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.     

Transesophageal stimulation of the left cardiac atrium in treatment of atrial flutter]

Transesophageal stimulation of the left cardiac atrium in the treatment of paroxysmal atrial flutter was assessed. An attempt of such a therapy in paroxysmal atrial flutter involved 20 patients. Cardiac atrium was stimulated with overdrive technique, with single or pair of stimuli and multiple impulses of various frequency and duration. Reversal to sinus rhythm was achieved in 10 patients (in 3 out of them through phase of atrial fibrillation transitory). Results confirm therapeutical value of the transesophageal stimulation of the left cardiac atrium in atrial flutter.     

心力衰竭合并房颤患者血浆脑钠肽水平及相关因素分析

目的:探讨心力衰竭合并房颤患者血浆脑钠肽水平变化及相关因素,为心血管疾病的临床诊断提供理论依据。方法:选取我院2011年1月-2013年1月收治的心力衰竭患者94例,分为窦性心律组和心房颤动组。分别抽取两组患者的血液样本并检测血浆中的BNP浓度,比较不同NYHA分级患者血浆内的脑钠肽水平的变化情况,记录左心房和左心室舒张末内径及房颤持续时间等。结果:心力衰竭合并心房颤动组与窦性心律组血浆BNP水平比较,心房颤动组高于窦性心律组;差异有统计学意义(P0.05);两组NYHA不同分级相互比较,Ⅱ级、Ⅲ级和Ⅳ级间的BNP水平,心房颤动组BNP水平均高于窦性心律组;差异显著具有统计学意义(P0.05);血浆BNP水平与患者年龄、左心房大小、左心室大小、房颤持续时间因素呈正相关(r分别为0.0.801,0.748,0.854和0.703,P0.05),与左心室射血分数呈负相关(r=-0.41,P0.05)。结论:BNP血浆浓度与心功能状态密切相关,BNP浓度的检测有助于临床心血管疾病的诊断。     

The role of stretching the sinus node artery in initiation of atrial fibrillation

In anaesthetised dogs with open chest (n = 10), against the background of the Gd3+ (a blocking agent of mechano-sensitive ion channels), acetylcholine perfusion induced no significant changes either in probability of atrial fibrillation occurrence or in the paroxysm duration. The Gd3+ did not alter the deceleration of the sinus rhythm either. Therefore the mechanism of spontaneous occurrence of atrial cholinergic fibrillation seems not to be associated with the trigger activity induced by an increased blood pressure in the right atrium.     

Loss of atrial contractility is primary cause of atrial dilatation during first days of atrial fibrillation

Atrial fibrillation (AF) induces a progressive dilatation of the atria which in turn might promote the arrhythmia. The mechanism of atrial dilatation during AF is not known. To test the hypothesis that loss of atrial contractile function is a primary cause of atrial dilatation during the first days of AF, eight goats were chronically instrumented with epicardial electrodes, a pressure transducer in the right atrium, and piezoelectric crystals to measure right atrial diameter. AF was induced with the use of repetitive burst pacing. Atrial contractility was assessed during sinus rhythm, atrial pacing (160-, 300-, and 400-ms cycle length), and electrically induced AF. The compliance of the fibrillating right atrium was measured during unloading the atria with diuretics and loading with 1 liter of saline. All measurements were repeated after 6, 12, and 24 h of AF and then once a day during the first 5 days of AF. Recovery of the observed changes after spontaneous cardioversion was also studied. After 5 days of AF, atrial contractility during sinus rhythm or slow atrial pacing was greatly reduced. During rapid pacing (160 ms) or AF, the amplitude of the atrial pressure waves had declined to 20% of control. The compliance of the fibrillating atria increased twofold, whereas the right atrial pressure was unchanged. As a result, the mean right atrial diameter increased by approximately 12%. All changes were reversible within 3 days of sinus rhythm. We conclude that atrial dilatation during the first days of AF is due to an increase in atrial compliance caused by loss of atrial contractility during AF. Atrial compliance and size are restored when atrial contractility recovers after cardioversion of AF.     

