经皮导管去肾动脉交感神经射频消融术治疗难治性高血压研究进展

2016-03-08 12:17杨超英阳慧苏雨江
海南医学 2016年19期
关键词:肾动脉难治性经皮

杨超英,阳慧,苏雨江

(中南大学湘雅附属海口医院海口市人民医院心血管内科,海南 海口 570208)

·综 述·

经皮导管去肾动脉交感神经射频消融术治疗难治性高血压研究进展

杨超英,阳慧,苏雨江

(中南大学湘雅附属海口医院海口市人民医院心血管内科,海南 海口 570208)

高血压是引起心脑血管死亡的重要基础疾病,难治性高血压是指服用包括利尿剂在内的3种最佳剂量降压药后血压仍难以达标,或者需服用4种或以上降压药血压才能达标的高血压。其引起并发症更多,引起的心脑血管事件发生率和死亡率更高。就这一类型的高血压,近几年出现了一种新型的非药物治疗方法——经皮导管去肾动脉交感神经射频消融术。本文就此治疗方法做一简要综述。

难治性高血压;去肾动脉交感神经术;介入性治疗;射频消融术

难治性高血压指在排除继发因素改善生活方式的基础上,应用包括利尿剂在内的足量合理的3种降压药物后血压仍在目标水平以上,或至少需要4种药物血压才能达标[1]。难治性高血压对患者危害极大,可导致严重的靶器官损伤和心血管风险,如不接受治疗生存年龄及生存质量将远远低于正常人。难治性高血压的治疗在近几年取得了巨大进步,经皮导管去肾动脉交感神经术(renal sympathetic denervation,RSD)是目前治疗难治性高血压的一大突破。本文就国内外关于RSD治疗难治性高血压的研究进展作一综述。

1 难治性高血压流行及治疗现状

中国高血压人群存在三高(发病率、死亡率、致残率)三低(知晓率、治疗率、控制率)的流行病学特点,其中约15%的高血压患者不规律服药,约75%的高血压患者服药但血压控制不能稳定在目标水平。高血压可导致严重的靶器官损伤和心血管风险,人口老龄化加剧、环境恶化、人们精神压力增大等因素的不断作用,全世界每年有7百多万人因高血压死亡[2-4]。高血压是影响人们生存质量和危及生命的常见慢性基础疾病之一,据2010年《中国高血压指南》显示,中国高血压患病率呈增长趋势,患病率约为20%,占全球高血压患者总人数的20%。最新数据显示,目前国内高血压患者已超过2亿,估计至2025年将升至3亿。其中难治性高血压发病率约占高血压发病率的10%[5-7]。比普通高血压病有更高的靶器官受损发生率、心血管事件发生率及死亡率。研究证实,有效控制血压能使心血管事件发生和死亡率减少8%~10%[8-9];血压不能稳定在目标水平患者发生脑卒中、心力衰竭、心肌梗死、肾功能不全等的风险是血压控制达标者的2.3倍[10]。高血压严重威胁着人类健康,为社会带来了极大的负担。难治性高血压的治疗主要为传统的多种药物联合应用,一般很难使难治性高血压患者血压稳定在目标水平,且存在药物依从性问题。国内国外学者不断探索新的降压措施,一种新型的非药物治疗方法——RSD应运而生。

2 经皮导管去肾动脉交感神经术降压机制

目前研究关于肾动脉交感神经影响血压的机制有两种:(1)肾动脉交感神经过度活跃引起肾素分泌过多致水钠潴留、肾动脉收缩最终引起持续性血压升高[11];(2)肾传入神经通过神经激肽受体途径发出的信号传到中枢神经系统,同时传到对侧肾脏,使肾动脉交感神经活性增强,发挥血管紧张性调节作用[12]。RSD从此机制中入手,通过导管头端温度及阻抗传感监测射频能量释放,透过肾动脉的内、中膜选择性毁坏外膜的肾动脉交感神经纤维来降低肾动脉交感神经活性,从而抑制交感神经过度兴奋达到降压目的。在弹性部位进行温控消融有效避免过热导致的不必要组织损伤确保了此技术的安全性。通过对术后患者即刻行肾动脉造影未见血管狭窄、穿孔及血栓形成的数据资料统计,证实了RSD的安全性[6,13]。肾功能方面,多项临床研究证实RSD不会引起肾小球滤过率的下降[13-14]。

