迷走神经刺激和乙酰胆碱灌注对心房肌电生理特性的影响

研究在体情况下迷走神经刺激(VNS)和乙酰胆碱(Ach)灌注对心房肌不同部位的电生理影响,并探讨其诱发心房颤动(AF)的机制。10只杂种犬自身随机对照,运用单相动作电位(MAP)记录技术,同步记录10只开胸犬的右心耳(RAA)、高位右房(HRA)、低位右房(LRA)、左心耳(LAA)、高位左房(HLA)、低位左房(LLA)的MAP,分别给予切断迷走神经、VNS、Ach灌注(分别做为对照组、VNS刺激组、Ach灌注组)后,观察诱发AF的情况和动作电位时程APD50、APD90和APD离散(dAPD)的变化。结果:10只犬在VNS刺激和Ach灌注同时,右心耳单一刺激分别有7只和6只犬诱发AF;VNS明显缩短APD50、APD90,其中RAA缩短最明显(APD50从72±5ms到19±4ms,APD90从136±7ms到43±5ms,P<0.001);Ach灌注也明显缩短APD50和APD90,与VNS相比,LLA的APD90缩短更明显(47±6msvs62±8ms,P<0.01);VNS明显升高心房肌APD50和APD90的离散(17±5msvs7±3ms,25±7msvs8±5ms,P<0.01)。结论:VNS和Ach灌注可引起APD缩短和离散升高,但影响的部位和程度稍有差异,都易诱发AF。     

心脏脂肪垫在肺静脉灶性放电引发心房颤动中的作用

探讨心脏脂肪垫在肺静脉灶性放电与心房颤动 (简称房颤 )中的作用。 14条狗麻醉后经右侧开胸暴露右侧肺静脉。将 8极电极标测导管缝在右上肺静脉用于起搏。另放一 8极电极导管固定在临近右肺静脉和左房交接处脂肪垫。术中监测ECG的II和aVR导联、血压和体温。以 0 .1ms刺激间期 ,2 0Hz刺激频率的直方波刺激脂肪垫的迷走神经丛 30～ 5 0s,随着电压从 1～ 4 .5V ,心率逐渐减少 (P <0 .0 5 ) ,同时出现房性早搏、房性心动过速和房颤。在刺激迷走神经丛的同时 ,以 2 0 0～ 80 0次 /分的频率刺激肺静脉 (对照组没有迷走神经丛刺激 )均能诱发房颤。在迷走神经丛刺激下 ,以S1S1330ms,S1S2 稍长于肺静脉不应期的配对间期刺激肺静脉诱发房颤。与对照组比较 ,在迷走神经刺激下 ,肺静脉刺激诱发房颤的房性早搏数 ,随着刺激电压从 0 .6到 3V的增加 ,从 7个减少到 2个 (P <0 .0 5 )。 7条狗局部去神经后 ,6条狗在同样肺静脉刺激诱发房颤的电压条件下不能诱发房颤 ,其中有 3条在电压大于 9V时诱发房颤。结论 :在临近右肺静脉和左房交接处脂肪垫刺激可以将肺静脉灶性放电转变成房颤。因此 ,临床上自发的迷走神经丛的张力增高是肺静脉灶性放电转变成房颤的基础。     

窦房结脂肪垫对犬右上肺静脉电生理特性影响的研究

目的研究不同水平刺激窦房结脂肪垫(SANFP)对右房(RA)及右上肺静脉(RSPV)的有效不应期(ERP)及心房颤动(简称房颤)诱发率的影响,探讨SANFP对房颤发生维持的作用。方法6只犬麻醉后经右侧开胸暴露RSPV及SANFP,以0.6～2,5,8mV三种不同电压强度水平、60ms频率刺激SANFP,同时以S1S2刺激观察三种水平下RA游离壁远、中、近端及RSPV远、中、近端ERP的变化;同样方法刺激SANFP以S1S1和S1S2程序刺激诱发房颤,测定房颤的诱发率。结果以5mV电压刺激窦房结脂肪垫RSPV近端ERP较基础时明显缩短(90±24msvs109±16ms,P<0.05),其房颤诱发率50%;以5,8mV电压刺激SANFP时RA游离壁近端、中端ERP变化较基础时明显缩短(96±20msvs117±14ms,65±20msvs117±14ms,P均<0.05),其房颤诱发率100%。结论窦房结脂肪垫可能在肺静脉起源的房颤的诱发和维持中起了重要作用。     

