Increased Risk Of Atrial Fibrillation Research Articles

High fitness might be associated with the development of new-onset atrial fibrillation in obese non-athletic adults.

Data on the association between AF and fitness are conflicting. The aim of this analysis was to investigate the association between fitness, obesity and incidence of atrial fibrillation (AF) among apparently healthy non-athlete adults. We investigated 20410 self-referred subjects who were annually screened in a tertiary medical centre. All subjects were free of AF and completed maximal exercise stress test according to the Bruce protocol at baseline. Fitness was categorised into age- and sex-specific quintiles (Q) according to the treadmill time. Subjects were categorised to low (Q1-Q2) and high fitness (Q3-5) groups. The primary end point was new-onset AF during follow-up. Mean age was 48±10years and 72% were men. A total of 463 (2.3%) events occurred during an average follow-up of 8±5years corresponding to an AF event rate of 0.3% per person year. Univariate and multivariate models showed that AF risk was similar in both fitness groups. However, AF event rate was 0.55% per person year among high fitness obese subjects, compared with 0.31% for low fitness obese subjects (P<.01). Subgroup interaction analysis showed that AF risk is obesity-dependent, such that in the obese group (≥30kg/m2 ) high fitness was independently associated with a significant 79% increased AF risk (95% CI 1.15-2.78; P=.01), whereas among non-obese subjects the rate of events was similar between both fitness groups (P for interaction=(.02)). Our findings suggest that high fitness might be associated with increased AF risk among obese subjects.

The risk of atrial fibrillation in patients with non-alcoholic fatty liver disease and a high hepatic fibrosis index

Previous epidemiological studies focusing on the association between liver disease and atrial fibrillation (AF) show interesting but inconsistent findings. Patients with liver disease have a higher AF risk; however, it is unknown whether the liver fibrosis index can predict AF risk. The medical records of a healthy population undergoing routine health examinations at Healthcare System Gangnam Center, Seoul National University Hospital, were reviewed retrospectively. After excluding subjects with a history of liver disease and known cardiovascular disease, 74,946 subjects with nonalcoholic fatty liver disease (NAFLD) were evaluated. The mean age was 51 ± 11 years, and 71.9% were male. AF was found in 380 (0.5%) subjects. Using univariate analyses, age, male sex, body mass index, hypertension, and diabetes were significantly associated with AF. The fibrosis 4 index (FIB 4) showed significant correlations with AF [unadjusted odds ratio (OR) 3.062 and 95% confidence interval (CI) 2.605–3.600, p = 0.000; adjusted OR 2.255 and 95% CI 1.744–2.915, p = 0.000, with cardiometabolic risk factors adjusted]. In conclusion, NAFLD subjects with higher FIB 4 were associated with increased AF risk. The noninvasive determination of liver fibrosis indices can have clinical implications on the early identification of NAFLD in patients at risk for AF.

Plasma Ceramides and Sphingomyelins in Relation to Atrial Fibrillation Risk: The Cardiovascular Health Study.

BackgroundCeramides exhibit multiple biological activities that may influence the pathophysiological characteristics of atrial fibrillation (AF). Whether the length of the saturated fatty acid carried by the ceramide or their sphingomyelin precursors are associated with AF risk is not known.Methods and ResultsAmong 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow‐up. We examined 8 sphingolipid species: ceramide and sphingomyelin species with palmitic acid and species with very‐long‐chain saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses, ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk (ie, per 2‐fold higher ceramide with behenic acid hazard ratio, 0.71; 95% CI, 0.59–0.86; sphingomyelin with behenic acid hazard ratio, 0.60; 95% CI, 0.46–0.77). In contrast, ceramides and sphingomyelins with palmitic acid were associated with increased AF risk (ceramide with palmitic acid hazard ratio, 1.31; 95% CI, 1.03–1.66; sphingomyelin with palmitic acid hazard ratio, 1.73; 95% CI, 1.18–2.55). Associations were attenuated with adjustment for NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of coronary heart disease.ConclusionsOur findings suggest that several ceramide and sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the fatty acid. Ceramides and sphingomyelins with palmitic acid were associated with increased AF risk, whereas ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk.

