Renal denervation: are we at a crossroads?

Excerpt

Since the first publication by Henry Krum in 2009 [1], it has been a bumpy road for renal denervation (RDN) for the treatment of sympathetic hyperactivity associated disease states, such as hypertension. After initial positive results of non-randomised and randomised trials, a true hype arose with more than 50 companies developing their own RDN system. The procedure was reimbursed in several countries in Europe and within a few years 15,000 to 20,000 procedures were performed. However, in 2014, the presentation of the sham-controlled blinded Symplicity HTN-3 trial at the scientific sessions of the American College of Cardiology and simultaneous publication in the New England Journal of Medicine caused a 180° turn in the thinking of many physicians about this potential novel treatment modality [2]. In contrast with previous trials, in Symplicity HTN-3 the mean decrease in office systolic blood pressure was only 14.13 mmHg in the treated group, but more surprisingly it was 11.74 mmHg in the sham control group. This resulted in a modest 2.39 mmHg difference in the RDN treated versus control group, lower than the preset superiority margin of 5 mmHg and thus not statistically significant. The differences observed using ambulatory blood pressure measurements (ABPM) were also too small to reach statistical significance (‑6.75 mmHg and -4.79 mmHg, respectively; a difference of -1.96 mmHg). The aftermath of these unexpected results caused subsequent trials to directly suspend patient recruitment. Furthermore, in most countries attention for RDN studies and referrals of patients declined steeply. Several important issues were identified such as the small number of patients with resistant hypertension being found to be eligible for RDN [3]. Also, blood pressure responses to RDN using the commercially available catheters were found highly variable, with a considerable number of non-responders. Third, the absence of good predictors and a periprocedural read-out of response to RDN is seen as a big caveat. Searching for an explanation for the neutral results of the Symplicity HTN-3 trial, among others the efficacy of the used catheter was questioned. In this light, besides renal nerve ablation with radiofrequency energy using different catheters, several other techniques came onto the market using alcohol injection and high frequency ultrasound. Also, a system to deliver energy to renal nerves using low-intensity focused ultrasound through an external ultrasound source has been developed and is currently being tested in a first-in-man study. …