Clinical Characteristics,Management, and Control of Permanent vs. Nonpermanent Atrial Fibrillation: Insights from the RealiseAF Survey

Background

Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample.

Methods and Results

Data from RealiseAF, an international, observational, cross-sectional survey of 10,491 patients with atrial fibrillation, were used to characterize permanent atrial fibrillation (N = 4869) and nonpermanent atrial fibrillation (N = 5622) patients. Permanent atrial fibrillation patients were older, had a longer time since atrial fibrillation diagnosis, a higher symptom burden, and were more likely to be physically inactive. They also had a higher mean (SD) CHADS₂ score (2.2 [1.3] vs. 1.7 [1.3], p<0.001), and a higher frequency of CHADS₂ score ≥2 (67.3% vs. 53.0%, p<0.001) and comorbidities, most notably heart failure. Physicians indicated using a rate-control strategy in 84.2% of permanent atrial fibrillation patients (vs. 27.5% in nonpermanent atrial fibrillation). Only 50.2% (N = 2262/4508) of permanent atrial fibrillation patients were controlled. These patients had a longer time since atrial fibrillation diagnosis, a lower symptom burden, less obesity and physical inactivity, less severe heart failure, and fewer hospitalizations for acute heart failure than uncontrolled permanent atrial fibrillation patients, but with more arrhythmic events. The most frequent causes of hospitalization in the last 12 months were acute heart failure and stroke.

Conclusion

Permanent atrial fibrillation is a high-risk subset of atrial fibrillation, representing half of all atrial fibrillation patients, yet rate control is only achieved in around half. Since control is associated with lower symptom burden and heart failure, adequate rate control is an important target for improving the management of permanent atrial fibrillation patients.     

Late Sodium Current in Human Atrial Cardiomyocytes from Patients in Sinus Rhythm and Atrial Fibrillation

Slowly inactivating Na⁺ channels conducting “late” Na⁺ current (I_Na,late) contribute to ventricular arrhythmogenesis under pathological conditions. I_Na,late was also reported to play a role in chronic atrial fibrillation (AF). The objective of this study was to investigate I_Na,late in human right atrial cardiomyocytes as a putative drug target for treatment of AF. To activate Na⁺ channels, cardiomyocytes from transgenic mice which exhibit I_Na,late (ΔKPQ), and right atrial cardiomyocytes from patients in sinus rhythm (SR) and AF were voltage clamped at room temperature by 250-ms long test pulses to -30 mV from a holding potential of -80 mV with a 100-ms pre-pulse to -110 mV (protocol I). I_Na,late at -30 mV was not discernible as deviation from the extrapolated straight line IV-curve between -110 mV and -80 mV in human atrial cells. Therefore, tetrodotoxin (TTX, 10 μM) was used to define persistent inward current after 250 ms at -30 mV as I_Na,late. TTX-sensitive current was 0.27±0.06 pA/pF in ventricular cardiomyocytes from ΔKPQ mice, and amounted to 0.04±0.01 pA/pF and 0.09±0.02 pA/pF in SR and AF human atrial cardiomyocytes, respectively. With protocol II (holding potential -120 mV, pre-pulse to -80 mV) TTX-sensitive I_Na,late was always larger than with protocol I. Ranolazine (30 μM) reduced I_Na,late by 0.02±0.02 pA/pF in SR and 0.09±0.02 pA/pF in AF cells. At physiological temperature (37°C), however, I_Na,late became insignificant. Plateau phase and upstroke velocity of action potentials (APs) recorded with sharp microelectrodes in intact human trabeculae were more sensitive to ranolazine in AF than in SR preparations. Sodium channel subunits expression measured with qPCR was high for SCN5A with no difference between SR and AF. Expression of SCN8A and SCN10A was low in general, and lower in AF than in SR. In conclusion, We confirm for the first time a TTX-sensitive current (I_Na,late) in right atrial cardiomyocytes from SR and AF patients at room temperature, but not at physiological temperature. While our study provides evidence for the presence of INa,late in human atria, the potential of such current as a target for the treatment of AF remains to be demonstrated.     