Abstract WMP39: Protein Phosphatase 1 Regulatory Subunit 12C Contributes to Atrial Myosin Light Chain Dephosphorylation in Atrial Fibrillation

Background: Atrial fibrillation (AF) increases stroke risk five-fold. Atrial hypocontractility from atrial myosin light chain (MLC2a) dephosphorylation contributes to stroke risk in AF. Recent proteomic data has shown increased protein phosphatase 1 subunit 12C (PPP1R12C) targeting to MLC2a in AF. However, it is unclear whether PPP1R12C causes MLC2a dephosphorylation in AF. Objective: Determine whether increased PPP1R12C expression causes MLC2a dephosphorylation and increases AF risk. Methods: Western blots and co-IPs were performed to evaluate the relationship among PPP1R12C, PP1c and MLC2a in human atrial tissues (AF vs SR). Mice with either a knockout (KO) or lentiviral (LV) cardiac overexpression of PPP1R12C were evaluated with invasive EP studies for AF inducibility vs WT controls. Results: In human AF, PPP1R12C was increased 4-fold ( P &lt;0.005, n=6) with an 88% reduction in S-19-MLC2a phosphorylation ( P &lt;0.05, n=4). PPP1R12C-PP1c and PPP1R12C-MLC2a binding was increased 2-fold in AF ( P &lt;0.05, n=6). AF burden in LV-12C mice increased nearly tenfold vs. KO and WT mice ( P &lt;0.05, n=6). Conclusion: In human AF, increased PPP1R12C expression is associated with reduced P-MLC2a through enhanced binding with the PP1c catalytic subunit. This dephosphorylation is a likely contributor to atrial hypocontractility and stroke risk in AF. Additionally, increased PPP1R12C expression in mice increases AF risk. Future studies will examine the effects of increased PPP1R12C expression upon atrial contractile function in mice.

The rs2236609 Polymorphism Is Related to Increased Risk Susceptibility of Atrial Fibrillation

Introduction: Genetic variations in the slow component of the delayed rectifier potassium channels (I_Ks) are reported to contribute to an increased susceptibility to arrhythmias. This study aims to investigate the frequency and the possible association of the rs2236609 polymorphism in the KCNE1 gene and the risk of atrial fibrillation (AF). Methods: This was a case-control study that recruited 100 patients suffering from AF (mean age 49.4 ± 15.1 years), and a control group of 95 healthy participants older than 55 years (mean age 59.8 ± 4.1 years) with no history of cardiovascular disease, hypertension, or diabetes. Genomic DNA was extracted from whole peripheral blood, and the desired fragment was amplified using polymerase chain reaction followed by restriction digestion with the NspI restriction enzyme. Results: The results showed a significant difference between the single-nucle­otide polymorphism variations in AF patients and controls (p < 0.022). The risk of AF in the GG genotype was significantly decreased (odds ratio [OR] 0.42; 95% confidence interval [Cl] 0.23–0.79). The risk of AF in the GA (OR 2.12; 95% Cl 1.11–4.06) and AA (OR 2.28, 95% Cl 0.57–9.1) genotypes was significantly increased. The odds of developing AF according to A allele counting was significantly increased (OR 2.1; 95% Cl 1.2608–3.638; p = 0.0048). Conclusion: Our results showed a significant increase in AF risk in people carrying the A allele, while the G allele might be considered as a protective allele.

Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.

The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.

Association of Total Reproductive Years With Incident Atrial Fibrillation, and Subsequent Ischemic Stroke in Women With Natural Menopause.

The association of lifetime exposure to endogenous sex hormone with incident atrial fibrillation (AF) and subsequent ischemic stroke has never been studied. This study involved 4 638 299 natural postmenopausal waomen aged ≥40 years without prior history of AF and with national breast cancer check-up between January 1, 2009 and December 31, 2014. The primary end point was incident AF, and the secondary end point was subsequent ischemic stroke once AF has developed. Cox proportional hazard regression analysis was used to estimate the risk of end points. During the mean follow-up of 6.3 years, shorter total reproductive years (<30 years) were associated with 7% increased risk of AF after adjusting for confounding variables (adjusted hazard ratio [aHR], 1.07 [95% CI, 1.05-1.09]). Risk of AF declined progressively with every 5-yearly increment in total reproductive years (P-for-trend <0.001). However, the prolonged (≥2 years) use of hormone replacement therapy after menopause was paradoxically associated with a 3% increase in AF risk (aHR, 1.03 [95% CI, 1.01-1.05]). For the secondary end point analysis, the risk of ischemic stroke after AF development significantly decreased with each 5-yearly increment in total reproductive years (with <30 years as reference; aHR, 0.93 [95% CI, 0.88-0.99] for 30-34 years; aHR, 0.84 [95% CI, 0.79-0.89] for 35-39 years; and aHR, 0.88 [95% CI, 0.80-0.97] for ≥40 years, P-for-trend <0.001). In women with natural menopause, shorter lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. Paradoxically, prolonged exogenous hormone replacement therapy increased the risk of incident AF.

