Depression in Atrial Fibrillation in the General Population

Background

Initial evidence suggests that depressive symptoms are more frequent in patients with atrial fibrillation. Data from the general population are limited.

Methods and Results

In 10,000 individuals (mean age 56±11 years, 49.4% women) of the population-based Gutenberg Health Study we assessed depression by the Patient Health Questionnaire (PHQ-9) and a history of depression in relation to manifest atrial fibrillation (n = 309 cases). The median (25th/75th percentile) PHQ-9 score of depressive symptoms was 4 (2/6) in atrial fibrillation individuals versus 3 (2/6) individuals without atrial fibrillation, . Multivariable regression analyses of the severity of depressive symptoms in relation to atrial fibrillation in cardiovascular risk factor adjusted models revealed a relation of PHQ-9 values and atrial fibrillation (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01–1.08; P = 0.023). The association was stronger for the somatic symptom dimension of depression (OR 1.08, 95% CI 1.02–1.15; P = 0.0085) than for cognitive symptoms (OR 1.05, 95% CI 0.98–1.11; P = 0.15). Results did not change markedly after additional adjustment for heart failure, partnership status or the inflammatory biomarker C-reactive protein. Both, self-reported physical health status, very good/good versus fair/bad, (OR 0.54, 95% CI 0.41–0.70; P<0.001) and mental health status (OR 0.61 (0.46–0.82); P = 0.0012) were associated with atrial fibrillation in multivariable-adjusted models.

Conclusions

In a population-based sample we observed a higher burden of depressive symptoms driven by somatic symptom dimensions in individuals with atrial fibrillation. Depression was associated with a worse perception of physical or mental health status. Whether screening and treatment of depressive symptoms modulates disease progression and outcome needs to be shown.     

Estimated Glomerular Filtration Rate and Proteinuria Are Separately and Independently Associated with the Prevalence of Atrial Fibrillation in General Population

Background

Both, proteinuria and a decline in glomerular filtration rate (GFR) are associated with greater cardiovascular mortality. However, few studies have explored that proteinuria and lower GFR are related with prevalent atrial fibrillation (AF).

Methods

This cross-sectional study was based on annual health check-up program of community-based population in Gunma, Japan from April 2011 to March 2012. A total of 20,019 adult participants were included. AF was ascertained by a standard 12-lead electrocardiogram. Cross-sectional association and correlates with prevalent AF were examined using multivariable logistic regression analysis.

Results

The overall prevalence of AF was 0.6% (2.2 % in participants with eGFR < 60 mL▪min^-1･1.73m^-2, 0.4% and 0.2% in those with eGFR 60 to 89 and ≧90 mL▪min^-1･1.73m^-2, p for trend <0.001). The multivariable odds ratio (OR) for AF was 2.86 (95 % CI 1.16 - 7.08, p<0.001) for eGFR< 60 mL▪min^-1▪1.73m^-2 versus eGFR≧ 90 mL▪min^-1▪1.73m^-2. This association remained significant with further adjustment for proteinuria. In addition, proteinuria was also strongly associated with increased prevalence of AF (OR 2.96, 95 % CI 1.55-5.68, p<0.001), an association that remained significant after adjustment for eGFR.

Conclusions

Proteinuria and lower eGFR are separately and significantly associated with prevalence of AF independent of well-established risk factors for AF in general population.     

Familial Atrial Fibrillation

Benign familial atrial fibrillation is of rare occurrence. A family in which three members manifested this disorder is reported. Apart from this, all three are in excellent health.The relative frequency of non-familial atrial fibrillation in otherwise well people, free from cardiac and metabolic disorders, is stressed. Only too frequently such cases have been and continue to be labelled with the stigma of serious disease with an unhappy prognosis. Serious injustice may be occasioned in such cases in many respects; for example, in the influence that this medical judgment may have on the insurability of young people so afflicted.Methods of exclusion of organic causes of this disorder are outlined and principles of management and treatment are discussed.     

