A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation

Human atrial fibrillation (AF) has been associated with increased atrial oxidative stress. In animal models, inhibition of reactive oxygen species prevents atrial remodeling induced by rapid pacing, suggesting that oxidative stress may play an important role in the pathophysiology of AF. NAD(P)H oxidase is a major source of superoxide in the cardiovascular system; however, whether this enzyme contributes to atrial oxidative stress in AF remains to be elucidated. We investigated the sources of superoxide production (using inhibitors and substrates of a range of oxidases, RT-PCR, immunofluorescence, and immunoblotting) in tissue homogenates and isolated atrial myocytes from the right atrial appendage (RAA) of patients undergoing cardiac surgery (n=54 in sinus rhythm [SR] and 15 in AF). A membrane-bound gp91phox containing NAD(P)H oxidase in atrial myocytes was the main source of atrial superoxide production in SR and in AF. NADPH-stimulated superoxide release from RAA homogenates was significantly increased in patients with AF in the absence of changes in mRNA expression of the p22phox and gp91phox subunits of the NAD(P)H oxidase. In contrast with findings in SR patients, NO synthases (NOSs) contributed significantly to atrial superoxide production in fibrillating atria, suggesting that increased oxidative stress in AF may lead to NOS "uncoupling." These findings indicate that a myocardial NAD(P)H oxidase and, to a lesser extent, dysfunctional NOS contribute significantly to superoxide production in the fibrillating human atrial myocardium and may play an important role in the atrial oxidative injury and electrophysiological remodeling observed in patients with AF.     

Role of Rac1 GTPase activation in atrial fibrillation.

OBJECTIVES: We aimed to study the role of Rac1 GTPase in atrial fibrillation (AF). BACKGROUND: The signal transduction associated with AF is incompletely understood. We hypothesized that activation of Rac1 GTPase contributes to the pathogenesis of AF via activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and production of reactive oxygen species. METHODS: Old mice with cardiac-specific overexpression of constitutively active V12Rac1 (RacET) were compared with wild-type (WT) and WT undergoing transaortic constriction (TAC). In addition, samples of human left atrial appendages were analyzed in patients with sinus rhythm (SR) compared with patients with permanent AF matched for atrial diameter. RESULTS: At age 16 months, 75% of RacET but no WT or TAC mice showed AF. Treatment of RacET with statins for 10 months did not alter weight or fibrosis of atria or ventricles but decreased cardiac Rac1 and NADPH oxidase activity and reduced the incidence of AF by 50%. The left atria of patients with AF showed increased fibrosis, up-regulation of NADPH oxidase activity, a 4-fold increase of Rac1 total protein and membrane expression as well as up-regulation of Rac1 activity. CONCLUSIONS: Chronic cardiac overexpression of Rac1 represents a novel mouse model for AF. Rac1 GTPase contributes to the pathogenesis of AF and identifies a target for the prevention and treatment of AF.     

心房肌缝隙连接蛋白40、43表达改变与心房颤动的关系

目的：研究心房颤动患者心房肌缝隙连接蛋白(Cx)40、43表达的改变，探讨Cx在房颤发生与维持中的作用。方法：39例接受开胸手术者分为房颤组和窦性心律组，手术时取右心耳及左心房各约100mg，采用Western blot与免疫组织化学技术，检测心房肌Cx40、Cx43表达量与分布的改变。结果：房颤组Cx40表达量在左心房、右心耳较窦性心律组高，Cx43表达量在左心房较窦性心律组高，在右心耳无差异。免疫组化显示房颤组Cx40、Cx43均分布紊乱，聚集于胞浆或核周。结论：房颤患者心房肌Cx40、Cx43表达增高，且分布异常，提示心房肌Cx40、Cx43表达改变与心房颤动的发生与维持有关。     

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。     

Left atrial appendage outflow velocity is superior to conventional criteria for predicting of maintenance of sinus rhythm after simple cryoablation of pulmonary vein orifices.