Calmodulin kinase II regulates atrial myocyte late sodium current, calcium handling, and atrial arrhythmia

Atrial fibrillation (AF) is the most common type of arrhythmia. Abnormal atrial myocyte Ca2+ handling promotes aberrant membrane excitability and remodeling that are important for atrial arrhythmogenesis. The sequence of molecular events leading to loss of normal atrial myocyte Ca2+ homeostasis is not established. Late Na+ current (INa,L) is increased in atrial myocytes from AF patients together with an increase in activity of Ca2+/calmodulin-dependent kinase II (CaMKII). The purpose of this study was to determine whether CaMKII-dependent phosphorylation at Ser571 on NaV1.5 increases atrial INa,L, leading to aberrant atrial Ca2+ cycling, altered electrophysiology, and increased AF risk. Atrial myocyte electrophysiology, Ca2+ handling, and arrhythmia susceptibility were studied in wild-type and Scn5a knock-in mice expressing phosphomimetic (S571E) or phosphoresistant (S571A) NaV1.5 at Ser571. Atrial myocytes from S571E but not S571A mice displayed an increase in INa,L and action potential duration, and with adrenergic stress have increased delayed afterdepolarizations. Frequency of Ca2+ sparks and waves was increased in S571E atrial myocytes compared to wild type. S571E mice showed an increase in atrial events induced by adrenergic stress and AF inducibility invivo. Isolated S571E atria were more susceptible to spontaneous atrial events, which were abrogated by inhibiting sarcoplasmic reticulum Ca2+ release, CaMKII, or the Na+/Ca2+ exchanger. Expression of phospho-NaV1.5 at Ser571 and autophosphorylated CaMKII were increased in atrial samples from human AF patients. This study identified CaMKII-dependent regulation of NaV1.5 as an important upstream event in Ca2+ handling defects and abnormal impulse generation in the setting of AF.

P4796Risk prediction of atrial fibrillation in the community combining biomarkers and genetics

Abstract Background Classical cardiovascular risk factors (CVRF), biomarkers and genetic variation have been suggested for risk assessment of atrial fibrillation (AF). Purpose To evaluate their clinical potential, we analysed their individual and combined effectiveness in AF prediction. Methods In N=6945 individuals of the FINRISK 1997 cohort, we assessed the predictive value of CVRF, N-terminal pro B-type natriuretic peptide (NT-proBNP) and 145 recently identified single nucleotide polymorphisms (SNPs) for incident AF. Results Over a median follow-up of 17.8 years, N=551 participants (7.9%) developed AF. In multivariable-adjusted Cox proportional hazard models, NT-proBNP (hazard ratio (HR) per standard deviation (SD) 1.90, 95% confidence interval (CI): 1.71–2.11, P&lt;0.001) and the polygenic risk score (PRS) (HR per SD 1.66, 95% CI: 1.51–1.84, P&lt;0.001) were significantly related to incident AF. The discriminatory ability improved asymptotically with increasing numbers of SNPs. Compared to a clinical model, AF risk prediction was significantly improved by addition of NT-proBNP and the PRS. The C-statistic for the combination of all CVRF, NT-proBNP and the PRS reached 0.82 compared to 0.77 for CVRF only (P&lt;0.001). Comparing the highest versus lowest quartile, age remained the strongest risk factor with a 15-fold increased risk of AF. The highest quartiles of NT-proBNP and the PRS both showed an approximately 3-fold increased AF risk compared to the lowest quartiles. C-Index for AF prediction Conclusions The PRS and the established biomarker NT-proBNP predicted incident AF comparably. Both provided incremental predictive value over standard clinical variables. Further improvements for the PRS are likely with the discovery of additional SNPs. Acknowledgement/Funding European Research Council, German Ministry of Research and Education, DZHK, European Union Seventh Framework Programme, CHANCES, THL