3 经皮导管去肾动脉交感神经术临床研究现状

Symplicity HTN-3研究是设有假手术组,双盲、多中心、前瞻性、随机对照的大样本关于RSD的临床研究,样本量达到535例[15],此研究对照组与治疗组处理区别在于对照组仅接受肾动脉造影检查不予射频消融,即所谓的假手术,治疗组则使用美敦力Symplicity导管系统进行了RSD治疗。2014年该研究结果显示:术后6个月两组间血压下降差异无统计学意义,表明RSD对难治性高血压的降压效果并不优于药物治疗;12个月后随访数据显示,Symplicity导管系统治疗难治性高血压患者没有发生严重并发症,但未达到预期的主要临床终点。许多学者对此困惑不解,追溯HTN-1研究和HTN-2研究的随访资料发现12个月后入组患者中也有13%~21%的患者收缩压下降不足10 mmHg(1 mmHg=1.33 kPa),而HTN-1研究随访3年的数据亦发现7.1%患者RDN治疗无反应[16-18]。HTN-3研究的阴性结果引来大片争议,甚至影响到了后续的一系列关于RSD的研究,但仍有不少学者对RSD充满信心。他们深入分析HTN系列研究发现:RSD可减少室性心律失常的发生频率,尤其那些无结构性心脏病的特发性心律失常的患者[19-20];此外还有慢性肾脏病[21]、阻塞性睡眠呼吸暂停[22]、糖代谢受损[22]、心脏衰竭[23-24]、心房颤动[25-26]等也都能在RSD后获益。国际心血管病杂志最新研究[27]发表:(1)双肾单根肾动脉的患者接受RSD术后3个和6个月,24 h动态血压及门诊血压持续显著下降,尤其是夜间血压下降明显,这种血压下降的幅度有明显的临床意义很可能与心脑血管事件发生率减少密切相关;(2)双肾单根肾动脉患者接受RSD后血压下降幅度明显大于有单肾双根肾动脉组;(3)术前和术后患者心率、血浆肌酐水平、肾小球滤过率变化均无明显差异;(4)术后不到10%的患者需要加大药物剂量控制血压,约20%的患者反而减少了药物剂量。此项研究为进一步证实RSD的安全性提供了依据,同时为研究RSD无反应与肾动脉解剖结构的相关性提供了参考。

RSD是目前治疗难治性高血压的一大突破。研究表明,RSD可降低全身交感神经活性,并可治疗其他以交感神经系统的过度激活为特征的疾病[28],如减少难治性高血压患者房颤、室性心律失常的发生率[29-30];逆转难治性高血压患者左室肥厚,改善心脏功能,改善动脉硬化[29,31-34];减少难治性高血压患者蛋白尿,改善其肾功能[12,21,35-36];改善难治性高血压血糖代谢,增加其胰岛素敏感性[37-38];减轻难治性高血压患者上呼吸道阻塞,减少睡眠呼吸暂停综合征的发生[22,38-39];有病例报告报道RSD不仅使需血液透析的难治性高血压患者平稳降压,还能减慢其肾素及血管紧张素转化酶的分泌速度[40];RSD对合并多囊卵巢综合征的难治性高血压患者也有治疗作用[41]。

4 展 望

RSD具有安全、创面小、恢复快、手术时间短等优势,如果能替代药物治疗有望获得更广阔的前景。但现在RSD相关研究仍处于不成熟阶段,这表现在以下几个方面:在患者的选择上需要肾动脉交感神经活性敏感的难治性高血压患者,怎么判断肾交感神经活性敏感,目前没有评判指标;技术方面,导管的材质、消融点多少和部位的选择等没有参考标准;肾交感神经具有再生能力,是否需要再次交感消融,多久后再次手术目前没有这方面的研究报道;预后方面,由于这项技术开展的时间还不够长,目前还没有确切数据证实RSD对延缓难治性高血压病病情进展及改善高血压病预后有积极意义;评价RSD的有效性的指标方面,据血压的下降的幅度以及持久性来定义这项技术的有效性有待进一步考证[42]。此外其对难治性高血压的治疗效果是否优于药物治疗存在争议,因为有以上多种问题的存在,国内这项技术并没有普及,中国大部分地区都还没有这门技术。虽然RSD病例数已经从开展时的十多例发展到了现有的2万多例,但RSD对难治性高血压的研究仍处于不成熟阶段,需要进一步探索。同时进一步研究RSD对合并有肾衰、糖尿病、心力衰竭、心律失常、多囊卵巢综合征等疾病的难治性高血压患者获益的作用机制将会为此类患者的治疗提供新的契机,开拓全新的领域。

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Researching progress of percutaneous radiofrequency catheter-based renal sympathetic denervation in the treatment of resistant hypertension.

YANG Chao-ying,YANG Hui,SU Yu-jiang.Department of Cardiovascular Medicine,Haikou Hospital Affiliated to Xiangya School of Medicine,Central South University,Haikou People's Hospital, Haikou 570208,Hainan,CHINA

Resistant hypertension is a special type of the high blood pressure,which is one of the basic diseases resulting in higher mortality and morbidity.Resistant hypertension is defined as blood pressure that remains above goal in spite of the concurrent use of 3 antihypertensive agents of different classes.Ideally,one of the agents should be a diuretic and all agents should be prescribed at optimal dose amount.It accompanies with more complications and higher incidence of cardiovascular events and mortality than other types of hypertension.Recently,there is a new type of non-pharmacological therapy,that is,percutaneous radiofrequency catheter-based renal sympathetic denervation.This review summarizes the research progress on the therapy.

Resistant hypertension;Renal sympathetic denervation;Interventional treatment;Radiofrequency

R544.1

A

1003—6350(2016)19—3194—04

10.3969/j.issn.1003-6350.2016.19.033

2015-12-31)

海南省自然科学基金(编号:SZR0506)

苏雨江。E-mail:13078955322@163.com

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