1、Fighting CVD 福建医科大学附属协和医院心内科 福建省冠心病研究所 陈良龙 MD PhD 起搏防治房颤： 果真形同鸡肋吗？ Fighting CVD 传统治疗 复律并维持窦律 :AD/DC 控制心室率 : 抗栓治疗 :包括抗凝及抗血小板聚集 AD治疗并不理想，特别是 AD的致心律失常作用，因此 ,非药物治疗受到了重视 . 非传统治疗 外科迷宫手术 导管消融术 心脏起搏治疗 房颤的治疗 Fighting CVD 起搏抑制房颤的理论基础 房性早搏是房颤发生最常见的触发因素 与房颤发生有关的因素还包括 : 显著心动过缓 ,如窦缓、 SSS 房内及房间传导阻滞 短长周期现象 心房复极离散度增
2、加 理论上，心房起搏可以阻止心脏停搏或心动过缓导致的心房不应期及 复极 离散度 改变、减少房内及房间传导时间、抑制心房异位兴奋点，从而预防 折返、颤动样传导及触发引起的房颤。 临床上，许多学者观察到植入生理性起搏器的房颤患者术后房颤发作频度 减少或持续时间缩短。 故而，起搏作为治疗和预防房颤的一种手段被提出来。 Fighting CVD 起搏抑制房颤的措施 起搏部位 常规 RA起搏 双心房起搏 右心房多部位起搏 特殊部位起搏： Bechmen束 多部位起搏使心房激动通过多个方向，减轻局部传导延迟，预防 功能性传导阻滞的发生，使双心房再同步，减少复极的离散度， 减轻心房的各向异性。 起搏程序 预
3、防 房颤 的心房超速起搏程序（ ODP） 抗心动过速起搏程序（ ATP） Fighting CVD 心房超速起搏对房颤的预防作用 心房超速起搏预防房颤发生的机制主要是 消除房颤的诱发因素，如抑制房性早搏消除早搏后的长间期现 象 此外，通过保持和控制心率及心律从而降低心房复极的离散度 目前临床应用的有二类 持续性起速起搏 (sustained atrial overdriving,SAO) 动态心房超速起搏 (dynamic atrial overdriving,DAO) Fighting CVD 设置的心房频率比患者自身频率一般 10%以上，通 常在 80-90bpm。设置心房起搏频率越快，则
4、患者自 主心率出现的机率越少，早搏的发生率则越低，从 而预防房颤的效果越好。 缺点 :起搏频率快，导致耗氧量增加，尤其不利于心 绞痛的病人。心率几乎全由起搏器控制，失去了心 率变异性。 持续性心房超速起搏（ SAO） Fighting CVD 动态心房超速起搏的特点是起搏器能持续检测自身窦 性 P波，并与房性早搏相鉴别。当检测到 16个窦性心搏 有 2次房性早搏出现，起搏器就会自动提高心房起搏频 率，并逐渐增加起搏频率直到稍超过房性早搏频率， 从而达到超速起搏的目的。 这种起搏频率逐渐增加的方式，比固定频率超速起搏 (SAO)要优越些，不但省电而且病人更适应，新近临床 实验显示 DAO使房颤发
5、生率显著降低，圣犹达公司 lntegrityTM AFxDR就是一种 DAO起搏器。 动态心房超速起搏 (DAO) Fighting CVD 主要产品 St.Jude Medical Trilogy DR+/DAO Model 2360L/2364L Integrity AFx DR Model 5346 Medtronic AT 500 Kappa 900 Vitatron Vita 900E ,9000 Fighting CVD AF Suppression Algorithm Overview 运算方式 Fighting CVD Sinus rate Dynamic atrial ove
6、rdrive Maximum tracking rate Basic lower rate Algorithm Overview Fighting CVD AF Suppression Algorithm Overview 保证心房起搏占 90%以上比例 起搏频率根据病人的自身心房活动而动态变化 在连续 16个心动周期中感知到 2个 P波， AF Suppression的起搏频率将自动提高 起搏的次数可由程控决定 经一段时间起搏后，频率会逐渐下降，同时检 测自身心房活动 Fighting CVD P A A A A A A A A A A A A A A A A 0 1 2 3 4 5 6 7
7、 8 9 10 11 12 13 14 15 16 Start 16-cycle counter P = P-wave A= Atrial pacing Only 1 P-wave was seen. Therefore, NO Overdrive occurs End 16-cycle counter Note: Notice how the algorithm starts with a “0” not a “1” AF Suppression Algorithm Overview Fighting CVD AF Suppression Algorithm Overview P A A A
8、 A A A A A A A A A A A P 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Start 16-cycle counter 2 P-waves were seen therefore, Overdrive occurs Start Overdrive P = P-wave A= Atrial pacing Fighting CVD 2 P-waves were seen therefore, Overdrive occurs AF Suppression Algorithm Overview P P Overdrive Rate Pacing R
9、ate Fighting CVD AF Suppression Algorithm Overview 低频超速抑制 (LRO) 150ppm: 每步增加 5 ppm Fighting CVD 1200 1 2Base Rate Pacing1200 ms (50 ppm) Overdrive Pacing1016 ms (59 ppm) While base rate pacing at 50 ppm (1200 ms), 2 P-waves occur in the 16-cycle window, the atrial pacing rate increases to 59 ppm (10
10、16 ms) AF Suppression Algorithm Overview Fighting CVD 0 1 2 3 4 5 6 7 8 AF Suppression Algorithm Overview While base rate pacing at 50 ppm (1200 ms), 2 P-waves within 16 cycles occur, the atrial pacing rate increases to 59 ppm (1016 ms) Fighting CVD AF Suppression Algorithm Overview 频率的恢复 : 12/8 法则
11、100 ppm 每步增加 12 ms 100 ppm 每步增加 8 ms Fighting CVD ECG continued on next slide. AF Suppression Algorithm Overview 2 P-waves within 16 cycles results in an atrial rate increase 12 mm/sec printer speed Rate Increase Fighting CVD AF Suppression Algorithm Overview Rate Recovery occurs when the interval i
