Higher Risk Of Atrial Fibrillation Research Articles

Circadian rhythm in atrial fibrillation detected by implantable loop recorder: a post-hoc analysis of a randomized clinical trial

Abstract Introduction Previous studies suggest the existence of circadian, weekly, and seasonal rhythms in the occurrence of atrial fibrillation (AF), which may be utilized to improve the yield of screening. The heterogeneity of AF natural history also necessitates better phenotyping to overcome the challenges of identifying candidates for screening and treatment. Purpose To explore the potential circadian rhythm in AF occurrence in persons without known arrhythmia but at high risk of AF and stroke. Methods Post-hoc analysis of the LOOP study (Atrial Fibrillation Detected by Continuous Electrocardiogram Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), which randomized 6004 AF naïve participants (≥70 years old with additional stroke risk factors) 1:3 to receive implantable loop recorder screening or usual care. All loop recorder data was extracted to obtain the date and time of AF episode onset, AF duration, mean and max heart rate (HR) during AF, and symptom annotations. New-onset AF episodes lasting ≥6 minutes were adjudicated, and all subsequent episodes were included in the analysis. Results A total of 41,713 AF episodes (median duration 18 (8-64) minutes) were identified among 430 participants (Table 1). The median number of episodes for each participant with AF was 21 (4-82) and the median AF burden was 0.17% (0.04%-0.83%) of time from debut to end of monitoring. The most and least frequent days of AF onset were Sunday (15.3%) and Friday (13.6%), respectively, while AF occurred slightly more often during spring (26%) than in other seasons. The median time of onset was 09:57:15 AM (05:15:30 AM – 03:33:00 PM). The most frequent time of onset was at 09:00 AM (rounded to the nearest hour), which was two times more likely than at 09:00 PM, and 22% of all episodes occurred between 08:00 and 11:00 AM (Figure 1). A total of 25,329 (61%) episodes occurred between midnight and noon (AM). Nocturnal episodes, defined as episodes with onset between 10:00 PM and 07:00 AM, occurred in 368 (86%) AF participants and constituted a median of 40% of all episodes and 37% (14%-63%) of each participant’s episodes. The median duration of nocturnal episodes was 28 (10-104) minutes compared to 14 (8-44) minutes for daytime episodes. The averaged heart rate during AF was 81 (71-96) beats per minute (BPM), while 330 (77%) participants had AF episodes with heart rates equal to or above 100 BPM, and the duration of these episodes was 50 (15-201) minutes compared to 30 (21-85) minutes for slower episodes (below 100 BPM). Conclusion A circadian pattern was observed for screening-detected AF. AF onset occurred predominantly between 08:00 and 11:00 AM, representing more than one in five episodes. Nocturnal AF occurred in most participants with AF and accounted for almost half of all episodes, while these episodes also lasted longer than daytime episodes. This may warrant future studies investigating the timing of AF screening.

Machine learning to predict incident atrial fibrillation in patients with acute stroke: FIND-AF STROKE

Abstract Background Atrial fibrillation (AF)-related strokes have a high rate of recurrence, and are associated with substantial morbidity, disability, healthcare expenditure, and mortality.(1-3) Detection of AF promises opportunity to prevent recurrent stroke through conversion of antiplatelet to anticoagulant therapy,(4,5) but use of extended monitoring has cost implications.(6) Thus accurately identifying patients with stroke at high risk for AF is important but previous previous models have been developed in small, unrepresentative cohorts.(7) Purpose To develop and validate a simple novel decision support tool for prediction of incident AF after hospitalisation with stroke through machine learning. Methods We developed the model (FIND-AF STROKE) in UK secondary care and death certificate-linked primary care health record data from individuals aged ≥30 years without known AF hospitalized with a stroke or transient ischaemic attack (Jan 2, 1998 to Feb 28, 2022), randomly divided into training (80%) and testing (20%) datasets. We evaluated logistic regression and random forest models for prediction of 2-year AF risk in the testing dataset with internal bootstrap validation, and compared against the CHA2DS2VASC score. Youden index was used to set a threshold for higher and lower risk. Results Of 35 530 UK individuals (mean age 72.1 (SD 12.7) years, 50.9% women), 1742 (4.8%) had developed incident AF at 2 years. Using feature importance a parsimonious version of the model was created requiring only age, sex, ethnicity (white versus other) and five comorbidities. In the testing dataset prediction performance for the random forest algorithm (area under the receiver operating characteristic (AUROC) 0.710, 95% CI 0.685 – 0.736) was superior to the CHA2DS2VASC score (0.645, 95% CI 0.617-0.672) (Figure 1). The threshold for higher risk using the Youden index was 4.81% which resulted in a negative predictive value of 97.6%, sensitivity 0.712, specificity 0.583. Of the post-stroke patients 44% were labelled at higher risk of AF, who were older, had a higher prevalence of comorbidities, and a 3.3-fold higher incidence of AF post-stroke, than those identified as lower risk (Table 1). Conclusions The machine learning FIND-AF STROKE decision support tool can accurately identify individuals at risk of incident AF after stroke to enable a targeted and cost-effective approach to extended monitoring. Validation within cohorts that have undergone extended monitoring post-stroke will give a more accurate estimation of yield at different risk thresholds.Figure 1

