Spatially distributed dominant excitation frequencies reveal hidden organization in atrial fibrillation in the Langendorff-perfused sheep heart

INTRODUCTION: Atrial fibrillation (AF) is characterized by complex wave propagation, yet periodic excitation suggesting a high degree of organization may be revealed during sustained AF. We provide a systematic quantification of the spatial distribution of dominant frequencies (DFs) of local excitation on the epicardium of the right atrial (RA) free wall and left atrial (LA) appendage of the isolated sheep heart during AF. The data reveal, for the first time, hidden organization, independent of the activation sequences or nature of electrograms. METHODS AND RESULTS: In 13 Langendorff-perfused sheep hearts, AF was induced in presence of 0.1 to 0.6 microM acetylcholine. Video movies (potentiometric dye di-4-ANEPPS) of the RA and LA (>30,000 and >20,000 pixels, respectively) were obtained at 120 frames/sec and a biatrial electrogram was recorded. Spectral analyses were performed on movies with DF maps constructed. During AF, the activity formed stable discrete domains with uniform DFs within each domain. Acceleration of AF increased the number of domains (R = 0.81, P < 0.0001) and the DF variance (R = 0.63, P < 0.001), indicating a decrease in organization. Also, the LA was faster and more homogeneous, with smaller number of DF domains, compared to the RA (P < 0.00001). CONCLUSION: In this model, AF is characterized by multiple domains with distinct DFs on the atrial epicardium. The decrease in domain area with increased rate suggests that AF results from high-frequency impulses that undergo spectral transformations. The LA is generally faster and more organized than the RA, suggesting that the sources for the impulses are localized to the LA.     

Frequency analysis in different types of paroxysmal atrial fibrillation.

OBJECTIVES: This study sought to investigate the regional frequency distribution from multiple bi-atrial sites in different types of paroxysmal atrial fibrillation (AF). BACKGROUND: A previous study showed a left atrium (LA) to right atrium (RA) frequency gradient in patients with paroxysmal AF. METHODS: Forty-four patients (age = 60 +/- 16, male patients = 27) with paroxysmal AF originating from the pulmonary veins (PVs) (n = 31) or superior vena cava (SVC) (n = 13) were included. Frequency analysis was performed on the intracardiac electrograms (7 s, 1 kHz/channel) recorded from PV, posterior LA, coronary sinus (CS), posterolateral RA, and SVC. The largest peak frequency was identified as the dominant frequency (DF). RESULTS: In the PV-AF patients, there was a frequency gradient from the PV ostium to the LA, RA, and SVC (8.5 +/- 3.3 Hz vs. 5.9 +/- 1.1 Hz vs. 5.2 +/- 0.85 Hz vs. 5.5 +/- 0.48 Hz, respectively, p < 0.001). The highest DFs were mostly located at the arrhythmogenic PV ostium (58%). The DFs of the arrhythmogenic PV and PV ostium were significantly higher than those of the non-arrhythmogenic PVs and PV ostia (p < 0.05). In the SVC-AF patients, there was a frequency gradient from the SVC to the RA, LA, and PV (8.0 +/- 2.4 Hz vs. 5.9 +/- 1.1 Hz vs. 5.9 +/- 0.7 Hz vs. 5.8 +/- 0.7 Hz, respectively, p = 0.001). The highest DFs were mostly located inside the SVC (77%) instead of the SVC ostium (as compared with PV-AF patients, p = 0.035). CONCLUSIONS: The location of the highest DF depended on the arrhythmogenic PV or SVC. A frequency gradient was present between the arrhythmogenic thoracic vein and atrium in all patients.     

Changes in I K, ACh single-channel activity with atrial tachycardia remodelling in canine atrial cardiomyocytes

