Atrial Fibrillation Subjects Research Articles

Ganoderma lucidum Polysaccharide Peptide Reduce Inflammation and Oxidative Stress in Patient with Atrial Fibrillation

BACKGROUND: Atrial fibrillation (AF) could be triggered by inflammation and oxidative stress. Ganoderma lucidum has an active substance in the form of β-glucan that can reduce inflammatory process and oxidative stress in rats. The objective of this study was to evaluate the effect of Ganoderma lucidum polysaccharide peptide (GLPP) in paroxysmal AF subjects with parameters of anti-inflammatory antioxidant, electrocardiography and health-related quality of life (HRQoL).METHODS: A randomized closed-label clinical trial with pre- and post-test design was conducted. After AF subjects selection, the subjects were randomized, interviewed and veni-punctured to isolate blood plasma. AF Subjects were then treated with placebo or GLPP for 90 days. Post-test blood plasma was collected on the following day after the 90th day. Then anti-inflammatory and antioxidant parameters were measured. After that, echocardiographic and HRQoL assessments were performed.RESULTS: A total of 38 subjects, 11 males and 27 females, completed the study with no significant changes in diets, physical activities, or medications. Comparing to control, the 90-days GLPP-treated subject characteristics were significant difference in systolic blood pressure, heart rate, malondialdehyde, high-sensitivity C-reactive protein, tumor necrosis factor-a, interleukin (IL)-1b, IL-6, primary (P)-wave dispersion, P-max, physical functioning, limitation to physical health, energy/fatigue, pain, and physical limitation.CONCLUSION: GLPP has several potential effects in AF subjects, including anti-inflammatory, antioxidant, and atrial remodelling, so that HRQoL of AF subjects could be improved. Hence, GLPP could suggested as a potential supplementing agent for AF management.KEYWORDS: atrial fibrillation, Ganoderma lucidum, inflammation, antioxidant, atrial remodelling, quality of life

Increased Monocyte Count is Related to the Development of Atrial Fibrillation in Subjects with Heart Failure

Determining subjects with heart failure (HF), who have a high risk of developing atrial fibrillation (AF), is crucial since it is related to an increase in morbidity and mortality. The importance of an increase in inflammatory response cannot be ignored in developing AF in subjects with HF. This study’s goal was to evaluate the relationship between the development of AF and monocyte count, the main components of the inflammatory response, in subjects with HF. Medical data of 158 subjects in total with sinus rhythm, admitted to the emergency department and hospitalized with systolic HF between January 2009 and February 2014, were analyzed prospectively. All the subjects followed up in terms of the development of AF. The subjects separated into two groups according to their rhythm at the end of the follow-up period. Group 1 included subjects who maintained sinus rhythm, while Group 2 included subjects with AF. Echocardiographic findings and laboratory data were collected. No statistically significant difference was determined between the groups concerning age, sex (p=0.056), hypertension, diabetes mellitus, and smoking status. The two groups differed significantly regarding the presence of moderate-to-severe mitral regurgitation (MR) [32 (28%) vs. 22 (51%), p=0.010] and monocyte count [560 (20-3100) vs. 800 (380-1510) μL, p<0.001]. The multivariate Cox regression model demonstrated that an association of monocyte count (HR=2.397, 95% CI =1.397-4.112, p=0.002) and moderate-to-severe MR (HR= 2.347, 95% CI=1.276-4.316, p=0.006) with the development of AF remained following the adjustment for the variables, which had determined to be statistically significant as a result of the univariate analysis and related to monocyte count. The present study concludes that increased monocyte count in subjects with HF is related to the development of AF. However, further large-scale research required for confirming the findings, as mentioned above.

Increased Monocyte Count is Related to the Development of Atrial Fibrillation in Subjects with Heart Failure