Relationship of serum vitamin D levels with atrial fibrillation incidence: The HUNT Study

Abstract Background Evidence on the association between serum vitamin D levels and incidence of atrial fibrillation (AF) was inconclusive. To elucidate the nature of the association, we studied the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and AF incidence in the Norwegian Trøndelag Health (HUNT) Study using both conventional observational and Mendelian Randomization (MR) approaches. Methods 3394 adult participants without AF diagnoses were followed up from HUNT3 (2006-2008) to 2021 in a prospective cohort. Average serum 25(OH)D levels over ten years between HUNT2 (1995-1997) and HUNT3 were calculated and categorized into <50 and ≥50 nmol/L as exposure. AF diagnoses were retrieved from hospital registers and validated by medical doctors. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Furthermore, a one-sample MR was conducted among 36,554 adults who participated in both HUNT2 and HUNT3. An externally weighted genetic risk score based on 19 vitamin D-related genetic variants, chosen for their clear biological functions in serum vitamin D transport, synthesis and metabolism, was used as instrument. We applied the Wald ratio method to assess the causal effect. Results During a median 13-year follow-up, 303 AF cases were diagnosed in the prospective cohort. Serum 25(OH)D level <50.0 nmol/L was associated with a 26% reduced incidence of AF (HR 0.74, 95% CI 0.58 to 0.95), compared to serum 25(OH)D ≥50 nmol/L after adjustment for confounders. Genetically determined 10 nmol/L decrease in serum 25(OH)D level was associated with a 7% reduced incidence of AF (HR 0.93, 95% CI 0.86 to 1.00) in the MR analysis. Sensitivity analyses supported this positive association. Conclusions We found a consistent positive association between serum 25(OH)D level and AF incidence in the Norwegian HUNT population using both observational and MR approaches. Key messages • Serum vitamin D levels appeared to be positively associated with the incidence of AF. • Vitamin D supplementation should be prescribed with caution, especially for people at high risk for AF.

Long-term weight change in midlife, cardiac magnetic resonance parameters, risk of atrial fibrillation: a large prospective cohort study

Abstract Background Although obesity is a well-established risk factor for atrial fibrillation (AF), the relationship between weight change and the risk of AF remains controversial. Furthermore, the extent to which obesity-associated AF risk is mediated by cardiac remodeling is unclear. Purpose We aimed to evaluate the impacts of obesity and weight change on the risk of atrial fibrillation, and the role of cardiac remodeling in obesity-AF association. Methods This is a population-based prospective cohort of UK Biobank participants recruited from 2006 to 2010. A total of 490,969 participants and 19,634 participants were included for BMI and BMI change analysis, respectively. Body mass index (BMI) was assessed at baseline and follow-up assessment (2012-2013). Cardiovascular measurements were derived from cardiovascular magnetic resonance. Cox proportional hazard models were used to assess the associations of obesity and change in BMI with AF. The nonlinear associations of BMI and BMI change with AF were tested using a restricted cubic spine (RCS). Mediation analysis was conducted to quantify the role of cardiac remodeling in the association between obesity and AF. Results Among the 490,969 participants included (mean age: 56.4 ± 8.1 years, 54.9% women), 33,297 incident AF cases were observed during a median follow-up of 14.0 years. Overweight (hazard ratio [HR], 1.12, 95% confidence interval [CI] 1.09-1.15, P < 0.001) and obesity (1.73, 1.68-1.78, P < 0.001) significantly increased the risk of AF, particularly in men, those with age < 60 years and low genetic risk. During a median follow-up of 4.43 years, 1,217 (6.2%) participants experienced > 2% BMI loss per year and 1,318 (6.7%) participants experienced > 2% BMI gain per year. Compared to stable BMI, BMI loss was associated with a lower risk of AF (0.75, 0.57-0.99, P = 0.039). In addition, we found that BMI loss from obesity to overweight was associated with a reduced risk of AF (0.74, 0.54-1.02, P = 0.069) compared with maintaining baseline BMI category. Participants with stable obesity had a higher risk of AF (1.81, 1.52-2.16, P < 0.001) than those with stable normal weight. In addition, RCS indicated BMI had a J-shaped association with AF while BMI change had a linear association with AF. Mediation analyses revealed that left ventricular myocardial mass, left atrial maximum volume, and left atrial minimum volume were the three strongest mediating factors between obesity and AF, with a mediated proportion of 85.28%, 64.43%, and 55.89% of the total effect, respectively. Conclusion BMI decrease over 2% per year was associated with a lower risk of AF, especially in those changing from obesity to overweight. Left ventricular myocardial mass plays a central role in mediating obesity-related AF. Our findings support weight management at the population level to mitigate the growing epidemic of AF and ways targeting left ventricular myocardial mass are waiting to be further explored.Associations of BMI, BMI change with AFThe mediating role of cardiac remodeling

