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致心律失常性右室心肌病的临床电生理研究

The Clinical Electrophysiology Study of Arrhythmogenic Right Ventricular Cardiomyopathy

【作者】 陈文生

【导师】 张澍;

【作者基本信息】 北京协和医学院 , 心血管内科学, 2011, 博士

【摘要】 第一部分:心律失常性右室心肌病室性心动过速的诱发研究目的旨在探索在ARVC的电生理检查过程中,高频刺激与常规程序刺激对于诱发VT的对比研究并明确室速诱发的特点能否为ARVC的诊断提供价值。背景室性心动过速(室速,VT),尤其ARVC室速(ARVC-VT)是心律失常诊断和治疗中的一大难题。虽然特发性室性心律失常的机制研究和导管消融已取得一定突破,但在器质性室速的导管消融方面进展缓慢,很大程度上是由于对室速的病基、机制以及消融策略的研究尚处于初级阶段,尤其是在电生理研究中对于诱发室速、复制临床室速以及评价消融终点等仍存在较多分歧,有必要进一步研究如何提高临床室速的诱发率,为进一步研究室速的机制提供基础,评价电生理研究中诱发室速的方法、高频刺激和常规程序刺激对于VT的诱发率的比较以及在对照研究中评价诱发室速的频率、室速的形态、持续时间等特征对于ARVC室速诊断的价值。方法62例诊断为ARVC患者(男性46例,女性16例),年龄17~62(39±13.7)岁。将其随机分为两组:A组29例以常规程序刺激(包括S2、S3、S3三个期前刺激)和Burst刺激(≤240bpm)诱发VT;B组33例以高频Burst刺激方法来诱发ARVC-VT,其刺激频率为250-340bpm之间,从250bpm开始刺激,每次刺激较上次增加1 Obpm,直到心室不应期或达到340bpm。若上述2种方法仍不能诱发VT,静滴异丙肾后,再重复上述刺激。86例明确诊断为阵发性室上速(PSVT)的患者(男性51例,女性35例),年龄14-72(42±37.2)岁。排除器质性心脏病,随机分为A组46例,B组40例,进行射频消融术成功后即进行上述刺激。分别比较ARVC及PSVT两大组的室速诱发率(%),诱发出室速的形态,室速持续时间,以及比较2种不同方法(A和B)对于诱发室速的效能。结果两大类患者中均显示A组的诱发率明显高于B组,ARVC组较PSVT组更容易被高频刺激诱发出室速,且诱发出的VT形态多、持续时间长、室速发作时的频率快,差异具有显著性(P<0.001), PSVT组用A和B两种诱发方式对室速的诱发率、形态数量、VT持续时间、VT频率以及静滴异丙肾后各项指标之间均未见显著性差异。结论高频Burst刺激显然较低频分级Burst刺激以及常规程序刺激在诱发ARVC患者的室速中有较高的效能,为研究ARVC室速提供了有效的方法,且ARVC室速的诱发率、形态数量、VT持续时间、VT频率较无器质性心脏病者有显著性差异,可考虑作为一项诊断性参数辅助ARVC的诊断,筛选出需要干预的患者。