AIMS: Although atrial tachycardia (AT) remodelling promotes agonist-independent, constitutively active, acetylcholine-regulated K+-current (I K,ACh) that increases susceptibility to atrial fibrillation (AF), the underlying changes in I K,Ach channel function are unknown. This study aimed to establish how AT remodelling affects I K,ACh single-channel function. METHODS AND RESULTS: I K,ACh single-channel activity was studied via cell-attached patch-clamp in isolated left atrial cardiomyocytes of control and AT (7 days, 400 min(-1)) dogs. Atrial tachycardia prolonged the mean duration of induced AF from 44 +/- 22 to 413 +/- 167 s, and reduced atrial effective refractory period at a 360 ms cycle length from 126 +/- 3 to 74 +/- 5 ms (n = 9/group, P < 0.001). In the absence of cholinergic stimulation, single-channel openings with typical I K,ACh conductance and rectification properties were sparse under control conditions. Atrial tachycardia induced prominent agonist-independent I K,ACh activity because of increased opening frequency (fo) and open probability (Po: approximately seven- and 10-fold, respectively, vs. control), but did not alter open time-constant, single-channel conductance, and membrane density. With maximum I K,ACh activation (10 micromol/L carbachol), channel Po was enhanced much more in control cells ( approximately 42-fold) than in AT-remodelled myocytes (approximately five-fold). The selective Kir3 current blocker tertiapin-Q (100 nmol/L) reduced fo and Po at -100 mV by 48 and 51%, respectively (P < 0.05 for each), without altering other channel properties, confirming the identity of I K,ACh. Atrial tachycardia had no significant effect on mRNA or protein expression of either of the subunits (Kir3.1, Kir3.4) underlying I K,ACh. CONCLUSION: Atrial tachycardia increases agonist-independent constitutive I K,ACh single-channel activity by enhancing spontaneous channel opening, providing a molecular basis for AT effects on macroscopic I K,ACh observed in previous studies, as well as associated refractoriness abbreviation and tertiapin-suppressible AF promotion. These results suggest an important role for constitutive I K,Ach channel opening in AT remodelling and support its interest as a potential target for AF therapy.     

Differential densities of muscarinic acetylcholine receptor and I(K,ACh) in canine supraventricular tissues and the effect of amiodarone on cholinergic atrial fibrillation and I(K,ACh)

BACKGROUND: Vagal nerve plays an important role in the induction and maintenance of atrial fibrillation (AF). This study investigated the differential densities of M2 receptor and acetylcholine-induced inward rectifier K+ current (I(K,ACh)) in atrial appendage, atrium, pulmonary vein (PV) and super vena cava (SVC) to discuss the role of atrial appendage and PV in cholinergic AF. METHODS AND RESULTS: In 10 dogs, action potential duration was determined at 24 sites during bilateral cervical vagal stimulation and amiodarone administration. AF could be induced at first in right atrial appendage (RAA) and right atrium (RA) without left atrial appendage (LAA) and left atrium (LA). Amiodarone decreased the initiation of AF in vivo. Western blot and patch clamp were used to determine M2 receptor and I(K,ACh) in RAA, LAA, RA, LA, PV and SVC. The densities of M2 receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PV and SVC (21.34 +/- 0.92 vs. 8.24 +/- 0.45 pA/pF, p < 0.05). Furthermore, the densities of the M2 receptor and I(K,ACh) in LAA and RAA were higher than that in LA (21.34 +/- 0.92 vs. 14.17 +/- 0.65 pA/pF, p < 0.05). After amiodarone administration, densities of I(K,ACh) in LA and RA were not different, but densities of I(K,ACh )were also less in atrium than in atrial appendage. CONCLUSIONS: Densities of the M2 receptor and I(K,ACh) are higher in atrial appendage than other sites. Atrial appendage perhaps plays an important role in initiation of cholinergic AF. However, PV and SVC less often play an important role in vagotonic paroxysmal AF. Reduced dispersion of I(K,ACh) is the mechanism for amiodarone to therapy AF.     

Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is associated with extracellular matrix remodeling involving atrial fibrosis and atrial dilatation. Angiotensin II mediated pathways and matrix metalloproteinases (MMPs) have been implicated in these processes. Our aim was to study atrial structural remodeling and the expression of the angiotensin receptor subtypes and MMPs and their inhibitors (TIMPs) in patients with mitral valve disease with and without AF. METHODS AND RESULTS: Biopsies from right and left atrial appendages (RA and LA) were taken from patients undergoing CABG (n=9, all in sinus rhythm (SR)) or mitral valve surgery (MVS; n=19; 9 with permanent AF and 10 in SR). Patients with MVS and AF had significantly larger atria (versus MVS and SR: p=0.02; versus CABG: p<0.01). The MVS patients had significantly more fibrosis than the control CABG group. Fibrosis was increased in both the AF and SR MVS groups in the LA, but only in the MVS-AF group in the RA. These AF patients had significantly more tricuspid regurgitation than SR patients. MMP-1 was down-regulated in LA of MVS patients (p=0.02) independent of the underlying rhythm (SR or AF; p=0.95). In RA biopsies, MMP-1 was down-regulated only in the MVS and AF group. MMP-9 was down-regulated in the MVS patients compared to CABG both in the RA and LA, and without a difference between the SR and AF groups. Protein expression of AT-1, AT-2, MMP-2, TIMP-1, -2 and -4, TNF-alpha, and TNF-alpha-converting enzyme did not differ significantly between the 3 groups. CONCLUSIONS: Concordant changes between MMP-expression and fibrosis during mitral valve disease, both in LA and RA, suggest involvement of MMPs in structural atrial remodeling. AF itself did not contribute to altered fibrosis or MMP-expression in the LA. The association between AF and RA changes may be precipitated by greater hemodynamic load due to tricuspid regurgitation in these patients.     