BACKGROUND: We sought to identify factors favoring long-term restoration of sinus rhythm (SR) in patients with atrial fibrillation (AF) who underwent a simple cryoablation of pulmonary vein orifices (PV-cryo) as part of their cardiac surgery. METHODS AND RESULTS: Of 101 patients with AF undergoing PV-cryo, the 71 in SR at discharge were grouped according to whether they maintained or lost SR (group SR, n = 61, and group AF, n = 10) after an average of 2.3 years. Atrial fibrillation present at discharge (n = 30) persisted during follow up. Comparisons were made to identify preoperative predictive factors, including transthoracic and transesophageal echocardiographic parameters. Of patients discharged from the hospital with SR, 92% (46 of 50) of those with AF duration of 3 years or less were in group SR, as were 92% (23 of 25) of those with left atrial dimension of 50 mm or less, and 93% (37 of 40) of those with average peak left atrial appendage outflow velocities (LAA-V) of at least 30 cm/s. Of 25 patients in group SR who had no paroxysmal AF and did not require antiarrhythmic drugs, all had LAA-V over 20 cm/s. Patients in group AF all had LAA-V under 40 cm/s. CONCLUSIONS: Left atrial appendage outflow velocities was the best predictor of whether SR was maintained long-term after PV-cryo.     

Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation

Atrial fibrillation (AF), the most common chronic arrhythmia, increases the risk of stroke and is an independent predictor of mortality. Available pharmacological treatments have limited efficacy. Once initiated, AF tends to self-perpetuate, owing in part to electrophysiological remodeling in the atria; however, the fundamental mechanisms underlying this process are still unclear. We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following cardiac surgery. In chronically instrumented dogs, we found that rapid (400 min(-1)) atrial pacing was associated with attenuation of the atrial effective refractory period (ERP). Treatment with ascorbate, an antioxidant and peroxynitrite decomposition catalyst, did not directly modify the ERP, but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing. Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration (a biomarker of peroxynitrite formation). Oral ascorbate supplementation attenuated both of these changes. To evaluate the clinical significance of these observations, supplemental ascorbate was given to 43 patients before, and for 5 days following, cardiac bypass graft surgery. Patients receiving ascorbate had a 16.3% incidence of postoperative AF, compared with 34.9% in control subjects. In combination, these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia. The full text of this article is available at http://www.circresaha.org.     

二尖瓣置换术后患者持续性心房颤动心率控制与节律控制的对比分析

目的 研究风湿性心脏病(风心病)二尖瓣置换术后心率控制与节律控制对患者远期预后的影响.方法 本试验采用回顾性分析.选择2006年在我院择期行二尖瓣置换术的患者197例,按术后心律情况分为窦性心律组(n=100)和心房颤动(房颤)组(n=97).收集患者基本资料,以患者手术结束为试验起始时间,随访术后发生脑卒中及心脏性死...     

Impact of left atrial size reduction and endocardial radiofrequency ablation on continuous atrial fibrillation in patients undergoing concomitant cardiac surgery: three-year results

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the efficacy of left atrial (LA) size reduction combined with radiofrequency (RF) ablation in the treatment of continuous atrial fibrillation (AF), by comparative analysis of the outcomes of patients undergoing RF ablation with and without LA size reduction. METHODS: A total of 46 patients with continuous AF and cardiac disease underwent cardiac surgery and RF ablation alone (group I, n = 20) or combined with LA size reduction (group II, n = 26). Patients were followed for three years postoperatively, with evaluation of cardiac rhythm, neurological complications, LA size (by echocardiography) and atrial contractility. RESULTS: At three years after surgery, sinus rhythm (SR) was restored in 61.1% and 70% of patients in groups I and II, respectively. Mean LA diameter was reduced from 60 +/- 15 mm to 57 +/- 5 mm in group I, and from 69 +/- 19 mm to 55 +/- 6 mm in group II. The overall three-year survival was 90% in group I, and 88.5% in group II. Three-year freedom from stroke was 88.9% and 86.2% in groups I and II, respectively. Two patients in each group received transvenous permanent pacemaker implantation. Atrial contractility was recovered in all patients with stable SR. CONCLUSION: LA size reduction improves SR conversion rate after RF ablation for continuous AF in patients undergoing concomitant cardiac surgery.     

