頑固性高血壓的介入治療腎神經(jīng)消融

1、頑固性高血壓的介入治療經(jīng)皮經(jīng)導(dǎo)管腎神經(jīng)消融術(shù)需要積極穩(wěn)妥開展臨床研究,,歷史回顧降壓藥物問世前，上世紀(jì)20-50年代，嘗試外科切除內(nèi)臟交感神經(jīng)治療高血壓，雖然降壓有效，中/遠(yuǎn)期生存率明顯提高，但圍術(shù)期的致死、致殘率高，中/遠(yuǎn)期并發(fā)癥多。,盡管當(dāng)代降壓藥物有長足發(fā)展，但仍有部分規(guī)范服藥的患者血壓不能達(dá)標(biāo),此外：交感神經(jīng)抑制劑、直接腎素抑制劑、非特異性血管擴(kuò)張劑、抗高血壓疫苗…,高血壓是全球公共衛(wèi)生的難題，難治性高血壓約占10%

2、-20%，有更高心血管事件風(fēng)險(xiǎn) Resistant hypertension: Circulation 2008;117: e510–26,理論基礎(chǔ)的啟示：尋找解決辦法,Sympathetic nervous system and the kidney in hypertension.,Carotid baroreflex and hypertension,腎交感神經(jīng)阻斷？,頸動脈體迷走神經(jīng)興奮？,經(jīng)導(dǎo)管腎交感神經(jīng)消融術(shù),Sy

3、mplicity HTN-1 Three Year and Symplicity HTN-2 One Year Summary,Sustained BP Reductions to Three YearsFirst Symplicity HTN-1 patient treated June 2007 Three year reporting shows no diminishment of effect and impressiv

4、e long term safetyFor 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 Con

5、firmed in Randomised StudySymplicity HTN-2 treatment population shows sustained treatment effect at 12 month follow-upControl cross-over patients also show significant BP reduction,Only the Symplicity? renal denervatio

6、n 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 (Kr

7、um, 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 duplexNo vascular abnormalities at any site of RF delivery

8、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 treated3 deaths within the follow-up perio

9、d; all unrelated to the device or therapyNo hypotensive events that required hospitalization There were no observed changes in mean electrolytes or eGFR,Expanded results presented at the American College of Cardiology

10、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 a

11、t 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 pati

12、ents had ≥10 mmHg reduction in SBP10% 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

13、= 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

14、 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,Physicians were allowed to make changes

15、 to medicationsOnce 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 Lanc

16、et. 2010.,RDNN=47,CrossoverN=35,Treated at Randomisation,Treated after 6-mo follow-up,,First-in-Man (AU),Series of Pilot Studies(EU, US & AU),Symplicity HTN-2Initial RCT(EU & AU),SYMPLICITY HTN-3US Pivotal

17、 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 inNew Indications(Approved Regions),,Tri

18、als under way,Comprehensive SYMPLICITY Clinical Trial Program follows over 5000 patients across multiple indications,,,This report,目前的初步結(jié)果鼓舞人心作為抑制交感神經(jīng)過度激活的一種新方法，可能有潛在巨大的臨床應(yīng)用前景。但仍有許多問題尚不明了，積極穩(wěn)妥的開展相關(guān)的臨床研究很有必要。,沒有即刻評價神經(jīng)消融技

19、術(shù)成功指標(biāo)Symplicity HTN-1中僅39%消融患者血壓控制達(dá)標(biāo)，即達(dá)到 BP<140/90 mm Hg6/45(13%)患者收縮壓下降不足10 mm Hg (non-response),操作簡單易行，需防止過度治療應(yīng)用為提高消融程度，增加消融能量、位點(diǎn)或時間， 可能增加腎動脈狹窄、動脈瘤等并發(fā)癥研發(fā)新一代專用消融導(dǎo)管，使操作更方便、省時、可靠,腎神經(jīng)有重要的生理功能，去神經(jīng)的中遠(yuǎn)期影響尚不清楚自分泌

20、或全身交感反饋機(jī)制可能使降壓效果不能持久傳入神經(jīng)不能再生，但傳出神經(jīng)再生是否會影響長期效果？目前的研究樣本量小，統(tǒng)計(jì)效能有限，中遠(yuǎn)期療效未明是否真正減少心腦血管事件及死亡？,費(fèi)用較高，效益/費(fèi)用比以及并發(fā)癥 / 終生用藥利弊如何權(quán)衡？,判定手術(shù)成功的即刻指標(biāo)和預(yù)測消融效果的檢測方法長期安全性和療效風(fēng)險(xiǎn)效益比的評價臨床適應(yīng)癥的選擇等方面,未來的臨床研究要探索,1. Renal Denervation in Patients

21、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 Impairme

22、nt Clinical Trial4. Recruiting Combined Treatment of Resistant Hypertension and Atrial Fibrillation 5. Renal Denervation in End Stage Renal Disease Patients With Refractory Hypertension6.Recruiting Sympathetic

23、Activity and Renal Denervation 7.阜外醫(yī)院 a) Active, on-going Renal Denervation in Patients With Resistant Hypertensionb) Active, on-going Renal Denervation in swine model,,相關(guān)試驗(yàn),我院改良的RDN入選標(biāo)準(zhǔn),排除標(biāo)準(zhǔn)(存在1項(xiàng)即排除):,常規(guī)選擇經(jīng)皮股動

24、脈路徑。目前設(shè)計(jì)的Symplicity® Catheter 導(dǎo)管推送桿長度為100CM，而經(jīng)橈動脈入路至腎動脈往往需要100CM以上的指引導(dǎo)管，因此射頻導(dǎo)管的頭端無法申出指引導(dǎo)管。如果以后有更長推送桿的射頻導(dǎo)管，橈動脈入路也是好的選擇,入路選擇,,指引導(dǎo)管的選擇,,,(1)抗凝：一般普通肝素5000-7500IU，要求ACT>250秒(2)止疼:射頻前經(jīng)靜脈予嗎啡和/或芬太尼(3)血管擴(kuò)張:射頻中如發(fā)現(xiàn)腎動脈收縮明顯

25、,予硝酸甘油100-200ug經(jīng)導(dǎo)管給藥(4)降壓:如血壓明顯升高,予硝普鈉經(jīng)靜脈泵入(5)心動過緩/血壓下降:阿托品0.5mg和/或多巴胺2-3mg經(jīng)靜脈推注,術(shù)中用藥與監(jiān)護(hù),射頻導(dǎo)管頭端自腎動脈遠(yuǎn)端至開口，螺旋型后撤，每隔5mm選一個點(diǎn)消融，射頻導(dǎo)管頭端充分貼壁后，每點(diǎn)傳遞能量8w,2分鐘，一般一條腎動脈要消融5-6個點(diǎn),術(shù)后觀察與隨訪,術(shù)后重點(diǎn)觀察血壓變化、腎功能和微量蛋白尿，要依據(jù)血壓下降的情況調(diào)整降壓藥。建議考慮口服阿司匹