Illusions of truths in the Symplicity HTN-3 trial: generic design strengths but neuroscience failings

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 renal denervation efficacy was assessed, 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 nonuniform between patients. It is probable that the degree of denervation has typically been suboptimal 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 confirm that renal denervation was not effectively or consistently achieved in the trial.