Influence of age on left atrial appendage function in patients with nonvalvular atrial fibrillation

BACKGROUND: Age is an independent risk factor for thromboembolism in nonvalvular atrial fibrillation (NVAF). An association between low left atrial appendage (LAA) Doppler velocities and thromboembolic risk in NVAF has been reported. Hypothesis: The study was undertaken to identify age-related differences in LAA function that may explain the higher thromboembolic rates in older patients with NVAF. METHODS: Forty-two consecutive patients (age 69+/-2 years [range 42-92], 24 [57%] men) with NVAF underwent transthoracic and transesophageal echocardiography. The following were compared in 22 patients younger and 20 older than 70 years: left ventricular (LV) diameter, mass and ejection fraction, left atrial (LA) diameter and volume, LAA area and volume, LAA peak emptying (PE) and peak filling (PF) velocities, presence and severity of spontaneous echo contrast (SEC) and mitral regurgitation (MR). RESULTS: Left atrial diameter (4.6+/-0.1 vs. 4.5+/-0.2 cm), LA volume (105+/-10 vs. 92+/-8 ml), LAA area (6.8+/-0.6 vs. 5.2+/-0.8 cm2), and LAA volume (5.6+/-0.9 vs. 3.9+/-1.0 ml) were similar (p>0.05) in both groups. Older patients had lower LAA PE (26+/-2 vs. 34+/-3 cm/s, p = 0.02) and PF (32+/-2 vs. 41+/-4 cm/s, p = 0.04) velocities, lower LV mass (175+/-13 vs. 234+/-21 gm, p = 0.02), higher relative wall thickness (0.52+/-0.02 vs. 0.43+/-0.03, p = 0.02), smaller LV diastolic diameter (4.3+/-0.1 vs. 5.2+/-0.2 cm, p < 0.001), and higher LV ejection fraction (62+/-2 vs. 55+/-2%, p = 0.025). Frequency and severity of SEC and MR were similar in both groups. Multivariate analysis identified older age as the only significant predictor of reduced LAA velocities. CONCLUSION: Compared with younger patients, older patients with NVAF have lower LAA velocities despite higher LV ejection fraction, smaller LV size, and similar LA and LAA volumes. These findings may explain the higher thromboembolic rates in older patients with NVAF.     

Lipoprotein(a), left atrial appendage function and thromboembolic risk in patients with chronic nonvalvular atrial fibrillation

Lipoprotein(a) (Lp(a)) has a prothrombotic effect by modulating the fibrinolytic system. The purpose of the present study was to determine whether serum Lp(a) levels are associated with an increased risk of thromboembolism in chronic nonvalvular atrial fibrillation (NVAF). Clinical, laboratory and transesophageal echocardiographic data were collected in 172 consecutive, non-anticoagulated patients with chronic NVAF. Thirty-four patients (thromboembolic group) had a recent (<1 month) embolic event and/or a left atrial thrombus on transesophageal echocardiography. The thromboembolic group had a higher frequency of spontaneous echo contrast (94 vs. 58%, p<0.0001), increased concentrations of Lp(a) (median: 31.5 vs. 15.5 mg/dl, p<0.0001) and fibrinogen (median: 352 vs. 314 mg/dl, p = 0.0015), larger left atrial dimensions (median: 5.1 vs. 4.8cm, p = 0.0078), and reduced left atrial appendage (LAA) flow velocities (median: 9.5 vs. 21.2 cm/s, p<0.0001) than the nonthromboembolic group. Multivariate analysis identified 3 independent predictors of thromboembolism: Lp(a) level > or =30 mg/dl (odds ratio (OR) 9.5, 95% confidence interval (CI) 4.4-20.4, p<0.0001), LAA flow velocity of <20 cm/s (OR 8.7, 95% CI 3.3-23.0, p = 0.0003) and a fibrinogen concentration of <377mg/dl (OR 3.2, 95% CI 1.5-6.9, p = 0.0201). The Lp(a) elevations and reduced LAA flow velocities are independently associated with thromboembolism in chronic NVAF.     