12、ncreases from 1016 ms to 1022 ms 25 mm/sec printer speed Fighting CVD ECG demonstrates Rate Recovery continuing until Base Rate of 1200 ms is reached (25 mm/sec) AF Suppression Algorithm Overview Continuous ECG Fighting CVD 2 P-waves were seen therefore, Overdrive occurs followed by Rate Recovery AF
13、 Suppression Algorithm Overview P P Overdrive Rate Pacing Rate Pacing Rate Rate Recovery Fighting CVD 起搏防治房颤临床试验 Fighting CVD Integrity AFx DR Model 5346 St. Jude Medical pulse generators Used for the trial: Atrial Dynamic Overdrive Pacing Trial- A (ADOPT-A) Trilogy DR+/DAO Model 2360L/2364L Fightin
14、g CVD ADOPT-A Clinical Trial Symptomatic AF Episodes via Event Recorder Follow-up Baseline, 30, 90, 180 days Device Assessment QOL DDDR Pacing AF Suppression-ON Symptomatic AF Episodes via Event Recorder Follow-up Baseline, 30, 90, 180 days Device Assessment QOL DDDR Pacing AF Suppression-OFF Pacema
15、ker Implant Trilogy DR DAO Integrity AFx DR Prospective Patient Blinded Randomized Study Design N=203 N=195 N=130 N=158 Fighting CVD ADOPT-A Clinical Trial *p0.0001 % Atrial Beats Paced* AF Suppression OFF 67.9 AF Suppression ON 92.9 Atrial Pacing Fighting CVD ADOPT-A Clinical Trial 5 (n = 122) 4.6
16、(n = 110) 90.4 (n = 2,180) 0 10 20 30 40 50 60 70 80 90 100 AF A Flutter Other Atrial Arrhythmias Atrial Arrhythmia Classification Atrial Arrhythmias (%) 随访时病人的心律失常 Fighting CVD ADOPT-A Clinical Trial 2.63% 1.73% 4.44% 1.37% 1.93% 3.19% 0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 3.0% 3.5% 4.0% 4.5% 5.0% 1-Month
17、3-Month 6-Month AF Burden (%) Follow up (n = 288) p 0.05 AFs OFF AFs ON 症状性 AF 负荷 Fighting CVD ADOPT-A Clinical Trial AFs OFF AFs ON Total Patients 158 130 Patients with AF Days 81 73 Total AF Days 682 421 Total Follow-up Duration (Days) 27,359 22,526 AF Burden 2.493% 1.869% AF Burden Reduction 25.0
18、3%， P 0.05 AF负荷 减少 Fighting CVD ADOPT-A Clinical Trial 0 1 2 3 4 5 6 7 8 9 10 6 Months Prior to Implant Implant to 6 Months Mean AF Episodes p 0.0001 8.1 4.2 8.3 4.1 4.3 11.5 3.2 8.5 AFs OFF AFs ON AF 事件的减少 Fighting CVD ADOPT-A Clinical Trial 88 90 92 94 96 98 100 0 30 60 90 120 150 180 Duration (Da
19、ys) (%) w/o Hospitalization* Freedom to first hospitalization (n = 288) 6% Reduction in Hospitalizations AFs OFF AFs ON p= NS 住院时间的减少 Fighting CVD ADOPT-A Clinical Trial Freedom from First Cardioversion (n=288) 降低了 63% 转复 90 92 94 96 98 100 0 30 60 90 120 150 180 (Duration) Days (%) w/o Cardioversio
20、n AFs OFF AFs ON p = 0.0925 Fighting CVD ADOPT-A Clinical Trial Event Classification AFs OFF AFs ON Lead Dislodgment 8 7 Pneumothorax 2 1 Myocardial Perforation 0 2 Cardiac Tamponade 0 1 System Infection 0 1 System Replacement 0 1 Total 10 13 并发症 Fighting CVD ADOPT-A Clinical Trial 死亡率 心衰时 主要的 死亡原 因
21、 (3 AFs ON, 3 AFs OFF) 没有与 AF相关 的死亡 原因 PATIENT DEATHS CAUSE OF DEATH AFs OFF AFs ON TOTAL Congestive Heart Failure 3 3 6 Unknown 1 1 2 Cerebral Vascular Accident 1 0 1 Cardiopulmonary Arrest 0 1 1 Chronic Obstructive Pulmonary Disease 0 1 1 Complication of Pericardiocentesis 1 0 1 Coronary Artery Di
22、sease 0 1 1 Pancreatic Cancer 0 1 1 Renal Shutdown 0 1 1 Respiratory Failure 0 1 1 Shock with Undetermined Etiology 0 1 1 Total 6 11 17 Fighting CVD ADOPT-A Clinical Trial 结论 AF Suppression 是安全的，并可以降低病窦 且伴有阵发性或持续性 AF的发病率。 AF Suppression 增加了 DDDR起搏器对房颤的 抑制作用。 Fighting CVD Prevention of Atrial Fibrill