心房重构与心房纤颤的病理学机制研究进展

目前,发生率最高的心率失常被认为是心房纤颤,且该病的发生率随着年龄的增长而上升。伴随着我国人口年龄结构的变化,心房纤颤在我国的发病率逐渐增加。了解该病的发生和发展的机制十分迫切。已经证明,心房重构是该病的重要发生机制。随着研究的加深,研究人员对心房重构与该病的病理学机制有了更加深刻的了解。现就心房纤颤和重构在发病中的机制进行回顾。     

Whole Exome Sequencing in Atrial Fibrillation

Atrial fibrillation (AF) is a morbid and heritable arrhythmia. Over 35 genes have been reported to underlie AF, most of which were described in small candidate gene association studies. Replication remains lacking for most, and therefore the contribution of coding variation to AF susceptibility remains poorly understood. We examined whole exome sequencing data in a large community-based sample of 1,734 individuals with and 9,423 without AF from the Framingham Heart Study, Cardiovascular Health Study, Atherosclerosis Risk in Communities Study, and NHLBI-GO Exome Sequencing Project and meta-analyzed the results. We also examined whether genetic variation was enriched in suspected AF genes (N = 37) in AF cases versus controls. The mean age ranged from 59 to 73 years; 8,656 (78%) were of European ancestry. None of the 99,404 common variants evaluated was significantly associated after adjusting for multiple testing. Among the most significantly associated variants was a common (allele frequency = 86%) missense variant in SYNPO2L (rs3812629, p.Pro707Leu, [odds ratio 1.27, 95% confidence interval 1.13–1.43, P = 6.6x10^-5]) which lies at a known AF susceptibility locus and is in linkage disequilibrium with a top marker from prior analyses at the locus. We did not observe significant associations between rare variants and AF in gene-based tests. Individuals with AF did not display any statistically significant enrichment for common or rare coding variation in previously implicated AF genes. In conclusion, we did not observe associations between coding genetic variants and AF, suggesting that large-effect coding variation is not the predominant mechanism underlying AF. A coding variant in SYNPO2L requires further evaluation to determine whether it is causally related to AF. Efforts to identify biologically meaningful coding variation underlying AF may require large sample sizes or populations enriched for large genetic effects.     

Robotic Ablation of Atrial Fibrillation

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between pulmonary vein (PV) and left atrium (LA) is created. This conduction block prevents AF, which is triggered by irregular electric activity originating from the PV. However, transmural atrial lesions are required which can be challenging. Re-conduction and AF recurrence occur in 20 - 40% of the cases. Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new remote catheter system (RCS), is presented. Objective of this article is to show feasibility of robotic AF ablation with a novel system. Materials and Methods: After interatrial trans-septal puncture is performed using a long sheath and needle under fluoroscopic guidance. The needle is removed and a guide wire is placed in the left superior PV. Then an ablation catheter is positioned in the LA, using the sheath and wire as guide to the LA. LA angiography is performed over the sheath. A circular mapping catheter is positioned via the long sheath into the LA and a three-dimensional (3-D) anatomical reconstruction of the LA is performed. The handle of the ablation catheter is positioned in the robotic arm of the Amigo system and the ablation procedure begins. During the ablation procedure, the operator manipulates the ablation catheter via the robotic arm with the use of a remote control. The ablation is performed by creating point-by-point lesions around the left and right PV ostia. Contact force is measured at the catheter tip to provide feedback of catheter-tissue contact. Conduction block is confirmed by recording the PV potentials on the circular mapping catheter and by pacing maneuvers. The operator stays out of the radiationfield during ablation. Conclusion: The novel catheter system allows ablation with high stability on low operator fluoroscopy exposure.     

Atrial Fibrillation and Colonic Neoplasia in African Americans

Background

Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American.

Methods

We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression.