Relationship between left atrial appendage function and left atrial thrombus in patients with nonvalvular chronic atrial fibrillation and atrial flutter.

The relationship between the left atrial appendage (LAA) function, as assessed by transesophageal echocardiography, and the incidence of left atrial thrombus was evaluated in 62 patients with nonvalvular chronic atrial fibrillation (AF; n=50) and atrial flutter (AFL; n=12). It was hypothesized that in both AF and AFL not only the LAA flow velocity (LAAFV), but also the frequency of the LAA movement (the LAA flow time, LAAFT) is a major contributing factor to thrombus formation. LAAFT was defined as the average duration of LAA flow with emptying and filling waves. The patients with AF were divided into 2 groups: lone AF (n=14) and non-lone AF (n=36). LAA thrombus was found in 6 patients with none-lone AF. LAAFV was lower and LAAFT was shorter in patients with thrombus as compared with patients without thrombus (12.0+/-2.2 cm/s vs 24.1+/-10.6 cm/s, 68.7+/-1.5 ms vs 72.9+/-3.3 ms, p<0.01, respectively). Patients with AFL had higher LAAFV and longer LAAFT than those with chronic AF. The present data suggest that, in addition to LAAFV, LAAFT characterized LAA function and might serve as a predictor of thrombus formation in chronic AF. With respect to LAA function, patients with lone AF or AFL are at low risk for thrombus formation.     

Platelet activation in patients with chronic nonvalvular atrial fibrillation

Increased platelet activity plays a key role in atherothrombotic events. Persistent platelet activity has been reported in patients with atrial fibrillation (AF) following myocardial infarction and in the chronic phase after ischemic stroke. However, platelet activity in patients with AF remains clear. This study investigated platelet reactivity (expressed by CD62p) in patients with chronic nonvalvular (NV) AF. Expression of CD62p was measured by flow cytometry in 62 consecutive patients with chronic NVAF (defined as sustained AF > 6 months) and no previous embolic events. The CD62p expression was also evaluated in 20 healthy subjects. Expression of CD62p was not different between AF patients and healthy subjects (P = 0.970). Additionally, CD62p expression did not differ between patients with and patients without the following atherosclerotic risk factors: hypertension, current smoking, and hypercholesterolemia (all P values > 0.1). Furthermore, CD62p expression did not differ between patients taking and not taking the following medications: warfarin, a statin, or an angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (all P values > 0.2). However, diabetes mellitus (DM) was strongly associated with increased CD62p expression (P < 0.0001). Multiple linear regression analysis demonstrated that only DM independently predicted increased CD62p expression (r2 = 0.509, regression coefficient = 3.044, P < 0.0001). In conclusion, compared to healthy subjects, CD62p expression was not significantly enhanced in chronic NVAF patients. However, CD62p expression was substantially elevated in diabetic patients with chronic NVAF.     

炎症与非瓣膜性心房颤动患者左心耳血栓相关性研究

目的探讨炎症与非瓣膜心房颤动(简称房颤)患者左心耳血栓之间的相关性。方法共入选经食管心脏超声检查患者68例,其中左心耳血栓者(血栓组)23例,无左心耳血栓者(对照组)45例。所有患者测量血高敏C反应蛋白(hs-CRP)水平。结果血栓组hs-CRP水平(1.66mg/L,0.49～2.60mg/L)明显高于对照组(0.83mg/L,0.47～1.32mg/L),在校正了CHA2DS2-VASc评分、左房大小、房颤类型等因素后,hs-CRP水平增高仍然是左心耳血栓形成的危险因素(OR=1.19,95%可信区间1.02～1.39,P=0.02)。结论炎症在非瓣膜房颤左心耳血栓的形成过程中发挥了一定的作用。     

