The "obesity paradox" in patients with atrial fibrillation: Insights from the Gulf SAFE registry.

Background: The prognostic impact of obesity on patients with atrial fibrillation (AF) remains under-evaluated and controversial. Methods: Patients with AF from the Gulf Survey of Atrial Fibrillation Events (Gulf SAFE) registry were included, who were recruited from six countries in the Middle East Gulf region and followed for 12 months. A multivariable model was established to investigate the association of obesity with clinical outcomes, including stroke or systemic embolism (SE), bleeding, admission for heart failure (HF) or AF, all-cause mortality, and a composite outcome. Restricted cubic splines were depicted to illustrate the relationship between body mass index (BMI) and outcomes. Sensitivity analysis was also conducted. Results: A total of 1,804 patients with AF and recorded BMI entered the final analysis (mean age 56.2 ± 16.1 years, 47.0% female); 559 (31.0%) were obese (BMI over 30 kg/m2). In multivariable analysis, obesity was associated with reduced risks of stroke/systematic embolism [adjusted odds ratio (aOR) 0.40, 95% confidence interval (CI), 0.18-0.89], bleeding [aOR 0.44, 95%CI, 0.26-0.74], HF admission (aOR 0.61, 95%CI, 0.41-0.90) and the composite outcome (aOR 0.65, 95%CI, 0.50-0.84). As a continuous variable, higher BMI was associated with lower risks for stroke/SE, bleeding, HF admission, all-cause mortality, and the composite outcome as demonstrated by the accumulated incidence of events and restricted cubic splines. This "protective effect" of obesity was more prominent in some subgroups of patients. Conclusion: Among patients with AF, obesity and higher BMI were associated with a more favorable prognosis in the Gulf SAFE registry. The underlying mechanisms for this obesity "paradox" merit further exploration.

Symptom Status, Clinical Subtypes, and Prognosis in Patients With Atrial Fibrillation from the Middle East Region (from the Gulf-SAFE Registry).

Atrial fibrillation (AF) is often asymptomatic. The prognosis of asymptomatic AF is at least similar or worse than symptomatic AF, but there are no such data from Middle East patients with AF. The Gulf-SAFE (Gulf Survey of Atrial Fibrillation Events) registry is a multicenter prospective survey of patients presenting with AF to participate medical institutions in 6 countries in the Gulf region. We investigated the prognostic outcomes of patients with asymptomatic AF in relation to clinical subtypes. A total of 2043 patients with AF were included; 541 were identified as having asymptomatic AF (26.5%) who tended to be older, with higher prevalences of hypertension, heart failure, coronary artery disease, diabetes, stroke, renal dysfunction, chronic obstructive pulmonary disease, and had higher Congestive heart failure, Hypertension, Age ≥75, Stroke (2 points), Congestive heart failure, Hypertension, Age ≥75 (2 points), Diabetes, Stroke (2 points), Vascular disease, Age 65-74, Sex category (CHA2DS2-VASc), and Hypertension, Age ≥65, Stroke, Bleeding history, liable INR, Elderly, Drug or alcohol use (HAS-BLED) scores (all p <0.05). After multivariable adjustment, asymptomatic AF was associated with higher risks of stroke/systematic embolism (SE) (adjusted odds ratio [aOR] 2.18, 95% confidence interval [CI] 1.10 to 4.34), all-cause mortality (aOR 2.85, 95% CI 1.90 to 4.28), and the composite outcome of stroke/SE, bleeding, and all-cause mortality (aOR 1.74, 95% CI 1.26 to 2.41). Patients with asymptomatic AF had fewer admissions for AF (aOR 0.53, 95% CI 0.32 to 0.83) and heart failure (aOR 0.58, 95% CI 0.38 to 0.86). The increased risk of stroke/SE in asymptomatic AF was more prominent among paroxysmal AF subtype (p for interaction = 0.028). In conclusion, in the Gulf-SAFE registry, patients with asymptomatic AF represent a nonbenign entity with worse outcomes compared with symptomatic AF. In paroxysmal AF, the higher risks of events were more prominent. The absence of "warning signs" and lack of timely admission in asymptomatic AF may be major reasons for the unfavorable prognosis.

Increased hemoglobin A1c level associates with low left atrial appendage flow velocity in patients of atrial fibrillation.

