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Renal Denervation in Hypertensive Patients
Hypertension ( IF 8.3 ) Pub Date : 2020-10-01 , DOI: 10.1161/hypertensionaha.120.15834
Alexandre Persu 1, 2 , Frédéric Maes 1, 2 , Jean Renkin 1 , Atul Pathak 3, 4
Affiliation  

A decade ago, when endovascular renal sympathetic denervation (RDN) using radiofrequency energy was first proposed as a treatment of resistant hypertension, the strategy of renal nerve ablation, by that time using the mono-electrode Simplicity catheter, was almost purely empirical, based on porcine model. It was advised to distribute a few ablation points along a spiral path to increase RDN efficacy, while avoiding both circumferential nerve destruction and side branch approach, considered as potentially dangerous. At most, it was whispered to target the upper proximal quadrant of the renal artery where the density of nerve fibers was purportedly the highest. Besides a few dissenting voices, expectations were huge, and some were thinking RDN would provide a simple solution to the overwhelmingly complex problem of hypertension. SYMPLICITY HTN-3 was expected to be the cherry on the cake, providing definitive evidence of the efficacy of RDN. As we all know this was not the case, for a number of reasons whose detailed analysis is beyond the scope of this Editorial. This failure was a signal for both investigators and companies that something had gone wrong in the development of RDN or that renal sympathetic nerves do not mediate the entire effect of sympathetic outflow in modulating blood pressure. Methodological and technical issues came to the forefront. Among many others, the optimal strategy to decrease renal sympathetic flow in an efficient and reproducible way was the object of intense debate. The negative results of SYMPLICITY HTN-3 were partly due, it was thought, to an insufficient number of ablation points in most patients, and a post hoc propensity score–adjusted analysis suggested a correlation between the number of ablation points and blood pressure decrease after RDN. Second, it was advocated that distal instead of proximal nerve fibers should be targeted in priority. Even though distal innervation was less dense than in the proximal part of the artery, distal nerves were indeed closer to the lumen and so more accessible to destruction. Finally, compared with RDN of main renal arteries alone, combined ablation of main renal arteries and branches resulted in improved blood pressure–lowering efficacy of RDN. The development of multielectrode radiofrequency and new-generation ultrasound renal nerve ablation systems has improved the reproducibility and completeness of RDN, and in the context of rigorously designed sham-controlled trials, the blood pressure–lowering effect of RDN is now consistently demonstrated. Denervation of small branches and accessory arteries remains challenging, but the issue is being partly solved with the design of smaller diameter catheters. Still, despite these technical improvements, the overall benefit of RDN remains modest, roughly equivalent to that of one antihypertensive drug, reliable noninvasive predictors of blood pressure response to RDN have not been consistently identified, and the potential impact of anatomic variability on the results of RDN remains to be properly addressed. In this context, the anatomic study of Garcia Touchard et al published in this issue of Hypertension could open new pathways to improve selection of patients and results of RDN. The authors meticulously dissected renal nerves of 60 kidneys from 30 randomly selected cadavers and carefully described their origin and trajectory. This painstaking task proved rewarding, as the authors’ findings challenge a number of preconceptions on renal nerve anatomy. In summary (Figure), (1) the classical basket-type arrangement at the origin of main renal arteries was found in only 17% of cases, and in fact in the majority of cases (57%), such a renal plexus simply did not exist; (2) instead, or in addition, renal innervation originated from large nerve bundles that formed the preaortic ganglia and splanchnic nerves; (3) in more than half of cases (73% on the right and 53% on the left), renal nerves bypassed the main renal artery and joined directly bifurcations or arterial branches. The presence of such late arriving nerves (LAN) and very late arriving nerves (VLAN) strongly correlated with the presence of extra-hilar arterial branching and polar arteries. In contrast, LAN and VLAN were not observed in case of accessory or multiple renal arteries. Finally, the ratio between the length of the main renal artery and the distance from ostium to renal hilum was negatively associated with the presence of LAN/VLAN. In other words, for a fixed ostium-hilum distance, the shortest the renal artery before bifurcation, the highest the probability of LAN/VLAN. The opinions expressed in this article are not necessarily those of the American Heart Association. From the Division of Cardiology, Cliniques Universitaires Saint-Luc (A. Persu, F.M., J.R.) and Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique (A. Persu, F.M.), Université catholique de Louvain, Brussels, Belgium; Department of Cardiovascular Medicine, Centre Hospitalier Princesse Grace, Monaco (A. Pathak); and Clinique Pasteur-ESH Hypertension Excellence Center, INSERM 1048, Toulouse, France (A. Pathak). Correspondence to Alexandre Persu, Division of Cardiology, Cliniques Universitaires St-Luc, 10 Ave Hippocrate, 1200 Brussels, Belgium. Email alexandre.persu@uclouvain.be Renal Denervation in Hypertensive Patients Back to Anatomy?