Atrial Fibrillation in Long QT Syndrome by Genotype

Long QT syndrome (LQTS) is caused by the abnormal function of ion channels, which may also affect atrial electrophysiology and be associated with the risk of atrial fibrillation (AF). However, large-scale studies of AF risk among patients with LQTS and its relation to LQTS manifestations are lacking. We aimed to assess the risk of AF and its relationship to the LQTS genotype and the long-term prognosis in patients with LQTS. Genotype-positive patients with LQTS (784 LQT1, 746 LQT2, and 233 LQT3) were compared with 2043 genotype-negative family members. Information on the occurrence of AF was based on physician-reported ECG-verified events. Multivariate Cox proportional hazards regression analyses were performed for ages 0 to 60 and after 60 years (reflecting an early and late-onset of AF) to assess the risk of incident AF by genotype and the relationship of AF to the risk of cardiac events defined as syncope, documented torsades de pointes, and aborted cardiac arrest or sudden cardiac death. In patients followed from birth to 60 years of age, patients with LQT3 had an increased risk of AF compared with genotype-negative family members (hazard ratio=6.62; 95% CI, 2.04-21.49; P<0.001), while neither LQT1 nor LQT2 demonstrated increased AF risk. After the age of 60 years, patients with LQT2 had significantly lower risk of AF compared with genotype-negative controls (hazard ratio=0.07; 95% CI, 0.01-0.53, P=0.011). AF was a significant predictor of cardiac events in patients with LQT3 through the age of 60 (hazard ratio=5.38; 95% CI, 1.17-24.82; P=0.031). Our data demonstrate an increased risk of early age AF in patients with LQT3 and also indicate a protective effect of the LQT2 genotype in it's association with a decreased risk of AF after the age of 60.

Association of Early-Stage Breast Cancer and Subsequent Chemotherapy With Risk of Atrial Fibrillation

Several types of cancer have been linked to a higher risk of developing atrial fibrillation (AF). Fewer data exist regarding early-stage breast cancer (EBC), for which cardio-oncology concerns are more pertinent. To investigate the association of EBC and subsequent chemotherapy with the risk of developing AF. This was a population-based, retrospective, matched cohort study conducted in Toronto, Ontario, Canada, of 68 113 women diagnosed with EBC between April 2007 and December 2016 who were matched 1:3 to a cancer-free control group based on birth year and receipt of breast imaging. Prevalence of AF before the index date (date of EBC diagnosis) was compared between the cohorts using the McNemar test. Cumulative incidence function curves were used to describe the AF incidence. To study preexisting AF, participants were matched before exclusion for prior AF. For the remaining analyses, we excluded women with prior AF before matching. An analysis was conducted beginning 1 year after the index date (ie, excluding AF diagnoses in year 1), which we stratified by chemotherapy exposure. Multivariable cause-specific regression was used to determine the hazard ratio (HR) associated with EBC relative to the controls and the association of chemotherapy with AF in patients with EBC. Breast cancer and chemotherapy. Incidence of AF. A total of 68 113 women with EBC and 204 330 cancer-free controls were included in the study; both groups had a mean (SD) age of 60 (13) years. Of the women with EBC, 44.3% were diagnosed as having stage I breast cancer; 38.7%, stage II; and 13.4%, stage III; cancer stage information was missing for 3.6% of the patients. No difference was observed in preexisting AF prevalence (5.3% in the EBC cohort vs 5.2% in controls; P = .21). At 10 years after the index date, the AF incidence was 7.4% (95% CI, 7.1%-7.7%) for women with EBC and 6.8% (95% CI, 6.7%-7.0%) for the controls (P < .001). The adjusted cause-specific HR was significantly elevated at year 1 (HR, 2.16; 95% CI, 1.94-2.41) and after year 5 (HR, 1.20; 95% CI, 1.11-1.30) but not during years 2 through 5. Analyses beginning 1 year after diagnosis showed attenuated differences that remained statistically significant: the cumulative incidence of AF at 9-year follow-up was 7.0% (95% CI, 6.7%-7.3%) for patients with EBC and 6.5% (95% CI, 6.3%-6.7%) for the cancer-free controls. The rate of AF was higher in women who received chemotherapy (adjusted HR, 1.23; 95% CI, 1.13-1.35) but was not associated with exposure to anthracyclines or trastuzumab. This study's findings suggest that patients with EBC may not have a higher prevalence of AF before cancer diagnosis. A higher rate of AF was observed in the first year and after 5 years following the EBC diagnosis. The rate of AF was higher in patients who received chemotherapy but appeared to not be associated with specific cardiotoxic agents. These findings suggest that the early and late periods of increased AF risk in EBC survivors warrant focused research to better understand the underlying causes and subsequent implications.

