Evaluating the novel parameters for assessing the LAA function and thrombus formation with nonvalvular atrial fibrillation

The dysfunction of left atrial appendage (LAA) is prone to form thrombus when atrial fibrillation (AF) sustained more than 48 h. Traditional 2D-TEE (transesophageal echocardiography) can not accurate evaluate the function of LAA. The purpose of this study is to analyze the relationship of LAA function parameters and thrombus formation in patients with non-valvular atrial fibrillation (NVAF) by real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). High risk patients can be identified according to the characteristics of ultrasonic index in patients with left atrial appendage thrombosis, which has important clinical value and significance in the risk assessment, guiding treatment and judging prognosis. We examined the relationship between the echocardiographic parameters of LAA function and the incidence of thrombus in 102 NVAF patients. They underwent RT-3D-TEE and left atrial appendage thrombus (LAAT)/severe spontaneous echocardiographic contrast (SSEC) was found in 67 patients (thrombus group) but absent in the remaining 35 patients (non-thrombus group). After measured by QLAB software, the LAA functional parameters were significantly associated with LAAT/SEC formation. Univariate analysis indicated that AF time, LAD, LVEF, LAA-OAmax, LAAVmax, LAAVI and LAAEF demonstrated a positive association (P < 0.05). However, logistic regression analysis identified that AF time (OR:1.73, P < 0.05)、LAAEF (OR:4.09, P < 0.01)and LAAVI (OR:3.28, P < 0.01) were independent predictors of LAAT/SSEC. In patients with nonvalvular atrial fibrillation, echocardiographic parameters of LAA function are significantly associated with LAAT/SSEC.     

An innovative appendage invagination procedure to reduce thrombus formation – a numerical model

Invagination is an innovative technique for closing the left atrial appendage (LAA) to reduce the risk of thrombi formation. The influence of LAA invagination on the flow fields in the atria was investigated based on a computational fluid dynamics. The simulation results demonstrated that the novel invagination process can eliminate low velocities (blood stasis) and low shear rate and thus decrease the risk of thrombus formation during atrial fibrillation. This innovative technique may enhance the clinical treatment of patients with atrial fibrillation by improving the atrial flow field while lowering the risk of creating emboli.     

Impact of left atrial appendage location on risk of thrombus formation in patients with atrial fibrillation

Biomechanics and Modeling in Mechanobiology - Most strokes in patients with atrial fibrillation (AF) are thought to arise from thrombus formation in the left atrial appendage (LAA). Assessing the...     

Left atrial appendage closure: outcomes and challenges

Whereas the left atrial appendage plays a rather minor role under physiological circumstances, it gains an importance in patients with atrial fibrillation. Compelling evidence has revealed that the left atrial appendage is implicated as the source of thrombus in the vast majority of strokes in atrial fibrillation. Oral anticoagulation remains the standard of care for stroke prevention in atrial fibrillation; nevertheless, this treatment has several limitations and is often contraindicated, particularly in the elderly population in whom the risk of stroke is high. Therefore, occluding the left atrial appendage is a logical approach to prevent thrombus formation and subsequent cardioembolic events in these patients. We present a review of clinical outcomes of patients with atrial fibrillation undergoing left atrial appendage closure and the challenges faced in this field.     

Left Atrial Appendage Morphology in Patients with Suspected Cardiogenic Stroke without Known Atrial Fibrillation