心力衰竭犬心房组织MMP-2和TIMP-1、2的基因表达及其与心房扩大及心房颤动的关系

目的探讨心力衰竭(简称心衰)犬心房组织基质金属蛋白酶-2(MMP-2)及其组织抑制因子1、2(TIMP-1、2)的基因表达及其与心房扩大及心房颤动(简称房颤)发生维持的关系。方法选健康成年杂种犬14只随机分为心室快速起搏致心衰组和对照组,采用Burst刺激诱发房颤,逆转录-聚合酶链式反应技术和免疫组化方法检测两组左右心房组织MMP-2和TIMP-1、2的mRNA和蛋白表达,采集心房标本前超声心动图测定左右心房收缩末期面积。结果心衰组左室射血分数下降、房颤的诱发和维持时间增加,左右心房均扩大。MMP-2的mRNA和蛋白表达在左右心房中均上调;TIMP-2的mRNA在左右心房中无明显改变,但MMP-2/TIMP-2的mRNA和蛋白的比值在左右心房中均升高(P<0.01);TIMP-1的mRNA和蛋白表达在左右心房中均下调。心衰组,房颤持续时间与左房面积呈正相关。结论心房组织MMP-2和TIMP-1、2的基因表达改变以及MMP-2/TIMP-2表达失衡可能是心衰时心房扩大及房颤发生与维持的分子机制之一。     

Neural mechanism of atrial fibrillation: insight from global high density frequency mapping

Frequency Mapping During Neurally Mediated AF. Background: It has been demonstrated that intrinsic cardiac autonomic activation of ganglionated plexi (GPs) exhibits a frequency gradient from the center to the periphery with limited mapping. Objective: We aimed to use a global mapping tool (Ensite Array) to identify the frequency distribution and clarify the interaction between the extrinsic/intrinsic autonomic systems. Methods: A mid sternal thoractomy was performed in anesthetized dogs. High frequency stimulation (20 Hz, 0.1 ms duration) was applied to locate the GPs and achieve vagosympathetic stimulation (VNS). There were 4 major GPs, which were located near the 4 pulmonary vein (PV) ostia, and a third fat pad (SVC‐Ao) GP that was located near the superior vena cava (SVC)‐right atrial (RA) junction. Results: Without VNS (n = 12), the left atrial (LA) mean (8.20 ± 0.11 vs 7.95 ± 0.30 Hz, P = 0.04) and max (9.86 ± 0.28 vs 9.43 ± 0.29 Hz, P = 0.03) DFs were higher during the PV ostial GP stimulation than the SVC‐Ao GP stimulation. The LA max DFs were located not only at the primary GPs but also the nearby secondary PV ostial GPs. The RA mean DF (8.36 ± 0.05 vs 7.99 ± 0.19 Hz, P = 0.04) was higher during SVC‐Ao GP stimulation than PV ostial GP stimulation. The max DF was located inside the SVC during SVC‐Ao GP stimulation and at the RA septum during PV ostial GP stimulation. With VNS (n = 12), the LA mean and max DFs between the PV ostial and SVC‐Ao GP stimulation were similar. The DF distribution shifted to non‐GP LA sites during both the PV ostial and SVC‐Ao GP stimulation. Conclusion: The findings indicate that the AF was caused by an interaction between the PV ostial GPs during intrinsic autonomic stimulation, whereas the non‐GP LA sites were responsible for the AF induced by an extrinsic neural input. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1049‐1056, September 2011)     