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.     

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.     

Giant left atrial appendage

A 42-year-old man was evaluated at our hospital because of paroxysmal atrial fibrillation. Physical examination and ECG during sinus rhythm were unremarkable (no signs of left atrial enlargement).     

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.     

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。     

Transitions among atrial fibrillation, atrial flutter, and sinus rhythm during procainamide infusion and vagal stimulation in dogs with sterile pericarditis

The mechanism of atrial flutter and fibrillation induced by rapid pacing in 22 dogs with 3-day-old sterile pericarditis was investigated by computerized epicardial mapping of atrial activation before and after administration of agents known to modify atrial electrophysiologic properties: procainamide, isoproterenol, and electrical stimulation of the vagosympathetic trunks. Before the administration of any of these agents, a total of 30 episodes of sustained atrial flutter (greater than 1 min duration, monomorphic; regular cycle length, 127 +/- 12 ms, mean +/- SD) was induced in 15 out of 22 dogs and 9 episodes of unstable atrial flutter (duration, less than 1 min; cycle length, 129 +/- 34 ms; monomorphic, alternating with fibrillation) were induced in the remaining 7 preparations. In the latter, administration of procainamide transformed unstable atrial flutter and atrial fibrillation to sustained atrial flutter (cycle length, 142 +/- 33 ms; n = 9 episodes). During control atrial flutter, atrial maps displayed circus movement of excitation in the right atrial free wall with faster conduction parallel to the orientation of intra-atrial myocardial bundles. Vagal stimulation changed atrial flutter to atrial fibrillation in 32 of 73 trials; this was associated with acceleration of conduction in the lower right atrium, leading to fragmentation of the major wave front. Isoproterenol produced a 6-25% increase of the atrial rate in 6 out of 14 trials of atrial flutter and induced atrial fibrillation in 4. After procainamide, the reentrant pathway was lengthened and conduction was slowed further in the right atrium. Maps obtained during unstable atrial flutter showed incomplete circuits involving the right atrium. Following procainamide infusion, the area of functional dissociation or block was enlarged and a stable circus movement pattern, which was similar to the pattern seen in control atrial flutter, was established in the right atrium. We conclude that (1) the transitions among atrial fibrillation, atrial flutter, and sinus rhythm occur between different functional states of the same circus movement substratum primarily located in the lower right atrial free wall, and (2) the anisotropic conduction properties of the right atrium may contribute to these reentrant arrhythmias and may be potentiated by acute pericarditis.     

Cardiac function-related gene expression profiles in human atrial myocytes

To obtain insights into the molecular pathogenesis of heart failure in humans, we have analyzed the expression profiles of>12,000 genes in a total of 17 human specimens of right atrial myocytes. From this large data set, we here tried to identify gene clusters, expression level of which is correlated precisely with clinical parameter values of cardiac function. We could reveal that cardiac myocytes with normal sinus rhythm were clearly differentiated, in the point of view of gene expression, from those with atrial fibrillation. Further, an expression profile-based prediction of arrhythmia by a newly developed "weighted-distance method" could efficiently diagnose our samples. We could even construct calculation formulae for the values of left ventricular ejection fraction based on the expression level of selected genes. To our best knowledge, this is the first report to indicate that pumping ability of heart can be predicted by any measures of atrium.     

Measuring blood pressure in the elderly: does atrial fibrillation increase observer variability?