BACKGROUND AND AIMS: High hemoglobin A1c (HbAlc) level is associated with increased cardiovascular disease risk and thromboembolic events [1]. The study sought to explored the association between HbAlc and left atrial appendage flow velocity (LAAV) among non-valvular atrial fibrillation (AF) patients. METHODS AND RESULTS: A total of 249 consecutive non-valvular AF patients who underwent transesophageal echocardiography (TEE) were divided into two subgroups according to the median of LAAV level (<45 cm/s, ≥45 cm/s). Blood samples and other baseline clinical data of all patients were collected and analyzed. The low LAAV group included 126 patients and the high LAAV group included 123 patients. Patients in the low LAAV group were older and had a higher percentage of persistent AF, chronic heart failure, and higher CHA2DS2-VASc score (P < 0.05). HbAlc level in the low LAAV group was significantly higher than the high LAAV group [6.1 (5.7-6.5)% vs 5.9 (5.6-6.2)%, P = 0.010]. The low LAAV group had larger left atrial diameter (LAD), left atrial area (LAA), higher left atrial pressure (LAP), and lower left ventricular ejection fraction (LVEF) (P < 0.05). Spearman rank correlation analysis showed that the HbAlc level was negatively correlated with LAAV (r = -0.211, P = 0.001). Multivariate analysis indicated that female gender (OR = 2.233, 95% CI 1.110-4.492, P = 0.024), persistent AF (OR = 6.610, 95% CI 3.109-14.052, P < 0.001), and HbAlc (OR = 1.903, 95% CI 1.092-3.317, P = 0.023) were independent factors that associated with low LAAV in AF patients. CONCLUSION: Increased HbAlc level is associated with decreased LAAV and may reflect a low contractile function of the left atrial appendage.

Refining age stratum of the C2HEST score for predicting incident atrial fibrillation in a hospital-based Chinese population.

BACKGROUND: The C2HEST score (C2: coronary artery disease [CAD] / chronic obstructive pulmonary disease [COPD] (1 point each); H: Hypertension; E: Elderly (Age≥75, doubled); S: Systolic heart failure (doubled); T: Thyroid disease (hyperthyroidism)) has been validated to predict incident atrial fibrillation (AF). Its performance in the hospital-based Chinese population has never been evaluated. METHODS: Risk factors for incident AF were investigated in a hospital-based population. Comparison of the C2HEST score and other clinical scores with the capacity of predicting incident AF was conducted using area under the curves (AUC), net reclassification index (NRI), integrated discriminative improvement (IDI), and decision curve analysis (DCA). An age-stratified criterion was used to refine the C2HEST score to form a modified C2HEST score (mC2HEST). The performance of the mC2HEST score was also evaluated. RESULTS: A total of 23,523 patients entered the study with 520 developed AF during 2.84 ± 3.56 years of follow-up. Risk factors for incident AF included age, male sex, hypertension, CAD, COPD, previous ischemic stroke, hyperthyroidism, and heart failure. Age ≥65 years has significantly increased the risk of AF, which was considered as the age cutoff for a modified C2HEST score (mC2HEST). The risk of AF increased by 89% per one-point increase of the mC2HEST score. The mC2HEST score showed better predictive performance (AUC of 0.809) compared with the original C2HEST (AUC of 0.752), CHA2DS2-VASc (0.756), HATCH (0.722), and HAVOC (0.758) scores, also as estimated by IDI, NRI and DCA. Among those enrolled after 2012, the mC2HEST score had numerically higher AUC (0.849) compared with the C2HEST score (0.826) and the other scores. CONCLUSION: In a hospital-based Chinese population, by refining the age strata of the original C2HEST score, the mC2HEST score had significantly increased predictive accuracy and discriminative capability for incident AF. The clinical benefits of the application of novel mC2HEST score needs further validation in multiple settings.

The Predictive Value of Growth Differentiation Factor-15 in Recurrence of Atrial Fibrillation after Catheter Ablation.

