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自主神经干预与心房颤动消融

自主神经干预与心房颤动消融. 江 洪 武汉大学人民医院. 迷走神经与房颤的关系. 迷走神经在房颤的诱发和维持都起重要作用. 房颤发作前有迷走 神经张力短时升高. 临床研究. Vikman S, et al. JACC. 2005;45:278-284. 阵发性房颤患者在房颤发作前数分钟先表现为交感 神经张力的升高，随后出现迷走神经张力占优势 持续性房颤病人电复律后，房颤在 48 小时内复发与 复律后迷走神经张力升高有关. Bettoni M, et al. Circulation. 2002;105:2753-2759.

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自主神经干预与心房颤动消融

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  1. 自主神经干预与心房颤动消融 江 洪 武汉大学人民医院

  2. 迷走神经与房颤的关系 迷走神经在房颤的诱发和维持都起重要作用 房颤发作前有迷走 神经张力短时升高 临床研究 Vikman S, et al. JACC. 2005;45:278-284

  3. 阵发性房颤患者在房颤发作前数分钟先表现为交感阵发性房颤患者在房颤发作前数分钟先表现为交感 神经张力的升高，随后出现迷走神经张力占优势 持续性房颤病人电复律后，房颤在48小时内复发与 复律后迷走神经张力升高有关 Bettoni M, et al. Circulation. 2002;105:2753-2759 Bertaglia E, et al. In J Cardiol. 2005;102:219-23

  4. 研究背景 房颤的自主神经机制研究 Chen PS. Circulation 2008,118:196-25 Chen PS. Circulation 2010,121:2615-23 Chen PS. Circulation 2011,123:2204-12 Chen PS. Heart Rhythm 2011,8:583-9 星状神经节 ＋ AF Po SS. JACC 2007,50:61-8 Lu Z . Cardiovasc Res 2009,84:245-52 Yu L. Circulation 2010,122:2653-9 Yu L . JCE 2011,22:455-63 ＋ 心房神经节

  5. 神经等级学说 Armour JA：Cardiac neuronal hierarchy in health and diease. AJP 2004;287:R262-71

  6. 自主神经干预治疗心房颤动 • GP消融 • 去肾交感神经消融 • 低强度刺激迷走神经耳支——治疗早期房颤 • 脊神经刺激（SCS)

  7. AF发生机制的经典假说 局灶驱动学说 多发子波 折返 主折返环伴颤动样传导

  8. 100 ms 房颤的起始 II V1 RAA LSPV RSPV LA LA PVP Pulmonary Vein Potentials (PVP) CS Firing Duration 0.35 sec 100 ms Mean CL 90 ms (Rate 665/min)

  9. Hypothesis for Pulmonary Vein Firing (and AF)Induced by Autonomic Stimulation “Calcium-Transient Triggering” University of Oklahoma Patterson et al, Heart Rhythm 2005; 2:624 Intracellular Calcium (Calcium Transient) Action Potential • Based on 2 Properties of • PV Myocardial Cells • Short action potential duration • - Intracellular calcium concentration • (calcium transient) remains high • after repolarization

  10. “Calcium-Transient Triggering” Hypothesis Rapid Rhythm Followed By Pause Sinus Rhythm Ca++ Ca++ Action Potential EAD EAD Triggered Firing Acetylcholine Shortens Action Potential Increased Autonomic (GP) Activity Triggered Firing EADs Norepinephrine Increases Calcium Loading

  11. PA View Aorta SVC Lasso Catheter 5 1 RPA LSPV RSPV 3 ARGP LA RIPV RA LIPV 2 LOM 4 IVC 1 = SLGP 2 = ILGP 3 = ARGP 4 = IRGP 5 = RPA-GP LV RV Lu et al. Cardiovascular Research. 2009

  12. s1s1=330ms 1ms coupling interval 40 ms S1 S1 200 Hz, 0.1 ms pulse duration HFS S2 train S2 train Atrial APD ERP 120 ms Neural APD 40ms ERP 1 ms