The left atrial appendage (LAA) is the typical origin for intracardiac thrombus formation. Whether LAA morphology is associated with increased stroke/TIA risk is controversial and, if it does, which morphological type most predisposes to thrombus formation. We assessed LAA morphology in stroke patients with cryptogenic or suspected cardiogenic etiology and in age- and gender-matched healthy controls. LAA morphology and volume were analyzed by cardiac computed tomography in 111 patients (74 males; mean age 60 ± 11 years) with acute ischemic stroke of cryptogenic or suspected cardiogenic etiology other than known atrial fibrillation (AF). A subgroup of 40 patients was compared to an age- and gender-matched control group of 40 healthy individuals (21 males in each; mean age 54 ± 9 years). LAA was classified into four morphology types (Cactus, ChickenWing, WindSock, CauliFlower) modified with a quantitative qualifier. The proportions of LAA morphology types in the main stroke group, matched stroke subgroup, and control group were as follows: Cactus (9.0%, 5.0%, 20.0%), ChickenWing (23.4%, 37.5%, 10.0%), WindSock (47.7%, 35.0%, 67.5%), and CauliFlower (19.8%, 22.5%, 2.5%). The distribution of morphology types differed significantly (P<0.001) between the matched stroke subgroup and control group. The proportion of single-lobed LAA was significantly higher (P<0.001) in the matched stroke subgroup (55%) than the control group (6%). LAA volumes were significantly larger (P<0.001) in both stroke study groups compared to controls patients. To conclude, LAA morphology differed significantly between stroke patients and controls, and single-lobed LAAs were overrepresented and LAA volume was larger in patients with acute ischemic stroke of cryptogenic or suspected cardiogenic etiology.     

Incidence and predictors of left atrial thrombus in patients with atrial fibrillation prior to ablation in the real world of China

BackgroundThe present study was to evaluate the value of CHADS2 and CHA2DS2VASC scores on predicting left atrial (LA) or left atrial appendage (LAA) thrombus in atrial fibrillation (AF) patients prior to ablation in the real world of China.Methods and resultsA total of 397 patients with non-valvular AF were analyzed to determine the relationship between CHADS2 and CHA2DS2VASC scores and LA/LAA thrombus identified on transesophageal echocardiography prior to radiofrequency ablation(RFA). LA/LAA thrombus was present in 38 patients (9.6%). There was a strong association between higher CHADS2 score or CHA2DS2VASC score and LA/LAA thrombus. No thrombus was identified in patients with CHA2DS2VASC score of 0 regardless of anticoagulation status. However, LA/LAA thrombus was detected in 2.9% patients with CHADS2 score of 0 without adequate anticoagulation, while no thrombus was present in the patients with CHADS2 score of 0 with adequate anticoagulation. Univariate analysis showed that heart failure (LVEF＜50%), LA≥40 mm, diabetes mellitus, previous stroke or TIA, CAD, hypertension, inadequate anticoagulation therapy, CHADS2 score of ≥2 and CHA2DS2VASC score of ≥2 were significantly associated with LA/LAA thrombus. Multivariable Cox regression analysis demonstrated that CHA2DS2VASC score of ≥2 (p = 0.02) and previous stroke or TIA (p = 0.04) were independently associated with LA/LAA thrombus regardless of anticoagulation status. ROC curve analysis showed that higher CHADS2 score and CHA2DS2VASC score could be similarly used to predict the presence of LA thrombus.ConclusionsBoth higher CHA2DS2VASC and CHADS2 scores were associated with LA/LAA thrombus in non-valvular AF patients prior to ablation. Although CHA2DS2VASC score and CHADS2 score had similar value to predict LA/LAA thrombus, CHA2DS2VASc score was better to identify low-risk patients for LA/LAA thrombus than CHADS2 score without anticoagulation. There will be a possibility of performing AF ablation or cardioversion in patients with a CHA2DS2VASC of 0 without TEE or anticoagulation therapy. The safety need to be verified by more multicentre randomized controlled clinical trails.     

Left Atrial Appendage Dysfunction in a Patient with Premature Ventricular Contractions - A Risk Factor for Stroke?

