Invited reviewThe future of renal denervation

- The theoretical basis for the renal denervation treatment of hypertension is sound
- In resistant hypertension the renal sympathetic outflow is highly activated, and a logical target
- Symplicity HTN-3 is a flawed study, but did emphasize the need for a procedural sham
- In future studies energy will be directed into the distal renal arteries, and renal artery divisions
- Testing for achieved renal denervation is key, but remains unsolved

The rationale for the renal denervation treatment of severe, drug-resistant essential hypertension remains valid, but the field is now at a procedural watershed. With the commonly flawed procedures of the past, most notably in the Symplicity HTN-3 trial, which typically directed ablating energy into the proximal renal arteries, coupled with the absence of testing for achieved denervation, who could guess which of the past negative renal denervation trials, if any, are valid? But renal denervation procedures will now be different in two important ways. First, energy will be directed into the distal renal arteries and renal artery branches, where the renal nerves lie closest to the artery lumen. The need for this change is emphatic and unequivocal. Second, the number of energy point applications will be increased to 12-16 bilaterally. This is required because local perivascular anatomy distorts energy flow, making it unpredictable, so that multiple overlapping energy doses are needed. Applying these principles in experimental animals achieves near-total renal sympathetic nerve ablation, and lowers blood pressure. The “smart” renal denervation trials of the future will include a sham procedure and 24-h ambulatory blood pressure endpoints, but more important than these, which in comparison is clinical trialist “tinkering”, will be the procedural revolution in ablative energy delivery.