Predicting response to renal denervation: aortic distensibility as a piece of the puzzle

Elevated blood pressure (BP) is a significant contributor to global mortality, being implicated in approximately 8.5 million deaths annually from conditions such as stroke, ischemic heart disease, vascular complications, and renal disorders. Evidence suggests that even a 10 mmHg reduction in systolic BP can lead to a 20% decrease in cardiovascular events [1,2]. Despite these findings, resistant hypertension remains a major clinical obstacle, with many patients failing to achieve adequate BP control even with the use of multiple antihypertensive agents. In recent years, catheter-based renal sympathetic denervation (RDN) has re- emerged as a potential therapy for these patients, supported by multiple sham-controlled trials demonstrating modest yet significant BP reductions (approximately 4–8 mmHg in 24-h systolic BP) without major adverse events [3]. The 2024 European Society of Cardiology Guidelines and the 2023 European Society of Hypertension Guidelines provide a class IIb recommendation that RDN may be considered as a treatment option for patients who have uncontrolled hypertension despite the use of antihypertensive drug combination therapy or for those with resistant hypertension with a three-drug regimen who express a preference to undergo renal denervation for BP control [4,5]. It can also be considered in patients that are nonadherent or intolerant of medication [5] or in those at high cardiovascular risk who express a preference for RDN [4]. However, clinical outcomes are variable, with approximately one-third of patients experiencing limited or no significant BP reduction following the procedure [6]. This variability in response has spotlighted the critical question of patient selection – identifying which patients are most likely to respond to RDN. Rather than applying RDN indiscriminately, the field is increasingly focused on prognostic markers that could guide therapy to those who will truly benefit. In this context, the study by Sagmeister P provides timely and relevant data assessing the long-term predictive accuracy of a previously published bivariate model based on preprocedural 24-h systolic blood pressure and magnetic-resonance-measured ascending aortic distensibility (mAAD). The most compelling contribution of this study lies in its prospective design and focused attempt to validate a simple, noninvasive prediction model beyond the immediate post-RDN phase. The model demonstrated reasonably strong predictive performance at 6 months (r2 = 0.451, AUC = 0.819), supporting its potential utility in identifying early responders. This is particularly valuable in a field where preprocedural markers of efficacy are limited and the need for refined patient selection is urgent. However, the study also makes clear that this predictive capacity diminishes at 12 months (r2 = 0.261, AUC = 0.787), raising questions about the long-term stability of RDN effects or the evolving influence of confounders such as medication changes, adherence, and vascular remodeling over time. This study has once again highlighted another important issue that warrants further discussion. Approximately 61% of patients experienced decreases of 7.3 ± 15.0 mmHg and 4.6 ± 9.5 mmHg in their 24 h systolic and diastolic BP, respectively, despite undergoing RDN and continuing medical therapy. What's more, only 22.8% of patients achieved controlled BP at 12 months. This relatively low rate of complete control underscores the persistent difficulty of treating resistant hypertension. It also serves as a reality check for the predictive model: even a “well designed” baseline predictor would still face the fact that a substantial subset of patients will remain hypertensive after RDN. It reinforces that RDN is not a cure all – many patients will still require high-intensity medical management post procedure. The quest to improve patient selection for RDN is far from over. This study provides a foundation, but several avenues for future research emerge to build upon and refine these findings. Perhaps most importantly, the current model should be validated in larger, more diverse populations. A multicenter study or registry that includes arterial stiffness measurements in RDN patients would allow testing the model's generalizability. In conclusion, this study's editorial takeaway is that baseline 24-h BP and aortic distensibility form a promising duo for anticipating how a patient might respond to renal denervation, particularly in the early months following the procedure. The research exemplifies a move toward evidence-based patient selection in device therapy for hypertension. Yet, the fading of predictive strength by one year and the inability to guarantee goal BP achievement remind us that hypertension is a multifactorial, chronic condition not easily “fixed” by a single intervention. Going forward, a multifaceted approach – combining hemodynamic, biochemical, and perhaps genetic markers – will likely be needed to sharpen our predictive capabilities. Until then, clinicians should embrace tools like this model as useful guides but remain vigilant in comprehensive care. The ultimate hope is that with better predictors and patient selection, RDN can be deployed to the right patients at the right time, maximizing benefit and minimizing unnecessary procedures in an era when precision medicine is the ideal. ACKNOWLEDGEMENTS None. Conflicts of interest There are no conflicts of interest.