A 16-year-old female with ventricular dysfunction and frequent ventricular arrhythmia presented with a cardioembolic stroke. Prior electrophysiology study and ablation was performed for ventricular tachycardia (VT). For remaining ventricular ectopy, the patient was maintained on carvedilol and mexiletine. After one year on this regimen, she presented with an acute stroke. Transesophageal echocardiography revealed no evidence of an intracardiac or ventricular thrombus but demonstrated markedly decreased left atrial appendage (LAA) flow velocity worsened during frequent premature ventricular contractions (PVC). In the absence of atrial fibrillation (AF), the LAA dysfunction was considered secondary to the frequent PVCs and was thought to be the underlying cause for the stroke. We present this case to highlight a potential under recognized association between LAA dysfunction and ventricular arrhythmia, similar to that observed with atrioventricular dyssynchronous pacing.     

左心房顿抑的影响因素和发生机制

心房顿 抑是 指与 复律 前 相比 ,心房 颤动 复律 后 心房 和 心耳 机械 功能 暂 时被 抑 制的 现象 .心房 颤动 复律 方式 、心房 颤 动持 续 的时 间、心 房的 大小 、潜在 的结 构 性心 脏 病是 影响 心房 顿 抑的 因 素 .目前 心 房顿 抑可 能的 机制 有 :单 纯 性心 房颤 动 引起 的心 房 细胞 结构 的 变化 ;心房 的心 肌 细胞 内钙 离 子的 变化 ;快速 房 性心 肌炎 和心 房纤 维 症 .这 里主 要讨 论 心房 颤动 复 律后 左心 房 和左 心耳 发 生的 顿抑 现 象 .     

Epicardial fat pad within the transverse sinus mimicking a left atrial appendage thrombus

The presence of left atrial thrombus is a contraindication to cardioversion or catheter ablation in patients with atrial fibrillation, due to the increased risk of systemic thromboembolism. Management of this situation includes changes in the anticoagulation regimen and repeat imaging tests. Accurate diagnosis of left atrial appendage thrombus is therefore essential but can sometimes be challenging. Multiple imaging modalities may sometimes be required in the setting of anatomical variations of the left atrial appendage and surrounding structures.We present the case of a patient awaiting ablation for atypical atrial flutter, who underwent a transthoracic echocardiogram that showed an echodense, mobile structure within the vicinity of the left atrial appendage, suggesting a possible thrombus. A cardiac CT demonstrated the image to correlate with an epicardial fat pad within the transverse sinus.     

Characterizing left atrial appendage functions in sinus rhythm and atrial fibrillation using computational models

Clinical studies show that the left atrial appendage, a blind-ended structure that is attached to the left atrium, may be the cause of 90% of atrial thrombi in atrial fibrillation (abnormal heart rhythm), and it is much reduced in sinus (normal) rhythm. In this paper, the effects of blood flows in left atrium and left atrial appendage are studied to help characterize the atrial appendage functions in sinus rhythm and atrial fibrillation using mathematical models. Our results show that the left atrial appendage is not functional in sinus rhythm because the atrial transmitral velocities remained almost identical for atria with and without appendage, which agrees with the current clinical observations. However, in atrial fibrillation, a proper atrial contraction is absent, which causes the second emptying velocity (A-wave) to be missing in both transmitral velocity and appendage filling/emptying velocity. Without the proper emptying of the blood, vortices generated in the chamber remain high strengths and with longer durations. They induce ineffective emptying of the blood in the atrium and appendage, which then lead to blood stagnation and subsequent thrombus formation.     