Results

The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9–2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7–1.6, P = 0.7) were not significantly associated AF compared to control group.

Conclusions

AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.     

紫草对心房颤动模型大鼠的影响

目的:探讨紫草对房颤模型大鼠的心房颤动的发生及发展的作用及相关机制。方法:大鼠通过尾静脉连续给乙酰胆碱-氯化钙(Ach-CaCl_2)造模。第6天开始,紫草组予紫草汤药灌胃,胺碘酮组予胺碘酮溶液灌胃,空白组和模型组予生理盐水灌胃。于第14天进行心电图检查并记录房颤的诱发时间及持续时间,之后,超声心电图检查以记录左房面积(LA area)、射血分数(EF%)、左室舒张末径(LVDD)、左室收缩末径(LVDS),以评估紫草对模型大鼠的心脏重构和功能的影响。结果:1.紫草降低心房颤动大鼠的心房颤动诱发率并缩短了心房颤动的持续时间;2.紫草使心房颤动大鼠的心房重构改善,表现为左房面积和左室内径的减小,但对EF值无明显影响。     

Orthostatic Change in Blood Pressure and Incidence of Atrial Fibrillation: Results from a Bi-Ethnic Population Based Study

Background

Autonomic fluctuations are associated with the initiation and possibly maintenance of atrial fibrillation (AF). However, little is known about the relationship between orthostatic blood pressure change, a common manifestation of autonomic dysfunction, and incident AF.

Methods

We examined whether supine-to-standing changes in systolic blood pressure (SBP) are associated with incident AF in 12,071 African American and white men and women aged 45–64 years, enrolled in the Atherosclerosis Risks in Communities (ARIC) study. Orthostatic hypotension (OH) was defined as a supine-standing drop in SBP by ≥20 mmHg or diastolic blood pressure by ≥10 mmHg. AF cases were identified based on study scheduled 12-lead ECG, hospital discharge ICD codes, and death certificates through 2009.

Results

OH was seen in 603 (5%) at baseline. During an average follow-up of 18.1 years, 1438 (11.9%) study participants developed AF. Incident AF occurred more commonly among those with OH than those without, a rate of 9.3 vs. 6.3 per 1000 person years, (p<0.001). The age, gender, and race adjusted hazard ratio (95%CI) of AF among those with OH compared to those without was 1.62 (1.34, 2.14). This association was attenuated after adjustment for common AF risk factors to HR 1.40 (1.15, 1.71), a strength similar to that of diabetes or hypertension with AF in the same model. A non-linear relationship between orthostatic change in SBP and incident AF was present after multivariable adjustment.

Conclusions

OH is associated with higher AF incidence. Whether interventions that decrease OH can reduce AF risk remains unknown.     

Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study)

Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are widespread diseases and have multiple common risk factors and comorbidities. No studies of association between ultrasonography-diagnosed NAFLD and AF exist in other than diabetic population. The goal of this prospective study was to study the value of NAFLD as a predictor of atrial fibrillation. This study had 958 subjects from the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort, and the mean follow-up time was 16.3 years. NAFLD was diagnosed if the subject had fatty liver in ultrasonography and no excess alcohol intake. AF was followed in the National Registers. In this study 249 subjects (26.0%) had NAFLD and 37 (14.9%) of these had AF whereas only 56 (7.9%) of those without NAFLD experienced AF during the follow-up time (p = 0.001). In the multiple Cox regression analysis including potential confounders (age, sex, study group, diabetes, body mass index (BMI), waist circumference, alcohol consumption, smoking, serum alanine aminotransferase concentration (ALT), systolic blood pressure, quick index, left ventricular mass index, left atrial diameter, coronary artery disease (CAD), atrial natriuretic peptide (ANP) and high sensitive C-reactive protein (hs-CRP)), NAFLD remained as an independent predictor of AF (Adjusted OR, 1.88 (95% Confidence interval (CI) 1.03–3.45)). In conclusion, our data shows that NAFLD is independently associated with the risk of AF.     

