Renal denervation revisited: is patient selection the missing link between failure and success?

Renal denervation (RDN) has re-emerged as a therapeutic option for hypertension following contemporary sham-controlled randomized trials demonstrating modest but consistent blood pressure (BP) reductions. Despite these advances, substantial heterogeneity in treatment response persists, sustaining debate regarding the clinical value and appropriate role of RDN. Increasing evidence suggests that patient-related factors, rather than device technology alone, may critically determine therapeutic success. This narrative review synthesizes evidence from randomized clinical trials, meta-analyses, and key observational studies published between 2009 and 2024. Relevant literature was identified through searches of PubMed, Embase, and major cardiovascular society publications. We evaluated the influence of hypertension phenotype, baseline BP, medication adherence, sympathetic nervous system activity, renal artery anatomy, and comorbid conditions on BP response to RDN. Accumulating data indicate that response to RDN is highly variable and strongly influenced by patient-specific characteristics. Sustained hypertension confirmed by ambulatory BP monitoring, higher baseline BP, features suggestive of sympathetic overactivity, favorable renal artery anatomy, and challenges with long-term medication adherence are consistently associated with greater BP reduction. In contrast, pseudoresistance, white-coat hypertension, advanced arterial stiffness, and unfavorable anatomy are linked to attenuated or inconsistent responses. Reassessment of sham-controlled trials highlights that observed BP reductions, although modest, are clinically meaningful when appropriately contextualized. The efficacy of RDN is highly context-dependent and should not be viewed as universal or ineffective. By shifting from a device-centered paradigm to mechanism-based patient phenotyping, RDN may be more accurately positioned as a targeted, adjunctive therapy within personalized hypertension management. A structured framework for patient selection may help reconcile prior controversies, optimize clinical implementation, and inform the design of future trials.