Effects of left ventricular systolic dysfunction on left atrial appendage and left atrial functions in patients with chronic nonvalvular atrial fibrillation

OBJECTIVE: It has been claimed that left ventricular (LV) systolic dysfunction impairs left atrial (LA) and left atrial appendage (LAA) functions. In this study, we compared the LA and LAA function parameters in patients with chronic nonvalvular atrial fibrillation (AF) with and without LV systolic dysfunction. METHODS AND RESULTS: The study population consisted of 28 patients with chronic nonvalvularAF. Group I consisted of 12 patients with LV systolic dysfunction (mean age: 61 +/- 14 years; LV ejection fraction: 44 +/- 6%), group II of 16 patients with normal LV systolic function (mean age: 52 +/- 15 years; LV ejection fraction: 65 +/- 3%). LV ejection fraction (EF) was measured by echocardiography utilizing bi-plane area length method.The following LA and LAA transoesophageal echocardiography parameters were obtained: I) LA diameter, 2) LAA ejection velocity, 3) LAA filling velocity, 4) LAA ejection fraction, 5) pulmonary venous (PV) systolic velocity, 6) PV diastolic velocity, 7) PV systolic velocity/diastolic velocity ratio.The left atrium diameter was significantly larger in group I than in group 11 (4.7 +/- 0.7 cm vs. 3.8 +/- 0.6 cm, p < 0.05).The LAA ejection velocity and LAA ejection fraction were significantly lower in group I than in group 11 (22.6 +/- 15.5 cm/s vs 37.5 +/- 11.3 cm/s and 26.9 +/- 20.8% vs. 41.3 +/- 10.9%, p < 0.05 for both comparisons).The PV systolic velocity and PV systolic velocity/diastolic velocity ratio were significantly smaller in group I than in group II (26.2 +/- 14.8 cm/s vs. 51.5 +/- 22 cm/s and 0.7 +/- 0.6 vs. 1.2 +/- 0.5, p < 0.05 for both comparisons).Although decreased LAA filling and PV diastolic velocities were determined in group I, no significant difference existed between groups I and II.Thrombus and/or spontaneous echo contrast (SEC) in the LA and/or LAA were more frequent in group I (75% vs. 18%, p < 0.05). CONCLUSION: These results indicate that LV systolic dysfunction impairs various LA and LA function parameters and is associated with an increased frequency of SEC and/or LA thrombus in patients with chronic nonvalvularAF.     

左心耳封堵器在非瓣膜性心房颤动患者中应用新进展

心房颤动（AF）是最常见、最普遍的心律失常,被称为21世纪的心血管流行病,目前没有治愈AF的方法。AF的最大风险是血栓形成并脱落,造成人体重要部位,特别是脑部血管的堵塞,引发脑卒中。缺血性脑卒中是AF的主要严重并发症,与其他类型的脑卒中相比,心源性脑卒中发病更急、瘫痪的程度更重、住院治疗的周期更长、复发率和病死率更高,造成患者生活质量差,经济负担重。研究表明90 %以上的非瓣膜性心房颤动（NVAF）患者缺血性脑卒中的栓子来源于左心耳。随着现代生物医学技术的创新发展,经皮左心耳封堵术的获益得到肯定,作为一种可替代的,特别是对于不适合口服抗凝药物治疗患者有了非药物性介入的治疗方法。本文对左心耳封堵术在AF的现代化应用进行阐述,详细介绍用左心耳封堵器的发展、国内外各类封堵器的优劣及其创新应用,为AF的临床治疗选择提供科学依据,为推动AF患者治疗提供参考。     

经皮左心耳封堵术在非瓣膜性心房颤动患者卒中预防中的应用

心房颤动(atrial fibrillation,AF)导致的卒中很常见,而且常常是灾难性的.尽管口服抗凝药是预防栓塞性卒中的基石,但它们也存在许多局限性,而且并非所有患者均能长期耐受.左心耳已被认定为非瓣膜性AF患者血栓形成的来源.目前已研发出多种左心耳封堵装置,并成功用于非瓣膜性AF患者的卒中预防,且围手术期并发症较少.文章对经皮左心耳封堵术在非瓣膜性AF患者卒中预防方面的应用进行了综述.     