不同部位刺激诱发心房颤动时碎裂电位的出现与分布

目的 探讨在心房和肺静脉不同部位行电刺激诱发心房颤动（简称房颤）时碎裂电位（CFAEs）的出现与分布。方法 22只成年健康杂种犬,常规麻醉,气管插管,切断双侧颈迷走神经干,破坏颈交感神经节,建立动物的去自主神经模型。双侧开胸,分别在右心耳、左心耳和四支肺静脉的近、中、远段行电刺激诱发房颤,观察在基础刺激、双侧强迷走刺激两种诱发条件下,房颤发作时CFAEs的分布情况。结果 刺激诱发房颤的部位与CFAEs出现的部位并不完全一致。双侧心房（心耳）及肺静脉口附近是房颤时CFAEs出现的高频部位。当伴有迷走神经刺激时,房颤的诱发率提高,CFAEs的出现频率也随之明显增加。结论 房颤时CFAEs的分布并不局限于心房或肺静脉的某一局部区域,而是在多个部位可同时标测到。迷走刺激条件下标测到CFAEs的频率增加。     

Gradients of atrial refractoriness and inducibility of atrial fibrillation due to stimulation of ganglionated plexi

Introduction . The mechanism(s) whereby atrial ectopy induces atrial fibrillation (AF) is still poorly understood.
Methods and Results . In 12 dogs, we determined the refractory period (RP) along the right atrium (RA) and right superior pulmonary vein (RSPV), and AF inducibility with and without concurrent stimulation of the anterior right ganglionated plexi (ARGP) at the base of the RSPV. Multielectrode catheters were attached to the RSPV and RA with the distal electrodes close to ARGP. The RP and window of vulnerability (WOV), i.e., the longest S₁–S₂ minus the shortest S₁–S₂ at which AF was induced, were measured before and during incremental levels of ARGP stimulation. Mapping of the onset of AF was performed using the EnSite® mapping system (St. Jude Medical, St. Paul, MN, USA) positioned in the RA.
A single premature depolarization (PD) from the RSPV that did not induce AF without ARGP stimulation could do so with ARGP stimulation. The onset of AF consistently arose at the myocardium subtending the ARGP. With GP stimulation, the average WOV at the RSPV-atrial junction was significantly wider than at the RA appendage (65 ± 27 vs. 8 ± 17 msec, P < 0.05) or further along the RSPV sleeve (48 ± 39 vs. 10 ± 20 msec, P < 0.05). Even without GP stimulation, high intensity (10–20 mA) premature stimuli delivered at the RA appendage induced AF, originating from atrial tissue subtending the ARGP, presumably due to axonal conduction that activated the ARGP.
Conclusion . GP stimulation, subthreshold for atrial excitation, converts isolated PDs into AF-inducing PDs, suggesting that autonomic tone may play a critical role in the initiation of paroxysmal AF.     

Autonomically induced conversion of pulmonary vein focal firing into atrial fibrillation

OBJECTIVES: This study was designed to determine the mechanism(s) whereby focal firing from pulmonary veins (PVs) is converted into atrial fibrillation (AF). BACKGROUND: The mechanism(s) whereby PV focal firing or even a single PV depolarization is converted into AF is unknown. METHODS: In 14 anesthetized dogs a right thoracotomy was performed to expose the right superior pulmonary vein (RSPV). An octapolar electrode catheter was sutured alongside the RSPV so that the distal electrode pair was adjacent to the fat pad containing autonomic ganglia (AG) at the veno-left atrial (LA) junction. An acrylic plaque electrode on the fat pad allowed AG stimulation at voltages ranging from 0.6 to 4.0 V. Multi-electrode catheters were sutured to the atria with their distal electrode pairs at the fat pad-atrial junctions. Right superior pulmonary vein focal firing consisted of S(1)-S(1) = 330 ms followed by as many as 11 atrial premature depolarizations (APDs) (A(2)-A(12)) whose coupling interval just exceeded RSPV refractoriness. RESULTS: Autonomic ganglia stimulation, without atrial excitation, caused a reduction in heart rate (HR): control 142 +/- 15/min, 4.0 V; 75 +/- 30/min, p /=9.3 V. CONCLUSIONS: The effects of AG stimulation at the base of the RSPV can provide a substrate for the conversion of PV firing into AF.     