The mechanisms underlying the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) are not well concerned. The study sought to explore the association between growth differentiation factor-15 (GDF-15) and the incidence of recurrent events among AF patients after the ablation procedure. We prospectively included 150 consecutive AF patients who underwent RFCA. Clinical information about the patients was collected. Blood samples on the second morning of hospital admission and three months after RFCA were collected, and enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of GDF-15. All participants were followed up at specific times (1st/3rd/6th/12th/18th/24th months) after RFCA to record recurrences events. During a median follow-up of 14.0 months, AF recurrence occurred in 37(24.7%) patients. Baseline serum GDF-15 level in the persistent AF group was significantly higher than the paroxysmal AF group [1140(854~1701)ng/L vs. 1062(651~1374)ng/L, P = 0.039]. Baseline serum GDF-15 level in the recurrence group was significantly higher than the nonrecurrence group [1287(889~1768) ng/L vs. 1062(694~1373)ng/L, P = 0.022]. Serum GDF-15 level at three months after RFCA was significantly lower than the baseline [870 (579~1270) ng/L vs. 1155 (735~1632)ng/L, P < 0.001]. The baseline GDF-15 correlated significantly with LAP (r = 0.296, P < 0.001) and LAAV(r = -0.235, P = 0.003). Kaplan-Meier analysis showed a significantly lower event-free survival time in the high baseline GDF-15 (≥1287.3 ng/L) group than the low baseline GDF-15 (<1287.3 ng/L) group (17.1 months vs. 20.4 months, Log Rank P = 0.017). In the multivariate Cox regression, baseline GDF-15(HR 1.053, 95% CI 1.007-1.100, P = 0.022) and LAD (HR 1.124, 95% CI 1.011-1.250, P = 0.030) were independent predictors of AF recurrence after RFCA. Our study indicated increased preprocedural GDF-15 is associated with left atrial remodeling and acts as a predictor of AF recurrence after ablation.

Association of Plasma C1q/TNF-Related Protein 3 (CTRP3) in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia characterized by atrial remodeling. Complement C1q tumor necrosis factor-related protein 3 (CTRP3) is one of the adipokines associated with obesity, diabetes, and coronary heart disease. The association between plasma CTRP3 levels and AF is uncertain. The aim of this study was to investigate whether plasma CTRP3 concentrations were correlated with AF. Our study included 75 AF patients who underwent catheter ablation at our hospital and 47 sinus rhythm patients to determine the difference in plasma CTRP3 concentrations. Blood samples before the ablation were collected, and ELISA was used to measure the concentrations of CTRP3. Plasma CTRP3 concentrations were significantly lower in AF patients compared with control group (366.9 ± 105.2 ng/ml vs. 429.1 ± 100.1 ng/ml, p = 0.002). In subgroup studies, patients with persistent AF had lower plasma CTRP3 concentrations than those with paroxysmal AF (328.3 ± 83.3 ng/ml vs. 380.0 ± 109.2 ng/ml, p = 0.037). The concentrations of plasma CTRP3 in the recurrence group after radiofrequency catheter ablation of AF were lower than those in the nonrecurrence group (337.9 ± 77.3 ng/ml vs. 386.6 ± 108.1 ng/ml, p = 0.045). Multivariate regression analysis revealed the independent correlation between plasma CTRP3 level and AF. Plasma CTRP3 concentrations were correlated with the presence of AF and AF recurrence.

Comprehensive metabolomic and proteomic analyses reveal candidate biomarkers and related metabolic networks in atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is an abnormal heart rhythm characterized by an irregular beating of the atria and is associated with an increased risk of heart failure, dementia, and stroke. Currently, the perturbation of plasma content due to AF disease onset is not well known. OBJECTIVES: To investigate dysregulated molecules in blood plasma of untreated AF patients, with the goal of identifying biomarkers for disease screening and pathological studies. METHODS: LC-MS based untargeted metabolomics, lipidomics and proteomics analyses were performed to find candidate biomarkers. A targeted quantification assay and an ELISA were performed to validate the results of the omics analyses. RESULTS: We found that 24 metabolites, 16 lipids and 16 proteins were significantly dysregulated in AF patients. Pathway enrichment analysis showed that the purine metabolic pathway and fatty acid metabolism were perturbed by AF onset. FA 20:2 and FA 22:4 show great linear correlational relationship with the left atrial area and could be considered for AF disease stage monitoring or prognosis evaluation. CONCLUSION: we used a comprehensive multiple-omics strategy to systematically investigate the dysregulated molecules in the plasma of AF patients, thereby revealing potential biomarkers for diagnosis and providing information for pathological studies.

Catheter ablation of supraventricular tachycardia in patients with dextrocardia and situs inversus.