Abstract 813: Downregulation of the Cardiac Sodium Channel Nav1.5 Mediates Obesity-Induced Atrial Fibrillation

Background: Obesity increases atrial fibrillation (AF) risk, but the underlying mechanisms are unclear. Emerging evidence supports reduced cardiac Na + channel (Nav1.5) expression and current ( I Na ) as one potential mechanism. Objective: We used an acquired (diet-induced obese, DIO) obese mouse model to test the hypothesis that obesity increases AF risk by downregulating Nav1.5. Methods: Weight, BP, plasma glucose, and F 2 -isoprostanes were measured in DIO mice and compared to controls. Echocardiography, EP studies, immunohistochemistry, Western blotting, cellular patch clamping and optical mapping studies were performed. Results: DIO (37.5±3.8) mice were heavier than controls ( 24.3 ±4.1;P &lt;0.001). AF burden was 355±383 sec in DIO mice vs. 8.3± 21.4 sec in controls ( P &lt;0.0001). Nav1.5 expression, I Na , atrial action potential duration (APD) and conduction velocity (CV) were reduced, and F 2 -IsoPs were increased. AF burden was reduced in the DIO model after chronic treatment with MitoTEMPO antioxidant, with partial restoration of the APD90, I Na and AP upstroke and reduction in F 2 -IsoPs. Conclusions: Mice with either acquired or genetic susceptibility to obesity are more prone to develop AF. And this is partially mediated by increased oxidative stress leading to downregulation of Nav1.5, shortened atrial APD and reduced atrial conduction velocity suggesting a possible reentrant mechanism of AF.

Weight and weight change and risk of atrial fibrillation: the HUNT study

Although obesity has been associated with risk of atrial fibrillation (AF), the associations of long-term obesity, recent obesity, and weight change with AF risk throughout adulthood are uncertain. An ambispective cohort study was conducted which included 15214 individuals. The cohort was created from 2006 to 2008 (the baseline) and was followed for incident AF until 2015. Weight and height were directly measured at baseline. Data on previous weight and height were retrieved retrospectively from measurements conducted 10, 20, and 40 years prior to baseline. Average body mass index (BMI) over time and weight change was calculated. During follow-up, 1149 participants developed AF. The multivariable-adjusted hazard ratios were 1.2 (95% confidence interval 1.0-1.4) for average BMI 25.0-29.9 kg/m2 and 1.6 (1.2-2.0) for average BMI ≥30 kg/m2 when compared with normal weight. The association of average BMI with AF risk was only slightly attenuated after adjustment for most recent BMI. In contrast, current BMI was not strongly associated with the risk of AF after adjustment for average BMI earlier in life. Compared with stable BMI, both loss and gain in BMI were associated with increased AF risk. After adjustment for most recent BMI, the association of BMI gain with AF risk was largely unchanged, while the association of BMI loss with AF risk was weakened. Long-term obesity and BMI change are associated with AF risk. Obesity earlier in life and weight gain over time exert cumulative effects on AF development even after accounting for most recent BMI.

Long-term blood pressure trajectories and incident atrial fibrillation in women and men: the Tromsø Study.