Determinants and consequences of atrial fibrosis in patients undergoing open heart surgery

OBJECTIVE: Atrial fibrillation (AF) is a frequent complication following open-heart surgery (OHS). Increased atrial fibrosis may indicate the presence of an intrinsic arrhythmogenic substrate. The aim of this prospective study was to determine whether atrial fibrosis is associated with increased prevalence of AF after OHS. METHODS: Right atrial appendages were obtained from 259 patients undergoing OHS; none of the patients had a history of AF. Atrial fibrosis was quantitatively analyzed with point counting. All patients were followed prospectively until hospital discharge. None of the patients received anti-arrhythmic prophylaxis. Post-operative AF was defined as an episode of AF lasting > or = 5 min. RESULTS: Quantitation of atrial fibrosis yielded a mean volume percentage of 15.8 +/- 4.3% (V%; range 4.6-32.4%). Patient age was found to correlate with the amount of atrial fibrosis (r = 0.165; P < 0.01) and surface P-wave duration (r = 0.249; P < 0.01). The degree of fibrosis combined with P-wave duration predicted post-operative AF (P < 0.01). Age (> 60 years) and P-wave duration (> or = 100 ms) were independent predictors of post-operative AF (age: relative risk 2.20; P-wave: relative risk 2.69; P < 0.05). The patients were divided into three groups: group 1, V% = 4.6-13.8%; group 2, V% = 13.9-23.1%; group 3, V% = 23.2-32.4%. A total of 52 patients (20.1%) developed AF, which occurred least commonly in group 1 (16.3%) and group 2 (21.2%) as compared with group 3 (33.3%). CONCLUSIONS: Atrial fibrosis provides a pathophysiological substrate for post-operative AF. The results support the importance of P-wave duration as a predictor of post-operative AF, and explain the increased prevalence of AF in elderly patients after OHS.     

扩张性心肌病患者心房Cx43蛋白的表达及其意义

目的:观察扩张性心肌病（dilated cardiomyopathy,DCM）患者心房连接蛋白43（Cx43）的表达、磷酸化的Cx43（pCx43）及其分布特征。探讨Cx43与房颤（atrial fibrillation,AF）之间的关系。方法: 18例接受心脏移植术的DCM患者中,8例无AF史且手术时为窦性心律（SR,SR组）,6例有AF史但手术时为SR（AF+SR组）,4例有AF史且手术时有AF（AF+AF组）。用超声心动图(ECG)测定左心房大小与左心室收缩功能;用免疫印迹法及免疫荧光染色法检测Cx43、pCx43及其分布。结果: DCM患者的左心房直径(LAD)、左室射血分数(LVEF)在SR、AF+SR、AF+AF组间均没有显著差异。与SR组相比,AF+SR组心房组织中Cx43和pCx43无显著差异;AF+AF组总Cx43的表达量及pCx43显著升高(P<0.01及P<0.05)。病理观察提示,AF+AF组Cx43和pCx43升高,Cx43向细胞两侧分布,且pCx43升高。结论: DCM患者的房颤节律伴随Cx43的表达、磷酸化及其分布异常。     

Combined metabolomic and proteomic analysis of human atrial fibrillation.