23、ation by Overdrive Atrial Septum Stimulation OASES study Fighting CVD OASES Study 326 patients enrolled. 71 patients excluded. 9 patients with atrial flutter. 7 patients on permanent AF. 55 protocol violations. 255 patients in the study. Male: 106 Female: 149 Age: 70.1 18.2 years Fighting CVD 方 法 85
24、 patients Right Atrial Appendage Pacing + AF 85 patients Low Atrial Septum Pacing + AF 85 patients Control group Pacing without AF Fighting CVD 结 果 P= 0.027 P= 0.033 P= 0.027 P= 0.033 Fighting CVD 结 果 RAA: 76.0 36.0 38.9 39.5 p0.033 LAS: 74.1 29.9 22.0 18.6 p0.027 Control: 0.5 0.5 0.6 0.4 ns DAO OFF
25、 DAO ON P = 0.037 Fighting CVD 结 论 低位右心房间隔部位低位右心房间隔部位 +DAO ON的起搏模式的起搏模式 是最有效的降低阵发性房颤病人是最有效的降低阵发性房颤病人 AF负荷的负荷的 起搏治疗方式。起搏治疗方式。 提高了病人的生活质量。提高了病人的生活质量。 Fighting CVD AF Suppression 是圣犹达公司为起搏器病人设计的优越的动态心 房超速抑制功能，以预防阵发性和持续性房颤（ AF)，降低病人 AF的发生； 减少有症状的 AF病人的住院时间； 减少持续性 AF病人转复的痛苦； 减少房性心律失常或固定较高心房频率起波引起 的心悸，使病人
26、感觉更舒服。 Fighting CVD The Atrial Therapy Efficacy and Safety Trial ATTEST study Fighting CVD ATTEST研究 la prospective, randomized study lto evaluate preventive pacing and anti-tachycardia pacing (ATP) in patients with symptomatic AF or AT. lDDDRP (AT500, Medtronic) with three atrial preventive pacing a
27、lgorithms and two ATP algorithms l368 pts were randomized one-month post-implant to all prevention and ATP therapies ON or OFF and followed for three months. lThe AT/AF burden and frequency were determined from daily device counters in 324 patients. Values shown are the median plus the 25th to 75th
28、percentiles; patients did not receive an activator to log symptomatic episodes until the one-month visit; all atrial therapies were OFF during the run-in period. AF atrial fibrillation; AT atrial tachycardia. Lee et al. The Effect of Atrial Pacing Therapies on Atrial Tachyarrhythmia Burden and Frequ
29、ency JACC Vol. 41, No. 11, 2003 June 4, 2003:192632 Figure 3. Histogram of atrial tachycardia/atrial fibrillation episode duration. The median episode frequency in each duration band was compared between the ON and OFF groups, and no significant differences were observed (p 0.17). Lee et al. The Eff
30、ect of Atrial Pacing Therapies on Atrial Tachyarrhythmia Burden and Frequency JACC Vol. 41, No. 11, 2003 June 4, 2003:192632 Fighting CVD ATTEST研究结论 lThis DDDRP pacemaker is safe, has accurate AT/AF detection, and provides ATP with 54% efficacy as defined by the device. lThe atrial prevention and te
31、rmination therapies combined did not reduce AT/AF burden or frequency in this patient population. Fighting CVD DAPPAF研究 lTo compare the safety, tolerance and effectiveness of overdrive high right atrial (RA),dual-site RA and support (DDI or VDI) pacing (SP) in patients with symptomatic atrial fibril
32、lation (AF) and bradycardia, and to determine optimal pacing methods for AF prevention. l 118 pts were randomized to each of three pacing modes in a crossover trial. Figure 1. (A) Freedom from crossover within 4.5 months of entering randomized treatment phase for each pacing mode. Dual right atrial
33、(RA) pacing shows a higher Proportion of pts able to remain in the randomized treatment mode as compared with other modes. Figure 1. (B) Freedom from all symptomatic AF in each randomized pacing mode in the entire study population. Dual RA pacing but not high RA pacing shows a trend to prolongation
