Renal Denervation for Treatment of Hypertension: a Second Start and New Challenges

Abstract

Following the publication of the randomized controlled but open-label trial Symplicity HTN-2, catheter-based renal sympathetic denervation was proposed as a novel treatment for drug-resistant hypertension. Thousands of procedures were routinely performed in Europe, Australia and Asia, and many observational studies were published. A sudden shift from overoptimistic views to radical scepticism occurred later, when the large US randomized sham-controlled trial Symplicity HTN-3 failed to meet its primary blood pressure lowering efficacy endpoint. Experts are divided on the reasons accounting for the large discrepancy between the results of initial studies and those of Symplicity HTN-3. Indeed, the blood pressure lowering effect associated with renal denervation was overestimated in initial trials due to various patient and physician-related biases, whereas it could have been underestimated in Symplicity HTN-3, which was well designed but not rigorously executed. Still, there is a large consensus on the need to further study catheter-based renal denervation in more controlled conditions, with particular emphasis on identification of predictors of blood pressure response. US and European experts have recently issued very similar recommendations on design of upcoming trials, procedural aspects, drug treatment, patient population and inclusion-exclusion criteria. Application of these new standards may represent a second chance for renal denervation to demonstrate--or not--its efficacy and safety in various patient populations. With its highly standardized treatment regimen, the French trial DENERHTN paved the way for this new approach and may inspire upcoming studies testing novel renal denervation systems in different populations.

Renal sympathetic denervation restores aortic distensibility in patients with resistant hypertension: data from a multi-center trial

“…Various factors might explain the considerable heterogeneity in the effects of RDN on BP. Newer studies aim to avoid the confounding effects of BP lowering drugs and the variation in adherence to medical treatment [27]. At this point, the results of the proof-of-concept trial SPYRAL HTN-OFF MED suggest efficacy of RDN on BP in the absence of antihypertensive medications [13, 28].…”

Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial

“…Male sex, baseline daytime ambulatory systolic BP (SBP), baseline nighttime ambulatory SBP and its standard deviation, changes in daytime ambulatory heart rate, low treatment score, high adherence to SSHAT were independently associated with the BP response, whereas ethnic origin and the number of ablations were not . Nevertheless, identification of predictive factors of BP response to RDN is still necessary to facilitate the selection of patients likely to benefit most from this invasive procedure …”

“…[1][2][3] Nevertheless, identification of predictive factors of BP response to RDN is still necessary to facilitate the selection of patients likely to benefit most from this invasive procedure. 4,5 The presence of abdominal aortic calcifications (AAC) is associated with greater aortic stiffness 6,7 and a poorer hemodynamic response to antihypertensive drugs. 8 However, it is unknown whether the loss of the viscoelastic and biomechanical properties of the aorta associated with AAC also affects the systemic and renal hemodynamic response to RDN in patients with resistant hypertension.…”

Renal vascular calcification and response to renal nerve denervation in resistant hypertension

“…[15,16] Or it could be the other way around those patients with low calcium scores will not respond to RDN because of inadequate catheter – renal nerve tissue contact due to for example noncalcified atherosclerotic plaques or large distance from endovascular wall to the nerve tissue in the adventitia which might lead to inadequate ablations. [17] Vink et al [18] have shown that RDN does not always result in circular lesions completely destroying the renal nerves. These considerations highlight, apart from exploring predictors of response, the need for a clear procedural end point of RDN.…”