Clustering of artificial intelligence derived plaque features for risk stratification for future atrial fibrillation development

Abstract Introduction We previously demonstrated that artificial intelligence (AI)-derived coronary artery plaque features are associated with future development of atrial fibrillation (AF) among patients undergoing CCTA(1). Our results suggest that phenotyping a large dataset of plaque features using data science techniques may reveal associations not visible from univariate analysis. Purpose Use data science analysis of AI-CT plaque characteristics to identify subpopulations at higher risk of AF. Methods We applied dimensionality reduction and visual cluster identification to phenotype our population of patients based on their AI-CT plaque features. We used a single center CCTA registry of patients with prior clinically-indicated CCTA (N=2700) from 2017-2020. Cases of new AF were defined by onset of AF on ECG or telemetry after CCTA via EMR search. Patients with AF prior to CCTA, history of mitral valve surgery, or postoperative AF were excluded. Controls were selected 1:1 by nearest neighbor propensity matching (R. v. 4.0.3.) based on age, sex, tobacco use, HTN, HLD, and diabetes. Atherosclerotic plaques were quantitatively analyzed using a commercially available FDA-approved AI coronary analysis software yielding stenosis area and diameter, remodeling index, volume of calcified/non-calcified/low-density plaques, and number of 2 or more high risk plaques. Uniform Manifold Approximation and Projection (UMAP) dimensionality reduction with cosine distance metric was used to reduce the plaque feature space from 80 dimensions (8 AI measurements per each of 10 anatomical vessel segments in all patients) to 2 dimensions on a scatter plot. Two non-contiguous clusters (i.e. plaque phenotypes) were identified based on visual analysis of UMAP feature reduction (Figure 1). Results 94 cases comprised the study cohort (47 cases and 47 controls). Mean age was 67±11 years. 38% were female. Mean CADRADS score was 1.8±1.52 and mean CAC was 325±622. Mean time from CT to AF was 281±300 days. The majority of AF patients (67%) fell into Cluster 1 (N=36), while Cluster 2 (N=58) contained most of the control subjects (75%). Treating Cluster 1 as a predictor of AF, the PPV and specificity of the UMAP reduction was 67% and 75% respectively, with NPV of 60% and sensitivity of 51% (Table 1). Left atrial volume index (LAVI) was significantly different between the 2 clusters, with mean 56.15±12.42 ml/m2 in Cluster 1 and 46.96±16.03 in Cluster 2 (p=0.0046). LAVI was also significantly different between control subjects in Cluster 1 vs 2, mean 54.84±11.6 vs 41.62±7.92 (p<0.001). Conclusions We demonstrated that UMAP-derived clustering of AI-CT plaque characteristics identifies novel phenotypes for future risk of AF among patients undergoing CCTA. Further, control patients in Cluster 1 were found to have a significantly higher LAVI compared to control subjects in Cluster 2, which supports that membership in Cluster 1 may increase risk of future development of AF.

Circulating ketone bodies, genetic predisposition, and incident atrial fibrillation

