

Panelist Jozef Bartunek, MD, PhD (Cardiovascular Center, Aalst, Belgium), said he was struck by the high rate of obstructive sleep apnea, which was present in more than 50% of patients in each group, and questioned whether the researchers saw a decrease in its incidence after renal denervation. Heradien said a subgroup analysis focusing on that and other comorbidities is forthcoming.

To TCTMD, Granada said he believes that the procedure could have potential in preventing recurrences of A-fib in carefully selected patients.

“The right patient is the one who has already had a first episode of A-fib,” he said. If additional studies confirm that renal denervation has an impact on subsequent ventricular rate, Granada added, it could lead to “an interesting and real application for this technology.”

Note: Granada is president and chief executive officer of the Cardiovascular Research Foundation, the publisher of TCTMD.