At the seven-year anniversary of the first
catheter-based renal
denervation procedure for resistant
hypertension, it is timely to reflect on the past, present, and future of the development and clinical application of this treatment. Unresolved procedural and technical questions are central: How much renal
denervation is optimal? How can this level of
denervation be achieved? What test for
denervation can be applied in renal
denervation trials? Will renal
denervation show a "class effect," with the different energy forms now used for renal nerve ablation producing equivalent blood pressure lowering? 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 commonly been suboptimal in renal
denervation trials; this criticism applying 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. Recently presented results from the Symplicity HTN-3 trial confirm that renal
denervation was not achieved effectively or consistently. Given this, and other difficulties in the execution of the trial relating to drug adherence, an idea mooted is that the US pivotal trial of the future may be in younger, untreated patients.