经皮左心耳封堵术预防非瓣膜性心房颤动患者脑卒中七例经验总结

<正>1病例资料内蒙古自治区人民医院急诊心血管内科于2015年5月在内蒙古自治区开展了左心耳封堵术,至今已成功为7位患者植入了左心耳封堵器。7例患者均为持续性非瓣膜病性心房颤动,其中男性4例,女性3例,年龄52~79岁,平均(68.0±7.3)岁。均已婚,汉族6例,蒙古族1例。既往曾患甲状腺功能亢进症1例,肾功能不全1例。术前曾确诊     

Growth differentiation factor 15 is associated with left atrial/left atrial appendage thrombus in patients with nonvalvular atrial fibrillation

Background

There is evidence suggesting that growth differentiation factor 15 (GDF‐15) appears to be associated with stroke in patients with atrial fibrillation (AF). AF‐related thromboembolic stroke is predominantly attributed to the thrombus from the left atrium (LA) or left atrial appendage (LAA).

Hypothesis

GDF‐15 is related to LA/LAA thrombus in nonvalvular AF (NVAF) patients.

Methods

A total of 894 patients with NVAF without anticoagulation therapy were included in this study. All patients routinely underwent transesophageal echocardiography for detection of LA/LAA thrombus. GDF‐15 was measured by enzyme‐linked immunosorbent assay. Logistic regression models were used to test for association.

Results

LA/LAA thrombus was detected by transesophageal echocardiography in 69 (7.72%) patients with AF. The GDF‐15 levels in the patients with LA/LAA thrombus were significantly higher than those without LA/LAA thrombus (log₁₀ GDF‐15: 2.989 ± 0.023 ng/L vs 2.831 ± 0.007 ng/L; P < 0.001). Logistic regression analysis showed that GDF‐15 was an independent risk factor for LA/LAA thrombus (odds ratio [per quarter]: 1.799, 95% confidence interval: 1.381‐2.344, P < 0.001) after adjusting for potential clinical risk factors. The optimal cutoff point for GDF‐15 predicting LA/LAA thrombus was 809.9 ng/L (sensitivity, 75.3%; specificity, 61.5%), determined by ROC curve. The area under the curve was 0.709 (95% confidence interval: 0.644‐0.770, P < 0.001).

Conclusions

Elevated GDF‐15 indicated a significantly increased risk for LA/LAA thrombus in NVAF patients. Thus, GDF‐15 might be a potentially useful adjunct in discriminating LA/LAA thrombus in NVAF patients.     

Effects of heart rate on flow velocity of the left atrial appendage in patients with nonvalvular atrial fibrillation

Background and hypothesis: Flow velocity of the left atrial appendage (LAA) is thought to be important in thrombus formation in association with blood stasis and the development of spontaneous echo contrast. The effects of heart rate on peak flow velocity of the LAA have not been studied in patients with nonvalvular atrial fibrillaton. Methods: Using transesophageal Doppler echocardiography, peak flow velocity of the LAA was measured at the junction between the left atrium and the LAA during left ventricular (LV) systole and diastole in 21 patients with nonvalvular atrial fibrillation. In six cases, the average peak flow velocity of the LAA for 10 consecutive beats with moderately long R-R intervals (LI beats) was compared with those for 3-5 consecutive beats with extremely short R-R intervals (SI bets). Results: Average peak flow velocity of the LAA during LV diastole was significantly higher than that during LV systole (26.5 ± 15.7 vs. 19.3 ± 10.4 cm/s, p<0.01). In SI beats, average peak flow velocity of the LAA was significantly lower than that in LI beats (17.1 ± 12.1 vs. 21.2 ± 12.9 cm/s, p<0.01). Conclusion: An increased heart rate reduced the peak flow velocity of the LAA in patients with nonvalvular atrial fibrillation, which would promote blood stasis in the LAA.     