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.     

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 2017 Survey of the Clinical Practice Patterns in the Management of Relapsing Graves Disease

Objective: Previous surveys from different world regions have demonstrated variations in the clinical management of Graves disease (GD). We aimed to investigate the clinical approach to GD relapse among endocrinologists.Methods: Electronic questionnaires were e-mailed to all members of the Israeli Endocrine Society. Questionnaires included demographic data and different scenarios regarding treatment and follow-up of patients with GD relapse.Results: The response rate was 49.4% (98/198). For a young male with GD relapse, 68% would restart antithyroid drug (ATD) (98% methimazole), while 32% would refer to radioactive iodine (RAI) treatment. Endocrinologists who treat >10 thyroid patients a week tended to choose ATDs over RAI (P = .04). In the case of GD relapse with ophthalmopathy, 50% would continue ATDs, whereas 22.4% would recommend RAI treatment and 27.6% surgery. Most endocrinologists (56%) would continue ATDs for 12 to 24 months. Seventy-five percent would monitor complete blood count and liver function (39% for the first month and 36% for 6 months), and 44% would recommend a routine neck ultrasound. In a case of thyrotoxicosis due to a 3-cm hot nodule, most endocrinologists (70%) would refer to RAI ablation, 46.4% without and 23.7% with a previous fine-needle aspiration. No significant differences were found regarding gender, year of board certification, or work environment.Conclusion: Our survey demonstrates diverging patterns in the diagnosis and management of GD relapse that correlate well with previous surveys from other countries on GD-naïve patients and a less than optimal adherence to recently published clinical guidelines.Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drug; CBC = complete blood count; GD = Graves disease; GO = Graves ophthalmopathy; LFT = liver function test; MMI = methimazole; PTU = propylthiouracil; RAI = radioactive iodine; TSI = thyroid-stimulating immunoglobulin     

持续正压通气治疗阻塞性睡眠呼吸暂停综合征并发心房纤颤的临床研究

目的:研究持续正压通气治疗阻塞性睡眠呼吸暂停综合征(OSAHS)并发心房纤颤的临床疗效。方法:选取2013年1月到2014年1月我院收治的OSAHS并发心房纤颤患者60例,按照随机数字表法将患者分为实验组和对照组,每组30例。对照组给予常规治疗,实验组在对照组的基础上给予持续正压通气治疗,两组均治疗1年。分析治疗前、后两组心率(HR)、血氧饱和度(SPO2)、左心射血分数(LVEF)、脑钠肽(BNP),并比较两组心房纤颤转复率、复发率和不良反应。结果:治疗后实验组HR、SPO2、LVEF以及BNP显著优于对照组,两组比较差异具有统计学意义(P0.05);治疗后实验组心房纤颤转复率显著高于对照组,心房纤颤复发率显著低于对照组,两组比较差异具有统计学意义(P0.05);两组不良反应发生率比较无统计学意义(P0.05)。结论:持续正压通气治疗OSAHS并发心房纤颤具有较好的效果,有利于改善心功能,提高心房纤颤转复率降低房纤颤复发率。     

Multiple Biomarkers and Atrial Fibrillation in the General Population

Background

Different biological pathways have been related to atrial fibrillation (AF). Novel biomarkers capturing inflammation, oxidative stress, and neurohumoral activation have not been investigated comprehensively in AF.