  13. A A H H 2:1 AV conduction block by HFS (1.5V) at the LSPV II A H A H A A A HBE LSPVD2 LSPV34 LIPVD2 LIPV34 LAA LA RSPVD2 RIPVD2 RAA RA 200 msec

  14. AV block just before initiation of AF II HBE LSPVD2 LSPV34 LIPVD2 LIPV34 LAA LA RSPVD2 RIPVD2 RAA RA 200 msec

  15. AF was initiated by HFS (1.5V) from RSPV aVL HBE RSPVD2 RSPV34 RSPV56 RIPVD2 RIPV34 RIPV56 RAAD2 RAA34 RAD2 RA34 300 msec

  16. No AF by HFS (12V) after GP ablation aVL HBE RSPVD2 RSPV34 RSPV56 RIPVD2 RIPV34 RIPV56 RAAD2 RAA34 RAD2 RA34 300 msec

  17. AF发生机制的经典假说 局灶驱动学说 多发子波 折返 主折返环伴颤动样传导

  18. LAA Pacing 1200/min for 6 hrs 心房电重构的神经机制 Right Thoracotomy Left Thoracotomy Anterior Right GP Superior Left GP SVC LPA RSPV LAA LSPV LA RA RAA RV LIPV LV RIPV IVC Inferior Left GP Inferior Right GP Lu Z, Jiang H and Sunny Po. Circ Arrhythmia Electrophysiol. 2008

  19. 14 dogs Group 1 Group 2 6 hr LAA pacing (1200/min) GP Ablation (ARGP+IRGP+SLGP +ILGP+LOM) EP Testing: ERP, AF Induction EP Testing: ERP, AF Induction GP Ablation (ARGP+IRGP+SLGP +ILGP+LOM) 6 hr LAA pacing (1200/min) EP Testing: ERP, AF Induction EP Testing: ERP, AF Induction

  20. Group 1: Change in ERP During Atrial Pacing ERP 2 x Threshold 200 ERP 10 x Threshold LSPV ERP (ms) 160 120 80 40 1 2 3 4 5 6 Baseline Duration of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ Arrhythmia Electrophysiol. 2008

  21. Group 1: Change in ERP after GP Ablation ERP 2 x Threshold 200 ERP 10 x Threshold LSPV GP Ablation ERP (ms) 160 120 80 40 1 2 3 4 5 6 Baseline Post-Abl Duration of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ Arrhythmia Electrophysiol. 2008

  22. Group 1: Change in AF Inducibility GP Ablation 1600 ∑ WoV (ms) 1200 800 400 0 1 2 3 4 5 6 Baseline Post-Abl Duration of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ Arrhythmia Electrophysiol. 2008

  23. Group 2: Change in ERP During Atrial Pacing ERP 2 x Threshold After GP Ablation 200 ERP 10 x Threshold LSPV GP Ablation ERP (ms) 160 120 80 40 1 2 3 4 5 6 Post-Abl Duration of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ Arrhythmia Electrophysiol. 2008

  24. Group 2: No Change in AF Inducibility After GP Ablation 1600 GP Ablation ∑ WoV (ms) 1200 800 400 0 1 2 3 4 5 6 Post-Abl Duration of Rapid Atrial Pacing (Hours) Lu Z, Jiang H and Sunny Po. Circ Arrhythmia Electrophysiol. 2008

  25. Autonomic GP Posterior Surface Anterior Surface Ganglionated Plexi (GP) Superior Left GP Anterior Right GP GP Axons Heavy Innervation of PVs Inferior Left GP Inferior Right GP MR Angiogram - PA Projection

  26. 心脏神经节消融治疗房颤 不同的消融靶点－类似的成功率? Wide PV Encircling Plus Linear LA Lesions With vs. Without PV Isolation / Linear Block Wide PV Encircling (PV Antrum) With vs. Without PV Isolation Ablation at Sites of CFAE / DF Without PV Isolation or Linear Lesions