经食道超声心动图评估特发性房颤左心房左心耳的价值

目的:研究经食道超声心动图(TEE)评估特发性房颤左心房左心耳的临床价值。方法:选择自2015年1月到2016年8月在医院接受诊治的特发性房颤患者100例纳入本次研究,阵发性房颤92例,记为阵发性房颤组;持续性房颤8例,记为持续性房颤组。另选同期在医院进行健康体检的心功能正常志愿者90例作为对照组。利用TEE对受试者进行检查,对比房颤组与对照组的左心房及左心耳参数,是否含有自发性显影(LASEC)的房颤患者的左心房及左心耳参数,利用TEE分析对房颤患者的预后情况。结果:阵发性房颤组左心房的前后径和左右径,左心耳血流最大的排空速度(Lev)均明显小于对照组,左心耳的面积变化率及最大的充盈速度(Lfv)均明显大于对照组,差异有统计学意义(P0.05)。持续性房颤组左心房的前后径和左右径均明显大于对照组,左心耳的面积变化率、Lev及Lfv均明显小于对照组,差异有统计学意义(P0.05)。阵发性房颤组左心房的前后径和左右径均明显小于持续性房颤组,左心耳的面积变化率、Lev及Lfv均明显大于持续性房颤组,差异有统计学意义(P0.05)。有LASEC者左心房的前后径和左右径均明显大于无LASEC者,左心耳的面积变化率、Lev及Lfv均明显小于无LASEC者,差异有统计学意义(P0.05)。100例房颤患者中发现34例LASEC,占34.00%,其中有18例患者合并有左心耳血栓,占18.00%。总计有66例患者接受导管射频消融疗法,占66.00%,均未在术中及术后7d内出现血栓及栓塞并发症。结论:利用TEE对特发性房颤的患者左心房及左心耳进行评估,有利于更好的辅助患者的临床治疗,值得重视。     

Digitalis Does not Improve Left Atrial Mechanical Dysfunction After Successful Electrical Cardioversion of Chronic Atrial Fibrillation

This study was designed to investigate whether administration of digitalis could improve mechanical function of left atrial appendage (LAA) and left atrium prospectively in patients with atrial stunning. Fifty-four consecutive patients in whom atrial stunning was observed immediately after cardioversion of chronic atrial fibrillation (AF) were randomized into digitalis or control group for 1 week following cardioversion. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were performed prior to, immediately following, 1 day after and 1 week after cardioversion to measure transmitral flow velocity and LAA flow velocity. Electrical cardioversion of AF elicited significantly slower left atrial appendage peak emptying velocity (LAA-PEV) and peak filling velocity (LAA-PFV) immediately following cardioversion in both groups. 1 day post cardioversion, there were no significant differences in transmitral E wave, A wave, E/A ratio, LAA-PEV, LAA-PFV or left atrial appendage ejection fraction (LAA-EF) between digitalis and control groups. 1 week post cardioversion, no significant differences were found in transmitral E wave, A wave, E/A ratio, LAA-PEV, LAA-PFV or LAA-EF between the two groups. The occurrence rates of spontaneous echo contrast were not significantly different between digitalis and control groups one day and one week post cardioversion. In conclusion, digitalis did not improve left atrial and appendage mechanical dysfunction following cardioversion of chronic AF. Digitalis did not prevent the development of spontaneous echo contrast in left atrial chamber and appendage. This may be due to the fact that digitalis aggravates intracellular calcium overload induced by chronic AF and has a negative effect on ventricular rate.     

Left atrial endocardium and prostacyclin.

In patients with rheumatic mitral stenosis, intracardiac thrombi are found mostly, for reasons still unknown, in the left atrium. We compared the release of PGI2 from the endocardium of the left atrium with that of the right ventricle and from the endothelium of the pulmonary arteries. Endocardial endothelial cells (EECs) were isolated from right ventricles (RV) and left atrial appendages (LAA) of porcine hearts, and vascular endothelial cells (VECs) from pulmonary arteries (PA) were obtained from the same animals. Cultured EEC and PA-VEC monolayers were placed in a pressure loading apparatus and incubated for 30 min under various pressures. After incubation, the supernatants were sampled and the 6-keto-PGF1 alpha contents measured. PGI2 release from LAA-EEC was much less than from RV-EEC or from PA-VEC. Moreover, transmural pressure did not enhance PGI2 release from LAA-EEC, although it did from RV-EEC and PA-EEC in a pressure-dependent manner. These results may explain why the left atrium is a common site for intracardiac thrombus formation in patients with mitral valve disease.     