Determining subjects with heart failure (HF), who have a high risk of developing atrial fibrillation (AF), is crucial since it is related to an increase in morbidity and mortality. The importance of an increase in inflammatory response cannot be ignored in developing AF in subjects with HF. This study’s goal was to evaluate the relationship between the development of AF and monocyte count, the main components of the inflammatory response, in subjects with HF. Medical data of 158 subjects in total with sinus rhythm, admitted to the emergency department and hospitalized with systolic HF between January 2009 and February 2014, were analyzed prospectively. All the subjects followed up in terms of the development of AF. The subjects separated into two groups according to their rhythm at the end of the follow-up period. Group 1 included subjects who maintained sinus rhythm, while Group 2 included subjects with AF. Echocardiographic findings and laboratory data were collected. No statistically significant difference was determined between the groups concerning age, sex (p=0.056), hypertension, diabetes mellitus, and smoking status. The two groups differed significantly regarding the presence of moderate-to-severe mitral regurgitation (MR) [32 (28%) vs. 22 (51%), p=0.010] and monocyte count [560 (20-3100) vs. 800 (380-1510) μL, p<0.001]. The multivariate Cox regression model demonstrated that an association of monocyte count (HR=2.397, 95% CI =1.397-4.112, p=0.002) and moderate-to-severe MR (HR= 2.347, 95% CI=1.276-4.316, p=0.006) with the development of AF remained following the adjustment for the variables, which had determined to be statistically significant as a result of the univariate analysis and related to monocyte count. The present study concludes that increased monocyte count in subjects with HF is related to the development of AF. However, further large-scale research required for confirming the findings, as mentioned above.

Abstract 16439: Is Pulmonary Venous Flow Pulsatility a Critical Determinant of Left Atrial Appendage Blood Stasis Risk?

Introduction: Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, most commonly in the left atrial appendage (LAA), and a resultant five-fold increase in the risk of ischemic stroke. The current standard of stratifying stroke risk, based on the CHA 2 DS 2 -VASc score, does not consider subject-specific LAA hemodynamics and blood stasis risk. We have developed a methodology for computing mean residence time of blood-borne particles in the LAA ( t m ), an index of LAA blood stasis, using 3D left atrial (LA) and LAA geometries and pulmonary venous (PV) inlet blood flow data. While subject-specific 3D geometry can be obtained readily, it is not easy to measure all LA inlet blood flow waveforms in vivo . Therefore, a sensitivity study of LAA t m to the inlet blood flow waveform characteristics (shape and magnitude) is needed. Hypothesis: PV flow pulsatility does not affect LAA t m . Methods: Cardiac computed tomography images of 10 AF subjects were obtained and LA and LAA geometries were reconstructed in 3D and subsequently meshed for computational fluid dynamics (CFD) analysis. We employed CFD analysis, modeling blood cells as neutrally buoyant tracers transported in the blood and used a systems-based approach, to quantify LAA t m . Each subject was simulated using four PV blood flow characteristics: (1) Normal-S , steady PV flow with cardiac output (CO) of 5.5 L/min; (2) AF-S , steady PV flow with reduced CO of 4.4 L/min; (3) Normal-P , normal pulsatile PV flow with normal CO = 5.5 L/min; and (4) AF-P , a typical AF pulsatile waveform where systolic phase and the reversal phase are diminished with reduced CO of 4.4 L/min. Results: Comparing the two steady flow groups, LAA t m significantly increased as CO was decreased ( Normal-S: 2.6±0.3 s, AF-S: 3.1±0.3 s, P =0.02). However, the presence of pulsatility did not affect LAA t m at both levels of CO: Normal-P: 2.4±0.2 s; Normal-S: 2.6±0.3 s, P =0.2 and AF-P: 2.9±0.3 s; AF-S: 3.1±0.3 s, P =0.3. Conclusions: LAA blood stasis risk, as quantified by LAA t m , is significantly affected by the steady PV flow magnitude (i.e., cardiac output) and not by PV flow pulsatility. Therefore, the subject-specific LAA blood stasis risk can be reliably estimated using subject-specific LA and LAA 3D geometries and subject-specific CO.

Association between cardiorespiratory fitness, obesity, and incidence of atrial fibrillation.

BackgroundThe interaction between cardiorespiratory fitness (CRF) and incidence of atrial fibrillation (AF) and the interaction between obesity and incidence of AF have been explored separately. Therefore, we evaluated the association between CRF, body mass index (BMI), and risk of developing AF in a cohort of middle-aged and older US Veterans.MethodsSymptom limited exercise tests (ETT) were conducted among 16,397 Veterans (97% male) from January 9,1987 to December 31,2017. No history of AF was evident at the time of the ETTs. CRF was expressed as quartiles of peak metabolic equivalents (METs) achieved within each age decile. Weight status was classified as normal (BMI < 25 kg/m2), overweight (BMI 25–30 kg/m2), obese (BMI 30–35 kg/m2), or severely obese (BMI > 35 kg/m2). Multivariable Cox proportional hazards regression models were used to compare the association between BMI, CRF categories, and incidence of AF.ResultsOver a median follow-up of 10.7 years, 2,155 (13.1%) developed AF. Obese and severely obese subjects had 13% and 32% higher risks for incidence of AF, respectively, vs. normal weight subjects. Overweight and obese subjects in the most fit quartile had 50% decline in AF risk compared to the least-fit subjects. Severely obese subjects had marked increases in AF risk (~50–60%) regardless of fitness level. Risk of developing AF increases with higher BMI and lower CRF.ConclusionImproving CRF should be advocated when assessing those at risk for developing AF.