BACKGROUND: Dextrocardia with situs inversus is a rare cardiac positional anomaly. Catheter ablation procedures performed in this set of patients have not been sufficiently reported. METHODS: A total of 10 patients with dextrocardia and situs inversus who received catheter ablation for supraventricular tachycardia (SVT) were included from a cohort of over 20 000 cases of catheter ablation for SVT in three centers from 2005 to 2016. All patients underwent electrophysiologic study and catheter ablation of SVT. Ablation targets were selected based on different tachycardia mechanisms with the primary endpoint of noninduction of tachycardia. RESULTS: The average age was 32.4 ± 5.6 years. Congenitally corrected transposition of great arteries (TGA) with situs inversus and D-looping of the ventricles and aorta (congenitally corrected TGA {I,D,D}) was found in four patients, while the other six patients exhibited mirror-image dextrocardia {I,L,L}. The mechanisms of SVT were atrioventricular nodal reentrant tachycardia in four patients, atrioventricular reentrant tachycardia in three, typical atrial flutter in one, intra-atrial reentrant tachycardia in one, and focal atrial tachycardia in one. Immediate procedural success was achieved in 9 out of 10 patients with no procedural complications. During a follow-up period of 6.3 ± 3.5 years on average, all patients remained free from recurrent tachycardia. CONCLUSIONS: For patients with dextrocardia and situs inversus, catheter ablation of SVT is safe and feasible. Differences in catheter maneuver and fluroscopy projection, along with difficulties in distorted anatomy are major obstacles for successful ablation.

Modified duct-to-mucosa versus conventional pancreaticoenterostomy for pancreaticoduodenectomy: a retrospective cohort study based on propensity score matching analysis.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains the most common neopathy after pancreatoduodenectomy (PD). An ideal pancreaticoenterostomy (PE) which can effectively reduce the incidence of CR-POPF and its potential neopathy is needed. We aimed to assess the efficacy of our modified duct-to-mucosa PE in the PD. METHOD: From January 2011 to December 2017, 233 consecutive patients with PD were retrospectively included from Shenzhen People's Hospital. After propensity score matching (PSM), there were 82 patients in both the modified duct-to-mucosa PE group (group A) and the conventional end-to-side inserting PE group (group B), respectively. The clinical course and the incidence of postoperative neopathy were compared between groups. Logistic regression method was utilized to analyze the association between PE approach and CR-POPF. RESULTS: The PE time was shorter in group A (9.3 ± 1.8 min vs. 21.5 ± 2.8 min, P < 0.001). The group A had significantly lower incidence of severe neopathy (Clavien-Dindo grade > II) [7.3% (5/82) vs. 17.1% (14/82), P = 0.028] and incidence of CR-POPF [1.2% (1/82) vs. 19.5% (12/82), P < 0.001] than the group B. Our modified duct-to-mucosa PE technique was associated with a reduced risk for CR-POPF (OR, 0.11 [95% CI, 0.02-0.57]; P = 0.009) as compared with the conventional end-to-side inserting PE. CONCLUSION: Compared with conventional end-to-side inserting PE, our modified duct-to-mucosa PE technique can effectively reduce the incidences of postoperative neopathy and CR-POPF. TRIAL REGISTRATION: Researchregistry3877 . Registered 24 March 2018. Retrospectively registered.

[Relationship between E/Em ratio and exercise capacity in patients with atrial fibrillation].

OBJECTIVE: To explore the relationship between the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/Em) and exercise capacity in patients with atrial fibrillation. METHODS: A total of 94 consecutive patients with non-valvular atrial fibrillation and preserved left ventricular ejection fraction admitted into our department from December 2011 to June 2013 were included. Echocardiography and cardiopulmonary exercise test were performed. According to E/Em, they were divided into two groups of normal E/Em (E/Em ≤ 9) and elevated E/Em (E/Em>9). The parameters of exercise capacity, including VO2max/kg, anaerobic threshold/kg (AT/kg) and exercise time duration were compared between two groups. And the determinants of VO2max/kg were identified by multivariate regression analysis. RESULTS: The number of patients was 57(60.6%) with normal E/Em and 37 (39.4%) with elevated E/Em. As compared to those with normal E/Em, the patients with elevated E/Em had lower VO2max/kg [(26 ± 4) vs (20 ± 4) ml × min⁻¹ × kg⁻¹, P < 0.001], lower AT/kg [(25 ± 4) vs (19 ± 5) ml ×min⁻¹ × kg⁻¹, P < 0.001] and shorter exercise time duration [(7.2 ± 1.3) vs (5.8 ± 1.3) min, P < 0.001]. Multivariate regression analysis revealed that three significant variables were independently associated with VO2max/kg: age (r = -0.412, P < 0.001), gender ((25 ± 5) and (21 ± 4) ml × min⁻¹ × kg⁻¹ for males and females separately, P < 0.001) and E/Em (r = -0.535, P < 0.001). CONCLUSION: E/Em was independently associated with exercise capacity in patients with atrial fibrillation.