风湿性心脏瓣膜病心房颤动患者心房结构重构及胶原的表达

目的检测风湿性心脏瓣膜病心房颤动患者心房结构重构及胶原的表达,探讨胶原在心房结构重构中的意义。方法选择行开胸心脏手术的风湿性心脏瓣膜病患者39例,将持续性心房颤动患者24例为房颤组,窦性心律患者15例为窦律组。取患者心房组织标本,应用HE染色及Masson染色进行组织学检查;免疫组织化学法检测心房组织中Ⅰ型、Ⅲ型胶原蛋白的表达。结果房颤组患者较窦律组左心房内径明显增大。房颤组患者心房有肌溶解、心肌肥厚及广泛间质纤维化的改变。与窦律组比较,房颤组患者的左、右心房组织胶原容积分数均明显增大,左、右心房Ⅰ型胶原蛋白的表达明显增加(P0.05),而Ⅲ型胶原蛋白表达无明显差异(P0.05)。结论心房颤动患者心房结构发生明显的病理改变,其中心房间质纤维化为主要特征,左心房改变最为明显。     

Frequency gradients during two different forms of fibrillation in the canine atria.

BACKGROUND: Atrial fibrillation (AF) is thought to be sustained by multiple reentrant wavelets or firing foci. OBJECTIVE: The aim of this study was to compare the spectral domain characteristics in the left atrium (LA) and right atrium (RA) in two different models of AF. METHODS: Rectangular 8 x 14 electrode arrays were placed on the LA and RA of 14 anesthetized dogs. AF episodes were induced with burst pacing and aconitine in each dog. For each model, AF was induced from the RA in six dogs and from the LA in six dogs. Dominant frequencies (DFs) were obtained using the fast Fourier transform of the unipolar recordings obtained from each electrode of the array. Standard deviation (SD) was used to compute the frequency dispersion within an atrium. Regularity of the signal was quantified using an organization index (OI). RESULTS: DFs were largest in the atrium where aconitine was applied. Aconitine AF had larger gradients than burst-pacing AF (5.0 +/- 4.5 vs. 0.9 +/- 1.0 Hz: P <.006). Aconitine AF when compared with burst-pacing AF had greater absolute LA-RA differences in the SD of DFs (2.3 +/- 1.9 vs. 0.2 +/- 0.2 Hz; P <.001) and in OI (0.11 +/- 0.07 vs. 0.06 +/- 0.07; P <.07). CONCLUSIONS: Differences in frequency gradients and organization were observed during AF induced by burst pacing and aconitine. This suggests that different mechanisms of AF are possible and may be identified with frequency domain analysis.     

Potential ionic mechanism for repolarization differences between canine right and left atrium

Experimental and clinical evidence suggests a critical role for the left atrium (LA) in atrial fibrillation (AF). In animal models, repolarization is faster in the LA than in the right atrium (RA), leading to more stable reentry circuits with a shorter intrinsic period in the LA. The ionic mechanisms underlying LA-RA repolarization differences are unknown. Therefore, we evaluated ionic currents and action potentials (APs) with the whole-cell patch clamp in isolated canine atrial myocytes. The density of the rapid delayed rectifier current (I(Kr)) was greater in the LA (eg, 1.83+/-0.10 pA/pF at +20 mV) than in the RA (1.15+/-0.07 pA/pF, P<0.01; n=16 cells per group). The slow and ultrarapid delayed rectifier, the inward rectifier, L-type Ca(2+), and transient outward K(+) currents were all comparable in the LA and RA. There were no differences in kinetic or voltage-dependent properties of currents in LA versus RA. Western blots of ether-a-go-go-related gene (ERG) protein in three RA and corresponding LA regions showed significantly greater ERG expression in LA. AP duration (APD) was shorter in the LA versus RA in both isolated cells and multicellular preparations, and the effective refractory period (ERP) was shorter in the LA compared with the RA in vivo. Dofetilide had significantly larger APD- and ERP-increasing effects in the LA compared with RA, and LA-RA repolarization differences were eliminated by exposure to dofetilide. We conclude that LA myocytes have larger I(Kr) than do RA myocytes, contributing importantly to the shorter APD and ERP in LA. The larger LA I(Kr) may participate in the ability of the LA to act as a "driver region" for AF, with potentially important implications for understanding AF mechanisms and antiarrhythmic therapy.     