34、of time interval to AF recurrence. Saksena et al. Improved Suppression of Recurrent Atrial Fibrillation With Dual-Site Right Atrial Pacing and Antiarrhythmic Drug Therapy JACC Vol. 40, No. 6, 2002 September 18, 2002:114050 Figure 2. Freedom from all symptomatic atrial fibrillation (AF) in each rando
35、mized pacing mode in study population receiving concomitant class 1 or 3 antiarrhythmic drugs (AAD on the left) or without concomitant drug therapy (AAD on the right). Dual right atrial (RA) pacing but not high RA pacing shows prolongation of time interval to AF recurrence as compared with support p
36、acing and a trend to prolongation as compared with high RA pacing in drug-treated patients. There is no difference in outcome in patients on any randomized pacing mode without concomitant drug therapy. Saksena et al. Improved Suppression of Recurrent Atrial Fibrillation With Dual-Site Right Atrial P
37、acing and Antiarrhythmic Drug Therapy JACC Vol. 40, No. 6, 2002 September 18, 2002:114050 Figure 3. Freedom from all symptomatic atrial fibrillation (AF) in each randomized pacing mode in study population receiving concomitant class 1 or 3 antiarrhythmic drugs with frequent (weekly events to two eve
38、nts in three months) AF at baseline. Dual right atrial (RA) pacing shows prolongation of time interval to AF recurrence as compared with high RA or support pacing in these patients. Saksena et al. Improved Suppression of Recurrent Atrial Fibrillation With Dual-Site Right Atrial Pacing and Antiarrhyt
39、hmic Drug Therapy JACC Vol. 40, No. 6, 2002 September 18, 2002:114050 Figure 4. Quality-of-life in the study population at baseline and in each randomized treatment mode for individual measures. Atrial fibrillation symptom checklist (paired analysis) in each randomized mode shows the benefits of bot
40、h overdrive pacing modes as compared with support pacing. Saksena et al. Improved Suppression of Recurrent Atrial Fibrillation With Dual-Site Right Atrial Pacing and Antiarrhythmic Drug Therapy JACC Vol. 40, No. 6, 2002 September 18, 2002:114050 Figure 5. Comparison of symptomatic or asymptomatic at
41、rial fibrillation (AF) events meeting high rate atrial (HRA) event detection criteria in the dual-site right atrial (RA) pacing or high RA pacing arms of the study. Data are presented as mean values per-day. A significant reduction in mean event frequency is observed for both AF end points in dual-s
42、ite RA pacing arm as compared with the high RA pacing arm, suggesting benefit with respect to both symptomatic and symptomatic AF. Saksena et al. Improved Suppression of Recurrent Atrial Fibrillation With Dual-Site Right Atrial Pacing and Antiarrhythmic Drug Therapy JACC Vol. 40, No. 6, 2002 Septemb
43、er 18, 2002:114050 Fighting CVD DAPPAF研究结论 lDual-site RA is safe and better tolerated than high RA and SP. lIn patients on antiarrhythmics, dual-site RA prolonged and high RA trended to prolong time-to-recurrent AF compared with SP. lDual-site RA provides superior symptomatic and asymptomatic AF pre
44、vention compared with high RA in patients with symptomatic AF frequency of 1/week. Fighting CVD 总 结 l DDDR-DAO是安全并可以耐受的。 l 多数较大规模随机实验证实、但部分试验未能证实：起搏（ DAO）能够降低 病窦伴阵发性或持续性 AF患者日后 AF的发病率（没有获得一致性数据）。 l 很少资料支持对无症状心动过缓患者使用心房起搏来防治房颤的发生。 l 因此 ,2006年 ACC/AHA/ESC房颤治疗新指南指出 : 永久性起搏防治房颤还没有确切推荐指征 ; 对无心动过缓、不需植入起搏器的患者 ,不应考虑用起搏的方法来预防 房颤。 谢 谢 !
