DEVICE-BASED APPROACHES FOR HYPERTENSION (M SCHLAICH, SECTION EDITOR) ConfidenHT™ System for Diagnostic Mapping of Renal Nerves Costas Tsioufis 1 & Kyriakos Dimitriadis 1 & Panagiotis Tsioufis 1 & Rafael Patras 1 & Maria Papadoliopoulou 1 & Zoi Petropoulou 1 & Dimitris Konstantinidis 1 & Dimitrios Tousoulis 1 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Purpose of Review To summarize the evidence regarding the distribution of renal nerves and their patterns of anatomic variations in animal and human settings. Moreover, the methodology and results of studies regarding renal nerve stimulation (RNS) in both preclinical and clinical models are presented. Recent Findings There are differences regarding the number and the size of renal fibers, as well as their distance from the lumen in the diverse parts of the main renal arteries and the branches. In both animals and humans, RNS is safe and results in an increase of blood pressure (BP) while the effect on heart rate varies. In this context, the ConfidenHT™ system constitutes an integrated solution for effective RNS in humans. Summary Due to the diversity of renal nerve anatomy in humans, arterial areas for more effective renal denervation cannot be homogenously defined. The concept of mapping of renal nerves can improve completeness of renal denervation therapies by means of integrated RNS solutions such as the ConfidenHT™ system. Keywords Renal nerves . Denervation . Renal stimulation . Hypertension Introduction Control of hypertension remains nowadays an unmet need, and technological advantages for reducing sympathetic drive have been used by means of transcatheter renal denervation (RDN) [1–3, 4•, 5, 6, 7••]. The first observational and random- ized RDN studies in patients with resistant hypertension have shown significant blood pressure (BP) reduction with a num- ber of diverse systems for renal nerve ablation [4•, 8•, 9•, 10•]. In contrast, a randomized sham-controlled trial in patients with resistant hypertension failed to prove benefit of the inter- ventional approach compared to a sham control procedure [7••]. The limitations of this study design and execution were acknowledged and reshaped the way RDN trials were de- signed [2, 11]. The recent interim analysis of the randomized sham-control SPYRAL HTN-OFF MED study exhibited bio- logical proof of principle for the BP-lowering efficacy of RDN in hypertensive patients on no antihypertensive medica- tions [12••]. This study strongly supports further research on the long-term efficacy of RDN as an alternative non- pharmacologic approach or synergistically with medical ther- apy in different facets of hypertensive disease [12••]. Along these lines, research was also focused on refinement of the RDN methodology due to the strong involvement of high sympathetic drive in the pathogenesis and evolution of hypertensive disease [2, 3]. This was achieved by a more in- depth analysis of the anatomic data regarding the distribution of the renal nerve network [13, 14•] and the identification of intraprocedural predictors of BP response [15••]. The latter could ameliorate treatment ablation strategies during the pro- cedure by appropriate “mapping” of the renal nerves along the renal arteries. The present review firstly summarizes available animal and human evidence on the anatomic distribution of renal nerves underscoring the variations and complexity of such research efforts. Secondly, a thorough “journey” in the scientific at- tempts to succeed in renal nerve stimulation (RNS) is present- This article is part of the Topical Collection on Device-Based Approaches for Hypertension * Costas Tsioufis ktsioufis@hippocratio.gr 1 First Cardiology Clinic, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, 108 Vas. Sofias Ave, 11527 Athens, Greece Current Hypertension Reports (2018) 20:49 https://doi.org/10.1007/s11906-018-0847-1