心房肌复极的电整复性与阵发性心房颤动发生机制的实验研究

目的 研究在体犬左、右心房肌的电整复性即动作电位时程整复性(APDR),观察其与阵发性心房颤动(房颤)发生的潜在机制.方法 使用单相动作电位技术记录14只犬左、右心房复极达90%的动作电位时程(APD_(90)),并通过S_1S_2程序刺激,观察APDR变化,即每一个舒张间期与刺激后发生心房肌复极APD_(90)的关系,并观察房颤的诱发情况.结果 APD_(90)左心房为(157.4±43.5)ms明显小于右心房(170.9±37.9)ms,P<0.05.心房肌在S_1S_2递减程序刺激下,左心房与右心房具有不同斜率的APDR曲线,左心房的APDR曲线斜率1.3±0.4大于右心房0.9±0.3,P<0.05.进行心房快速起搏S_1S_2刺激时,14只犬中共诱发出18阵房颤,其中左心房刺激发作12阵,明显多于右心房6阵(P<0.05).结论 左、右心房间具有单相动作电位时程的异质性及APDR不均一的复极特性,是诱发折返、发生和维持房颤的基质之一.     

Dynamics of wavelets and their role in atrial fibrillation in the isolated sheep heart

BACKGROUND: The multiple wavelet hypothesis is the most commonly accepted mechanism underlying atrial fibrillation (AF). However, high frequency periodic activity has recently been suggested to underlie atrial fibrillation in the isolated sheep heart. We hypothesized that in this model, multiple wavelets during AF are generated by fibrillatory conduction away from periodic sources and by themselves may not be essential for AF maintenance. METHODS AND RESULTS: We have used a new method of phase mapping that enables identification of phase singularities (PSs), which flank individual wavelets during sustained AF. The approach enabled characterization of the initiation, termination, and lifespan of wavelets formed as a result of wavebreaks, which are created by the interaction of wave fronts with functional and anatomical obstacles in their path. AF was induced in six Langendorff-perfused sheep hearts in the presence of acetylcholine. High resolution video imaging was utilized in the presence of a voltage sensitive dye; two-dimensional phase maps were constructed from optical recordings. The major results were as follows: (1) the critical inter-PS/wavelet distance for the formation of rotors was 4 mm, (2) the spatial distribution of wavelets/PSs was non-random. (3) the lifespan of PSs/wavelets was short; 98% of PSs/wavelets existed for < 1 rotation, and (4) the mean number of waves that entered our mapping field (15.7 +/- 1.6) exceeded the mean number of waves that exited it (9.7 +/- 1.5; P < 0.001). CONCLUSIONS: Our results strongly suggest that multiple wavelets may result from breakup of high frequency organized waves in the isolated Langendorff-perfused sheep heart, and as such are not a robust mechanism for the maintenance of AF in our model.     

The mechanisms of an increased dominant frequency in the left atrial posterior wall during atrial fibrillation in acute atrial dilatation

BACKGROUND: Previous studies have shown that the highest dominant frequency (DF) is located in the left atrium (LA) during atrial fibrillation (AF) in pacing-induced AF. However, there have been few studies on the mechanisms of the increased DF of AF during acute atrial dilatation. The purpose of this study was to investigate the mechanisms of the increased maximal DF (max DF) in pacing-induced AF during acute atrial dilatation. METHODS: In eight Langendorff-perfused canine hearts (26 +/- 2 kg), noncontact balloon catheters were placed into the right atrium (RA) and LA, respectively. AF was induced by extrastimulation pre- and postdilatation in the atrium (0 and 15 cm H(2)O, respectively). Fast Fourier transformation analysis was performed to analyze the max DF and harmonic index (HI) from the bi-atrial unipolar virtual electrograms during AF. The fibrillation cycle lengths were obtained from different atrial sites. The number of wavefronts was analyzed during AF. The frequency of regional splitting was defined as the number of wavefront splits per second in different atrial regions during AF. The percentage of the low-voltage zones (<0.5 mV) was defined as the ratio of the area of the low-voltage zones to the total atrial surface area. RESULTS: The DF was measured during AF. The shortest fibrillation cycle length was located in the LA posterior wall and became shorter during acute atrial dilatation. The max DF was located in the LA posterior wall and increased during acute atrial dilatation (7.1 +/- 0.8 vs 8.8 +/- 2.1, P = 0.02). The max DF of the LA correlated with the wavefront number (r = 0.797, P < 0.001 predilatation; r = 0.860, P < 0.001 postdilatation). The splitting of wavefronts facilitated the formation of new wavefronts. During acute atrial dilatation, the frequency of regional splitting was closely correlated with the percentage of the low-voltage zones (r = 0.876, P < 0.001). Furthermore, the LA posterior wall had a higher percentage of the low-voltage zones than the other sites. CONCLUSION: In acute atrial dilatation, the percentage of the low-voltage zones increased, especially in the LA posterior wall, which correlated with the regional splitting of the AF wavefronts. The increase in the splitting facilitated the formation of new wavefronts and resulted in a higher max DF during acute atrial dilatation.     