OBJECTIVES: We sought to decipher metabolic processes servicing the increased energy demand during persistent atrial fibrillation (AF) and to ascertain whether metabolic derangements might instigate this arrhythmia. BACKGROUND: Whereas electrical, structural, and contractile remodeling processes are well-recognized contributors to the self-perpetuating nature of AF, the impact of cardiac metabolism upon the persistence/initiation of this resilient arrhythmia has not been explored in detail. METHODS: Human atrial appendage tissues from matched cohorts in sinus rhythm (SR), from those who developed AF post-operatively, and from patients in persistent AF undergoing cardiac surgery were analyzed using a combined metabolomic and proteomic approach. RESULTS: High-resolution proton nuclear magnetic resonance (NMR) spectroscopy of cardiac tissue from patients in persistent AF revealed a rise in beta-hydroxybutyrate, the major substrate in ketone body metabolism, along with an increase in ketogenic amino acids and glycine. These metabolomic findings were substantiated by proteomic experiments demonstrating differential expression of 3-oxoacid transferase, the key enzyme for ketolytic energy production. Notably, compared with the SR cohort, the group susceptible to post-operative AF showed a discordant regulation of energy metabolites. Combined principal component and linear discriminant analyses of metabolic profiles from proton NMR spectroscopy correctly classified more than 80% of patients at risk of AF at the time of coronary artery bypass grafting. CONCLUSIONS: The present study characterized the metabolic adaptation to persistent AF, unraveling a potential role for ketone bodies, and demonstrated that discordant metabolic alterations are evident in individuals susceptible to post-operative AF.     

Alterations in contractile protein composition and function in human atrial dilatation and atrial fibrillation

The cellular mechanisms responsible for contractile dysfunction associated with atrial fibrillation (AF) are still poorly understood. Atrial fibrillation is often preceded by atrial dilatation. This study aimed to explain contractile alterations associated with AF and their relation to atrial dilatation, by studying the relationships between atrial dimensions, contractile protein composition, force production and Ca(2+)-sensitivity. Force development was determined in mechanically isolated single skinned cardiomyocytes from right atrial appendages from patients with sinus rhythm without (SR;n=9), or with atrial dilation (SR+AD;n=11) or atrial fibrillation (AF;n=16). Echocardiography showed that, compared to the SR group, mean right atrial dimensions were increased by 18% and 35% in the SR+AD and AF group, respectively (P<0.05). Protein composition was determined by 1- and 2-dimensional gel electrophoresis. Compared to the SR group, the AF group exhibited: a reduction in the kinetics of force redevelopment (K(tr)) in isolated atrial cardiomyocytes, enhanced protein expression of the slow myosin heavy chain isoform (beta-MHC), an increase in troponin T (TnT) phosphorylation and a marked increase (70%) of the cytoskeletal protein desmin. Significant correlations were observed between the right atrial major axis (RA(major)) and beta-MHC expression as well as the desmin/actin ratio. Our findings indicate that dilatation may influence cardiomyocyte stability through altered desmin expression, but that it does not predispose to the alterations in contractile function observed in AF.     

卡托普利对心房颤动心房组织细胞外信号调节激酶的影响

目的 探讨血管紧张素转化酶(ACE)抑制剂对心房颤动(房颤)心房组织细胞外信号调节激酶的影响。方法 52例风湿性心脏病患者分成四组,窦性心律组、窦性心律 卡托普利组、慢性房颤组(房颤>6个月)、慢性房颤 卡托普利组。外科手术时取右心耳组织,采用逆转录-聚合酶链反应测定细胞外信号调节激酶(ERK)mRNA量,免疫印迹法(Western blotting)测定激活ERK蛋白质量。结果 ERK_2 mRNA量在窦性心律组和窦性心律 卡托普利组明显低于慢性房颤组和慢性房颤 卡托普利组(P<0.01),窦性心律组和窦性心律 卡托普利组比较、慢性房颤组和慢性房颤 卡托普利组比较差异无显著性(P>0.05);激活ERK_1/ERK_2量在慢性房颤 卡托普利组明显低于慢性房颤组(P<0.01),但明显高于窦性心律组和窦性心律 卡托普利组(P<0.01)。结论 ACE抑制剂可部分阻断房颤时心房组织内“致纤维化”信号转导通路的激活,对心房结构重构产生一定的有益的影响。     