Methods and Results

In the population-based Gutenberg Health Study (n = 5000), mean age 56±11 years, 51% males, we measured ten biomarkers representing inflammation (C-reactive protein, fibrinogen), cardiac and vascular function (midregional pro adrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [Nt-proBNP], sensitive troponin I ultra [TnI ultra], copeptin, and C-terminal pro endothelin-1), and oxidative stress (glutathioneperoxidase-1, myeloperoxidase) in relation to manifest AF (n = 161 cases). Individuals with AF were older, mean age 64.9±8.3, and more often males, 71.4%. In Bonferroni-adjusted multivariable regression analyses strongest associations per standard deviation increase in biomarker concentrations were observed for the natriuretic peptides Nt-proBNP (odds ratio [OR] 2.89, 99.5% confidence interval [CI] 2.14–3.90; P<0.0001), MR-proANP (OR 2.45, 99.5% CI 1.91–3.14; P<0.0001), the vascular function marker MR-proADM (OR 1.54, 99.5% CI 1.20–1.99; P<0.0001), TnI ultra (OR 1.50, 99.5% CI 1.19–1.90; P<0.0001) and. fibrinogen (OR 1.44, 99.5% CI 1.19–1.75; P<0.0001). Based on a model comprising known clinical risk factors for AF, all biomarkers combined resulted in a net reclassification improvement of 0.665 (99.3% CI 0.441–0.888) and an integrated discrimination improvement of >13%.

Conclusions

In conclusion, in our large, population-based study, we identified novel biomarkers reflecting vascular function, MR-proADM, inflammation, and myocardial damage, TnI ultra, as related to AF; the strong association of natriuretic peptides was confirmed. Prospective studies need to examine whether risk prediction of AF can be enhanced beyond clinical risk factors using these biomarkers.     

Prospectively Quantifying the Propensity for Atrial Fibrillation: A Mechanistic Formulation

The goal of this study was to determine quantitative relationships between electrophysiologic parameters and the propensity of cardiac tissue to undergo atrial fibrillation. We used a computational model to simulate episodes of fibrillation, which we then characterized in terms of both their duration and the population dynamics of the electrical waves which drove them. Monte Carlo sampling revealed that episode durations followed an exponential decay distribution and wave population sizes followed a normal distribution. Half-lives of reentrant episodes increased exponentially with either increasing tissue area to boundary length ratio (A/BL) or decreasing action potential duration (APD), resistance (R) or capacitance (C). We found that the qualitative form of fibrillatory activity (e.g., multi-wavelet reentry (MWR) vs. rotors) was dependent on the ratio of resistance and capacitance to APD; MWR was reliably produced below a ratio of 0.18. We found that a composite of these electrophysiologic parameters, which we term the fibrillogenicity index (Fb = A/(BL*APD*R*C)), reliably predicted the duration of MWR episodes (r² = 0.93). Given that some of the quantities comprising Fb are amenable to manipulation (via either pharmacologic treatment or catheter ablation), these findings provide a theoretical basis for the development of titrated therapies of atrial fibrillation.     

Low Left Atrial Compliance Contributes to the Clinical Recurrence of Atrial Fibrillation after Catheter Ablation in Patients with Structurally and Functionally Normal Heart

Stiff left atrial (LA) syndrome was initially reported in post-cardiac surgery patients and known to be associated with low LA compliance. We investigated the physiological and clinical implications of LA compliance by estimating LA pulse pressure (LApp) among patients with atrial fibrillation (AF) and structurally and functionally normal heart. Among 1038 consecutive patients with LA pressure measurements before AF ablation, we included 334 patients with structurally and functionally normal heart (81.7% male, 54.1±10.6 years, 77.0% paroxysmal AF) after excluding those with hypertension, diabetes, and previous ablation or cardiac surgery. We measured LApp (peak-nadir LA pressure) at the beginning of the ablation procedure and compared the values with clinical parameters and the AF recurrence rate.AF patients with normal heart were younger and more frequently male and had paroxysmal AF, a lower body mass index, and a lower LApp compared to others (all p<0.05).Based on the median value, the low LA compliance group (LApp≥13mmHg) had a smaller LA volume index and lower LA voltage (all p<0.05) compared to the high LA compliance group. During a mean follow-up of 16.7±11.8 months, low LA compliance was independently associated with two fold-higher risk of clinical AF recurrence (HR:2.202; 95%CI:1.077–4.503; p = 0.031).Low LA compliance, as determined by an elevated LApp, was associated with a smaller LA volume index and lower LA voltage and independently associated with higher clinical recurrence after catheter ablation in AF patients with structurally and functionally normal heart.     