The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States ¹. Since AF affects primarily elderly people, its prevalence increases parallel with age. As such, it is expected that 15.9 million Americans will be affected by the year 2050 ². Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current treatments for AF include rate control, rhythm control and prevention of stroke ³.The American College of Cardiology, American Heart Association, and European Society of Cardiology currently recommended rate control as the first course of therapy for AF ³. Rate control is achieved by administration of pharmacological agents, such as β-blockers, that lower the heart rate until it reaches a less symptomatic state ³. Rhythm control aims to return the heart to its normal sinus rhythm and is typically achieved through administration of antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation therapy. Rhythm control methods, however, have not been demonstrated to be superior to rate-control methods ^4-6. In fact, certain antiarrhythmic drugs have been shown to be associated with higher hospitalization rates, serious adverse effects ³, or even increases in mortality in patients with structural heart defects ⁷. Thus, treatment with antiarrhythmics is more often used when rate-control drugs are ineffective or contraindicated. Rate-control and antiarrhythmic agents relieve the symptoms of AF, including palpitations, shortness of breath, and fatigue ⁸, but don''t reliably prevent thromboembolic events ⁶.Treatment with the anticoagulant drug warfarin significantly reduces the rate of stroke or embolism ^9,10. However, because of problems associated with its use, fewer than 50% of patients are treated with it. The therapeutic dose is affected by drug, dietary, and metabolic interactions, and thus requires detailed monitoring. In addition, warfarin has the potential to cause severe, sometimes lethal, bleeding ². As an alternative, aspirin is commonly prescribed. While aspirin is typically well tolerated, it is far less effective at preventing stroke ¹⁰. Other alternatives to warfarin, such as dabigatran ¹¹ or rivaroxaban ¹² demonstrate non-inferiority to warfarin with respect to thromboembolic events (in fact, dabigatran given as a high dose of 150 mg twice a day has shown superiority). While these drugs have the advantage of eliminating dietary concerns and eliminating the need for regular blood monitoring, major bleeding and associated complications, while somewhat less so than with warfarin, remain an issue ^13-15.Since 90% of AF-associated strokes result from emboli that arise from the left atrial appendage (LAA) ², one alternative approach to warfarin therapy has been to exclude the LAA using an implanted device to trap blood clots before they exit. Here, we demonstrate a procedure for implanting the WATCHMAN Left Atrial Appendage Closure Device. A transseptal cannula is inserted through the femoral vein, and under fluoroscopic guidance, inter-atrial septum is crossed. Once access to the left atrium has been achieved, a guidewire is placed in the upper pulmonary vein and the WATCHMAN Access Sheath and dilator are advanced over the wire into the left atrium. The guidewire is removed, and the access sheath is carefully advanced into the distal portion of the LAA over a pigtail catheter. The WATCHMAN Delivery System is prepped, inserted into the access sheath, and slowly advanced. The WATCHMAN device is then deployed into the LAA. The device release criteria are confirmed via fluoroscopy and transesophageal echocardiography (TEE) and the device is released.     

房颤患者心房肌细胞的原代培养与应用

探索成功培养房颤(atrial fibrillation,AF)患者原代心房肌细胞的方法,能够为房颤发病机制的研究奠定实验基础。取心胸外科行迷宫手术患者的左心耳,利用I型胶原蛋白酶消化法培养房颤患者的原代心房肌细胞,通过免疫组化进行鉴定,同时对培养的心房肌细胞进行初步研究。与动物实验相反,房颤患者心房肌细胞缝隙连接蛋白40(connexin40,Cx40)及Kv1.5钾离子通道蛋白的表达量均降低。由此可见直接研究成人房颤患者的心房肌细胞具有更高的可靠性,同时也证明了房颤患者心房肌细胞的培养是研究其发病机制的基础。