  27. GP消融前后高频电刺激的变化

  28. Study Population 83 pts • AF Type • - Paroxysmal AF - 55 pts (66%) - Persist AF (>48 hrs) - 28 pts (34%)

  29. Ablation Success After GP Ablation and Antrum Isolation (Single Procedure) 40/42 95% 36/42 86% 50/54 93% 61/71 86% 69/80 86% 100 No AF 69/83 83% Patients Free of AF or AF & AT 90 No AF or AT 80 36/42 86% 70 43/54 80% 60 49/71 69% (%) 55/80 69% 51/83 61% 50 Parox and Persist AF 40 30 20 Months Post Ablation 10 1 3 6 12 12 (mean 22)

  30. 单次手术成功率

  31. Heart Rhythm. 2013 Ganglionated plexus ablation vs linear ablation in patients undergoing pulmonary vein isolation for persistent/long-standing persistent atrial fibrillation: a randomized comparison. PVI+线性消融（N=132） vs PVI+GP消融（N=132） 入选持续性或长期持续性房颤 随访至少3年 以植入式心电记录仪随时观察患者心律 比较单次手术效果 术后停用所有抗心律失常药物 12个月窦律比例：47% vs 54% p=0.29 3年窦律比例：34% vs 49% p=0.035 房扑发生率：18% vs 6% p=0.002 再次手术后窦律比例：52% vs 68% p=0.006

  32. 肾动脉交感神经消融（RSD） 2009年澳大利亚莫那什大学的Krum教授等首次提出RSD术治疗顽固性高血压的新思路，为顽固性高血压的治疗带来新的曙光 2009的Symplicity HTN-1试验及2010年的Symplicity HTN-2试验等均证实了短期内RSD治疗顽固性高血压的安全性及有效性

  33. “一肾一夹”高血压模型 高血压模型组实验羊LA直径增大、LA功能下降、AERP缩短、房颤诱发率增高、房颤发作时程延长、心房炎症、纤维化加重 高血压可改变心房电重构及结构重构，可促进房颤的发生发展 猜测：RSD可控制房颤的发生发展 Dennis H， Heart Rhythm 2010

  34. RSD与房颤相关研究 动 物 实 验：急性实验

  35. RSD降低房颤时的心室率 RSD延长实验猪的RR间期及PQ间期，即减慢心室率（延长房室结传导时间） Linz D et al. Hypertension 2013

  36. RSD缩短房颤持续时间，但不抑制房颤所致心房电重构，不影响房颤诱发性和房颤周长RSD缩短房颤持续时间，但不抑制房颤所致心房电重构，不影响房颤诱发性和房颤周长

  37. Linz D et al. Hypertension 2013

  38. RSD抑制气道负压（阻塞性睡眠呼吸暂停模型）所致心房ERP缩短及房颤诱发性增加，但不影响GP刺激所致心房ERP缩短RSD抑制气道负压（阻塞性睡眠呼吸暂停模型）所致心房ERP缩短及房颤诱发性增加，但不影响GP刺激所致心房ERP缩短

  39. RSD不能抑制电刺激引起的压力感受性反射所致心房ERP缩短和房颤诱发性增加RSD不能抑制电刺激引起的压力感受性反射所致心房ERP缩短和房颤诱发性增加 Linz D, et al. J CE 2013

  40. 房颤持续时间 RSD可减少快速心房起搏诱发的房颤的持续时间与次数 房颤诱发次数 Zhao et al. JICE 2012

  41. RSD对快速心房起搏所致AERP缩短无明显影响 RSD对GP刺激所致AERP下降无明显影响 疑问：RSD能否改善心房电重构？

  42. RSD与房颤相关研究 动 物 实 验：慢性实验

  43. RSD可抑制快速心房起搏所致心房基质重构

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