中文翻译:

高血压患者的肾去神经支配

十年前,当首次提出使用射频能量进行血管内肾交感神经去神经支配 (RDN) 作为治疗顽固性高血压时,当时使用单电极 Simplicity 导管的肾神经消融策略几乎完全是经验性的,基于猪模型。建议沿螺旋路径分布一些消融点以提高 RDN 功效,同时避免被认为具有潜在危险的环神经破坏和侧支方法。最多,据说目标是肾动脉的上近端象限,那里的神经纤维密度据称最高。除了少数反对声音外,人们的期望也是巨大的,一些人认为 RDN 将为极其复杂的高血压问题提供一个简单的解决方案。SYMPLICITY HTN-3 有望成为锦上添花,提供 RDN 功效的确切证据。众所周知,事实并非如此,其详细分析超出了本社论的范围。这种失败对研究人员和公司来说都是一个信号,即 RDN 的发展出了问题,或者肾交感神经没有介导交感神经流出在调节血压方面的全部作用。方法论和技术问题成为首要问题。其中,以有效和可重复的方式减少肾交感神经流量的最佳策略是激烈争论的对象。SYMPLICITY HTN-3 的阴性结果部分是由于,据认为,大多数患者的消融点数量不足,事后倾向评分调整分析表明消融点数与 RDN 后血压降低之间存在相关性。其次,提倡以远侧神经纤维为靶点,而不是近侧神经纤维为重点。尽管远端神经支配不如动脉近端部分密集,但远端神经确实更靠近管腔,因此更容易被破坏。最后,与单独的主肾动脉 RDN 相比,主肾动脉和分支的联合消融导致 RDN 的降血压功效提高。多电极射频和新一代超声肾神经消融系统的发展提高了 RDN 的可重复性和完整性,并在严格设计的假对照试验背景下,RDN 的降血压作用现已得到一致证明。小分支和附属动脉的去神经支配仍然具有挑战性,但通过设计更小直径的导管,这个问题正在得到部分解决。尽管如此,尽管有这些技术改进,但 RDN 的总体益处仍然不大,大致相当于一种抗高血压药物的益处,尚未一致确定 RDN 血压反应的可靠无创预测因子,以及解剖变异对结果的潜在影响RDN 仍有待妥善解决。在此背景下,Garcia Touchard 等人在本期 Hypertension 上发表的解剖学研究可为改善患者选择和 RDN 结果开辟新途径。作者从随机选择的 30 具尸体中精心解剖了 60 个肾脏的肾神经,并仔细描述了它们的起源和轨迹。这项艰巨的任务证明是有益的,因为作者的发现挑战了对肾神经解剖学的一些先入之见。综上所述(图),(1)仅在 17% 的病例中发现了主要肾动脉起源处的经典篮式排列,而实际上在大多数病例中(57%),这种肾丛只是不存在; (2) 相反或另外,肾神经支配起源于形成主动脉前神经节和内脏神经的大神经束;(3)半数以上(右侧73%,左侧53%)肾神经绕过肾主动脉直接汇入分叉或动脉分支。这种迟到神经 (LAN) 和极迟到神经 (VLAN) 的存在与肺门外动脉分支和极动脉的存在密切相关。相比之下,在辅助或多个肾动脉的情况下未观察到 LAN 和 VLAN。最后,主肾动脉的长度与从口到肾门的距离之间的比率与 LAN/VLAN 的存在呈负相关。也就是说,对于固定的口门距离,分叉前的肾动脉最短,LAN/VLAN的概率最高。本文中表达的观点不一定是美国心脏协会的观点。来自 Cliniques Universitaires Saint-Luc (A. Persu, FM, JR) 心脏病学部和心血管研究中心,Institut de Recherche Expérimentale et Clinique (A. Persu, FM, JR) Persu, FM), Université catholique de Louvain, 布鲁塞尔, 比利时; 心血管内科,中心医院格蕾丝公主,摩纳哥(A. Pathak);和倩碧巴斯德-ESH 高血压卓越中心,INSERM 1048,图卢兹,法国 (A. Pathak)。致信 Alexandre Persu,心脏病学系,Cliniques Universitaires St-Luc, 10 Ave Hippocrate, 1200 Brussels, Belgium。电子邮件 alexandre.persu@uclouvain.be 高血压患者的肾脏去神经术回到解剖学?10 Ave Hippocrate, 1200 布鲁塞尔, 比利时。电子邮件 alexandre.persu@uclouvain.be 高血压患者的肾脏去神经术回到解剖学?10 Ave Hippocrate, 1200 布鲁塞尔, 比利时。电子邮件 alexandre.persu@uclouvain.be 高血压患者的肾脏去神经术回到解剖学?
更新日期:2020-10-01
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