心脏血管内迷走神经丛刺激与阵发性心房颤动的动物模型制作

探讨心脏血管内迷走神经丛刺激与阵发性心房颤动 (简称房颤 )的动物模型制作。 32条Mongrel狗活体心脏大血管 :冠状窦、左右肺动脉、左房、上下腔静脉等处插入 7F蓝状电极进行迷走神经丛刺激 ,刺激频率为 2 0Hz,刺激间期 0 .1ms,刺激电压 1～ 4 0V ,刺激时间 30～ 5 0s。为了避免神经丛刺激直接对心房的影响 ,于刺激迷走神经丛的同时在P波后发放 2 0 0Hz、2 0～ 5 0ms的PS2 心房高频刺激 ,使迷走神经刺激落入心房的不应期。在这些心脏血管迷走神经丛刺激时减慢窦性心律 ,且减慢速度呈电压依赖。在一定的刺激强度下 ,窦性心律能够达到最大减低 (从75 0± 10 2ms至 15 6 0± 2 30ms) ,心房肌不应期显著缩短 (从 175± 13ms缩至 96± 2 3ms) ,同时出现房性早搏、房性心动过速和房颤 ,且重复性很好。应用 β 阻断剂 (esmolol1mg/kg)时 ,提高了房颤诱发域值 ;迷走神经阻断剂 (atropine1～ 2mg/kg)可以完全阻断房颤的诱发。结论 :蓝状电极非常有利于快速在静脉血管腔内找到迷走神经丛刺激位点 ;心脏大血管处存在迷走神经丛 ,刺激这些神经丛能够复制出与临床灶性阵发性房颤非常类同的房颤 ,迷走神经阻断剂可阻断这类房颤的诱发。     

Low-level vagosympathetic nerve stimulation inhibits atrial fibrillation inducibility: direct evidence by neural recordings from intrinsic cardiac ganglia

Intrinsic Cardiac Ganglia Activity Inhibited by Low‐Level Vagal Stimulation . Introduction: We hypothesized that low‐level vagosympathetic stimulation (LL‐VNS) can suppress atrial fibrillation (AF) by inhibiting the activity of the intrinsic cardiac autonomic nervous system (ICANS). Methods and Results: Wire electrodes inserted into both vagosympathetic trunks allowed LL‐VNS at 10% or 50% below the voltage required to slow the sinus rate or atrioventricular conduction. Multielectrode catheters were attached to atria, atrial appendages and all pulmonary veins. Electrical stimulation at the anterior right and superior left ganglionated plexi (ARGP, SLGP) was used to simulate a hyperactive state of the ICANS. Effective refractory period (ERP) and window of vulnerability (WOV) for AF were determined at baseline and during ARGP+SLGP stimulation in the presence or absence of LL‐VNS. Neural activity was recorded from the ARGP or SLGP. ARGP+SLGP stimulation induced shortening of ERP, increase of ERP dispersion and increase of AF inducibility (WOV), all of which were suppressed by LL‐VNS (10% or 50% below threshold) at all tested sites. Sham LL‐VNS failed to induce these changes. The effects of LL‐VNS were mediated by inhibition of the ICANS, as evidenced by (1) LL‐VNS suppression of the ability of the ARGP stimulation to slow the sinus rate, (2) the frequency and amplitude of the neural activity recorded from the ARGP or SLGP was markedly suppressed by LL‐VNS, and (3) the spatial gradient of the ERP and WOV from the PV‐atrial junction toward the atrial appendage was eliminated by LL‐VNS. Conclusions: LL‐VNS suppressed AF inducibility by inhibiting the neural activity of major GP within the ICANS. (J Cardiovasc Electrophysiol, Vol. 22, pp. 455‐463)     

