Phenotype-Guided Renal Denervation: the Key to Therapeutic Response.

Area of Science:

• Cardiovascular Medicine
• Nephrology
• Interventional Cardiology

Background:

• Renal denervation (RDN) is re-emerging for hypertension treatment after recent trials showed blood pressure reduction.
• Variability in patient response to RDN highlights the need to understand determinants of treatment efficacy.
• Patient phenotype, not device limitations, is increasingly recognized as the primary driver of response heterogeneity.

Purpose of the Study:

• To review evidence on factors influencing patient response to renal denervation.
• To identify clinical and mechanistic determinants of variability in RDN outcomes.
• To guide patient selection for optimizing RDN therapy in hypertension management.

Main Methods:

• Narrative review synthesizing data from randomized trials, meta-analyses, and observational studies.
• Examination of determinants of RDN response across clinical and mechanistic domains.
• Focus on patient phenotype, ambulatory blood pressure, baseline levels, medication adherence, sympathetic activity, renal anatomy, and comorbidities.

Main Results:

• Patients with sustained hypertension, high baseline blood pressure, and sympathetic overactivity show greater benefit from RDN.
• Pseudoresistance, white-coat hypertension, vascular stiffness, and unfavorable anatomy are linked to reduced or inconsistent RDN response.
• Moderate blood pressure reduction from RDN is clinically meaningful in appropriately selected populations.

Conclusions:

• Phenotype-guided patient selection is crucial for optimizing RDN effectiveness and reconciling inconsistent trial results.
• RDN is best positioned as a targeted adjunctive therapy within personalized hypertension management strategies.
• Future research should focus on mechanism-based selection to enhance RDN's clinical implementation and utility.