This week, the first non-blinded, prospective, randomized industry-sponsored Symplicity HTN-2 Trial of drug-refractory hypertension using endovascular low-power radiofrequency ablation within the renal arteries in 52 patients was reported. It is thought that this form of catheter ablation denervates the perivascular sympathetic innervation of the kidneys decreasing renin production and, therefore, blood pressure. (The guys over at Medgadget have some cool industry-sponsored pictures and videos about this technology). The ablation therapy in this trial appeared to carry promise at better blood pressure lowering compared to conventional medical therapy:
106 (56%) of 190 patients screened for eligibility were randomly allocated to renal denervation (n=52) or control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52 patients who underwent renal denervation and 51 (94%) of 54 controls were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p < 0.0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p < 0.0001). At 6 months, 41 (84%) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51 controls (p < 0.0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment.This is an interesting study, but the long-term effects of this therapy to the renal arteries remains to be seen. The effects of low energy (6-8 watts of energy)applied over 2 min for each lesion will likely have variable effects at the tissue level.
Electrophysiologists have had a long history of experience with radiofrequency energy to ablate things. We have learned over the years that catheter tip temperature bears little resemblance to the tissue temperatures achieved. We know that low, long power applications make for larger lesions, provided tip catheter contact is stable. The low power applications used in this technology may have significant effects on surrounding tissues.
But we've also learned about the challenges with this technology inside vascular structures. We have learned (the hard way) about the development on intimal hyperplasia and later stenosis of vessels with radiofrequency ablation (in our case - pulmonary vein stenosis). If bilateral renal artery stenosis were to occur, how might the patient's blood pressure behave? Similarly, we have learned that stents placed in arteries cause inflamation and restenosis as well. Are we to think, naively, that inflamation inside renal arteries that have burn lesions applied inside them are more resistant to inflamation and later stenosis?
Hard to know.
Some protective effect against burns probably exists within the lumen of arteries thanks to the cooling effect of the brisk blood flow there. This convective cooling effect of the blood flow might be why these patients fared as well as they did while sufficient effects of heating occured in the outer adventitial layers of the renal arteries.
But there's also the question: what if it works too well? There are very effective treatments for patients with orthostatic hypotension (blood pressure that falls excessively with standing). It is interesting that one such patient was described in the USA Today article that covered this trial, but no mention of this complication occured in the peer-reviewed journal article published in Lancet which said:
Minor periprocedural events requiring treatment and possibly related to the procedure consisted of one femoral artery pseudoaneurysm that was treated with manual compression, one post-procedural drop in blood pressure resulting in a reduction in antihypertensive drugs, one urinary tract infection, one extended hospital admission for assessment of paraesthesias, and one case of back pain that was treated with analgesics and resolved after 1 month. Seven (13%) of 52 patients who underwent renal denervation had transient intraprocedural bradycardia requiring atropine; none had any sequelae.No doubt a much larger trial will be forthcoming to evaluate these concerns. Still, this innovation might offer an interesting option for drug-refractory hypertension in the future but the jury's still out on it's long-term safety profile.