第二部分:致心律失常性右室心肌病室速的动态基质标测研究背景室性心动过速是ARVC患者心源性猝死的主要原因。多数ARVC室速起源于异常的电生理病基,所以确定致心律失常病基有助于室速的定位和确定消融策略。非接触性心内膜激动标测系统(EnSite3000)可以进行ARVC室速的动态基质标测,确定室速传导的关键峡部从而指导制定合适的消融策略。方法本研究入选了62例致心律失常性右室心肌病患者,男性46例,女性16例。平均年龄39±13.7岁。其中20例患者有晕厥史或晕厥前症状,7例患者曾植入ICD。将多极矩阵电极(MEA)经左侧锁骨下静脉送至右室心尖部或经左/右侧股静脉途径送至右室流出道部位构建右室模型后,于右室心尖、流出道、游离壁、间隔部位分别在起搏和窦律下进行DSM标测;之后诱发室速,通过EnSite3000系统做动态基质标测,ARVC室速的机制主要包括:局灶性、微折返型和大折返型,局灶起源和微折返机制的VT多分布在低电压区,而三尖瓣环周围、右室流出道是大折返波阵面的主要传导区。消融方式根据标测结果决定,包括在VT起源点消融、异常病基的片状消融、环三尖瓣口、右室流出道的线性消融等。结果62例患者共诱发出138种室速,室速的平均频率为226±32.2bpm,室速频率范围从130bpm至310bpm。92种室速的频率大于200bpm。62例患者中有44例患者有2种以上的室速形态。于非接触式标测的指导下进行病基消融。即刻成功率为89%,其余的患者均获消融改善。结论在EnSite3000系统的指导下的动态基质标测有助于寻找VT的最早激动点,明确心动过速时腔内等电势图沿阻滞线、解剖屏障、慢传导区或病变组织的波形运动,能明确标记激动传导径路从而指导致心律失常性右室心肌病室速的消融。第三部分:致心律失常性右室心肌病室速射频消融的研究目的旨在探索非接触式标测指导下消融致心律失常性右室心肌病室速的有效性和安全性。背景心内非接触式标测提供一个快速而准确的等势图,从而有利于指导消融致心律失常性右室心肌病。方法32例致心律失常性右室心肌病患者,男性26例,女性6例。平均年龄37.2±13.8岁。这些患者均接受了射频消融手术。其中14例患者有晕厥史或晕厥前症状,另有2例患者曾植入ICD。结果32例患者共诱发出67种室速,室速的平均频率为210±32.2bpm,室速频率范围从130bpm至310bpm。42种室速的频率大于200bpm。32例患者中有24例患者有2种以上的室速形态。于非接触式标测的指导下,标出室速的最早激动点,行片状消融。平均随访28.6±16个月(9-72),无一例患者发作过晕厥或晕厥前症状,无一例患者死亡。手术无任何并发症。在随访结束时,81.3%的患者在不用药物的情况下,无室速发作,其余的患者均获得消融改善。结论在非接触式标测的指导下,致心律失常性右室心肌病快室速经片状消融后,可消除室速发生的病基,使室速难以诱发。未植入ICD的患者未出现心脏停搏或猝死,某些患者于消融后可能会出现延迟效应。