OBJECTIVE--To compare the interobserver and intraobserver variability of blood pressure measurements in geriatric patients in atrial fibrillation and in sinus rhythm. DESIGN--Prospective assessment of blood pressure measurements carried out in random order in two groups of elderly patients by five doctors unaware of the aims of the study. SETTING--Acute assessment wards for geriatric medicine, Cardiff Royal Infirmary. PATIENTS--50 Elderly patients in sinus rhythm and 50 in atrial fibrillation. MAIN OUTCOME MEASURES--Interobserver and intraobserver variability of blood pressure measurements in the two groups expressed as the coefficient of variability and compared by the Mann-Whitney U test. RESULTS--Interobserver variability was significantly greater in the patients with atrial fibrillation for both systolic and diastolic pressures. Intraobserver variability was significantly greater in the atrial fibrillation group for diastolic pressures but the difference was not significant for systolic pressures. These differences were not related to pulse rate, age, or level of blood pressure. CONCLUSIONS--The findings suggest that in the presence of atrial fibrillation physicians'' interpretations of Korotkoff sounds are less uniform, which may have important clinical implications. Possibly a standardised methodology may overcome this problem.     

Fluid–structure interaction in a fully coupled three-dimensional mitral–atrium–pulmonary model

This paper aims to investigate detailed mechanical interactions between the pulmonary haemodynamics and left heart function in pathophysiological situations (e.g. atrial fibrillation and acute mitral regurgitation). This is achieved by developing a complex computational framework for a coupled pulmonary circulation, left atrium and mitral valve model. The left atrium and mitral valve are modelled with physiologically realistic three-dimensional geometries, fibre-reinforced hyperelastic materials and fluid–structure interaction, and the pulmonary vessels are modelled as one-dimensional network ended with structured trees, with specified vessel geometries and wall material properties. This new coupled model reveals some interesting results which could be of diagnostic values. For example, the wave propagation through the pulmonary vasculature can lead to different arrival times for the second systolic flow wave (S2 wave) among the pulmonary veins, forming vortex rings inside the left atrium. In the case of acute mitral regurgitation, the left atrium experiences an increased energy dissipation and pressure elevation. The pulmonary veins can experience increased wave intensities, reversal flow during systole and increased early-diastolic flow wave (D wave), which in turn causes an additional flow wave across the mitral valve (L wave), as well as a reversal flow at the left atrial appendage orifice. In the case of atrial fibrillation, we show that the loss of active contraction is associated with a slower flow inside the left atrial appendage and disappearances of the late-diastole atrial reversal wave (AR wave) and the first systolic wave (S1 wave) in pulmonary veins. The haemodynamic changes along the pulmonary vessel trees on different scales from microscopic vessels to the main pulmonary artery can all be captured in this model. The work promises a potential in quantifying disease progression and medical treatments of various pulmonary diseases such as the pulmonary hypertension due to a left heart dysfunction.

     

Protective mechanism of SIRT1 on Hcy‐induced atrial fibrosis mediated by TRPC3

High plasma levels of homocysteine (Hcy) are regarded as a risk factor for atrial fibrillation (AF), which is closely associated with the pathological consequence of atrial fibrosis and can lead to heart failure with a high mortality rate; here, we show that atrial fibrosis is mediated by the relationship between canonical transient receptor potential 3 (TRPC3) channels and sirtuin type 1 (SIRT1) under the stimulation of Hcy. The left atrial appendage was obtained from patients with either sinus rhythm (SR) or AF and used to evaluate the relationship between the concentration of Hcy and a potential mechanism of cardiac fibrosis mediated by TRPC3 and SIRT1. We next performed transverse aortic constriction (TAC) in mouse to investigate the relationship. The mechanisms underlying atrial fibrosis involving TRPC3 and SIRT1 proteins were explored by co‐IP, BLI and lentivirus transfection experiments. qPCR and WB were performed to analyse gene and protein expression, respectively. The higher level of atrial fibrosis was observed in the HH mouse group with a high Hcy diet. Such results suggest that AF patients may be more susceptible to atrial fibrosis and possess a high probability of progressing to hyperhomocysteinemia. Moreover, our findings are consistent with the hypothesis that TRPC3 channel up‐regulation leads to abnormal accumulation of collagen, with the down‐regulation of SIRT1 as an aetiological factor of high Hcy, which in turn predisposes to atrial fibrosis and strongly enhances the possibility of AF.     