Expression of angiotensin II receptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease

TIVES: We postulated a change of angiotensin II receptor subtype expression in patients with lone atrial fibrillation (AF) and AF with underlying mitral valve disease (MVD) both compared with sinus rhythm (SR). BACKGROUND: Atrial fibrillation is a progressive disease associated with electrical and structural remodeling. Angiotensin II (ANGII) is involved in the process of myocardial remodeling. Actions of ANGII are mediated by ANGII receptor subtypes 1 and 2 (AT(1) and AT(2)). METHODS: Left atrial (LA) and right atrial (RA) tissue samples were obtained from patients with AF or SR with or without underlying MVD. The AT(1) and AT(2) protein levels were measured by quantitative Western blotting techniques. RESULTS: The AT(1) protein level in the LA was significantly increased in patients with AF (all forms) compared with SR (p < 0.05), whereas AT(2) expression was not significantly altered. Comparison of the subgroups revealed a similar increase of AT(1) in both paroxysmal AF and chronic AF with or without MVD. Additionally, investigations of ANGII receptor subtypes in the RA did not exhibit any significant changes either in AT(1) or in AT(2) in patients with AF versus SR. Underlying MVD did not significantly affect AT(2) receptor subtype expression in LA. CONCLUSIONS: Atrial fibrillation is associated with an up-regulation of AT(1) in LA, but not in RA, and did not appear to influence the AT(2) expression in the atrium. Because we found an enhanced expression of AT(1)in the LA, we conclude that AT(1) might be involved in the pathogenesis of AF in the LA.     

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients in sinus rhythm (SR) via activation of 5-HT(4) receptors, but its effects in atrial cells from patients with atrial fibrillation (AF) are unknown. The whole-cell perforated patch-clamp technique was used to record L-type Ca(2+) current (I(CaL)), action potential duration (APD) and arrhythmic activity at 37 degrees C in enzymatically isolated atrial cells obtained from patients undergoing cardiac surgery, in SR or with chronic AF. In the AF group, 5-HT (10microM) produced an increase in I(CaL) of 115+/-21% above control (n=10 cells, 6 patients) that was significantly smaller than that in the SR group (232+/-33%; p<0.05; n=27 cells, 12 patients). Subsequent co-application of isoproterenol (1microM) caused a further increase in I(CaL) in the AF group (by 256+/-94%) that was greater than that in the SR group (22+/-6%; p<0.05). The APD at 50% repolarisation (APD(50)) was prolonged by 14+/-3ms by 5-HT in the AF group (n=37 cells, 14 patients). This was less than that in the SR group (27+/-4ms; p<0.05; n=58 cells, 24 patients). Arrhythmic activity in response to 5-HT was observed in 22% of cells in the SR group, but none was observed in the AF group (p<0.05). Atrial fibrillation was associated with reduced effects of 5-HT, but not of isoproterenol, on I(CaL) in human atrial cells. This reduced effect on I(CaL) was associated with a reduced APD(50) and arrhythmic activity with 5-HT. Thus, the potentially arrhythmogenic influence of 5-HT may be suppressed in AF-remodelled human atrium.     

Impairment of left atrial function predicts post-operative atrial fibrillation after coronary artery bypass graft surgery.