Computational modeling of hemodynamics and risk of thrombosis in the left atrial appendage using patient-specific blood viscosity and boundary conditions at the mitral valve

Biomechanics and Modeling in Mechanobiology - Hemodynamics play a vital role for the risk of thrombosis in the left atrial appendage (LAA) and left atrium (LA) for patients with atrial...     

Echocardiographic [correction of Ehocardiographic] evaluation of regional left atrial function after rapid atrial pacing

Rapid regular atrial pacing (RAP) produces changes in atrial function similar to those caused by atrial fibrillation in animal models. Left atrial appendage (LAA) function represents regional atrial function. The aim of our study was to investigate the influence of RAP on left atrial regional function and to evaluate the reversibility of changes after termination of pacing in a canine model. Eight dogs were subjected to RAP (400 bpm) for 16 days. Transesophageal echocardiography was performed at baseline, immediately after RAP and 4 weeks after the termination of RAP. The LAA peak late emptying velocity (LAA-E) and filling wave (LAA-f) were measured. LAA-E velocities were significantly reduced and filling wave velocities (LAA-f) were significantly less negative after RAP compared with the baseline values. Four weeks after termination of pacing, the LAA-E and LAA-f velocities were normal. RAP results in impaired regional atrial systolic and diastolic function. The changes were completely reversible 4 weeks after termination of pacing. These results suggest that the LAA is mechanically stunned after RAP.     

High-density activation map of atrial tachycardia within left atrial appendage

Identification of the critical isthmus of the reentrant tachycardia is essential to maximize the effect of catheter ablation (CA) and to minimize the myocardial injury of CA. An 81-year-old woman presented recurrent palpitations after CA of atrial fibrillation (AF) and atrial tachycardia (AT). She had moderate aortic valve stenosis and coronary artery disease. She had received a pulmonary vein isolation, left atrial (LA) posterior wall isolation, and LA anterior linear ablation for atrial fibrillation 1 year prior. At the start of the procedure, she was in sinus rhythm. Atrial burst pacing induced an AT (230msec). High-density mapping revealed a figure-of-eight activation pattern within the LA appendage (LAA), accounting for 99% of the tachycardia cycle length. The critical isthmus was identified at the mid LAA and the local electrogram of the critical isthmus was not fractionated. A single radiofrequency application at the critical isthmus of the AT, terminated the AT. She was free from any ATs for 28 months.Radiofrequency ablation of the localized reentrant AT was usually performed targeting long fractionated electrograms. In our case, the local electrogram at the critical isthmus was not fragmented compared with the LAA distal part. Long fractionated electrograms were recorded at a more distal part of the LAA than the common isthmus and we could avoid the potential risk of a perforation. A recent developed 3-dimensional electro-anatomical mapping system can identify the critical isthmus and allow us to select a new therapeutic strategy for a critical isthmus ablation of an AT within the LAA.     

微电极阵列芯片技术研究48h房颤犬左、右心耳电生理特性

目的应用微电极阵列芯片（microelectrode arrays chip,MEA）技术评价48 h房颤（atrial fibrillation,AF）犬左、右心耳（LAA、RAA）的电生理特性。方法随意来源犬12只,以600次/分起搏右心房建立AF模型,分为48 h AF组（n=6）和对照组（n=6）。造模成功后迅速开胸剪取LAA、RAA,置于盛有台式液的MEA中,分别记录AF组及对照组LAA、RAA场电位（field action potential,FAP）形态、振幅、放电频率及激动传导情况。结果 AF组LAA、RAA组织FAP节律绝对不齐,LAA（185.22±25.62）次/分,较对照组（156.44±8.88）次/分增加15.67%（P〈0.01）,RAA（102.39±16）次/分,较对照组（156.44±8.88）次/分减慢34.62%（P〈0.01）。48 h AF组LAA组织电压（458.33±26.73）μV较对照组（740.55±18.93）μV降低38.11%（P〈0.01）,RAA（504.83±39.93）μV较对照组（840.56±18.93）μV明显降低（P〈0.01）,48 h房颤组LAA组织FAP时程（45.28±8.59）ms较对照组（70.77±6.98）ms缩短15 ms（P〈0.01）。RAA（61.78±7.1）ms较对照组（75.83±7.63）ms缩短14 ms（P〈0.01）。48 h AF组LAA、RAA FAP传导异质性增加。结论应用MEA技术可反映心肌组织片场电位电生理特性,48 h AF后LAA放电频率增加,频率绝对不齐,LAA、RAA电压降低,场电位时程延长。     

