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  • Special Features - Renal Denervation and Sympathetic Nerve System
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Current problems in renal denervation and a hope to break the stage

Hypertension Research volume 46, pages 2654–2660 (2023)Cite this article

Abstract

Renal denervation (RDN) is currently confronted with the considerable heterogeneity of different post-procedural blood pressure responses. The challenges predominantly arise from not only the lack of selection of appropriate responders but also the absence of detection for the successful endpoints of intervention. In this paper, we summarize the significant characteristics of potentially appropriate hypertensive patients and propose a hopeful way to improve the accuracy of RDN, that is, the application of three-dimensional reconstruction technology combined with electrical renal nerve stimulation to guide the radiofrequency catheter ablation, which may promote the development of selective and accurate RDN in real-world clinical practice.

This paper focuses on two current critical concerns of renal denervation (RDN): appropriate patient selection and the improvement in the accuracy of selective RDN. A hopeful way of accurate RDN may be the combination of 3D electroanatomic mapping systems for the renal artery with modified renal nerve stimulation (RNS) techniques and technology for appropriate hypertensive candidates.

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References

  1. Azizi M, Sanghvi K, Saxena M, Gosse P, Reilly JP, Levy T, et al. Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. Lancet. 2021;397:2476–86.

    Article  CAS  Google Scholar 

  2. Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Lobo MD, et al. Six-month results of treatment-blinded medication titration for hypertension control following randomization to endovascular ultrasound renal denervation or a sham procedure in the RADIANCE-HTN SOLO Trial. Circulation. 2019;139:2542–53.

  3. Böhm M, Kario K, Kandzari DE, Mahfoud F, Weber MA, Schmieder RE, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020;395:1444–51.

    Article  Google Scholar 

  4. Schmieder RE, Mahfoud F, Mancia G, Azizi M, Böhm M, Dimitriadis K, et al. European Society of Hypertension position paper on renal denervation 2021. J Hypertens. 2021;39:1733–41.

    Article  CAS  Google Scholar 

  5. Ahmad Y, Francis DP, Bhatt DL, Howard JP. Renal denervation for hypertension: a systematic review and meta-analysis of randomized, blinded, placebo-controlled trials. JACC Cardiovasc Interv. 2021;14:2614–24.

    Article  Google Scholar 

  6. Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017;390:2160–70.

    Article  PubMed  Google Scholar 

  7. Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018;391:2335–45.

    Article  PubMed  Google Scholar 

  8. Fengler K, Rommel KP, Blazek S, Besler C, Hartung P, von Roeder M, et al. A three-arm randomized trial of different renal denervation devices and techniques in patients with resistant hypertension (RADIOSOUND-HTN). Circulation. 2019;139:590–600.

    Article  PubMed  Google Scholar 

  9. Brouwers S, Sudano I, Kokubo Y, Sulaica EM. Arterial hypertension. Lancet. 2021;398:249–61.

    Article  CAS  Google Scholar 

  10. Kandzari DE, Böhm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018;391:2346–55.

    Article  PubMed  Google Scholar 

  11. Lauder L, Mahfoud F, Azizi M, Bhatt DL, Ewen S, Kario K, et al. Hypertension management in patients with cardiovascular comorbidities. Eur Heart J, 2023;44:2066–77.

  12. Mahfoud F, Townsend RR, Kandzari DE, Kario K, Schmieder RE, Tsioufis K, et al. Changes in plasma renin activity after renal artery sympathetic denervation. J Am Coll Cardiol. 2021;77:2909–19.

    Article  CAS  PubMed  Google Scholar 

  13. Matanes F, Khan MB, Siddiqui M, Dudenbostel T, Calhoun D, Oparil S. An update on refractory hypertension. Curr Hypertens Rep. 2022;24:225–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Schmieder RE, Bosch A. Editorial comment: renal denervation. Hypertens Res. 2022;45:241–3.

    Article  PubMed  Google Scholar 

  15. Kario K, Yokoi Y, Okamura K, Fujihara M, Ogoyama Y, Yamamoto E, et al. Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial. Hypertens Res. 2022;45:221–31.

  16. Gosse P, Cremer A, Kirtane AJ, Lobo MD, Saxena M, Daemen J, et al. Ambulatory Blood pressure monitoring to predict response to renal denervation: a post hoc analysis of the RADIANCE-HTN SOLO study. Hypertension. 2021;77:529–36.

    Article  CAS  PubMed  Google Scholar 

  17. Lauder L, Azizi M, Kirtane AJ, Böhm M, Mahfoud F. Device-based therapies for arterial hypertension. Nat Rev Cardiol. 2020;17:614–28.

    Article  Google Scholar 

  18. Böhm M, Tsioufis K, Kandzari DE, Kario K, Weber MA, Schmieder RE, et al. Effect of heart rate on the outcome of renal denervation in patients with uncontrolled hypertension. J Am Coll Cardiol. 2021;78:1028–38.

    Article  PubMed  Google Scholar 

  19. Böhm M, Mahfoud F, Townsend RR, Kandzari DE, Pocock S, Ukena C, et al. Ambulatory heart rate reduction after catheter-based renal denervation in hypertensive patients not receiving anti-hypertensive medications: data from SPYRAL HTN-OFF MED, a randomized, sham-controlled, proof-of-concept trial. Eur Heart J. 2019;40:743–51.

    Article  PubMed  Google Scholar 

  20. Egan BM. Baseline heart rate predicts the blood pressure response to renal denervation in untreated hypertension. J Am Coll Cardiol. 2021;78:1039–41.

