顽固性高血压的介入治疗肾神经消融.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,顽固性高血压的介入治疗肾神经消融,历史回顾,降压药物问世前，上世纪,20-50,年代，尝试外科切除内脏交感神经治疗高血压，虽然降压有效，,中,/,远期生存率明显提高，,但围术期的致死、致残率高，中,/,远期并发症多。,尽管当代降压药物有长足发展，但仍有部,分规范服药的患者血压不能达标,此外：,交感神经抑制剂、直接肾素抑制剂、非特异性血管扩张剂、抗高血压疫苗,高血压是全球公共卫生的难题，难治性高血压约占,10%-20%,，有更高心血管事件风险,Resistant hypertension,:,Circulation 2008;117:e51026,理论基础的启示：寻找解决办法,Sympathetic nervous system and the kidney in hypertension.,Carotid baroreflex and hypertension,肾交感神经阻断？,颈动脉体迷走神经兴奋？,经导管肾交感神经消融术,Symplicity HTN-1 Three Year and Symplicity HTN-2 One Year Summary,Sustained BP Reductions to Three Years,First Symplicity HTN-1 patient treated June 2007,Three year reporting shows no diminishment of effect and impressive long term safety,For patients that have completed 3 year follow up,100%have been classified as responders(10 mmHg reduction),while at 6 months 71%of patients were classified as responders.,Superior Results Confirmed in Randomised Study,Symplicity HTN-2 treatment population shows sustained treatment effect at 12 month follow-up,Control cross-over patients also show significant BP reduction,Only the Symplicity renal denervation system has proven safe,superior and sustained BP reductions,Significant,Sustained Blood Pressure Reductions to at Least 3 Years,Expanded results presented at the American College of Cardiology Annual Meeting 2012(Krum,H.),p,0.01 for,from baseline for all time points,Impressive Safety Record Continues in Long Term Follow-up,81 patients with 6-month renal CTA,MRA or duplex,No vascular abnormalities at any site of RF delivery,One progression,of a pre-existing stenosis unrelated to RF treatment(stented without further sequelae),One new moderate stenosis which was not hemodynamically relevant and not treated,3 deaths within the follow-up period;all unrelated to the device or therapy,No hypotensive events that required hospitalization,There were no observed changes in mean electrolytes or eGFR,Expanded results presented at the American College of Cardiology Annual Meeting 2012(Krum,H.),Percentage Responders Increases Over Time,Responder was defined as an office SBP reduction 10 mmHg,(n=143),(n=148),(n=144),(n=130),(n=107),(n=59),(n=24),(n=24),Expanded results presented at the American College of Cardiology Annual Meeting 2012(Krum,H.),Symplicity HTN-2:RDN Superior to Medical Management,Reductions Sustained to 12M,from Baseline,to,6 Months(mmHg),Primary Endpoint:,84%of RDN patients had 10 mmHg reduction in SBP,10%of RDN patients had no reduction in SBP,Systolic,Diastolic,Systolic,Diastolic,Expanded results presented at the American College of Cardiology Annual Meeting 2012(Esler,M.),RDN(n=49),from Baseline,to,12 Months(mmHg),Systolic,Diastolic,Primary Endpoint,(6M post Randomisation),Latest Follow-up,(12M post Randomisation),Latest Follow-up:,Control crossover(n=35):-24/-8 mmHg(Analysis on patients with SBP 160 mmHg at 6 M),p,0.01 for,from baseline,p,0.01 for,difference between RDN and Control,Medication Changes at 6 and 12 Months Post-Renal Denervation,RDN(n=47),6 month,12 months,Decrease(#Meds or Dose),20.9%(9/43),27.9%(12/43),Increase(#Meds or Dose),11.6%(5/43),18.6%(8/43),Crossover(n=35),6 months