Left Atrial Appendage Volume Increased in More Than Half of Patients with Cryptogenic Stroke

Background

Ischemic strokes without a well-defined etiology are labeled as cryptogenic, and account for 30–40% of strokes in stroke registries. The left atrial appendage (LAA) is the most typical origin for intracardiac thrombus formation when associated with atrial fibrillation. Here, we examined whether increased LAA volume detected with cardiac computed tomography (cCT) constitutes a risk factor in cryptogenic stroke patients.

Methods

This study included 82 stroke/TIA patients (57 males; mean age, 58 years) with a diagnosis of cryptogenic stroke after extensive radiological and cardiological investigations. Cases were classified using the TOAST criteria modified by European Association of Echocardiography recommendations for defining cardiac sources of embolism. Forty age- and gender-matched control subjects without cardiovascular diseases were selected for pair-wise comparisons (21 males; mean age, 54 years). LAA volume adjusted for body surface area was measured three dimensionally by tracing the LAA borders on electrocardiogram-gated CT slices.

Results

In control subjects, mean LAA volume was 3.4±1.1 mL/m². Mean+2SD, which was considered the upper limit for normal LAA volume was 5.6 mL/m². In paired Student t-test between the patient group and matched controls, LAA volume was 67% larger in cryptogenic stroke/TIA patients (5.7±2.0 mL/m² vs. 3.4±1.1 mL/m²; P<0.001). Forty-five (55%) patients with cryptogenic stroke/TIA had enlarged LAA.

Conclusion

LAA is significantly enlarged in more than half of patients with cryptogenic stroke/TIA. LAA thrombosis may contribute to the pathogenesis of stroke in patients considered to have cryptogenic stroke after conventional evaluation.     

Remodeling of atrial ATP-sensitive K⁺ channels in a model of salt-induced elevated blood pressure

Hypertension is associated with the development of atrial fibrillation; however, the electrophysiological consequences of this condition remain poorly understood. ATP-sensitive K(+) (K(ATP)) channels, which contribute to ventricular arrhythmias, are also expressed in the atria. We hypothesized that salt-induced elevated blood pressure (BP) leads to atrial K(ATP) channel activation and increased arrhythmia inducibility. Elevated BP was induced in mice with a high-salt diet (HS) for 4 wk. High-resolution optical mapping was used to measure atrial arrhythmia inducibility, effective refractory period (ERP), and action potential duration at 90% repolarization (APD(90)). Excised patch clamping was performed to quantify K(ATP) channel properties and density. K(ATP) channel protein expression was also evaluated. Atrial arrhythmia inducibility was 22% higher in HS hearts compared with control hearts. ERP and APD(90) were significantly shorter in the right atrial appendage and left atrial appendage of HS hearts compared with control hearts. Perfusion with 1 μM glibenclamide or 300 μM tolbutamide significantly decreased arrhythmia inducibility and prolonged APD(90) in HS hearts compared with untreated HS hearts. K(ATP) channel density was 156% higher in myocytes isolated from HS animals compared with control animals. Sulfonylurea receptor 1 protein expression was increased in the left atrial appendage and right atrial appendage of HS animals (415% and 372% of NS animals, respectively). In conclusion, K(ATP) channel activation provides a mechanistic link between salt-induced elevated BP and increased atrial arrhythmia inducibility. The findings of this study have important implications for the treatment and prevention of atrial arrhythmias in the setting of hypertensive heart disease and may lead to new therapeutic approaches.