Pulmonary vein encircling ablation alters the atrial electrophysiologic response to autonomic stimulation

Objective Pulmonary vein encircling ablation is often effective in the treatment of atrial fibrillation (AF). The success of the procedure does not depend upon creation of continuous lines of block. Thus mechanisms by which pulmonary vein encircling can cure AF remain unclear. Stimulation of cardiac autonomic ganglia alters atrial refractoriness and potentiates AF. We hypothesized that pulmonary vein encircling alters atrial autonomic function and that these alterations account in part for prevention of AF recurrences following ablation. Methods Atrial effective refractory periods (ERP) and AF inducibility were quantified in ten dogs before and during central autonomic nerve stimulation. Pulmonary vein encircling ablation was then performed and electrophysiologic testing repeated. In two dogs subjected to sham procedures measurements were repeated without performance of ablation. Hearts were examined histologically. Results Autonomic nerve stimulation led to decreased atrial refractoriness and increased AF inducibility and duration. Each of these effects were attenuated following pulmonary vein encircling (e.g., mean ERP decreased before (−23.7 ± 1.8, p < 0.001) but not after ablation (−2.3 ± 1.9, p = 0.25); AF inducibility increased by 26% before vs. 5% after ablation). No attenuation was seen in the sham operated animals. Histologic analysis following pulmonary vein encircling demonstrated destruction of some but not all autonomic ganglia. Conclusion Autonomic stimulation shortens atrial refractory periods and potentiates AF. Pulmonary vein encircling ablation partially destroys atrial autonomic inputs, attenuates the refractory period shortening effect of autonomic stimulation and decreases AF inducibility. Destruction of autonomic ganglia may contribute to the anti-fibrillatory effects of pulmonary vein encircling and warrants further investigation. Potential conflict of interest: PSS is a consultant to and receives grant support from Biosense Webster Research Support. This study was supported by a research alliance with Medtronic Inc., Minneapolis, MN.     

Inducibility of Atrial Fibrillation After GP Ablations and “Autonomic Blockade”: Evidence for the Pathophysiological Role of the Nonadrenergic and Noncholinergic Neurotransmitters

Autonomic Blockade and Atrial Fibrillation . Background: Recent clinical reports that used cholinergic and adrenergic blockade (CAB) as an alternative to ganglionated plexi (GP) ablation to terminate atrial fibrillation (AF) showed mixed results. We investigated the role of other neurotransmitters in AF inducibility. Methods: In 23 pentobarbital anesthetized dogs, a left and right thoracotomy allowed the attachment of electrode catheters to the left and right pulmonary veins and atrial appendages (AA). Programmed stimulation was used to determine the effective refractory periods (ERP) and AF inducibility, measured by the window of vulnerability (WOV). AF duration in response to acetylcholine (Ach; 100 mM) applied to the AA was measured before and after GP ablation + CAB and with vagus nerve stimulation (VNS). After GP ablation + CAB, Ach induced AF duration was determined in response to vasoactive intestinal peptide (VIP) and its specific antagonist ([Ac‐Tyr1,D‐phe2]‐VIP). Results: GP ablation + CAB significantly prolonged ERP, eliminated WOV, and suppressed the duration of Ach induced AF (P ≤ 0.01 for all). Also slowing of the heart rate by VNS was essentially blocked; however, with Ach 100 mM applied to the AA, VNS, and VIP applied to the AA markedly prolonged AF duration. This effect was blocked by the VIP antagonist. Conclusions: Neither GP ablation nor CAB can fully suppress AF inducibility arising from the atrial neural network. Our findings suggest that other neurotransmitters, such as VIP released during VNS, can promote sustained AF despite GP ablation and “autonomic blockade,” which may further define the substrate for AF outside the pulmonary vein‐atrial junctions. (J Cardiovasc Electrophysiol, Vol. 24, pp. 188‐195, February 2013)     