    Article  PubMed  Google Scholar 

  21. Mahfoud F, Mancia G, Schmieder R, Narkiewicz K, Ruilope L, Schlaich M, et al. Renal denervation in high-risk patients with hypertension. J Am Coll Cardiol. 2020;75:2879–88.

    Article  PubMed  Google Scholar 

  22. Fengler K, Rommel KP, Hoellriegel R, Blazek S, Besler C, Desch S, et al. Pulse wave velocity predicts response to renal denervation in isolated systolic hypertension. J Am Heart Assoc. 2017;6:e005879.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kario K, Kagitani H, Hayashi S, Hanamura S, Ozawa K, Kanegae H. A Japan nationwide web-based survey of patient preference for renal denervation for hypertension treatment. Hypertens Res. 2022;45:232–40.

    Article  PubMed  Google Scholar 

  24. Verdecchia P, Cavallini C, Angeli F. Advances in the treatment strategies in hypertension: present and future. J Cardiovasc Dev Dis. 2022;9:72.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Gal P, de Jong MR, Smit JJ, Adiyaman A, Staessen JA, Elvan A. Blood pressure response to renal nerve stimulation in patients undergoing renal denervation: a feasibility study. J Hum Hypertens. 2015;29:292–5.

    Article  CAS  PubMed  Google Scholar 

  26. de Jong MR, Adiyaman A, Gal P, Smit JJ, Delnoy PP, Heeg JE, et al. Renal nerve stimulation-induced blood pressure changes predict ambulatory blood pressure response after renal denervation. Hypertension. 2016;68:707–14.

    Article  PubMed  Google Scholar 

  27. Liu H, Chen W, Lai Y, Du H, Wang Z, Xu Y, et al. Selective renal denervation guided by renal nerve stimulation in canine. Hypertension. 2019;74:536–45.

    Article  CAS  PubMed  Google Scholar 

  28. van Amsterdam WA, Blankestijn PJ, Goldschmeding R, Bleys RL. The morphological substrate for renal denervation: nerve distribution patterns and parasympathetic nerves. A post-mortem histological study. Ann Anat. 2016;204:71–9.

    Article  Google Scholar 

  29. Cheng X, Zhang Y, Chen R, Qian S, Lv H, Liu X, et al. Anatomical evidence for parasympathetic innervation of the renal vasculature and pelvis. J Am Soc Nephrol. 2022;33:2194–210.

    Article  CAS  PubMed  Google Scholar 

  30. Kiuchi MG, Esler MD, Fink GD, Osborn JW, Banek CT, Böhm M, et al. Renal denervation update from the international sympathetic nervous system summit: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73:3006–17.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhou H, Li Y, Xu Y, Liu H, Lai Y, Tan K, et al. Mapping renal innervations by renal nerve stimulation and characterizations of blood pressure response patterns. J Cardiovasc Transl. 2022;15:29–37.

    Article  Google Scholar 

  32. Liu H, Li Y, Zhou H, Chen W, Xu Y, Du H, et al. Renal nerve stimulation identifies renal innervation and optimizes the strategy for renal denervation in canine. J Transl Med. 2023;21:100.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sandhu A, Nguyen DT. Forging ahead: Update on radiofrequency ablation technology and techniques. J Cardiovasc Electr. 2020;31:360–9.

    Article  Google Scholar 

  34. Leshem E, Zilberman I, Barkagan M, Shapira-Daniels A, Sroubek J, Govari A, et al. Temperature-controlled radiofrequency ablation using irrigated catheters: maximizing ventricular lesion dimensions while reducing steam-pop formation. JACC Clin Electrophy. 2020;6:83–93.

    Article  Google Scholar 

  35. Tzafriri AR, Keating JH, Markham PM, Spognardi AM, Stanley JR, Wong G, et al. Arterial microanatomy determines the success of energy-based renal denervation in controlling hypertension. Sci Transl Med. 2015;7:265r–285r.

    Article  Google Scholar 

  36. Okamura K, Satou S, Kato Y, Kogata Y, Matsushima M, Shirai K, et al. Intravascular ultrasound can be used to locate nerves, but not confirm ablation, during renal sympathetic denervation. J Clin Med Res. 2021;13:556–62.

    Article  PubMed Central  Google Scholar 

  37. Satou S, Okamura K, Konishi R, Shirai K, Urata H. Observation of renal sympathetic nerves by intravascular ultrasound. Hypertens Res. 2019;42:1092–4.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to Liang Wang for his graphical artwork.

Funding

This work was partly supported by the National Natural Science Foundation of China (Grant Number: 32071110, YY and Grant Number: 82000471, WC)

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Authors and Affiliations

  1. Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, No. 288 Tianwen Avenue, Nan’an District, Chongqing, China

    Xinyu Hu, Hao Zhou, Weijie Chen, Dan Li, Huaan Du, Tianli Xia & Yuehui Yin

  2. Department of Cardiology, Chongqing University Fuling Hospital, Chongqing, China

    Xinyu Hu

  3. Chongqing Cardiac Arrhythmias Therapeutic Service Center, Chongqing, China

    Hao Zhou, Weijie Chen, Dan Li, Huaan Du, Tianli Xia & Yuehui Yin

  4. Chongqing Key Laboratory of Arrhythmias, Chongqing, China

    Yuehui Yin

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Correspondence to Yuehui Yin.

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Hu, X., Zhou, H., Chen, W. et al. Current problems in renal denervation and a hope to break the stage. Hypertens Res 46, 2654–2660 (2023). https://doi.org/10.1038/s41440-023-01380-1

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