AimsTo explore sex-specific associations between long-term individual blood pressure (BP) patterns and risk of incident atrial fibrillation (AF) in the general population.Methods and resultsBlood pressure was measured in 8376 women and 7670 men who attended at least two of the three population-based Tromsø Study surveys conducted in 1986–87, 1994–95, and 2001. Participants were followed for incident AF throughout 2013. Latent mixed modelling was used to identify long-term trajectories of systolic BP and hypertension. Cox regression was used to estimate associations between the identified trajectories and incident AF. Elevated systolic BP throughout the exposure period (1986–2001) independently and differentially increased risk of AF in women and men. In women, having elevated systolic BP trajectories doubled AF risk compared to having persistently low levels, irrespective of whether systolic BP increased, decreased, or was persistently high over time, with hazard ratios of 1.88 (95% confidence interval 1.37–2.58), 2.32 (1.61–3.35), and 1.94 (1.28–2.94), respectively. In men, those with elevated systolic BP that continued to increase over time had a 50% increased AF risk: 1.51 (1.09–2.10). When compared to those persistently normotensive, women developing hypertension during the exposure period, and women and men with hypertension throughout the exposure period had 1.40 (1.06–1.86), 2.75 (1.99–3.80), and 1.36 (1.10–1.68) times increased risk of AF, respectively.ConclusionLong-term BP and hypertension trajectories were associated with increased incidence of AF in both women and men, but the associations were stronger in women.

Metabolically Healthy Obesity and Risk for Atrial Fibrillation: The HUNT Study.

Atrial fibrillation (AF) is the most common arrhythmia and has been described as a global epidemic. Although AF is associated with both obesity and its metabolic consequences, little is known about the association between metabolically healthy obesity and AF. In a population-based study, 47,870 adults were followed for incident AF from 2006 to 2008 until 2015. Participants were classified according to BMI and metabolic status (using waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and glucose) at baseline. During a median follow-up of 8.1 years, 1,758 participants developed AF. Compared with metabolically healthy individuals with BMI < 25 kg/m2 , the multivariable-adjusted hazard ratios for metabolically healthy and unhealthy obesity were 1.6 (95% CI: 1.2 to 2.1) and 1.6 (95% CI: 1.3 to 1.9), respectively. AF risk increased according to the severity of obesity. Metabolically healthy and unhealthy obesity increased AF risk to a similar extent. Severity of obesity was positively associated with AF risk regardless of metabolic status.

Atrial fibrillation in the cardiometabolic patient.

Prevalence of obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) is growing alarmingly, and the number of affected people continues to escalate. Such cardiometabolic states exert many deleterious effects on the heart as they are associated with adverse left ventricular (LV) remodeling and, most notably, with a marked increase in the risk of developing atrial fibrillation (AF) and subsequent stroke. Epidemiological studies clearly show a strong association between obesity and AF, with a 4-5% increase in AF risk for every unit increase in BMI. The increased risk of developing AF in cardiometabolic patients is explained by changes in volume status, energy substrate utilization, tissue metabolism and systemic inflammation, all factors promoting elevation in left atrial and systolic blood pressure, LV systo-diastolic dysfunction, with subsequent atrial stretch and "triggers" for AF. In the present review, we critically discuss available evidence on AF risk in the cardiometabolic patient. Specific aspects will be discussed: 1) epidemiology and prognosis of AF in patients with obesity, MetS and T2D; 2) molecular mechanisms involved in the pathophysiology of metabolic cardiomyopathy and left atrial remodeling; 3) advances in medical therapy including weight loss strategies and lifestyle changes; 4) new oral anticoagulants and stroke risk in obese and diabetic patients; 5) effectiveness and safety of AF catheter ablation. Taken together, these novel insights point to the development of new therapeutic strategies to combat the burden of AF in patients with cardiometabolic disturbances.

Chronic obstructive pulmonary disease and the development of atrial fibrillation

BackgroundChronic obstructive pulmonary disease (COPD) has been associated with atrial fibrillation (AF). More insight into the epidemiology and underlying mechanisms is required to optimize management. MethodsThe Rotterdam Study is a large, population-based cohort study with long-term follow-up. Time dependent Cox proportional hazard models were constructed to study the effect of COPD on incident AF, adjusted for age, sex and pack years of cigarette smoking, and additionally stratified according to exacerbation frequency, left atrial size and baseline systemic inflammatory levels. Results1369 of 10,943 subjects had COPD, of whom 804 developed AF. The AF incidence rate was 14 per 1000 person years in COPD and 8 per 1000 person years in subjects without COPD. The adjusted hazard ratio (HR) for COPD subjects to develop AF as compared to subjects without COPD was 1.28 (95%CI [1.04, 1.57]). COPD subjects with frequent exacerbations had a twofold increased AF risk (HR 1.99 [1.42, 2.79]) and COPD subjects with a left atrial size ≥40 mm also had an elevated AF risk (HR 1.77 [1.07, 2.94]). COPD subjects with baseline systemic inflammatory levels above the median had significantly increased AF risks (hsCRP≥1.83 mg/L: HR 1.51 [1.13, 2.03] and IL6 ≥ 1.91 ng/L: HR 2.49 [1.18, 5.28]), whereas COPD subjects below the median had in both analyses no significantly increased AF risk. ConclusionsCOPD subjects had a 28% increased AF risk, which further increased with frequent exacerbations and an enlarged left atrium. The risk was driven by COPD subjects having elevated systemic inflammatory levels.