Evaluation of 3D guided electroanatomic mapping for ablation of atrial fibrillation in reference to CT-Scan image integration

Background  Anatomical guided atrial fibrillation (AF) catheter ablation relies on the assumption that the left atrium reconstruction anatomy (LARA) using a 3D mapping system precisely matches the patient’s CT scan anatomy (real anatomy). This study investigates whether this postulation is accurate using CT scan image integration. Patients and methods  Thirty consecutive patients (23 men, mean age = 51.9 ± 9.9 years) with symptomatic drug-refractory paroxysmal (n = 21) or persistent (n = 9) AF underwent a circumferential, 2 × 2, pulmonary vein (PV) radiofrequency (RF) ablation using the CARTOMERGE system. Left atrium (LA) anatomy was first reconstructed and RF design lines drawn on this LARA. After a CT-scan image of the LA was integrated into the 3D system, RF lesions were deployed 10 ± 5 mm outside the PV ostia (PVO) onto the CT-scan LA surface. The match between the actual RF lines and the RF design lines was analyzed off-line after catheter withdrawal. Results  Circumferential RF design lines were divided into four segments encircling both the right and left PVs. Design segments matched the actual RF segments in a proportion varying from 23% up to 83%. A mean of 2.8 ± 1.6 segments per patient were inaccurately designed that extended a mean of 3.8 ± 2.3mm inside the adjacent PV or 6.7 ± 1.8mm inside the left atrial appendage (LAA). Seven patients (23%) had four or more segments incorrectly designed. Conclusions  Our study reveals the inaccuracy of 3D anatomic guided RF ablation with respect to the LA anatomical structures that could be possibly improved when combined with CT-scan image integration.     

Clinical outcome of left atrial ablation for paroxysmal atrial fibrillation is related to the extent of radiofrequency ablation

Background  The exact mechanism of eliminating atrial fibrillation (AF) by catheter ablation techniques is not known. We investigated whether the extent of atrial damage conferred by radiofrequency lesions is a predictor of success after ablation, regardless of the method employed for ablation. Methods  Ninety consecutive patients with paroxysmal AF subjected to ostial–antral pulmonary vein isolation (n = 41) or circumferential (n = 49) catheter ablation were studied. Results  At 1 year follow-up, 16 out of 41 patients (39%) with ostial–antral ablation and 16 out of 49 patients (32.6%) with circumferential ablation had AF recurrences (p = 0.5). The mean duration of radiofrequency ablation lesions was statistically significantly shorter in patients with recurrence of AF compared to those with sinus rhythm 1 year after ablation (22.3 ± 4.2 min vs. 27.2 ± 4.5 min, respectively, p value < 0.001). Radiofrequency ablation time was inversely associated with the risk of recurrence of AF 1 year after ablation and this relationship remained even after adjustment for potential confounding factors such as age, sex, left atrial size, and type of ablation technique (ostial–antral or circumferential; HR  =  0.80, 95% CI: 0.72–0.87, p < 0.001). Conclusions  Duration of radiofrequency energy delivery is an independent predictor of clinical outcome at 1 year follow-up both among patients undergoing circumferential as well as ostial–antral ablation.     

Impact of “hybrid therapy” on long-term rhythm control and arrhythmia related hospitalizations in patients with drug-refractory persistent and permanent atrial fibrillation