In vivo porcine left atrial wall stress: Effect of ventricular tachypacing on spatial and temporal stress distribution

Animal models of ventricular tachypacing (VTP) have been successfully used to reproduce the relevant features observed in patients with atrial fibrillation, such as increased atrial pressure and volume, ion-channel alterations and fibrosis. After performing VTP on a healthy Yorkshire pig, we measured an increase in volume of 60%, a two-fold rise in pressure, and a complex pattern of local mechanical, histological and biochemical changes, including a generalized stiffening of the wall. A protocol recently developed was employed to generate computational models of the porcine left atrium mechanics in healthy conditions and after VTP. Comparison of the stress distribution in the healthy vs. VTP case provided a map of how pressure overload affects and modifies left atrium mechanics. Overall, a positive increase in stress was computed after the VTP treatment. Regions of large increase in the stresses post-VTP were the appendage boundaries, the area around the lower pulmonary vein and the area in the front of the atrium towards the appendage. Due to the elevated stress, the back of the atrium mainly modified its mechanical response, while the appendage remodeled both its shape and its mechanical properties. Large changes in the shape of the mitral valve annulus could be observed as a consequence of the remodeling in the front of the atrium. The relation between local mechanical stress and remodeling that emerges from the results is in agreement with our hypothesis that the structural changes in the atrium are a consequence of a stress-mediated mechanism.     

Effect of increased left atrial pressure on breathing frequency in anesthetized dog

Distension or loading of the isolated canine left heart caused reflex tachypnea in prior studies. The object of the present effort was to explore the possibility that this depended primarily on atrial distension. Cardiopulmonary bypass perfusion and ligation of pulmonary veins were used to isolate the left-heart chambers of anesthetized dogs. Simultaneous distension of the beating left atrium and fibrillating ventricle stimulated breathing frequency (f), whereas isolated ventricular distension did not. At other times, intervals of atrial fibrillation were imposed under two different conditions: 1) while the right heart and lungs were bypassed and systemic perfusion was provided by the left ventricle using blood returned to the left atrium by pump and 2) while the ventricles fibrillated and systemic perfusion was supplied directly by the pump. Atrial fibrillation increased left atrial pressure and stimulated f in condition 1. In condition 2, f increased only if fibrillation was associated with a rise in left atrial pressure. Vagal cooling blocked the effect of fibrillation. I conclude that left atrial distension may initiate reflex tachypnea.     

The ligament of Marshall as a parasympathetic conduit

The objective of the study was to investigate the morphology, distribution, and electrophysiological profile of the autonomic fibers that innervate the ligament of Marshall (LOM). Gross anatomical dissections were performed in 10 dogs. Sections of the left vagus nerve, left stellate ganglion, and the LOM were immunostained to identify adrenergic and cholinergic nerves. Hearts were also stained for acetylcholinesterase to identify epicardial cholinergic nerves. In vivo electrophysiological studies were performed in another 10 dogs before and after LOM ablation. The anatomical examination revealed that the LOM is innervated by a branch of the left vagus. Immunohistochemistry confirmed that these nerve bundles are predominantly cholinergic (cholinergic-to-adrenergic ratio of 12.6 +/- 3.9:1). Cholinergic nerves originating in the LOM were found to innervate surrounding left atrial structures, including the pulmonary veins, left atrial appendage, coronary sinus, and posterior left atrial fat pad. Ablation of the LOM significantly attenuated effective refractory period shortening at distant sites, such as pulmonary veins and left atrial appendage, in response to vagal stimulation (vagal-induced ERP decrease in the left atrium: baseline vs. postablation = 17 vs. 4%; P = 0.0056). In conclusion, the LOM contains a predominance of cholinergic nerve fibers. Cholinergic fibers arising from the LOM innervate surrounding structures and contribute to the electrophysiological profile of the left atrium. These findings may provide a basis for the role of the LOM in the genesis and maintenance of atrial fibrillation.