post-RDN,Decrease(#Meds or Dose),18.2%(6/33),Increase(#Meds or Dose),15.2%(5/33),Physicians were allowed to make changes to medications,Once the 6 month primary endpoint was reached*,*,Further analysis of Medications is ongoing,Symplicity RDN Safety Record Continues to be Strong in Expanded Results,Symplicity HTN-2 Investigators.,The Lancet,.2010.,Baseline,6 month,12 months,eGFR(ml/min/1.73m,2,),76.9 19.3(n=49),77.118.8(n=49),78.217.4(n=45),Cystatin C(mg/L),0.910.25(n=38),0.980.36(n=40),0.980.30(n=38),RDN,N=47,Baseline,6 month,12 months,eGFR(ml/min/1.73m,2,),88.8 20.7(n=35),89.319.5(n=35),85.218.3(n=35),Cystatin C(mg/L),0.78 0.17(n=27),0.820.16(n=26),0.890.20(n=26),Crossover,N=35,Treated at Randomisation,Treated after,6-mo follow-up,First-in-Man(AU),Series of Pilot Studies,(EU,US&AU),Symplicity HTN-2,Initial RCT,(EU&AU),SYMPLICITY HTN-3,US Pivotal Trial(US),Global SYMPLICITY Registry,(Approved Regions),Expand HTN Indication,(Approved Regions),Post-Market Registry,(US),SYMPLICITY HF,Symplicity HTN-1,（,n=153),Pilot Studies in,New Indications,(Approved Regions),Trials under way,Comprehensive SYMPLICITY Clinical Trial Program follows over 5000 patients across multiple indications,This report,目前的初步结果鼓舞人心,作为抑制交感神经过度激活的一种新方法，可能有潜在巨大的临床应用前景。但仍有许多问题尚不明了，积极稳妥的开展相关的临床研究很有必要。,没有即刻评价神经消融技术成功指标,Symplicity HTN-1,中仅,39%,消融患者血压控制达标，即达到,BP140/90 mm Hg,6/45(13%),患者收缩压下降不足,10 mm Hg(non-response),操作简单易行，需防止过度治疗应用,为提高消融程度，增加消融能量、位点或时间，,可能增加肾动脉狭窄、动脉瘤等并发症,研发新一代专用消融导管，使操作更方便、省时、可靠,肾神经有重要的生理功能，去神经的中远期影响尚不清楚,自分泌或全身交感反馈机制可能使降压效果不能持久,传入神经不能再生，但传出神经再生是否会影响长期效果？,目前的研究样本量小，统计效能有限，中远期疗效未明,是否真正减少心脑血管事件及死亡？,费用较高，效益,/,费用比以及并发症,/,终生用药利弊如何权衡？,判定手术成功的即刻指标和,预测消融效果的检测方法,长期安全性和疗效,风险效益比的评价,临床适应症的选择等方面,未来的临床研究要探索,1.Renal Denervation in Patients With Resistant Hypertension and Obstructive Sleep Apnea,2.Renal Denervation in Patients With Uncontrolled Hypertension(Symplicity HTN-3),3.Renal Denervation in Patients With Chronic Heart Failure&Renal Impairment Clinical Trial,4.Recruiting Combined Treatment of Resistant Hypertension and Atrial Fibrillation,5.Renal Denervation in End Stage Renal Disease Patients With Refractory Hypertension,6.Recruiting Sympathetic Activity and Renal Denervation,7.,阜外医院,a)Active,on-going Renal Denervation in Patients With Resistant Hypertension,b)Active,on-going Renal Denervation in swine model,相关试验,我院改良的,RDN,入选,标准,入选标准,(5,项均需满足,):,1.,肾动脉直径,4mm,且长度,20mm,2.,年龄,18,岁，,65,岁,3.,收缩压,160 mmHg,和,/,或舒张压,100 mmHg,（平均三次诊室,/,病房测量）,4.,规律服用三种或以上常规剂量抗高血压药物,5.,估测,GFR,（,eGFR,）,45,ml/min,排除标准,(,存在,1,项即排除,):,肾动脉异常的情况包括：,1.,任一侧肾动脉血流动力学或解剖学上明显的狭窄（,50%,）；,2.,之前曾行肾动脉球囊成形术或置入过支架；,3.,任一侧肾脏存在多支肾动脉，且直径,4mm,（,MRA/CTA/,血管造影评价）,心血管不稳定包括：,1.,六个月内心肌梗死、不稳定性心绞痛或脑血管病事件,2.,存在血管内血栓或不稳定斑块的广泛动脉粥样硬化,3.,血流动力学明显改变的心脏瓣膜疾病,4.,左心功能不全,EF250,秒,(2),止疼,:,射频前经静脉予吗啡和,/,或芬太尼,(3),血管扩张,:,射频中如发现肾动脉收缩明显,予硝酸甘油,100-200ug,经导管给药,(4),降压,:,如血压明显升高,予硝普钠经静脉泵入,(5),心动过缓,/,血压下降,:,阿托品和,/,或多巴胺,2-3mg,经静脉推注,术,中用药与监护,射频导管头端自肾动脉远端至开口，螺旋型后撤，每隔,5mm,选一个点消融，射频导管头端充分贴壁后，每点传递能量,8w,2,分钟，一般一条肾动脉要消融,5-6,个点,术后观察与随访,术后重点观察血压变化、肾功能和微量蛋白尿，要依据血压下降的情况调整降压药。建议考虑口服阿司匹林,50-100mg/,天，共一个月，预防肾动脉,射频,后血栓形成,阜外医院,10,例顽固性高血压患者,RDN,（,Symplicity,Catheter,导管）,一个月随访结果,无降压应答,2,例（,2/10,）,较基线血压下降,20/10mmHg,较基线降压药数量或剂量下降,8,例（,8/10,）,肾功能与尿常规无显著变化,无并发症发生,谢谢观赏,