Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART) 6-month follow-up of a randomised, controlled trial

作者全名：Wang, Jie; Yin, Yuehui; Lu, Chengzhi; Lu, Zhibing; Hu, Jialu; Wang, Yue; Ge, Junbo; Jiang, Hong; Yao, Chen; Yan, Xiaoyan; Ma, Wei; Qi, Xiaoyong; Dang, Yi; Chen, Shaoliang; Zhu, Jiancheng; Wang, Dongmei; Ding, Chao; Wang, Weimin; Liu, Jian; Wang, Yanbin; Li, Hui; Pan, Zhenhua; Cui, Kaijun; Li, Chengzong; Liang, Xinjian; Chen, Weijie; Sobotka, Paul A.; Zhang, Jingjing; Esler, Murray; Sun, Ningling; Chen, Minglong; Huo, Yong

作者地址：[Wang, Jie] Nanjing Med Univ, Affiliated Hosp 1, Nanjing 210029, Peoples R China; [Wang, Jie] Columbia Univ, Vagelos Coll Phys & Surg, Dept Med, Div Cardiol, New York, NY 10032 USA; [Yin, Yuehui; Chen, Weijie] Chongqing Med Univ, Affiliated Hosp 2, Dept Cardiol, Chongqing 400010, Peoples R China; [Lu, Chengzhi] Tianjin First Cent Hosp, Dept Cardiol, Tianjin 300190, Peoples R China; [Lu, Zhibing; Jiang, Hong] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China; [Lu, Zhibing; Hu, Jialu] Wuhan Univ, Zhongnan Hosp, Dept Cardiol, Wuhan 430071, Peoples R China; [Ge, Junbo] Fudan Univ, Zhongshan Hosp, Dept Cardiol, Shanghai 200032, Peoples R China; [Jiang, Hong; Yao, Chen] Peking Univ, Hlth Sci Ctr, Beijing 100034, Peoples R China; [Ma, Wei; Huo, Yong] Peking Univ First Hosp, Dept Cardiol, Beijing 100034, Peoples R China; [Yan, Xiaoyan; Qi, Xiaoyong; Dang, Yi] Hebei Gen Hosp, Dept Cardiol, Shijiazhuang 050057, Peoples R China; [Chen, Shaoliang; Zhu, Jiancheng] Nanjing First Hosp, Dept Cardiol, Nanjing 210012, Peoples R China; [Wang, Dongmei; Ding, Chao] Norman Bethune Int Peace Hosp, Dept Cardiol, Shijiazhuang 050082, Peoples R China; [Wang, Weimin; Liu, Jian] Peking Univ, Peoples Hosp, Dept Cardiol, Beijing 100044, Peoples R China; [Wang, Yanbin] Taiyuan Cent Hosp, Dept Cardiol, Taiyuan 030009, Peoples R China; [Li, Hui; Pan, Zhenhua] Daqing Oilfield Gen Hosp, Dept Cardiol, Daqing 163458, Peoples R China; [Cui, Kaijun] Sichuan Univ, West China Hosp, Dept Cardiol, Chengdu 332001, Peoples R China; [Li, Chengzong] Xuzhou Med Univ, Affiliated Hosp, Dept Cardiol, Xuzhou 221002, Peoples R China; [Liang, Xinjian] Shenzhen Peoples Hosp, Dept Cardiol, Shenzhen 430060, Guangdong, Peoples R China; [Sobotka, Paul A.] Ohio State Univ, Coll Med, Dept Cardiol, Columbus, OH 43210 USA; [Zhang, Jingjing] SyMap Med Suzhou LTD, Suzhou 215123, Peoples R China; [Esler, Murray] Baker IDI Heart & Diabet Inst, Melbourne, Australia; [Sun, Ningling] Peking Univ, Peoples Hosp, Heart Ctr, Dept Hypertens, Beijing 100044, Peoples R China; [Chen, Minglong] Nanjing Med Univ, Affiliated Hosp 1, Dept Cardiol, Nanjing 210029, Peoples R China

通信作者：Wang, J (通讯作者)，Nanjing Med Univ, Affiliated Hosp 1, Nanjing 210029, Peoples R China.; Huo, Y (通讯作者)，Peking Univ First Hosp, Dept Cardiol, Beijing 100034, Peoples R China.; Esler, M (通讯作者)，Baker IDI Heart & Diabet Inst, Melbourne, Australia.; Sun, NL (通讯作者)，Peking Univ, Peoples Hosp, Heart Ctr, Dept Hypertens, Beijing 100044, Peoples R China.; Chen, ML (通讯作者)，Nanjing Med Univ, Affiliated Hosp 1, Dept Cardiol, Nanjing 210029, Peoples R China.

来源：ECLINICALMEDICINE

ESI学科分类：　

WOS号：WOS:001241639400001

JCR分区：Q1

影响因子：9.6

年份：2024

卷号：72

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Hypertension; Renal denervation; Renal nerve mapping; Selective ablation; Drug burden; Medication adherence

摘要：Background Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (< 140 mmHg). Methods We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP < 140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) x (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (>= 70 bpm), OSBP (>= 150 mmHg and <= 180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP >= 130 mmHg or daytime SBP >= 135 mmHg or nighttime SBP >= 120 mmHg), renal artery stenosis (< 50%) and renal function (eGFR > 45 mL/min/1.73 m(2)). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (>= 5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (>= 5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (< 140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP >= 150 mmHg and <= 180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p < 0. 001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP < 140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).

基金机构：SyMap Medical (Suzhou), LTD, Suzhou, China

基金资助正文：SyMap Medical (Suzhou), LTD, Suzhou, China.