【Abstract】 PartⅠ:inducting ventricular tachycardia in patient with Arrhythmogenic right ventricular cardiomyopathyObjective:This study was aimed to compare the high-frequency stimulation to the conventional stimulation in patients with ARVC and VT, and evaluate ventricular tachycardia induction characters whether can be used to diagnose ARVC.Background:Ventricular tachycardia is a big puzzle for treatment in arrhythmia, especially for ARVC patients. Although we get great progress in idiopathic ventricular tachycardia about the mechanism and catheter ablation, however, the further stuy in catheter ablation for the structural ventricular tachycardia is limited, that is because the study about VT substrate, VT mechanism and ablation strategy are still in early stage, there are different argues about VT induction and ablation end point, so it is necessary to do further study how to improve the VT induction rate, which is the basis for VT mechanism study. This study was to evaluate the effect of the high-frequency stimulation and conventional stimulation in ARVC patients and the value of the VT rate, the VT morphology and the VT last time to diagnosis for ARVC.Methods Sixty two consecutive ARVC patients (46 males and 16 females) were enrolled in the study (ARVC group), the mean age was 39±13.7 years. They were assigned in a random fashion to two groups. The conventional stimulation (CS, up to 3 extrastimuli in 2 right ventricular sites, as well as incremental stimulation up to 240 bpm) was applied in group A (n=29), and the high-frequency stimulation (HS) was applied in group B (n=33). HS was started from 250 bpm with 1 to 1 capture for at least 4 seconds with a step of 10 bpm till the VT was induced or the 1 to 1 capture was lost. This procedure was repeated after the ablation of induced VT was completed in ARVC Isoproterenol was infused when it was needed.86 consecutive PSVT patients (51 males and 35 females) without structural disease were enrolled in control group (PSVT group). They were assigned in a random fashion to two groups to induce VT (group A and group B). And then compare the two stimulations in the PSVT group, the VT last time and the effect.Results The study indicated that the rate of VT induction was much higher in group A than group B. VT was easier to be induced in ARVC group than PSVT group. And the VT morphology, last time and rate had obviously difference (P<0.001) between ARVC and PSVT group, but there is no difference in PSVT group between these two different stimulations.Conclusion It is more effect for high-frequency stimulation than conventional stimulation in ARVC-VT patients. The VT morphology and last time and yield of ARVC-VT had obviously difference between the ARVC group and the PSVT group, so they can used to diagnose ARVC in early stage, and used for screening ARVC patients.PartⅡ:Dynamic substrate mapping ventricular tachycardias in arrhythmogenic right ventricular cardiomyopathyBackground:ventricular tachycardia (VT) is the major reason for sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. Most VTs originate from the abnormal substrate, so mapping the arrhythmogenic substrate can contribute to locate the target and choose the best ablation strategy. Non-contact endocardial activation mapping system (EnSite 3000) can perform dynamic substrate mapping for ARVC-VT, which is useful to find the critical isthmus, after that giving the best ablation strategy.Methods:Sixty two consecutive ARVC patients (46 males and 16 females) were enrolled in the study, the mean age is 39±13.7 years.20 patients had a history of syncope/presyncope,7 patients had an implantable ICD previously implanted. A multiple electrode array (MEA) catheter was positioned in the right ventricular (RV) through the left subclavian or femoral vein approach, after the geometry of RV was completed, pacing at right ventricular apex, right ventricular outflow tract, right ventricular free wall and right ventricular septum, and then performed DSM with these paced QRS and sinus rhthm QRS, VT induced after DSM.There were 3 kinds of mechanisms for ARVC-VT:focal, microreentrant, macroreentrant. Focal and microreent VT most located in low voltage area, macroreent most conduct through peritricuspid annulus and right ventricular outflow tract. Ablation strategy was determined by mapping result, such as ablation at origination, regional ablation abnormal substrate or linear ablation the peritricuspid annulus or right ventricular outflow tract.Results:One hundred and thirty eight VTs were induced in 62 ARVC patients, the mean VT rate was 226±32.2 bpm (130~310 bpm), there were 92 episodes of VT that had a heart rate≥200 bpm and 44 of 62 ARVC patients had≥2 morphologies of VT. Ablation the VT under the guidance of non-contact mapping with DSM, acute success was achieved in 89% (55/62) patients.While the rest patients achieved a modified success.Conclusions:under the guidance of non-contact mapping with DSM, the earliest activation of VT can be easily found, and it is clear to see the activation conduction, which help us to choose the best ablation strategy.Part III:Ablation ventricular tachycardia of arrhythmogenic right ventricular cardiomyopathyObjective:This study was aimed to estimate the safety and effective of ablation the ventricular tachycardia of arrhythmogenic right ventricular cardiomyopathy.Background:Intracardiac non-contact mapping provides a rapid and accurate isopotential mapping that facilitates catheter ablation of the ventricular tachyarrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods:Thirty-two consecutive patients (26 men and 6 women, mean 37.2±13.8 years) were treated with ablation. Fourteen patients had a history of syncope/pre-syncope. Two patients had an implantable cardiac defibrillator (ICD) previously implanted.Results:There were 67 ventricular tachycardias (VTs) induced in the 32 patients. The average VT rate was 210±32.2 (130-310) bpm. There were 42 episodes of VT that had a heart rate≥200 bpm and 24 of the 32 patients (75%) had≥2 morphologies of VT. Regional ablation was applied by targeting the earliest VT activation sites under the guidance of non-contact mapping. Acute success was achieved in 84.4% (27/32) patients, and significant improvement was seen in 15, 6%(5/32) patients as evidenced by a slower rate of VT. None of the patients experienced syncope/pre-syncope or sudden death during the 28.6±16 (9-72) month follow-up。There were no complications of the procedure. At the end of follow-up, 81.3% of the patients were free of VT without medication while the rest of the patients achieved a modified success.Conclusions:The rapid ventricular tachyarrhythmias in ARVC patients can be abolished or improved significantly by regional RF catheter ablation under the guidance of non-contact mapping. There was no sudden cardiac arrest or death in those patients without ICD implantation. Delayed efficacy may occur in some patients after ablation.

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