Premature Atrial and Ventricular Contraction Detection using Photoplethysmographic Data from a Smartwatch.

We developed an algorithm to detect premature atrial contraction (PAC) and premature ventricular contraction (PVC) using photoplethysmographic (PPG) data acquired from a smartwatch. Our PAC/PVC detection algorithm is composed of a sequence of algorithms that are combined to discriminate various arrhythmias. A novel vector resemblance method is used to enhance the PAC/PVC detection results of the Poincaré plot method. The new PAC/PVC detection algorithm with our automated motion and noise artifact detection approach yielded a sensitivity of 86% for atrial fibrillation (AF) subjects while the overall sensitivity was 67% when normal sinus rhythm (NSR) subjects were also included. The specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy values for the combined data consisting of both NSR and AF subjects were 97%, 81%, 94% and 92%, respectively, for PAC/PVC detection combined with our automated motion and noise artifact detection approach. Moreover, when AF detection was compared with and without PAC/PVC, the sensitivity and specificity increased from 94.55% to 98.18% and from 95.75% to 97.90%, respectively. For additional independent testing data, we used two datasets: a smartwatch PPG dataset that was collected in our ongoing clinical study, and a pulse oximetry PPG dataset from the Medical Information Mart for Intensive Care III database. The PAC/PVC classification results of the independent testing on these two other datasets are all above 92% for sensitivity, specificity, PPV, NPV, and accuracy. The proposed combined approach to detect PAC and PVC can ultimately lead to better accuracy in AF detection. This is one of the first studies involving detection of PAC and PVC using PPG recordings from a smartwatch. The proposed method can potentially be of clinical importance as this enhanced capability can lead to fewer false positive detections of AF, especially for those NSR subjects with frequent episodes of PAC/PVC.

Preoperative soluble VCAM-1 contributes to predict late mortality after coronary artery surgery.

BackgroundSoluble vascular cell adhesion molecule‐1 has been associated with long‐term cardiovascular mortality in patients with stable coronary artery disease and to the development of new atrial fibrillation in subjects with cardiovascular risk factors but no evidence of cardiac disease.HypothesisPreoperative soluble vascular cell adhesion molecule‐1 predicts the risk of future all‐cause death and cardiovascular death among patients submitted to elective coronary artery bypass surgery.MethodsFrom a cohort of 312 patients who underwent elective coronary artery bypass surgery prospectively followed for a median of 6.7 years, we evaluated the prognostic role of preoperative soluble vascular cell adhesion molecule‐1, inflammatory markers, CHA2DS2‐VASc score and development of postoperative atrial fibrillation (POAF). Univariable and multivariable Cox regression analyses were performed to establish an association of these parameters with long term all‐cause death and cardiovascular death.ResultsDuring 2112 person‐years of follow‐up, we observed 41 deaths, 10 were cardiovascular deaths. Independently increased levels of preoperative soluble vascular cell adhesion molecule‐1, POAF, and CHA2DS2‐VASc score were associated with all‐cause mortality. After multivariate adjustment, elevated preoperative soluble vascular cell adhesion molecule‐1 and POAF were the only independent predictors of all‐cause death. Also, preoperative soluble vascular cell adhesion molecule‐1, POAF, and CHA2DS2‐VASc score resulted in being independent predictors of cardiovascular mortality.ConclusionsIncreased circulating levels of preoperative soluble vascular cell adhesion molecule‐1, together with POAF and CHA2DS2‐VASc score, were significantly associated with future all‐cause death and cardiovascular death among patients submitted to coronary artery bypass surgery.

Digital Image Processing Features of Smartwatch Photoplethysmography for Cardiac Arrhythmia Detection.

The aim of our work is to design an algorithm to detect premature atrial contraction (PAC), premature ventricular contraction (PVC), and atrial fibrillation (AF) among normal sinus rhythm (NSR) using smartwatch photoplethysmographic (PPG) data. Novel image processing features and two machine learning methods are used to enhance the PAC/PVC detection results of the Poincaré plot method. Compared with support vector machine (SVM) methods, the Random Forests (RF) method performs better. It yields a 10-fold cross validation (CV) averaged sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), and accuracy for PAC/PVC labels of 63%, 98%, 83%, 94%, and 93%, respectively, and a 10-fold CV averaged sensitivity, specificity, PPV, NPV, and accuracy for AF subjects of 92%, 96%, 85%, 98%, and 95%, respectively. This is one of the first studies to derive image processing features from Poincaré plots to further enhance the accuracy of PAC/PVC detection using PPG recordings from a smartwatch.

Intra-study and inter-technique validation of cardiovascular magnetic resonance imaging derived left atrial ejection fraction as a prognostic biomarker in heart failure with preserved ejection fraction

The aim of this study was to assess the agreements of both biplane and short-axis Simpson’s (SAX) methods for left atrial ejection fraction (LAEF) calculation utilising cardiovascular magnetic resonance imaging (CMR) in heart failure with preserved ejection fraction (HFpEF) and evaluate their relation to clinical outcomes. One hundred and thirty six subjects (HFpEF n = 97, controls n = 39) underwent CMR, six-minute walk tests and blood sampling in our prospective, observational, single-centre study. Overall, LAEF (%) was lower in HFpEF patients compared to controls (SAX 34 ± 13 vs 47 ± 8, biplane 34 ± 16 vs 51 ± 11; p < 0.0001 for both). Atrial fibrillation (AF) was present in 24% of HFpEF and was associated with higher LA volumes and lower LAEF compared to sinus rhythm (p < 0.0001) with both methods. Biplane LAEF correlated strongly with SAX measurements (overall Pearson’s r = 0.851, sinus rhythm r = 0.651, AF r = 0.882; p < 0.0001). Biplane LAEF did not differ significantly compared to SAX LAEF (overall 34 ± 16 vs 34 ± 13%; p = 0.307) except in AF subjects in whom biplane LAEF was lower (mean difference 2 ± 4%, p = 0.013). There were 44 composite events (25 deaths, 19 HF hospitalizations) in HFpEF during median follow-up of 1429 days. LAEF below the median was associated with increased risk of composite endpoints (Log-Rank biplane p < 0.0001; SAX p = 0.009). In multivariable Cox proportional hazards regression analysis, both biplane LAEF (hazard ratio [HR] 0.604; 95% confidence interval [CI] (0.406–0.900); p = 0.013) and SAX LAEF (HR 0.636; CI 0.441–0.918; p = 0.016) remained independent predictors along with indexed extracellular volume. CMR LAEF, derived from either the short-axis or biplane method is lower in HFpEF compared to healthy controls and remains a strong marker of prognosis.

Neurophysiological status of patients with non-valve atrial fibrillation

Aim. To evaluate the neuropsychological parameters from the main cognitive domains (neurodynamic functions, attention and short-term memory) and the brain electrical activity in patients with non-valve atrial fibrillation (AF).Methods. 21 patients with the mean age of 61 [56; 67] years with non-valve AF who were admitted to the Department of Interventional Diagnosis and Treatment at the Research Institute for Complex Issues of Cardiovascular Disease were included in the study. The control group consisted of 17 healthy individuals with the mean age of 55 [49; 62] years. All patients underwent neuropsychological screening and computerized testing of neurodynamic functions, attention and short-term memory along with electroencephalographic studies. Statistical analysis was performed using the STATISTICA 10.0 software package.Results. Mild cognitive impairment was observed in 43% of patients with non-valve AF accompanied by ischemic brain matter changes according to the findings of magnetic resonance imaging. Patients with AF had slower complex sensorimotor reaction, more errors, worse directed attention, memorization of words and meaningless syllables in comparison with healthy individuals. In addition, patients with AF and healthy subjects had differences in the fronto-occipital gradient of theta-2 rhythm. The worst neurodynamic parameters were associated with a greater power of theta rhythms predominantly in the posterior parts of the brain only in patients with AF.Conclusion. Patients with non-valve AF had cognitive deficit with impaired executive control, attention and short-term memory as well as the slowing of cortical electrical activity in comparison to healthy individuals. The data obtained in our study are beneficial for developing an individual approach to prevent the development and progression of cognitive impairment in patients with AF.

P4133Atrial fibrillation in elderly patients with syncope and dementia: clinical insights from a large multicenter Italian registry

Abstract Background Syncope and dementia have a high prevalence in elderly individuals. Atrial fibrillation (AF) frequently occurs at advanced age. The coexistence of these conditions can be indicative of a clinically relevant frail status. Purpose The aim of this study was to evaluate the characteristics and the long-term outcome of AF patients with dementia and a history of syncope. Methods We evaluated the Syncope and Dementia (SYD) Registry. Data were collected by 11 Geriatric Departments between 2012 and 2016. Follow-up was closed at the 12-month evaluation. Results During the study period, 522 patients (women – 324, 62.1%; MMSE: 17±6) were enrolled. Of these 138 (26.4%) have or presented a history of AF. Patients with AF were older (85±6 vs. 83±6 years, p=0.012), with a higher heart rate (78±17 vs. 73±14 bpm, p&lt;0.001), had a more complex clinical picture with an increased number (3.9±2.0 vs. 3.0±1.8, p&lt;0.001) and severity (1.8±0.3 vs. 1.6±0.4, p&lt;0.001) of comorbidities, as assessed with the Cumulative Illness Rating Scale. In particular, the prevalence of diabetes (28.3 vs. 20.1%, p=0.047), heart failure (13.8 vs. 7.3%, p=0.023) and stroke/TIA (26.1 vs. 17.7%, p=0.035) was higher in patients with the arrhythmia. Cardiac syncope was more frequently diagnosed at the final evaluation (18.8 vs. 4.9%, p&lt;0.001). Even if the use of antipsychotics (13.0 vs. 27.6%, p=0.001) and cholinesterase inhibitors (6.5 vs. 16.4%, p=0.004) were less used in AF subjects, the total number of prescribed drugs was higher (6.9±2.9 vs. 5.9±2.7, p&lt;0.001). At multivariate analysis (overall predictivity: 75%), AF patients were characterized by advanced age (p=0.041), a higher severity of comorbidities (p&lt;0.001), a greater number of drugs (p=0.020), an increased heart rate (p=0.004) and a more frequent presence of cardiac symptoms (p=0.049). At one-year follow-up (8 patients lost), the mortality rate in AF patients was 27.7% (N=36/130). Deceased patients presented a greater degree of disability (number of lost activities of daily living: 3.7±2.3 vs. 2.8±1.9, p=0.020) and a higher heart rate at baseline (85±17 vs. 76±15 bpm, p=0.006). Multivariate analysis (overall predictivity: 74%) confirmed the association of disability (p=0.039) and heart rate (p=0.045) with prognosis. Conclusions AF is frequently present in patients with dementia and a history of syncope. It is usually associated with a more complex clinical picture and high long-term mortality. Heart rate and a higher degree disability seem to be related to prognosis. Acknowledgement/Funding None

482Direct oral anticoagulant rivaroxaban in very old and frail patients: A one-year prospective follow-up of a large-scale cohort (SAFIR-AC)

Abstract Background/Introduction Age is one of the strongest predictors/risk factors for ischemic stroke in subjects with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) have been shown to be effective in the prevention of this condition; however, clinical evidence on bleeding risk with this therapeutic strategy in very old and frail geriatric patients is poor. Purpose To assess bleeding risk in French geriatric patients aged ≥80 years and diagnosed with AF newly treated with rivaroxaban. Methods Subjects, presenting to one of 33 geriatric centers, with non-valvular AF and recent initiation of a treatment with rivaroxaban were enrolled in the study and followed-up every 3 months for 12 months. Clinical and routine laboratory data and evaluation scores, such as HAS-BLED, HEMORR2HAGES, ATRIA, and CHA2DS2-VASc, as well as comprehensive geriatric evaluation were reported. Major bleeding, as defined in ROCKET AF study, was reported at each visit, and this primary outcome was adjudicated by an independent committee. Results of this cohort were compared with findings from a similar cohort treated with vitamin K antagonists (VKAs) from the same centers (n=924). Results A total of 1045 subjects were enrolled in the study of whom 995 (95%) had a one-year follow-up (analyzed population). The mean (standard deviation (SD)) age was 86.0 (4.3) years, with the majority of patients being female (61%), 23% aged 90 years or older, and 48% having an estimated glomerular filtration rate (eGFR) &lt;50 mL/min. The main comorbidities were hypertension in 77% of subjects, malnutrition 49%, anemia 43%, dementia 39%, heart failure 36%, and falls 27%. The mean (SD) score for CHA2DS2-VASc was 4.8 (1.4), HAS-BLED 2.4 (0.9), Mini-Mental State Examination (MMSE) 21.5 (6.9), Activities of Daily Living (ADL) 4.4 (1.9), and Charlson Comorbidity Index 6.7 (2.0). The one-year rate of major bleeding events was 6.4% of which 0.8% were fatal and 1.1% intracranial hemorrhages (ICH), whereas the one-year rate of ischemic stroke was 1.4% and all-cause mortality 17.9%. Computed with VKA cohort findings and adjusted for age, gender, eGFR and Charlson score, this would result in a hazard ratio of 0.54 (95% confidence interval [CI], 0.38 to 0.78) for major bleeding, 0.36 (0.17 to 0.76) for ICH, 0.62 (0.29 to 1.33) for ischemic stroke, and 0.82 (0.65 to 1.02) for all-cause mortality, in favor of rivaroxaban. Conclusions This is the first large-scale prospective study in geriatric population in AF subjects treated with DOAC (rivaroxaban) Major bleeding risk appeared higher in very old than younger population, however major bleeding and ICH rates were significantly lower with rivaroxaban than with VKAs when used in the same geriatric population. This study indicates that Rivaroxaban can be used in very old and frail patients for the treatment of non-valvular AF. Acknowledgement/Funding Unrestricted grant from Bayer

Integrative Analysis Reveals Key Circular RNA in Atrial Fibrillation.

Circular RNAs (circRNAs) are an emerging class of RNA species that may play a critical regulatory role in gene expression control, which can serve as diagnostic biomarkers for many diseases due to their abundant, stable, and cell- or tissue-specific expression. However, the association between circRNAs and atrial fibrillation (AF) is still not clear. In this study, we used RNA sequencing data to identify and quantify the circRNAs. Differential expression analysis of the circRNAs identified 250 up- and 126 down-regulated circRNAs in AF subjects compared with healthy donors, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the parental genes of the dysregulated circRNAs indicated that the up-regulated parental genes may participate in the process of DNA damage under oxidative stress. Furthermore, to annotate the dysregulated circRNAs, we constructed and merged the competing endogenous RNA (ceRNA) network and protein-protein interaction (PPI) network, respectively. In the merged network, 130 of 246 dysregulated circRNAs were successfully characterized by more than one pathway. Notably, the five circRNAs, including chr9:15474007-15490122, chr16:75445723-75448593, hsa_circ_0007256, chr12:56563313-56563992, and hsa_circ_0003533, showed the highest significance by the enrichment analysis, and four of them were enriched in cytokine-cytokine receptor interaction. These dysregulated circRNAs may mainly participate in biological processes of inflammatory response. In conclusion, the present study identified a set of dysregulated circRNAs, and characterized their potential functions, which may be associated with inflammatory responses in AF. To our knowledge, this is the first study to uncover the association between circRNAs and AF, which not only improves our understanding of the roles of circRNAs in AF, but also provides candidates of potentially functional circRNAs for AF researchers.

Impact of anatomical features of the left atrial appendage on outcomes after cryoablation for atrial fibrillation

AimsPulmonary vein isolation (PVI) using cryoballoon has been accepted as a safe and effective method for treatment of atrial fibrillation (AF). Despite advances in catheter-based technologies, some patients still experience AF recurrence. In this study, we aimed to compare left atrial appendage (LAA) morphology in AF patients and subjects with sinus rhythm and also investigate the association between LAA morphology and success of PVI using cryoballoon in subjects with AF. MethodsIn this prospective study, 359 AF patients who underwent pre-ablation computed tomographic angiography (CTA) scan between January 2013–March 2016 were included as the patient group. 100 age and gender-matched subjects in sinus rhythm who had no AF episodes in 24-h Holter monitoring that underwent CTA were included as the control group. ResultsNon-chicken wing LAA morphology was more common in AF patients (p < 0.001). LAA was significantly deeper (p < 0.001) and short-axis diameter of LAA orifice and LAA orifice area were significantly larger (p < 0.001) in AF patients. Low take-off type morphology of LAA was more common in controls compared to AF patients (p = 0.006). At a median follow-up of 37 months, only longitudinal-axis left atrial diameter on CT (p = 0.003) and cauliflower-type LAA morphology (p = 0.004) were independent predictors of AF recurrence. ConclusionThis is the first study in the literature that investigates the relationship between anatomical variations of LAA and AF recurrence following cryoablation. Our findings demonstrate that cauliflower-type LAA morphology is associated with two-fold increased risk of AF recurrence.

Noise Detection in Electrocardiogram Signals for Intensive Care Unit Patients.

Long term electrocardiogram (ECG) signals recorded in an intensive care unit (ICU) are often corrupted by severe motion and noise artifacts (MNA), which may lead to many false alarms including inaccurate detection of atrial fibrillation (AF). We developed an automated method to detect MNA from ECG recordings in the Medical Information Mart for Intensive Care (MIMIC) III database. Since AF detection is often based on identification of irregular RR intervals derived from the QRS complexes, the main design focus of our MNA detection algorithm was to identify corrupted QRS complexes of the ECG signals. The MNA in the MIMIC III database contain not only motion-induced noise, but also a plethora of non-ECG waveforms, which must also be automatically identified. Our algorithm is designed to first discriminate between ECG and non-ECG waveforms using both time and spectral-domain properties. For the segments of data containing ECG waveforms, a time-frequency spectrum and its sub-band decomposition approach were used to identify MNA, and high frequency noise ECG segments, respectively. The algorithm was tested on data from 35 subjects in normal sinus rhythm and 25 AF subjects. The proposed method is shown to accurately discriminate between segments that contained real ECG waveforms and those that did not, even though the latter were numerous in some subjects. In addition, we found a significant reduction (> 94%) in false positive detection of AF in normal subjects when our MNA detection algorithm was used. Without using it, we inaccurately detected AF owing to the MNA.

Interatrial septal fat thickness and left atrial stiffness are mechanistic links between nonalcoholic fatty liver disease and incident atrial fibrillation.

Recently, a clear evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident atrial fibrillation (AF). Yet, the underlying pathogenesis is speculative. Thereby, we aimed to investigate the hypothesis that, interatrial thickness (IAST) and left atrial stiffness (LASt) might have mechanistic links between NAFLD and AF. Echocardiography and speckle-tracking assessment of left atrial function, transient elastography (TE) of the liver, basal ECG, and Holter monitoring were performed in 180 patients with (NAFLD) and 80 subjects without NAFLD. Patients with NAFLD had higher values of IAST (P<0.001), LASt (<0.001), and E/e' ratio (<0.003) compared with controls. IAST was correlated with LASt (r=0.413; P<0.001). 15.6% of patients with NAFLD had AF. More so, patients with increased IAST/LASt had a higher incidence of AF (25%) vs 3.8% in those with normal IAST/LASt. The LASt and IAST increased significantly in those with AF compared with those without (P<0.001). Patients who experienced AF had higher values (P<0.01) of TE (kPa). The degree of liver stiffness TE (kPa) was correlated with both IAST and LASt (r=461, r=0.535; P<0.001). Furthermore, multivariate regression analysis showed that LASt and IAST were independent predictors of incident AF in subjects with NAFLD. Our data suggest that increased IAST and LASt index are independently associated with incident atrial fibrillation in patients with NAFLD. Increased IAST and LASt index might provide mechanistic links between NAFLD and incident atrial fibrillation.

Collagen Biomarkers and Incidence of New Onset of Atrial Fibrillation in Subjects With No Overt Cardiovascular Disease at Baseline: The Multi-Ethnic Study of Atherosclerosis.

Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). Plasma procollagen type III N-terminal propeptide (PIIINP) reflects collagen synthesis and degradation while collagen type I carboxy-terminal telopeptide (ICTP) reflects collagen degradation. We aimed to study baseline plasma PIIINP and ICTP and their associations with incident AF in participants initially free of overt cardiovascular disease. In a stratified sample of the Multi-Ethnic Study of Atherosclerosis, initially aged 45-84 years, 3071 participants had both PIIINP and ICTP measured at baseline. Incident AF in 10-year follow-up was based on a hospital International Classification of Diseases code for AF or atrial flutter, in- or outpatient Medicare claims through 2011 (primarily in those aged 65-84 years), or ECG 10 years after baseline (n=357). The associations of PIIINP and ICTP with incident AF were estimated using Poisson regression with follow-up time offset. Baseline PIIINP (5.50±1.55 µg/L) and ICTP (mean±SD, 3.41±1.37 µg/L) were positively related (both P<0.0001) to incident AF in a model adjusting for age, race/ethnicity, and sex, with an apparent threshold (relative incidence density 2.81 [1.94-4.08] for PIIINP ≥8.5 µg/L [3.5% of the sample] and 3.46 [2.36-5.07] for ICTP ≥7 µg/L [1.7% of the sample]). Findings were attenuated but remained statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function. Additional adjustment for other risk factors and biomarkers of inflammation did not alter conclusions. Plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk for AF.

Rs12976445 Polymorphism Is Associated with Post-Ablation Recurrence of Atrial Fibrillation by Modulating the Expression of MicroRNA-125a and Interleukin-6R.

BackgroundThis study aimed to identify the relationship between miR-125a polymorphism rs12976445 and the post-ablation recurrence of atrial fibrillation (AF), as well as to explore the underlying mechanism of miR-125a in AF recurrence.Material/MethodsMicroarray analysis was performed to search for miRNAs potentially involved in the regulation of AF recurrence, while real-time PCR (polymerase chain reaction) and Western blot analyses were carried out to study the expression of miR-125a (microRNA-125a), IL-6R (interleukin-6 receptor), and IL-16 (interleukin-16) in different experimental groups, so as to understand the regulatory relationships among miR-125a, IL-6R, and IL-16. Subsequently, a logistic regression analysis was utilized to investigate the survival status of recurrent AF in subjects harboring different genotypes of rs12976445.ResultsThe subjects in the GG and GC/CC groups of miR-125a polymorphism rs12976445 showed no obvious difference regarding all demographic characteristics that were collected in this study. In addition, 19 miRNAs were identified as potentially involved in the regulation of AF recurrence. Among these miRNAs, 6 were upregulated and 13 were downregulated in the group with early recurrence. According to real-time PCR results, the expression of miR-125a was dramatically upregulated in LRAF (late recurrence of atrial fibrillation) as well as in subjects harboring the GG genotype. On the contrary, the level of IL-6R mRNA was dramatically downregulated in LRAF and subjects harboring the GG genotype. Furthermore, IL-6R was confirmed as a candidate target of miR-125a by a luciferase reporter assay.ConclusionsMicroRNA-125a polymorphism rs12976445 plays a role in AF recurrence via the regulation of IL-6R.

Abstract P345: Short Sleep Duration is Associated With Atrial Fibrillation in a Clinical Cohort

Introduction: Patients who self-report short sleep duration are thought to have a higher risk of atrial fibrillation (AF), but objective data are lacking and it is not clear if this association is independent of sleep apnea. In this cross-sectional investigation, we evaluated the association between objectively measured sleep duration and AF in patients undergoing diagnostic sleep study. Methods: We evaluated all 30,572 patients who underwent in-laboratory diagnostic sleep study at one of six centers within the University of Pittsburgh Medical Center system from March 1999 to December 2015. Total sleep time (TST), apnea hypopnea index (AHI), percent sleep with oxygen saturation &lt; 90% (Per90), and cardiac rhythm on overnight EKG were extracted from sleep study reports using automated algorithms. Multivariable linear regression was used to model TST as a function of rhythm accounting for age, sex, body mass index (BMI) and sleep apnea severity using both AHI and Per90. We also performed a sensitivity analysis using patients whose AF status was confirmed by an inpatient or outpatient ICD-9 code at any point up to one day prior to the date of the sleep study. Results: The cohort was 52.0% female, aged 50.8±14.6 years (mean ± std dev), had a BMI of 33.7 ± 8.7 kg/m 2 , and an AHI of 17.4 ± 22.6 events/hr. Of the 30,572 patients, 369 (1.2%) had AF, 60 had a paced rhythm, 28,844 were in sinus, and 1299 had unclear rhythm. After adjusting for age and sex, TST was lower by 34 minutes (95% confidence interval, 26-42) in patients in AF compared to those in sinus rhythm. After further adjustment for BMI, AHI and Per90, TST was 28 minutes (18-38) lower for those in AF. The TST difference between patients in AF and sinus was primarily related to reduction in stage 2 non-REM sleep; AF patients had 32 minutes (22-41) less stage 2 sleep after adjustment. In a sensitivity analysis limited to 268 AF subjects with at least one AF diagnostic code and 26,239 sinus rhythm subjects without an AF diagnostic code, TST was 29 minutes (17-41) shorter in AF patients after adjustment. Conclusion: After accounting for differences in demographics and sleep apnea severity, patients with AF sleep about half an hour less on objective assessment. Our findings support an association between short sleep and AF. Future prospective studies are needed to determine if short sleep may be a novel mechanism for the development of AF.

Association of serum nesfatin-1 concentrations with atrial fibrillation

Nesfatin-1, a newly discovered adipokine, inhibits inflammatory response. Inflammation is involved in the mechanism of atrial fibrillation (AF). We aim to determine the association between serum nesfatin-1 concentrations and AF. A population of 200 patients with AF and 108 patients without AF were enrolled in this study. These patients were divided into three subgroups of paroxysmal AF, persistent AF, and permanent AF. Serum nesfatin-1 concentrations were lower in AF patients than in controls. Logistic regression analysis showed that serum nesfatin-1 concentrations were inversely associated with AF. Serum nesfatin-1 concentrations in permanent AF patients decreased compared with those in persistent and paroxysmal AF groups. In addition, persistent AF patients showed reduced serum nesfatin-1 concentrations compared with paroxysmal AF subjects. Serum nesfatin-1 concentrations were negatively correlated with left atrial diameter. In conclusion, serum nesfatin-1 concentrations were inversely correlated with AF development.