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.     

Comparable Ascertainment of Newly-Diagnosed Atrial Fibrillation Using Active Cohort Follow-Up versus Surveillance of Centers for Medicare and Medicaid Services in the Atherosclerosis Risk in Communities Study

Objective

Increasingly, epidemiologic studies use administrative data to identify atrial fibrillation (AF). Capture of incident AF is not well documented. We examined incidence rates and concordance of AF diagnosis based on active cohort follow-up versus surveillance of Centers for Medicare and Medicaid Services data in the Atherosclerosis Risk in Communities study.

Methods

Atherosclerosis Risk in Communities cohort participants without prevalent AF enrolled in fee-for-service Medicare, with inpatient and outpatient coverage, for at least 12 continuous months between 1991 and 2009 were included. In active Atherosclerosis Risk in Communities study follow-up, annual telephone calls captured hospitalizations and deaths with incident AF diagnosis codes. For Centers for Medicare and Medicaid Services data, incident AF was defined by billed inpatient and outpatient diagnoses.

Results

Of 10,134 eligible cohort participants, 738 developed AF according to both Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services data; an additional 93 and 288 incident cases were identified using only Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services data, respectively. Incidence rates per 1,000 person-years were 10.8 (95% confidence interval: 10.1–11.6) and 13.6 (95% confidence interval: 12.8–14.4) in Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services, respectively; agreement was 96%; kappa was 0.77 (95% confidence interval: 0.75–0.80). Earlier AF ascertainment by one system versus the other was not associated with any cardiovascular disease risk factors, after accounting for sociodemographic factors. Additional Centers for Medicare and Medicaid Services events did not alter observed associations between risk factors and AF.

Conclusion

Among fee-for-service enrollees, AF incidence rates were slightly lower for active cohort follow-up than for Centers for Medicare and Medicaid Services surveillance, because the latter included outpatient atrial fibrillation. Concordance was high and combining the two approaches could provide a more complete picture of newly-diagnosed 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.     

Shensongyangxin Capsules for Paroxysmal Atrial Fibrillation: A Systematic Review of Randomized Clinical Trials

Objective

To evaluate the evidence for the effectiveness and safety of Shensongyangxin Capsules (SSYX) for treating paroxysmal atrial fibrillation (PAF).

Methods

We searched for randomized clinical trials for SSYX in PAF up to June 2015. The Cochrane risk of bias tool was used to assess the methodological quality. RevMan 5.3 was used to synthesize the results.

Results

We included 22 trials involving 2,347 PAF patients. The quality of the included studies was generally poor. The results of the meta-analysis showed that SSYX plus routine treatment was more effective at improving P-wave dispersion (Pwd) and the frequency of PAF attacks compared with routine treatment alone. The results from the included trials that compared SSYX plus routine treatment and arrhythmic drugs plus routine treatment were inconsistent. Trials reported on Pwd, quality of life, frequency of PAF attacks or maintenance rate of sinus rhythm and found that SSYX combined with anti-arrhythmic drugs plus routine treatment was more effective than anti-arrhythmic drugs plus routine treatment. Four of the trials reported adverse events, indicating that SSYX was potentially safer than anti-arrhythmic drugs.

Conclusions

There appears to be some benefit from the use of SSYX. However, due to poor methodological quality, we could not draw confirmative conclusions regarding the beneficial effect of using SSYX.     

A Decision-Making System with Reject Option for Atrial Fibrillation Prediction Without ECG Signals

ObjectivesThis paper presents a new method for Atrial Fibrillation detection based on the belief functions theory.Materials and methodsThe theoretical framework allows to handle missing and uncertain data, to aggregate evidence in an independent order of sources of information and to reject a decision in case of insufficient supporting evidence. The proposed method is evaluated on real signals acquired from Intensive Care Units available in the MIMIC-III database and compared to state-of-the-art technologies and methods.ResultsThe precision of the suggested method is 90.03%, which is 2% more than existing methods in the literature.ConclusionWhile almost all existing methods rely on high frequency sampled ECG signals, mainly at 125 Hz, to achieve a good accuracy, our proposed approach achieves a comparable performance using low frequency sampled physiological signals at 0.016 Hz without the need for an ECG which allows for a significant reduction in energy consumption, in data size and in processing complexity.     

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.     

Recent Trends in Imaging for Atrial Fibrillation Ablation

Catheter ablation provides an important treatment option for patients with both paroxysmal and persistent atrial fibrillation. It mainly involves pulmonary vein isolation and additional ablations in the left atrium in persistent cases. There have been significant advancements in this procedure to enhance the safety and effectiveness. One of them is the evolution of various imaging modalities to facilitate better visualization of the complex left atrial anatomy and the pulmonary veins in order to deliver the lesions accurately. In this article, we review the electroanatomic mapping systems including the magnetic-based and impedence-based systems. Each of these mapping systems has its own advantages and disadvantages. In addition, we also discuss the role of intracardiac echocardiography and three dimensional rotational angiography in atrial fibrillation ablation.     