非瓣膜性心房颤动患者围术期的抗凝治疗

大多数非瓣膜性心房颤动(NVAF)患者需长期应用口服抗凝药物,以减少中风及系统性栓塞的风险。这些患者在接受外科手术或侵入性操作时出血风险增加,部分患者在围术期需暂时中断抗凝治疗。近年来,对于NVAF患者围术期暂时中断抗凝治疗的适应症、时间、暂时中断口服抗凝药物后抗凝治疗的桥接,以及术后抗凝治疗的重新应用已有较多的临床研究。本文简要介绍NVAF患者围术期抗凝治疗的研究现状。     

Relationship between body mass index and left atrial appendage thrombus in nonvalvular atrial fibrillation

Atrial fibrillation and obesity are two major growing epidemics in the United States and globally. Obese people are at the increased risk of developing atrial fibrillation. The contribution of obesity as an independent risk factor for stroke in the setting of atrial fibrillation remains unclear. We tested the hypothesis that non-valvular atrial fibrillation (NVAF) patients with increased body mass index (BMI) would be at increased risk for the development of left atrial appendage thrombus (LAAT). Consecutive, anticoagulation naïve patients with NVAF referred for a transesophageal echocardiogram (TEE) between January 1, 2007 and October 21, 2009 were approached for study participation. All clinical, laboratory, and TEE measurement data were collected prospectively. Within a group of 400 anticoagulation naïve NVAF patients (mean age 63 ± 15 years, 28 % women; 17 % with LAAT) the prevalence of LAAT was similar across all BMI categories (normal 13 %, overweight 19 %, obese 16 %, morbidly obese 16 %; p = 0.71). Despite a higher CHADS₂ score and a higher prevalence of both hypertension and diabetes mellitus, elevated BMI was not an independent predictor of LAAT when analyzed as either a continuous variable, across BMI WHO categories, a dichotomous variable stratified at values above versus below 27 kg/m², or BMI stratified on atrial fibrillation duration. Despite a higher prevalence of major risk factors for thromboembolism, the prevalence of LAAT was not increased in overweight, obese, and morbidly obese patients.     

非瓣膜性心房颤动患者的综合治疗

心房颤动(AF)是临床上最常见的心律失常类型,既往AF管理侧重于AF相关栓塞预防以及心室率和节律的控制。近年来,AF综合管理的理念逐渐普及。AF综合管理强调在做好AF相关栓塞预防及症状控制的基础上,同时关注患者生活质量的改善以及合并症的管理,以进一步改善患者的预后。本文就非瓣膜性心房颤动患者的抗凝治疗、症状管理及危险因素的控制作一综述。     

Clinical value of left atrial appendage flow for prediction of long-term sinus rhythm maintenance in patients with nonvalvular atrial fibrillation