Background Recently, a “hybrid therapy” strategy has been used for successful rhythm control in persistent and permanent atrial fibrillation (AF) patients. The impact of this strategy on arrhythmia recurrences and subsequent AF related hospitalizations are unknown. Materials and Methods Forty-seven patients (66 ± 10 years) with symptomatic persistent (N = 26) or permanent (N = 21) AF underwent “hybrid therapy” and were followed for 24 ± 15 months. All patients underwent linear right atrial ablation and implantation of pacemaker or atrioventricular defibrillator (AVICD) capable of continuous right atrial pacing with previously ineffective antiarrhythmic drug therapy for AF prevention. Device data-logs were used to monitor AF recurrences. Results Freedom from permanent AF was 97, 90, and 83% at 6 months, 2 and 3 years, respectively. Sixteen patients (34%) had no recurrent AF after “hybrid therapy.” Thirty-one patients (66%) had a total of 55 AF recurrences (mean 1.8 per patient). There was a significant reduction in the mean AF related hospitalizations (from 3.5 ± 2.8 to 0.57 ± 1.1 per patient), cardioversion hospitalizations (from 3.5 ± 2.2 to 0.38 ± 0.5 per patient) and DC cardioversions (from 3.1 ± 3.9 to 0.7 ± 0.5 per patient) after hybrid therapy compared to event rates before therapy (p < 0.05 for all). Conclusions Rhythm control improves significantly with hybrid therapy in patients with persistent and permanent AF refractory to drugs and cardioversion therapy. This improvement is associated with a significant reduction in AF related hospitalizations and need for cardioversion therapy.     

Induction of atrial fibrillation in mice by rapid transesophageal atrial pacing

Objective: Atrial fibrillation (AF) as an “indicator arrhythmia” for enhanced atrial vulnerability in mouse hearts has not yet been systematically examined. We therefore evaluated a transesophageal rapid atrial stimulation protocol for the induction of AF in C57Bl/6 mice. Methods: 40 C57Bl/6 mice (19 female and 21 male; 5.2 ± 2.1 months; 18 – 27 g) were examined by closed chest transesophageal atrial stimulation. Baseline ECG and electrophysiological parameters, AF-inducing stimulation cycle length (CL) and AF duration were analyzed. Results: The surface ECG demonstrated a significantly faster heart rate in female mice (R-R: 138.7 ± 19.9 ms versus 150.5 ± 15.7 ms, P < 0.05). AF was inducible in 90 % of the population and not inducible in 4 mice, all female (21 % in this subgroup). Mean induction CL was 27.4 ± 7.3 ms. Mean AF duration was 26.9 ± 42.6 s before spontaneous termination. In a subgroup of 4 female and 4 male mice (mean age 7.5 months), successive testing of AF induction showed a range of higher susceptibility to AF at stimulus amplitudes of 3.0 – 4.0 mA and stimulation CLs between 15 – 25 ms. AF induction was observed to be constantly reproducible in the individual animals. No correlation to pacing stimulus length and amplitude was found. Conclusions: This study demonstrates that it is possible to reproducibly induce self-terminating AF and supraventricular arrhythmias in mice by transesophageal atrial burst stimulation. The presented method allowing serial testings of the same animal can be a useful tool in further investigations with transgenic mice and might be helpful in the characterization of underlying genetic or molecular mechanisms of AF. Received: 26 April 2002, Returned for revision: 21 May 2002, Revision received: 17 June 2002, Accepted: 24 June 2002 Correspondence to: J. W. Schrickel, MD     

Is there an evidence of pulmonary vein stenosis following epicardial microwave ablation of atrial fibrillation?

Background  Surgical ablation techniques using microwave energy are an alternative to catheter based ablation therapy in the treatment of atrial fibrillation (AF). However, little is known about potential procedure-related complications. We investigate, whether there is evidence of pulmonary vein stenosis (PVST) in patients with atrial fibrillation undergoing epicardial microwave ablation. Methods  14 patients (ten males and four females) with AF and structural heart disease underwent cardiac surgery for the underlying disease and concomitant ablation of AF using microwave energy. In these patients with a mean age of 71 ± 8 years microwave energy was applied epicardially on the beating heart. Ablation was implemented using a flexible microwave tool with a 40 mm long tip to create isolation of the pulmonary veins. Each application was performed with 65 watt for 90 s. Follow-up was performed twice at a mean of 207 ± 73 days and 395 ± 102 days. Patients were evaluated by 12-lead-ECG and echocardiography. Multidetector helical computer tomographic (MDCT) imaging was done in seven patients to show morphology of the pulmonary veins. Results  On second follow-up 11 patients were seen. ECG showed sinus rhythm in six patients (55 %) and atrial fibrillation in five patients (45%). MDCT showed a moderate pulmonary vein stenosis (50–70%) in one patient. The patient did not suffer from palpitations, dyspnea, angina or syncope. Conclusions  Epicardial microwave ablation is an accepted treatment of atrial fibrillation. The procedure can be done off-pump on the beating heart. Nevertheless, pulmonary vein stenosis is a possible complication of this procedure, which should be kept in mind and evaluated during the follow-up.     