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide ^1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope ^{4, 5}. Patients with AF have a five-fold higher risk of stroke ⁶.Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% ⁷. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range ^8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug ⁸.The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF ^12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers ⁴. CA is a well-established treatment for AF symptoms ^{14, 15}, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy ¹⁶.Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation ¹⁷, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) ¹⁸. This device received the Conformité Européenne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy ¹⁹.Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding ²⁰ or other warfarin-associated problems.The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS₂ score of greater than 1 ²¹. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.     

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.     

Disrupted Calcium Release as a Mechanism for Atrial Alternans Associated with Human Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, but our knowledge of the arrhythmogenic substrate is incomplete. Alternans, the beat-to-beat alternation in the shape of cardiac electrical signals, typically occurs at fast heart rates and leads to arrhythmia. However, atrial alternans have been observed at slower pacing rates in AF patients than in controls, suggesting that increased vulnerability to arrhythmia in AF patients may be due to the proarrythmic influence of alternans at these slower rates. As such, alternans may present a useful therapeutic target for the treatment and prevention of AF, but the mechanism underlying alternans occurrence in AF patients at heart rates near rest is unknown. The goal of this study was to determine how cellular changes that occur in human AF affect the appearance of alternans at heart rates near rest. To achieve this, we developed a computational model of human atrial tissue incorporating electrophysiological remodeling associated with chronic AF (cAF) and performed parameter sensitivity analysis of ionic model parameters to determine which cellular changes led to alternans. Of the 20 parameters tested, only decreasing the ryanodine receptor (RyR) inactivation rate constant (ki_Ca) produced action potential duration (APD) alternans seen clinically at slower pacing rates. Using single-cell clamps of voltage, fluxes, and state variables, we determined that alternans onset was Ca²⁺-driven rather than voltage-driven and occurred as a result of decreased RyR inactivation which led to increased steepness of the sarcoplasmic reticulum (SR) Ca²⁺ release slope. Iterated map analysis revealed that because SR Ca²⁺ uptake efficiency was much higher in control atrial cells than in cAF cells, drastic reductions in ki_Ca were required to produce alternans at comparable pacing rates in control atrial cells. These findings suggest that RyR kinetics may play a critical role in altered Ca²⁺ homeostasis which drives proarrhythmic APD alternans in patients with AF.     

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。     

N-terminal Pro-Brain Natriuretic Peptide And Atrial Fibrillation

NT-proBNP is produced from both atria and ventricles. The primary regulation of production is at the synthesis level. The plasma half-life of NT-proBNP is 60-120 min. Cutoff value of NT-proBNP for diagnosis of heart failure is 125 pg/ml in the age group below 75 years and 450 pg/ml in the age group above 75 years. It increases in atrial fibrillation and drops after successful cardioversion. High levels predict development of atrial fibrillation (AF) in healthy persons with sinus rhythm (SR). Some studies concluded that baseline level predicts maintenance of SR after cardioversion of AF while some others found that it did not. Many studies have proven that it is useful in monitoring rhythm stability after cardioversion of AF. Since it is increased in many other conditions, out of which some may also cause AF, care must be taken before ascribing changes in its level to AF alone.     

Computational Mapping Identifies Localized Mechanisms for Ablation of Atrial Fibrillation

Atrial fibrillation (AF) is the most common heart rhythm disorder in the Western world and a common cause of hospitalization and death. Pharmacologic and non-pharmacologic therapies have met with limited success, in part due to an incomplete understanding of the underlying mechanisms for AF. AF is traditionally characterized by spatiotemporally disorganized electrical activation and, although initiating triggers for AF are described, it is unclear whether AF is sustained by spatially meandering continuous excitation (re-entrant waves), localized electrical sources within the atria, or some other mechanism. This has limited therapeutic options for this condition. Here we show that human AF is predominantly caused by a small number (1.8±0.9) of localized re-entrant waves or repetitive focal beats, that remain stable with limited spatial migration over prolonged periods of time. Radiofrequency ablation that selectively targeted the sites of these sources was able to immediately terminate fibrillation and eliminate the arrhythmia with high success. Our results show that human AF, despite apparent spatiotemporal disorganization, is often perpetuated by a few spatially-constrained and temporally conserved sources whose targeted ablation can eliminate this complex rhythm disorder.     

Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

BackgroundAtrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene.MethodsA total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study.ResultsIn single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared ‘TT’ haplotype with the common ‘TC’ haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with ‘TC’, carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with ‘TT’ haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF.ConclusionsVia a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor.