Robust Artificial Intelligence Tool for Atrial Fibrillation Diagnosis: Novel Development Approach Incorporating Both Atrial Electrograms and Surface ECG and Evaluation by Head-to-Head Comparison With Hospital-Based Physician ECG Readers.

BACKGROUND: Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high-risk patients is important but labor-intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. METHODS AND RESULTS: We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI-based tool for subsequent AF detection using ECG records alone. A total of 5 million 30-second epochs from 329 patients were annotated as AF or non-AF by expert ECG readers for AI training and validation, while 5 million 30-second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. CONCLUSIONS: Use of both atrial electrograms and surface ECG permitted development of a robust AI-based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.

The prognostic value of whole-genome DNA methylation in response to Leflunomide in patients with Rheumatoid Arthritis.

Objective: Although Leflunomide (LEF) is effective in treating rheumatoid arthritis (RA), there are still a considerable number of patients who respond poorly to LEF treatment. Till date, few LEF efficacy-predicting biomarkers have been identified. Herein, we explored and developed a DNA methylation-based predictive model for LEF-treated RA patient prognosis. Methods: Two hundred forty-five RA patients were prospectively enrolled from four participating study centers. A whole-genome DNA methylation profiling was conducted to identify LEF-related response signatures via comparison of 40 samples using Illumina 850k methylation arrays. Furthermore, differentially methylated positions (DMPs) were validated in the 245 RA patients using a targeted bisulfite sequencing assay. Lastly, prognostic models were developed, which included clinical characteristics and DMPs scores, for the prediction of LEF treatment response using machine learning algorithms. Results: We recognized a seven-DMP signature consisting of cg17330251, cg19814518, cg20124410, cg21109666, cg22572476, cg23403192, and cg24432675, which was effective in predicting RA patient's LEF response status. In the five machine learning algorithms, the support vector machine (SVM) algorithm provided the best predictive model, with the largest discriminative ability, accuracy, and stability. Lastly, the AUC of the complex model(the 7-DMP scores with the lymphocyte and the diagnostic age) was higher than the simple model (the seven-DMP signature, AUC:0.74 vs 0.73 in the test set). Conclusion: In conclusion, we constructed a prognostic model integrating a 7-DMP scores with the clinical patient profile to predict responses to LEF treatment. Our model will be able to effectively guide clinicians in determining whether a patient is LEF treatment sensitive or not.

Impact of proinflammatory epicardial adipose tissue and differentially enhanced autonomic remodeling on human atrial fibrillation.

OBJECTIVES: The mechanisms underlying atrial fibrillation are yet to be elucidated. We sought to investigate the interactions among autonomic remodeling, epicardial adipose tissue, inflammation, and atrial fibrillation. METHODS: Myocardium and adjacent epicardial adipose tissue of the left atrial appendage, right atrial appendage, and pulmonary vein muscle sleeves were obtained from 61 consecutive patients (35 with atrial fibrillation, 26 with no atrial fibrillation) during mitral valve surgeries. Patients were divided into the atrial fibrillation group and no atrial fibrillation group according to the history and Holter monitoring before surgery. Sympathetic and parasympathetic innervation were evaluated by tyrosine hydroxylase and choline acetyltransferase staining, respectively. Atrial fibrosis as well as cytokines/adipokines and related inflammatory proteins and signaling pathways in the epicardial adipose tissue were examined. RESULTS: Immunohistochemical studies revealed significantly increased tyrosine hydroxylase (+) and choline acetyltransferase (+) neural elements in the left atrial appendage and pulmonary vein muscle sleeve myocardium, as well as adjacent epicardial adipose tissue in the atrial fibrillation group, particularly the pulmonary vein muscle sleeve sites. The receiver operating curve identified a threshold ratio (tyrosine hydroxylase/choline acetyltransferase) of 0.8986 in the epicardial adipose tissue (sensitivity = 82.86%; specificity = 80.77%; area under the curve = 0.85, 95% confidence interval = 0.76-0.95, P < .0001). More patients with a higher tyrosine hydroxylase/choline acetyltransferase ratio (≥0.8986) had atrial fibrillation. Expression levels of the genes and related proteins of the ß1 adrenergic, mitogen-activated protein kinase, and nuclear factor kappa B signaling pathways were higher in patients with a higher tyrosine hydroxylase/choline acetyltransferase ratio. The tyrosine hydroxylase/choline acetyltransferase ratio also correlated with fibrosis. CONCLUSIONS: Differentially enhanced autonomic remodeling and proinflammatory and profibrotic cytokines/adipokines in the epicardial adipose tissue adjacent to the pulmonary vein muscle sleeve site may work synergistically to promote atrial fibrillation.

Automatic quantitative measurement of left atrial pressure using mitral regurgitation spectrum: clinical study on comparison with floating catheter.

INTRODUCTION: To explore how to measure LAPEq accurately and quantitatively, that is, the left atrial pressure (LAP) measured and calculated by equation method using mitral regurgitation spectrum. METHODS: The mitral regurgitation spectrum, pulmonary arteriolar wedge pressure (PAWP) and invasive arterial systolic pressure of radial artery of 28 patients were collected simultaneously, including 3 patients with rheumatic heart disease, 15 patients with mitral valve prolapse and 10 patients with coronary artery bypass grafting, patients with moderate or above aortic stenosis were excluded. LAPBp (Doppler sphygmomanometer method), LAPEq (Equation method) and LAPC (Catheter method) were measured synchronously, and the measurement results of the three methods were compared and analyzed. A special intelligent Doppler spectrum analysis software was self-designed to accurately measure LAPEq. This study had been approved by the ethics committee of the Northern Theater General Hospital (K-2019-17), and applied for clinical trial (No. Chictr 190023812). RESULTS: It was found that there was no significant statistical difference between the measurement results of LAPC and LAPEq (t = 0.954, P = 0.348), and significant correlation between the two methods [r = 0.908(0.844, 0.964), P < 0.001]. Although the measurement results of LAPC and LAPBP are consistent in the condition of non-severe eccentric mitral regurgitation, there are significant differences in the overall case and weak correlation between the two methods [r = 0.210, (-0.101, 0.510), P = 0.090]. In MVP patients with P1 or P3 prolapse, the peak pressure difference of MR was underestimated due to the serious eccentricity of MR, which affected the accuracy of LAPBP measurement. CONCLUSIONS: It was shown that there is a good correlation between LAPEq and LAPC, which verifies that the non-invasive and direct quantitative measurement of left atrial pressure based on mitral regurgitation spectrum is feasible and has a good application prospect.

Preventive Effect of Berberine on Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common complications of cardiac surgery, but the underlying factors governing POAF are not well understood. The aim of this study was to investigate the efficacy of berberine administration on POAF. METHODS: We conducted a randomized, double-blind, placebo-controlled trial with patients who underwent isolated coronary artery bypass grafting in China to study the impact of oral berberine on the incidence of POAF. A total of 200 patients who underwent coronary artery bypass grafting were randomized into the berberine group (n=100) and the placebo group (n=100). All patients underwent 7-day continuous telemetry and Holter monitoring. RESULTS: The primary outcome was the incidence of POAF at 7 days. Secondary outcomes included clinical outcomes, POAF burden, intestinal endotoxin, and serum inflammatory biomarker levels. The POAF incidence was reduced from 35% to 20% under berberine treatment (hazard ratio, 0.5 [95% CI, 0.29-0.78]; P=0.0143). Perioperative mortality and morbidity did not differ between the 2 groups. POAF burden and the dose of amiodarone were significantly reduced in the berberine group. Oral berberine significantly decreased lipopolysaccharide, CRP (C-reactive protein), and IL (interleukin)-6 levels. Elevated lipopolysaccharide after surgery has been associated with POAF. CONCLUSIONS: Our results showed that administration of berberine may be effective for reducing the occurrence of POAF after coronary artery bypass grafting. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000028839.

Development and validation of a nomogram for predicting stroke risk in rheumatoid arthritis patients.

We developed and validated a nomogram to predict the risk of stroke in patients with rheumatoid arthritis (RA) in northern China. Out of six machine learning algorithms studied to improve diagnostic and prognostic accuracy of the prediction model, the logistic regression algorithm showed high performance in terms of calibration and decision curve analysis. The nomogram included stratifications of sex, age, systolic blood pressure, C-reactive protein, erythrocyte sedimentation rate, total cholesterol, and low-density lipoprotein cholesterol along with the history of traditional risk factors such as hypertensive, diabetes, atrial fibrillation, and coronary heart disease. The nomogram exhibited a high Hosmer-Lemeshow goodness-for-fit and good calibration (P > 0.05). The analysis, including the area under the receiver operating characteristic curve, the net reclassification index, the integrated discrimination improvement, and clinical use, showed that our prediction model was more accurate than the Framingham risk model in predicting stroke risk in RA patients. In conclusion, the nomogram can be used for individualized preoperative prediction of stroke risk in RA patients.

Calcium-Induced Autonomic Denervation in Patients With Post-Operative Atrial Fibrillation.

BACKGROUND: Post-operative atrial fibrillation (POAF) is associated with worse long-term cardiovascular outcomes. OBJECTIVES: This study hypothesized that injecting calcium chloride (CaCl2) into the major atrial ganglionated plexi (GPs) during isolated coronary artery bypass grafting (CABG) can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity. METHODS: This proof-of-concept study randomized 200 patients undergoing isolated, off-pump CABG to CaCl2 (n = 100) or sodium chloride (sham, n = 100) injection. Two milliliters of CaCl2 (5%) or sodium chloride (0.9%) was injected into the 4 major atrial GPs during CABG. All patients received 7-day continuous telemetry and Holter monitoring. The primary outcome was incidence of POAF (≥30 s) in 7 days. Secondary outcomes included length of hospitalization, POAF burden, average ventricular rate during AF, plasma level of inflammatory markers, and actionable antiarrhythmic therapy to treat POAF. RESULTS: The POAF incidence was reduced from 36% to 15% (hazard ratio: 0.366; 95% confidence interval: 0.211 to 0.635; p = 0.001). Length of hospitalization did not differ between the 2 groups. POAF burden (first 7 post-operative days), the use of amiodarone or esmolol, and the incidence of atrial couplets and nonsustained atrial tachyarrhythmias were significantly reduced in the CaCl2 group. Heart rate variability data showed a decrease in both high-frequency and low-frequency power in the CaCl2 group with a preserved low-frequency/high-frequency ratio, suggesting that the sympathetic/parasympathetic balance was not perturbed by CaCl2 injection. CONCLUSIONS: Injection of CaCl2 into the 4 major atrial GPs reduced the POAF hazard by 63%. Inhibition of GP function by Ca-mediated neurotoxicity may underlie the therapeutic effect. (Calcium Autonomic Denervation Prevents Postoperative Atrial Fibrillation; ChiCTR1800019276).

Recovery of atrial contractile function after cut-and-sew maze for long-standing persistent valvular atrial fibrillation.

OBJECTIVE: The recovery of atrial contractile (AC) after maze has been concerned and even questioned. Now, studied the AC recovery degree and its influencing factors. METHOD: 237 patients with valvular long-standing persistent atrial fibrillation (AF) were retrospectively grouped according to whether sinus rhythm(SR) maintained and AC restored: SR-AC (163 cases), SR-no-AC (41 cases) and AF-no-AC (33 cases). SR-AC were grouped according to Em/Am ratio. Em/Am≤2 showed that the AC recovered well. RESULTS: The SR maintained rate (161/177, 90.96%) in patients underwent the cut-and-sew maze III (CSM) was significantly higher than that in cryoablation (43/60, 71.7%). Preoperative AF duration had no significant difference among three groups (P = 0.679). Maze methods had significant relationship with whether SR recovered, P < 0.05, but no significant relationship with whether AC recovered in SR maintained patients (P = 0.280). Nearly 80% (163/204) patients can recover AC, among 156 patients (156/204, 76.5%) recovered contractile of left and right atrium, and 63 (63/204, 30.1%) recovered significant left atrial contractile, that is, Em/Am≤2. Whether AC was significantly restored was not related to maze methods, P = 0.370. AC recovered degree in rheumatic heart disease (RHD) patients was worse than that in mitral valve prolapse (MVP) patients, P = 0.004. CONCLUSION: To sum up, the CSM is safe and effective, and the atrial contractile function recovery was found in 80%. The key to the success of maze is to form a complete and lasting electrical isolation, and there was no difference in the rate of atrial contractile recovery when postoperative SR was maintained, no matter what maze method is used. MVP patients should be treated with maze more actively than RHD patients.

Quality of life and influencing factors of patients with rheumatoid arthritis in Northeast China.

PURPOSE: Rheumatoid arthritis (RA) is a disease with a high disability rate, resulting in severe family and social burden. The aim of treatment is to improve the health-related quality of life (QoL) of patients. The purpose of this study was to evaluate the QoL of patients with RA in Northeast China and analyze its influencing factors. METHODS: The study group consisted of 200 patients diagnosed with RA. The control group consisted of 200 healthy subjects. All subjects were residents in Northeast China. The investigation was conducted by questionnaire survey and electronic medical record. The WHOQOL-BREF, The Short-Form 36 Health Survey (SF-36) and Quality of Life Instruments for Chronic Diseases-RA (QLICD-RA) were used as questionnaires. RESULTS: The QoL scores acquired by SF-36, WHOQOL-BREF and QLICD-RA scales showed significant differences between RA and control groups (P < 0.001). Multiple regression analysis showed that sleep duration (P = 0.001), psychological counseling (P < 0.001) and C4 level (P = 0.001) influenced the SF-36 scale evaluation model. IgA levels (P < 0.001) and being overweight (P = 0.030) were included in the WHOQOL-BREF evaluation model. Adequate sleep (P = 0.001) and psychological counseling(P = 0.050) entered the QLICD-RA scale evaluation model (P = 0.050), in which psychological counseling, normal C4 levels and being overweight were protective factors for RA, insufficient sleep and IgA levels were risk factors for RA. CONCLUSIONS: The QoL of RA patients is generally lower than those of healthy subjects in the Northeast China, Northeast China. Sleep duration, BMI (Body mass index), psychological counseling, C4 and IgA levels are factors that influence the QoL scores of RA patients.

Development and validation of a nomogram to predict coronary heart disease in patients with rheumatoid arthritis in northern China.

We developed and validated a nomogram to predict coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) in northern China. We analyzed a cohort of RA patients admitted to the Department of Rheumatology and Immunology of the First Affiliated Hospital of China Medical University from 2011 to 2017. To select a high-performance model for clinical data prediction, we evaluated the F1-scores of six machine learning models. Based on the results, we selected multivariable logistic regression analysis for the development of a prediction model. We then generated an individualized prediction nomogram that included age, sex, hypertension, anti-cyclic citrullinated peptide antibody positivity, the erythrocyte sedimentation rate, and serum LDL-cholesterol, triglyceride and HDL-cholesterol levels. The prediction model exhibited better discrimination than the Framingham Risk Score in predicting CHD in RA patients. The area under the curve of the prediction model was 0.77, with a sensitivity of 63.9% and a specificity of 77.2%. The nomogram exhibited good calibration and clinical usefulness. In conclusion, our prediction model was more accurate than the Framingham Risk Score in predicting CHD in RA patients. Our nomogram combining various risk factors can be used for the individualized preoperative prediction of CHD in patients with RA.

Exploring metabolic and inflammatory abnormalities in rheumatoid arthritis patients developing stroke disease: a case-control study using electronic medical record data in northern China.

OBJECTIVES: Intend to investigate the roles of serum lipids, inflammatory markers, and serological status in rheumatoid arthritis and stroke patients by using case-control study. MATERIALS AND METHODS: Clinical data were retrieved from the electronic medical record of the First Affiliated Hospital of China Medical University during January 2011 to March 2018. The obtained data were categorized into case groups and three control groups, in the ratios of 1:2, respectively, with all matching age and gender. Multinomial logistic regression analysis and restricted cubic spline were conducted examining the associations between serum lipids, inflammatory markers, serological status, and the risk of stroke among RA patients. RESULTS: The present studies included 1057 study subjects. The elevated ESR, LDL-C levels, and much higher CRP levels ≥ 230 mg/L were independent risk factors for RA patients in developing stroke. Furthermore, we found that ESR and LDL-C levels could exhibit a linear association with the risk of comorbid stroke while CRP level had a nonlinearity association with stroke risk among RA patients. CONCLUSIONS: A close monitoring is required for RA patients with dyslipidemia and elevated inflammatory markers, and the primary stroke preventive strategies should be directed against these risk factors.