Abstract Background Ketone bodies (KB) are essential alternative fuel sources for the myocardium. However, the evidence on the level of circulating KB and heart disorders is inconsistent. Whether the total and individual KB are associated with risk of onset atrial fibrillation (AF) in the general population and in individuals with different genetic susceptibilities to AF are still unclear. Purpose To examine the association between circulating KB and AF risk and to further test whether genetic risk could modify the above association. Methods In the UK Biobank, 247,304 participants (mean age 56.5, 45.3% men) with available data on KB and without baseline AF were included. The concentrations of KB, including β-hydroxybutyrate (β-OHB), acetoacetate, and acetone, were measured using nuclear magnetic resonance, and the values of KB were increased by one and then log10-transformed for analyses. The genetic risk of AF was based on the standard polygenic risk score. The definitions of AF were based on the ICD-10 code I48, which was linked to primary care, hospital admission electronic health records and death records. Cox proportional hazard model was used to estimate the hazard ratio (HR) with 95% confidence interval (CI). Results During a median follow-up of 13.8 years, 16,936 cases of onset of AF were recorded. After adjusting for age, sex, race, Townsend index, education, alcohol intake frequency, smoking status, healthy diet, metabolic equivalent, body mass index, systolic blood pressure (SBP), total cholesterol, estimated glomerular filtration rate, cardiovascular diseases, and diabetes, elevated total KB, β-OHB, acetoacetate, and acetone were all with the risk of AF (HR, 95% CI per 10-fold increase: 1.20, 1.13-1.28; 1.13, 1.07-1.19; 1.12, 1.06-1.18; and 1.78, 1.57-2.01, respectively). The highest risk of AF was observed among individuals at high genetic risk to AF and had the highest quartile of total KB (HR 2.91, 95% CI 2.66-3.19). Participants who had low genetic risk were more susceptible to high total KB for incident AF (p for interaction = 0.036). The associations of total KB, β-OHB, and acetone with AF risk were more prominent for men (HR, 95% CI per 10-fold increase: 1.32, 1.22-1.44; 1.22, 1.14-1.31; 2.01, 1.72-2.36) than for women (p for interaction <0.05). The association between total KB and AF risk was strengthened in individuals <60 years, current smokers, and those with SBP<130 mmHg (p for interaction = 0.033, 0.021, and 0.017, respectively). Conclusions Circulating KB concentrations were associated with AF risk, with acetone showing the strongest relationship with AF. Individuals at low genetic risk were more susceptible to the level of total KB for incident AF. Our findings suggest that KB may be a biomarker, particularly for identifying individuals without AF at baseline who are at low genetic risk. The additive value of plasma KB to a risk prediction score warrants further investigation.

Association of serum testosterone levels with left atrial size, function, and risk of atrial fibrillation in adult men: observational and mendelian randomization analyses

Abstract Background Numerous studies have investigated the association between serum testosterone levels, testosterone replacement therapy (TRT), and cardiovascular risk. However, research examining the relationship between testosterone levels and atrial fibrillation (AF) risk remains limited. We comprehensively analyzed the association between total testosterone (TT) levels, intermediary phenotypes such as left atrium (LA) size and function, and the risk of AF in middle-aged and older men. Methods We utilized data from the UK Biobank, a population-based prospective cohort, focusing on 179,988 White men who had complete serum TT level data and no AF history. Observational associations between TT levels and LA imaging traits, as well as AF risk, were estimated using multivariable regression and time-dependent Cox regression models, treating TT levels as a time-varying variable. Genetic associations were examined by Mendelian randomization (MR), using both UK Biobank and external large consortia genome-wide association study data. Results During the median follow-up of 11.8 years (IQR 10.9–12.5), we observed 13,847 incident AF cases (7.7%). Participants with normal TT levels (≥ 300 ng/dL) showed a 15% reduced risk of AF (HR of 0.85 [95% CI, 0.82–0.89]) compared to those with low TT (< 300 ng/dL). Interestingly, participants undergoing TRT experienced a 51% higher risk of AF (1.51 [1.09–2.07]). Furthermore, each 1-standard deviation increase in TT levels was associated with a reduced AF risk (OR of 0.91 [0.89–0.93]) and an improved LA emptying fraction (1.29 [1.06–1.58]). Applying age-specific cutoff values for low TT levels highlighted a more pronounced AF risk reduction in participants with normal TT. MR analyses supported these observations, suggesting potential causal relationships between TT levels and both LA function and AF risk. Conclusions Our findings suggest that low TT levels are associated with reduced LA function and increased risk of AF, both observationally and genetically, indicating that serum TT could serve as a surrogate marker or even a potential causal mediator in the development of AF.Abstract tableAbstract figure

Left atrial enlargement: a crucial indicator for identifying atrial fibrillation in patients with hypertension

