Renal denervation for severe hypertension: Past, present and future

The seven-year anniversary of the first catheter-based renal denervation procedure for resistant hypertension nears. At the “end of the beginning”, it is timely to reflect on the next phase in the development and clinical application of renal denervation in hypertension treatment. Unresolved procedural and technical questions are central: how much renal denervation is optimal; is unilateral denervation, now commonly used, beneficial; will renal denervation show a “class effect”, with the different energy forms now used for renal nerve ablation producing equivalent blood pressure lowering? The Achilles heel in catheter-based studies of renal denervation for severe hypertension is the almost universal failure to apply a confirmatory test for renal denervation. When I have assessed renal denervation efficacy, using measurements of the spillover of norepinephrine from the renal sympathetic nerves to plasma, the only test validated to this point, denervation was found to be incomplete and non-uniform between patients. It is probable that the degree of denervation has typically been sub-optimal in renal denervation trials. This criticism applies with special force to the Symplicity HTN-3 trial, where the proceduralists, although expert interventional cardiologists, had no prior experience with the renal denervation technique. Their learning curve fell during the trial, a shortcoming accentuated by the fact that one third of operators performed one procedure only. Recently presented results from the Symplicity HTN-3 trialists confirms that renal denervation was not effectively or consistently achieved in the trial.