Antiarrhythmic effects of vasostatin-1 in a canine model of atrial fibrillation

Antiarrhythmic Effects of Vasostatin‐1 . Background: We examined the antiarrhythmic effects of vasostatin‐1, a recently identified cardioregulatory peptide, in canine models of atrial fibrillation (AF). Methods and Results: In 13 pentobarbital‐anesthetized dogs bilateral thoracotomies allowed the attachment of multielectrode catheters to superior and inferior pulmonary veins and atrial appendages (AA). Rapid atrial pacing (RAP) was maintained for 6  hours. Each hour, programmed stimulation was performed to determine the window of vulnerability (WOV), a measure of AF inducibility, at all sites. During the last 3  hours, vasostatin‐1, 33  nM, was injected into the anterior right (AR) ganglionated plexus (GP) and inferior right (IR) GP every 30  minutes (n = 6). Seven dogs underwent 6  hours of RAP only (controls). At baseline, acetylcholine, 100  mM, was applied on the right AA and AF duration was recorded before and after injection of vasostatin‐1, 33  nM, into the ARGP and IRGP. In separate experiments (n = 8), voltage–sinus rate response curves (surrogate for GP function) were constructed by applying high‐frequency stimulation to the ARGP with incremental voltages with or without vasostatin‐1. Vasostatin‐1 significantly decreased the duration of acetylcholine‐induced AF (11.0 ± 4.1 vs 5.5 ± 2.6 min, P = 0.02). The cumulative WOV (the sum of individual WOVs) significantly increased (P < 0.0001) during the first 3  hours and decreased toward baseline in the presence of vasostatin‐1 (P < 0.0001). Cumulative WOV in controls steadily increased. Vasostatin‐1 blunted the slowing of sinus rate with increasing stimulation voltage of ARGP. Conclusions: Vasostatin‐1 suppresses AF inducibility, likely by inhibiting GP function. These data may provide new insights into the role of peptide neuromodulators for AF therapy. (J Cardiovasc Electrophysiol, Vol. 23, pp. 771‐777, July 2012)     

Effect of Bachmann's bundle pacing on atrial fibrillation: electrophysiologic assessment

BACKGROUND: It has recently been reported that simultaneous multisite atrial pacing, Bachmann's bundle (BB) pacing, and coronary sinus (CS) pacing are useful for preventing the induction of atrial fibrillation (AF). HYPOTHESIS: We investigated whether a simple pacing approach via BB could reduce the induction of AF by extrastimuli (S2) from the right atrial appendage (RAA). METHODS: Programmed electrical stimulation was performed from the RAA and the area of BB at the superior aspect of the atrial septum, and bipolar recordings were obtained from the RAA, BB, and CS in 14 patients. RESULTS: In five patients, AF was induced with critically timed RAA-S2 delivered during RAA pacing. However, AF was not induced in any patient when RAA-S2 was delivered during BB pacing. The duration of the P wave during BB pacing was significantly shorter than that during RAA pacing and sinus rhythm (BB 80 +/- 16 ms vs. RAA 106 +/- 36 ms vs. sinus rhythm 100 +/- 24 ms, p < 0.05). The intra-atrial conduction time to the distal coronary sinus (CSd) caused by early S2 at the RAA was significantly reduced by BB pacing (BB 114 +/- 22 ms vs. RAA 157 +/- 35 ms, p < 0.001). CONCLUSION: Bachmann's bundle pacing reduces atrial conduction time caused by RAA-S2 and may be useful for preventing the induction of AF.     