Importance of right and left atrial dilation and linear ablation for perpetuation of sustained atrial fibrillation

INTRODUCTION: Atrial dilation associated with increasing atrial pressure plays an apparent role in the development of atrial fibrillation (AF). We characterized a new model of separate and biatrial dilation in the Langendorff-perfused rabbit heart. The aim of this study was to examine if sustained AF in this model (1) would be inducible by separate right atrial (RA) and left atrial (LA) dilation; (2) would be reproducibly inducible at the same pressure level; and (3) could be suppressed by RA, LA, or biatrial ablation. METHODS AND RESULTS: Intra-atrial pressure was increased stepwise in the RA (n = 13), LA (n = 12), or both atria (n = 25) until sustained AF could be induced or a pressure of 20 cm H2O was reached. The stimulation protocol was repeated once in RA and LA dilation (n = 9) and three times in biatrial dilation (n = 7). Then, RA orifices (superior and inferior caval veins, tricuspid valve annulus, and foramen ovale) or LA orifices (pulmonary veins, mitral valve annulus, and foramen ovale) were connected by radiofrequency (RF) lesions. Sustained AF was rendered inducible in 100% of hearts with biatrial dilation, but in only 92% of hearts with RA dilation and 67% with LA dilation. Inducibility of sustained AF was reproducible. Under biatrial dilation, not RA ablation (0/10 hearts; P = NS) but LA ablation (4/11 hearts; P < 0.05) and biatrial ablation (16/21; P < 0.01) reduced the inducibility of sustained AF. CONCLUSION: The inducibility of sustained AF due to increased intra-atrial pressure differs between the RA and LA. LA and biatrial lesions, not RA RF lesions, reduce the ability to perpetuate sustained AF.     

Biatrial substrate properties in patients with atrial fibrillation

Introduction: The atrial substrate plays an important role in the maintenance of atrial fibrillation (AF). Further investigation of the biatrial substrate may be helpful for understanding the mechanism of AF. The aim of this study was to investigate the properties of right and left atrial (RA and LA) substrate in AF patients and their impact on the catheter ablation.
Methods: Biatrial electroanatomic mapping using a three-dimensional mapping system (NavX) was performed in 117 consecutive patients with paroxysmal (n = 99) and persistent (n = 18) AF. The biatrial voltage and total activation time (TAT) were obtained during sinus rhythm.
Results: The LA had a lower voltage (1.6 ± 0.5 vs 2.0 ± 0.6 mV, P < 0.001) than the RA. The TAT correlated with the voltage (r =–0.65, P< 0.001). The patients with persistent AF had a lower atrial voltage, higher coefficient of variance for the LA voltage, longer LA TAT, and more extensive scar than those with paroxysmal. The patients with recurrent AF after catheter ablation had a lower LA voltage and higher incidence of LA scarring than those without recurrence. A scar located in the low anteroseptal or low posterior wall of LA was related to recurrence of AF. LA scarring was the independent predictor of AF recurrence after catheter ablation.
Conclusion: The LA voltage was lower than the RA, and the atrial voltage correlated with the TAT. Electroanatomical remodeling of the atria could be crucial to the maintenance of AF. The LA substrate properties may play an important role in the recurrence of AF after catheter ablation of AF.     

Remodeling of atrial dimensions and emptying function in canine models of atrial fibrillation.