Cryoballoon Ablation for Paroxysmal Atrial Fibrillation in Septuagenarians: a Prospective Study

Aims

To evaluate the effects of pulmonary vein isolation (PVI) in terms of feasibility, safety and success rate on a midterm follow-up period in septuagenarians undergoing ablation with the Arctic Front Cryoballoon for atrial fibrillation (AF).

Methods and Results

We prospectively enrolled 21 patients aged 70 years or older (14 male; age 73 ± 2.5 years) elected to circumferential PVI with the 28mm cryoballoon for symptomatic drug resistant paroxysmal AF. A total number of 82 pulmonary veins (PV) were evidenced. Successful isolation could be obtained in all 82 (100%) PV ostia at the end of procedure. No major complication occurred during procedure. At a mean follow-up of 11.5 ± 4.7 months following ablation, 62% of patients did not present recurrence of atrial arrhythmias.

Conclusion

Cryoballoon ablation may be feasible and safe in older patients. Moreover a large proportion of the latter did not present AF recurrence during follow-up.     

Interleukin-6 Is a Risk Factor for Atrial Fibrillation in Chronic Kidney Disease: Findings from the CRIC Study

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic kidney disease (CKD). In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. AF was determined at baseline by self-report and electrocardiogram (ECG). Plasma concentrations of interleukin(IL)-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor-β, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects developed new-onset AF. There was no significant association between inflammatory biomarkers and past history of AF. After adjustment for demographic characteristics, comorbid conditions, laboratory values, echocardiographic variables, and medication use, plasma IL-6 level was significantly associated with presence of AF at baseline (Odds ratio [OR], 1.61; 95% confidence interval [CI], 1.21 to 2.14; P = 0.001) and new-onset AF (OR, 1.25; 95% CI, 1.02 to 1.53; P = 0.03). To summarize, plasma IL-6 level is an independent and consistent predictor of AF in patients with CKD.     

Spotted Wing Drosophila Prefer Low Hanging Fruit: Insights into Foraging Behavior and Management Strategies

Spotted wing drosophila, Drosophila suzukii, is an invasive insect that attacks ripe, small fruit such as raspberries, blackberries and blueberries. Little is known about its foraging ecology and current trapping methods and monitoring systems are ineffective at commercial scales. In semi-field studies, we evaluated adult alightment and ovipositional preference within and among raspberry plants using sentinel Tangletrap-coated and clean raspberry fruit, respectively, positioned within the exterior and interior plant canopy at four different heights (60, 85, 110 and 135 cm from the base) and conducted in field cages using sexually mature adults. Alightment of adults on Tangle-trap-coated fruit indicated a preference for fruit positioned at lower heights and/or interior locations based on significantly greater numbers being captured on sentinel sticky-coated berries at the two lowest heights. Oviposition in clean raspberry fruit also yielded a similar pattern. In mark-release-recapture studies conducted in the field, spotted wing drosophila prefer sentinel sticky fruit positioned on exterior rows as they alighted on these berries in significantly greater numbers than fruit at in the central portion of the plot. Likewise, in field trials with wild fly populations, infestations were significantly greater in edge rows compared with interior rows. Collectively, our results suggest that monitoring and behaviorally based management strategies may be more effective if they target adults foraging in the lower canopy of small fruit plants located on the crop perimeter.     