Deferasirox (Exjade®) significantly improves cardiac T2* in heavily iron-overloaded patients with β-thalassemia major

Noninvasive measurement of tissue iron levels can be assessed using T2* magnetic resonance imaging (MRI) to identify and monitor patients with iron overload. This study monitored cardiac siderosis using T2* MRI in a cohort of 19 heavily iron-overloaded patients with β-thalassemia major receiving iron chelation therapy with deferasirox over an 18-month period. Overall, deferasirox therapy significantly improved mean ± standard deviation cardiac T2* from a baseline of 17.2 ± 10.8 to 21.5 ± 12.8 ms (+25.0%; P = 0.02). A concomitant reduction in median serum ferritin from a baseline of 5,497 to 4,235 ng/mL (−23.0%; P = 0.001), and mean liver iron concentration from 24.2 ± 9.0 to 17.6 ± 12.9 mg Fe/g dry weight (−27.1%; P = 0.01) was also seen. Improvements were seen in patients with various degrees of cardiac siderosis, including those patients with a baseline cardiac T2* of <10 ms, indicative of high cardiac iron burden. These findings therefore support previous observations that deferasirox is effective in the removal of myocardial iron with concomitant reduction in total body iron.     

Accuracy of integration of multislice computed tomography imaging into three-dimensional electroanatomic mapping for real-time guided radiofrequency ablation of left atrial fibrillation—Influence of heart rhythm and radiofrequency lesions

Circumferential radiofrequency ablation around the orifices of the pulmonary veins is a curative catheter-based therapy of paroxysmal and persistent atrial fibrillation (AF). Three-dimensional cardiac image integration is a promising new technology to visualize the complex left atrial anatomy and neighbouring structures. This study aimed to validate the accuracy of integrating multislice computed tomography (MSCT) into three-dimensional electroanatomic mapping (EAM) to guide radiofrequency catheter ablation (CA) of AF. Forty consecutive patients (34 male, mean age 56 ± 10 years) with multidrug-resistant AF underwent 16-slice MSCT 1 day before radiofrequency CA. MSCT data were processed and imported to the Carto™ EAM system. Using the CartoMerge™ Image Integration Module, the generated EAM was aligned with the MSCT images. An integrated statistical algorithm provided information about the accuracy of the fusion process. In every single patient, MSCT images could be aligned with the EAM. Mean distance between the EAM points (n = 63 ± 14) and the MSCT surface was 1.6 ± 1.2 mm with no difference between sinus rhythm versus AF (p = 0.145) and no distinction between patients in paroxysmal versus persistent/permanent AF despite a significant difference in left atrial diameters. An average of 388 ± 81 radiofrequency ablation points were taken within the procedures resulting in a mean distance of 2.3 ± 1.8 mm between the EAM points and the MSCT image after the ablation procedure. There was a significant difference of alignment accuracy before and after radiofrequency CA (p < 0.001). MSCT images can be accurately integrated into three-dimensional EAM. Pre-interventional cardiac rhythm does not influence the precision of fusion. Accuracy of fusion deteriorates after radiofrequency CA.     

Analysis of <Emphasis Type="Italic">in vivo</Emphasis> left atrial appendage morphology in patients with atrial fibrillation: a direct comparison of transesophageal echocardiography,planar cardiac CT,and segmented three-dimensional cardiac CT

Purpose  Recent development of percutaneous left atrial appendage (LAA) occlusion devices has underscored the need for an accurate understanding of LAA morphology and the interchangeability of results from differing imaging modalities. The purpose of this study is to assess LAA morphology and location in AF patients, directly comparing transesophageal echocardiography (TEE), planar cardiac computed tomography (CT), and three-dimensional segmented CT reconstructions. Methods  Fifty-three patients underwent adequate TEE and cardiac CT. Quantitative measurements of maximal LAA orifice diameters, widths, and depths were obtained from each imaging modality. Left atrial and LAA volumes were measured using segmented CT. Results  The mean LAA orifice diameter for segmented CT, planar CT, and TEE was 28.5 ± 4.5, 26.3 ± 4.1, and 26.1 ± 6.4 mm, respectively. Conclusions  LAA orifice measurements among these imaging modalities are not interchangeable. This difference may be clinically significant because of the need for accurate sizing of LAA occlusion devices. Use of preprocedural segmented CT may improve initial device sizing.