OBJECTIVES: Atrial tachycardia-induced remodeling (ATR) and ventricular tachypacing-induced heart failure (HF) create experimental substrates for atrial fibrillation (AF), and both have been reported to produce atrial dilation and hypocontractility. The relative importance of changes in atrial size and contractility in the two models is unknown. This study compared changes in atrial dimensions and emptying in ATR versus HF dog models and related them to AF promotion. METHODS: In ATR dogs (n=11), the right atrium (RA) was paced at 400/min for 42 days. In HF dogs (n=10), the right ventricle was paced at 240 bpm for 2 weeks, followed by 3 weeks at 220 bpm. Transthoracic echocardiography was performed at baseline and weekly thereafter. At a terminal electrophysiological study, RA effective refractory period (ERP) was recorded and AF induced repeatedly by atrial burst pacing to measure mean AF duration (DAF). RESULTS: Left atrial (LA) systolic area increased by 10.0% in ATR versus 48.2% in HF dogs (P=0.008), with significant time-dependent changes in HF (P=0.0001), but not ATR (P=0.16). LA diastolic area increased over time in both groups (P=0.004, 0.0001 for ATR and HF respectively), but increases were much larger in CHF (80.2%) compared to ATR (24.2%, P=0.0002). Similar findings were obtained for RA. Fractional area shortening (FAS) decreased by 19.4% (ATR) versus 41.8% (HF, P=0.007) in LA and 13.7% (ATR) versus 33.7% (HF, P=0.03) in RA. RA ERP correlated with DAF in ATR dogs (r=-0.79, P<0.001), but not in HF dogs (r=0.20, P=NS). DAF and diastolic areas of RA and LA were highly correlated (r=0.71, 0.77; P<0.01 for each) in HF dogs, but not in ATR dogs (r=-0.18, 0.29; P=NS). CONCLUSIONS: Remodeling of atrial size and emptying function is much greater in HF than in ATR. Whereas in ATR, electrophysiological remodeling is of prime importance in AF promotion, structural remodeling (as reflected in changes in atrial size and contraction) appears much more important in HF-induced AF.     

Right atrial appendage thrombosis in atrial fibrillation: its frequency and its clinical predictors

This study assesses the incidence of right atrial (RA) chamber and appendage thrombosis in patients with atrial fibrillation (AF) in relation to RA appendage morphology and function. Transthoracic and multiplane transesophageal echocardiography were performed in 102 patients with AF to assess the incidence of RA and left atrial (LA) thrombi and spontaneous echo contrast. Both right and left ventricular sizes, atrial chamber and appendage sizes and function were measured. Twenty-two patients in sinus rhythm served as the control group (SR). Complete visualization of the RA appendage was feasible in 90 patients with AF. Patients with AF had lower tricuspid annular excursion (p = 0.008) and larger RA chamber area (p = 0.0001) than patients in SR. In addition, RA appendage areas were larger (p <0.05) and RA ejection fraction and peak emptying velocities (both p <0.0001) were lower in patients with AF patients than in those in SR. Equivalent differences were found for the LA appendage. Six thrombi were found in the RA appendage and 11 thrombi in the LA appendage in AF patients. Spontaneous echo contrast was found in 57% and 66% in the right atrium and in the left atrium, respectively. AF patients with RA appendage thrombi had a larger RA area (p = 0.0001), and lower RA appendage ejection fraction and emptying velocities (both p = 0.0001) than patients without thrombi. Spontaneous echo contrast was detected in all patients with thrombi. Spontaneous echo contrast was the only independent predictor of RA (p = 0.03) and LA appendage thrombosis (p = 0.036). In conclusion, multiplane transesophageal echocardiography allows the assessment of RA appendage morphology and function. RA spontaneous echo contrast is the only independent predictor of RA appendage thrombosis.     

Simultaneous biatrial computerized mapping during permanent atrial fibrillation in patients with organic heart disease

INTRODUCTION: Activation patterns during permanent atrial fibrillation (AF) in patients with organic heart diseases are unclear. METHODS AND RESULTS: We studied six patients with permanent AF and organic heart diseases undergoing surgery. The duration of AF averaged 4.9+/-7.6 years. Computerized epicardial mappings of the right atrial (RA) free wall and the left atrial (LA) posterior wall were simultaneously performed with 224 bipolar electrodes at 3-mm spatial resolution. In the RA, large wavefronts and conduction blocks were frequently observed. The lines of block correlated with the crista terminalis and large pectinate muscles. In contrast, the LA had rapid repetitive activities originated from corners of the electrode plaque, near the four pulmonary veins (PVs). On average, 2.8+/-1.2 sites of rapid repetitive activities were identified per patient. They activated continuously, intermittently, or alternately during AF. The mean activation cycle length in the RA (196+/-22 msec) was significantly longer than that in the LA (179+/-26 msec; P = 0.004). The maximum dominant frequency in the LA was higher than that in the RA (6.41+/-1.18 Hz vs 5.66+/-0.55 Hz; P = 0.049). The maximum dominant frequency was consistently located in areas with rapid repetitive activations near the PVs. CONCLUSION: During human permanent AF associated with organic heart diseases, the activation cycle length was shorter in the LA posterior wall than in the RA free wall. Rapid repetitive activities are consistently observed in the LA posterior wall, at or near the PVs.     