AIMS: Despite the prevalence of atrial fibrillation (AF) occurring after cardiac surgery, its pathophysiology is incompletely understood. Specifically, whether left atrial (LA) structural remodelling occurs, contributing to a decrement in atrial function and AF has not been previously determined. This study sought to determine the relationship between LA function and post-operative AF. METHODS AND RESULTS: Three hundred patients undergoing elective coronary artery bypass graft surgery were monitored with intraoperative transoesophageal echocardiography to determine LA function and dimensions. Post-operative AF was monitored with continuous telemetry until hospital discharge. The relationship between clinical factors versus LA function and dimension was assessed using multi-variate logistic regression. By univariate analysis, patients who subsequently developed post-operative AF had a larger LA area and LA appendage area, and lower LA ejection fraction measured in the pre-bypass period compared to those without subsequent AF. By multivariable analysis, in addition to clinical data including age (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.16, P<0.0001), body surface area (OR 13.31, 95% CI 1.87-94.5, P=0.0097) and white race, post-bypass atrial systolic function (atrial filling fraction 0.36, OR 2.51, 95% CI 1.03-6.13, P=0.04) and abnormal relaxation of the left ventricle (E duration 270 ms) (OR 2.89, 95% CI 1.34-6.24, P=0.0067) independently increased the risk of post-operative AF. CONCLUSION: These results demonstrate that some of the structural and functional changes in the atria common to chronic AF in the elderly population are also prevalent in surgical patients who develop post-operative AF, suggesting that post-operative and chronic AF may have similar pathophysiology.     

Superior left atrial approach to the mitral valve: incidence of postoperative arrhythmia

BACKGROUND AND AIM OF THE STUDY: The superior left atrial approach to mitral surgery involves exposure of the mitral valve through a longitudinal, craniocaudally orientated incision in the roof of the left atrium. The study aim was to evaluate the incidence of postoperative arrhythmias following this procedure. METHODS: Fifty-nine patients underwent either mitral valve repair (n = 20), mitral valve replacement (n = 26) or an associated procedure (n = 13), including aortic valve replacement, coronary artery bypass grafting and atrial septal defect closure. Eight patients had undergone previous surgery on the mitral valve. Patients were classified according to their preoperative rhythm: sinus rhythm (SR), paroxysmal or chronic atrial fibrillation (AF), or permanent pacing. Changes in cardiac rhythm were evaluated postoperatively, after four weeks, and at late follow up (mean 23.8 months). RESULTS: Preoperatively, 24 patients had shown SR, 10 had paroxysmal AF, 24 had chronic AF, and one patient had permanent pacing. At the time of discharge, SR was recorded in 18 patients who had SR preoperatively, in seven who had paroxysmal AF preoperatively, and in one patient who had chronic AF preoperatively. At follow up, SR was seen in 19 patients with preoperative SR, in seven with paroxysmal AF preoperatively, and in two with chronic AF preoperatively. Four patients received permanent pacemakers postoperatively due to total heart block or bradycardia. CONCLUSION: The superior left atrial approach to mitral valve surgery appears to be safe as it maintains the sinus rhythm in a high proportion of patients postoperatively. In addition, it is not normally prone to technical complications.     

Histologic assessment of right atrial appendage myocardium in patients with atrial fibrillation after coronary artery bypass graft surgery

Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. Despite the prevalence of AF occurring after cardiac surgery, its pathophysiology is incompletely understood. Our previous study demonstrated that age and left atrial enlargement were independent predictors of postoperative AF. Accordingly, the purpose of this study was to determine whether cellular changes such as fibrosis and/or hypertrophy occurred in the atrium in patients who subsequently developed postoperative AF. Right atrial appendage tissue was obtained during atriotomy in patients undergoing elective CABG surgery. Quantitative assessment of atrial fibrosis was performed with Sirius red stain, and atrial cell diameter was measured with the HE stain. Linear regression, t test, chi2 test or Fisher exact test were used for statistical analysis. Sixty-one patients (mean age 71 +/- 8 years) were studied. Increasing age was significantly associated with fibrosis (beta 0.3, 95% CI: 0.06-0.55, p = 0.017). The amount of right atrial fibrosis tended to correlate with the incidence of postoperative AF (p = 0.08). Cell diameter was not significantly different between patients with versus without postoperative AF (p = 0.85). These results suggest that the age-related atrial fibrosis rather than cellular hypertrophy may be important in the pathogenesis of AF after CABG surgery and should be further investigated.