Ten Lifestyle Modification Approaches to Treat Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia affecting three million people in the United States (US). Across different races in the US, the incidence of other races was comparable to that of Caucasian population. This points towards the importance of certain lifestyle modifications that can help prevent and treat this disorder. This article discusses 10 such factors. Smoking has been linked to AF, with almost 36% risk reduction if quit. Hypertension has 56% increased risk of atrial fibrillation in which the role of lifestyle changes is well known. Similarly, alcohol-induced atrial fibrillation has 10% increased risk of atrial fibrillation. On the other hand, several case reports document red bull as the cause of atrial fibrillation. Moreover, the risk of atrial fibrillation is four times higher in patients with obstructive sleep apnea (OSA) independent of other confounding variables. Additionally, it has been shown that acute sleep deprivation increases AF risk by 3.36 times. Furthermore, diabetes mellitus and obesity also contribute greatly to atrial fibrillation. This risk has been shown to be around 40% more with diabetes. Diet itself has an impact: numerous studies have shown Mediterranean diet to reduce the risk of AF and cerebrovascular accident in addition to olive oil, fruits and vegetables. Even emotions are important with 85% less AF on ‘happy days’. Needless to mention, yoga has been well demonstrated to have almost 24% reduction in AF. Similarly, physical activity in all forms is beneficial. In summary, lifestyle modifications reduce the incidence of AF, induce more AF remission and also produce successful ablation outcomes.

High-sensitivity cardiac troponin I and risk of incident atrial fibrillation hospitalisation in an Australian community-based cohort: The Busselton health study

ObjectiveThe identification of individuals at risk of atrial fibrillation (AF) remains a challenge. We investigated whether high-sensitive cardiac troponin I (hs-cTnI) is an independent predictor of incident atrial fibrillation (AF) hospitalisation in an Australian community-based cohort. MethodsSerum hs-cTnI was measured in 1641 men and 2189 women in the Busselton Health Study 1994/1995 Cohort aged 25–84 years at baseline. Data on incident AF hospitalisation over 20 years follow-up were obtained by data linkage. ResultsHs-cTnI was detectable (>1.2 ng/L) in 65.5% of participants (males 81.4%, females 53.6%) at baseline. There were 179 (10.9%) AF events in men and 208 (9.5%) in women. In the multivariable-adjusted model, hs-cTnI was a significant predictor of AF event with hazard ratio 1.21 (95% CI 1.11–1.32, P < 0.001) in the whole cohort, 1.17 (95% CI 1.01–1.35, P = 0.037) in men and 1.22 (95% CI 1.08–1.37, P = 0.001) in women for a doubling of baseline hs-cTnI. In women, a graded and significant increase in risk of AF was observed across hs-cTnI categories from ≥1.3 ng/L, whereas in men only the highest category (≥6.0 ng/L) had significantly increased risk compared with individuals with hs-cTnI ≤1.2 ng/L. Addition of categorical hs-cTnI to standard risk factors for AF improved risk estimation in females (C-statistic increment 0.006, P = 0.04) but not males (increment 0.005, P = 0.12) and net reclassification improvement was not significant in either sex. ConclusionsHigh-sensitive cTnI level is an independent predictor of incident AF hospitalisation in a community-based cohort but does not improve risk stratification.

OP-51 - Is Patent Foramen Ovale Increasing Atrial Premature Contraction Frequency?

Objective: Foramen ovale is an opening between the left and right atria during intrauterine life and usually closes after birth. The incomplete closure of this opening is called patent foramen ovale (PFO). It has been shown that patients with PFO have high atrial fibrillation (AF) frequency, but the relationship between atrial premature contraction (APC) and PFO has not been investigated. Some studies have reported that increased APC increases AF risk in patients with atrial septal defects. The aim of the study is to investigate whether the frequency of APC is increasing in healthy young subjects with PFO.