Biatrial and three-dimensional mapping of spontaneous atrial arrhythmias in patients with refractory atrial fibrillation

INTRODUCTION: While atrial fibrillation (AF) initiation in the pulmonary veins has been well-studied, simultaneous biatrial and three-dimensional noncontact mapping (NCM) has not been performed. We hypothesized that these two techniques would provide novel information on triggers, initiation, and evolution of spontaneous AF and permit study of different AF populations. METHODS AND RESULTS: The origin of atrial premature beats (APBs), onset of spontaneous AF and its evolution were analyzed in 50 patients with AF in the presence or absence of structural heart disease (SHD) and in different AF presentations (group A: Persistent, group B: Paroxysmal). In 45 patients, spontaneous APBs in the right atrium (RA; n = 60) and left atrium (LA; n = 25) with similar regional distributions regardless of heart disease status were demonstrated. In total, 22 patients (44%) had > or =2 disparate regional origins. Biatrial regional foci were seen with equal frequency in patients with SHD (31%), without SHD (40%), in group A (32%), and in group B (36%). Biatrial mapping and NCM showed organized monomorphic atrial tachyarrhythmias arising in the RA (17), septum (17), or LA (21) and were classified as atrial flutter (RA = 34, LA = 8), macro-reentrant atrial tachycardia (RA = 1, LA = 3) or focal atrial tachycardia (RA = 2, LA = 7). Their regional distribution was more extensive in patients with SHD and persistent AF compared with patients without SHD or paroxysmal AF. Simultaneous biatrial tachycardias were observed only in group A patients and those with SHD. CONCLUSIONS: Simultaneous biatrial and NCM permits successful AF mapping in different AF populations and demonstrates a biatrial spectrum of spontaneous triggers and tachycardias. Organized monomorphic tachycardias with multiple unilateral or biatrial locations are commonly observed in human AF. Patients with heart disease or persistent AF have a more extensive distribution as well as simultaneous coexistence of multiple tachycardias during AF.     

Differences in organization between acute and chronic atrial fibrillation in dogs

OBJECTIVES: The purpose of this study was to determine differences in acute and chronic atrial fibrillation (AF) "organization" in canine models. BACKGROUND: Electrophysiologic changes occur during atrial remodeling, but little is known about how remodeling affects AF organization. We hypothesized that atrial remodeling induced by long-term rapid atrial rates heterogeneously decreases AF organization. METHODS: In seven dogs, acute AF was induced by atrial burst pacing, and in eight dogs chronic AF was created by six weeks of continuous rapid atrial pacing. Atrial fibrillation was epicardially mapped from the right atria (RA) and left atria (LA). Atrial cycle length (CL), spatial organization and activation maps were compared. Spatial organization was quantified by an objective signal processing measure between multiple electrograms. RESULTS In acute AF, mean CL was slightly shorter in the LA (124 +/- 16 ms) than it was in the RA (131 +/- 14 ms) (p < 0.0001). In chronic AF, LA CL (96 +/- 14 ms) averaged 24 ms shorter than RA CL (121 +/- 18 ms) (p < 0.0001). Right atria and LA in acute AF had similar levels of organization. In chronic AF, the LA became approximately 25% more disorganized (p < 0.0001) while the RA did not change. In acute AF, a single broad wave front originating from the posterior and medial atrium dominated LA activation. In chronic AF, LA activation was more complex, sustaining multiple reentrant wavelets in the free wall and lateral appendage. CONCLUSIONS: Acute and chronic AF exhibit heterogeneous differences in CL, organization and activation patterns. The LA in chronic AF is faster and more disorganized than it is in acute AF. Differences in the models may be due to heterogeneous electrophysiologic remodeling and anatomic constraints. The design of future AF therapies may benefit by addressing the patient specific degree of atrial remodeling.