Attraction of Rotors to the Pulmonary Veins in Paroxysmal Atrial Fibrillation: A Modeling Study

Maintenance of paroxysmal atrial fibrillation (AF) by fast rotors in the left atrium (LA) or at the pulmonary veins (PVs) is not fully understood. To gain insight into this dynamic and complex process, we studied the role of the heterogeneous distribution of transmembrane currents in the PVs and LA junction (PV-LAJ) in the localization of rotors in the PVs. We also investigated whether simple pacing protocols could be used to predict rotor drift in the PV-LAJ. Experimentally observed heterogeneities in I_K1, I_Ks, I_Kr, I_to, and I_CaL in the PV-LAJ were incorporated into two- and pseudo three-dimensional models of Courtemanche-Ramirez-Nattel-Kneller human atrial kinetics to simulate various conditions and investigate rotor drifting mechanisms. Spatial gradients in the currents resulted in shorter action potential duration, minimum diastolic potential that was less negative, and slower upstroke and conduction velocity for rotors in the PV region than in the LA. Rotors under such conditions drifted toward the PV and stabilized at the shortest action potential duration and less-excitable region, consistent with drift direction under intercellular coupling heterogeneities and regardless of the geometrical constraint in the PVs. Simulations with various I_K1 gradient conditions and current-voltage relationships substantiated its major role in the rotor drift. In our 1:1 pacing protocol, we found that among various action potential properties, only the minimum diastolic potential gradient was a rate-independent predictor of rotor drift direction. Consistent with experimental and clinical AF studies, simulations in an electrophysiologically heterogeneous model of the PV-LAJ showed rotor attraction toward the PV. Our simulations suggest that I_K1 heterogeneity is dominant compared to other currents in determining the drift direction through its impact on the excitability gradient. These results provide a believed novel framework for understanding the complex dynamics of rotors in AF.     

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.     

上胸段硬膜外阻滞治疗慢性心力衰竭合并房颤的临床研究

目的:比较上胸段硬膜外阻滞对有无合并房颤的扩张型心肌病心衰患者的疗效差异。方法:入选40例扩张型心肌病心衰患者,根据入院心电图有无房颤分为房颤组和非房颤组。所有患者均在抗心力衰竭常规治疗基础上,给予胸段硬膜外阻滞治疗4周,比较治疗前、后NYHA心功能分级、血浆N末端脑钠肽前体(NT-pro BNP)水平、左室射血分数(LVEF)、左室舒张期内径(LVEDD)及左房前后径(LAD)的变化情况。结果:与治疗前比较,两组患者经治疗后的NYHA心功能分级、NT-pro BNP、LVEF、LVEDD及LAD均明显改善(均P0.05),差异有统计学意义,但两组间各指标治疗前后的差值无统计学意义(P0.05)。结论:对于慢性心力衰竭合并房颤的患者而言,给予抗心力衰竭常规治疗基础上联合上胸段硬膜外阻滞治疗有效,且房颤的存在与否不影响上胸段硬膜外阻滞的疗效。     

肌钙蛋白I水平检测对急诊房颤患者的临床意义

目的:探讨房颤患者急诊入院时检测肌钙蛋白I(Tn I)水平的临床作用及预测价值。方法:回顾性分析我院523例房颤患者的临床资料,将资料中数据进行统计学分析处理。患者分为三组:1组患者Tn I轻度升高;2组患者Tn I正常;3组患者未检测Tn I,分别就三组患者的基线特征以及就诊时的症状展开数据比较,并且单变量及多变量分析Tn I升高的预测因子。设置主要终点为1年内所有原因导致的死亡及心肌梗死(MI),患者从入院时起随访1年,记录期间的MI发生情况及死亡情况。结果:173例患者(33%)Tn I轻度升高(均值0.56 ng/m L),225例患者(43%)Tn I正常,125例患者(24%)未检测Tn I。住院期间1组患者(50%)的心功能检查异常明显高于组2和组3(28%和29%,P≤0.001),1组患者(22%)主要终点发生率明显高于2组(10%)和3组患者(15%)(P=0.002),有统计学意义。结论:肌钙蛋白I轻度升高与冠脉疾病(CAD)发生率增加及MI发生率增加有关,但对于总体死亡率无影响。