OBJECTIVES: This study evaluated the role of various clinical and echocardiographic parameters, including the left atrial appendage (LAA) anterograde flow velocity, for prediction of the long-term preservation of sinus rhythm (SR) in patients with successful cardioversion (CV) of nonvalvular atrial fibrillation (AF). BACKGROUND: Echocardiographic parameters for assessing long-term SR maintenance after successful CV of nonvalvular AF are not accurately defined. METHODS: Clinical, transthoracic echocardiographic and transesophageal echocardiographic (TEE) data--measured in AF lasting >48 h--of 186 consecutive patients (116 men, mean age: 65 +/- 9 years) with successful CV (electrical or pharmacologic) were analyzed for assessment of one-year maintenance of SR. RESULTS: At one-year follow-up, 91 of 186 (49%) patients who underwent successful CV continued to have SR. Mean LAA peak emptying flow velocity was higher in patients remaining in SR for one year than in those with AF relapse (41.7 +/- 20.2 cm/s vs. 27.7 +/- 17.0 cm/s; p < 0.001). On multivariate logistic regression analysis, only the mean LAA peak emptying velocity >40 cm/s (p = 0.0001; chi(2): 23.9, odds ratio [OR] = 5.2, confidence interval [CI] 95% = 2.7 to 10.1) and the use of preventive antiarrhythmic drug treatment (p = 0.0398; chi(2): 4.2; OR = 2.0, CI 95% = 1.0 to 3.8) predicted the continuous preservation of SR during one year, outperforming other univariate predictors such as absence of left atrial spontaneous echocardiographic contrast during TEE, the left atrial parasternal diameter <44 mm, left ventricular ejection fraction >46% and AF duration <1 week before CV. The negative and positive predictive values of the mean LAA peak emptying velocity >40 cm/s for assessing preservation of SR were 66% (CI 95% = 56.9 to 74.2) and 73% (CI 95% = 62.4 to 83.3), respectively. CONCLUSIONS: In TEE-guided management of nonvalvular AF, high LAA flow velocity identifies patients with greater likelihood to remain in SR for one year after successful CV. Low LAA velocity is of limited value in identifying patients who will relapse into AF.     

非瓣膜性房颤患者右心耳右心房超声特征与心肌细胞凋亡关系的研究

目的研究非瓣膜性心房纤颤（NV-AF）右心耳（RAA）及右心房超声特征与心房肌细胞凋亡的关系。方法采用经食管超声观察25例NV-AF患者（观察组）和15例窦性心律者（对照组）的RAA及右心房变化,心肌细胞原位末端标记法（TUNEL法）检测RAA的心肌细胞凋亡指数。结果观察组RAA耳充血、排血峰速及速度积分、RAA及右心房射血分数均较对照组显著减小,RAA面积增大,心房肌细胞凋亡指数增高（P〈 0．05）。RAA内自发性超声造影（SEC）现象检出率占16％,RAA及右心房内未发现血栓。对照组未检出SEC或血栓。相关分析显示,心房肌细胞凋亡指数与RAA充流、排血峰速、RAA及右房射血分数呈负相关（P均〈 0．05）,而与RAA及右心房面积呈正相关（P均〈0．05）,与右心室射血分数无相关性（P〉0．05）。结论NV-AF患者的RAA及右心房改变与心房肌细胞凋亡密切相关,心肌细胞凋亡是其病理过程的中间或基础环节之一。     

缬沙坦对慢性非瓣膜性心房颤动者左房重塑的干预研究

目的观察缬沙坦对老年慢性非瓣膜性心房颤动(Af)患者左房重塑的影响并探讨其作用机制。方法选择54例老年慢性非瓣膜性心房颤动患者(病史>6月),随机分为缬沙坦组和对照组,2组常规治疗无明显差异,缬沙坦组加用缬沙坦80mg/d,疗程为12月。应用超声心动图记录50例窦性心律者(窦律组)及2组Af患者治疗前及治疗3、6、12月后左房内径(LAD),同时应用放射免疫分析法测定血清Ⅲ型前胶原末端肽(PⅢP)含量,随访治疗期间心脑血管事件的发生。结果Af患者LAD、PⅢP较窦律组明显增高。治疗前及治疗后3月、6月,2组Af患者LAD无明显差异(P>0·05);治疗12月后对照组LAD明显大于缬沙坦组(P<0·01);从治疗后6月起缬沙坦组PⅢP即有明显下降,与对照组相比差异显著(P<0·05,P<0·01);且PⅢP含量与左房内径呈正相关(r=0·4785,P<0·01);治疗期间缬沙坦组心脑血管事件发生率明显低于对照组(P<0·01)结论缬沙坦可能通过抑制心房局部肾素-血管紧张素系统(RAS),减少心肌胶原的合成与分泌,减轻心房纤维化,阻抑左房进行性扩大,改善心房顺应性,降低Af患者心脑血管事件的发生。