Abstract Background Left atrial enlargement resulting from hypertension is closely linked to the development and persistence of atrial fibrillation (AF). The newly proposed staging recognizes AF as disease continuum, which makes us aware that AF prevention should focus on the Pre-AF stage, and atrial enlargement is one of the important manifestations in this stage. Previous scoring systems, such as CHA2DS2-VASc and C2HEST, along with the recently highlighted left atrial diameter (LAD), have been significant tools for predicting AF occurrence. However, a comprehensive assessment of their utility is currently lacking. Purpose This study aims to explore the role of left atrial size in identifying atrial fibrillation (AF) among hospitalized hypertensives, and to compare its recognition effectiveness with previous scoring systems. Methods We conducted a cross-sectional analysis within hospitalized hypertensives. The discovery, internal and external validation datasets were established. The XGBoost was employed to identify key variables related to AF occurrence, which were ranked based on their importance scores. To gauge the predictive prowess of LAD regarding AF occurrence, we plotted the receiver operating characteristic curve (ROC) and calculated the area under the curve (AUC). This enabled us to pinpoint the LAD cutoff value corresponding to the maximum Youden index, indicative of susceptibility to AF. Subsequently, Youden index determined the optimal cutoff value from the ROC curve. Delong’s test compared the identification abilities of different tools within the same dataset. Logistic regression analysis assessed the correlation between clinical variables and left atrial size. Results The XGBoost revealed 17 variables affecting AF occurrence in hypertensives, with LAD, age, and HF ranking among the top 3 (Figure 2a). LAD had a more pronounced impact on AF occurrence than other variables. LAD-based identification of AF in hypertensives had AUC of 0.827 (95%CI: 0.816-0.837), with an optimal cutoff of 38mm. Subgrouping the study population by LAD≥38mm, ROC curves showed AUCs of 0.757 (95%CI: 0.745-0.768) for the discovery set, 0.750 (95%CI: 0.731-0.768) for internal validation, and 0.759 (95%CI: 0.743-0.776) for external validation. LAD≥38mm had a more higher and stable AUC value for judging the AF occurrence than CHA2DS2-VASc and C2HEST scores (Figure 2b). Hypertensives with LAD≥38mm had a 9.72-fold higher AF risk than those with LAD<38mm. Conclusion LAD is a pivot determinant for AF occurrence. LAD≥38mm is a valuable identifier for high-risk hypertensives prone to AF.Figure 1.Center illustrationFigure 2.XGboost and Delong’s test of ROC

Safety of left atrial appendage amputation during cardiothoracic surgery

Abstract Background Patients with atrial fibrillation (AF) are at risk for ischemic strokes, often originating from the left atrial appendage (LAA). Preventive LAA amputation (LAAA) during cardiac surgery has been shown to reduce ischemic stroke risk, both in patients with and without AF. However, the short-term safety and functional implication of LAAA in non-AF patients remain poorly understood. Besides possible surgical complications, there are suggestions that LAAA could lead to postoperative AF or influence neurohumoral changes resulting in fluid overload. Purpose To evaluate the safety of LAAA in patients without a history of AF undergoing routine cardiac surgery. Methods Patients underwent elective cardiac surgery between May 5 2015 and April 18 2018 in two high volume centers. Main inclusion criteria were a CHA2DS2-VASc≥ 2 and no history of AF. Patients without a history of AF, that participated in the PREDICT-AF study underwent concomitant LAAA and were compared with patients undergoing cardiothoracic surgery who were approached for participation in PREDICT-AF, but declined and subsequently did not undergo LAAA. Informed consent for the retrospective use of data was obtained through an opt-out procedure in these patients. The primary outcome of this analysis was the number of patients with any serious adverse event within 30 days postoperatively. Secondary outcomes were AF within 30 days postoperatively, death, rethoracotomy, time on extra corporal circulation(ECC) and heart failure related symptoms assessed through congestion on x-chest and weight trends. Adverse events were independently adjudicated by a cardiothoracic surgeon using pre-specified definitions. Results 150 patients in PREDICT-AF underwent LAAA. 284 Eligible patients declined participation and formed the control group. Patients in the LAAA group were more frequently male (87.3% vs 72.5%; p=0.001), were taller (176.0cm ± 8.2 vs 172.6cm ± 9.9; p<0.001) and weighed more (86.1kg CI[80.0, 92.2] vs 81.6kg CI[71.9, 91.1]; p=0.001) compared to controls. There were no significant differences in occurrences of serious adverse events (8% vs 12%; p=0.265), deaths (1.3% vs 1.8%; p=1) or rethoracotomies (3.3% vs 1.8%; p=0.483) between the LAAA and control group. Also, there was no difference in the incidence of postoperative AF (57, 38% vs 90, 31.7%; p=0.225), ECC time (104.5 minutes CI[81.0, 129.0] vs 98.0 CI[80.0, 124.5] p=0.371) or the presence of chest x-ray congestion (26.0% vs 27.8%; p=0.771) between the groups (Figure 1A). The spline plot of perioperative weight change from baseline, reveals no notable differences between the two groups (Figure 1B). Conclusion LAAA during routine cardiothoracic surgery is not associated with more surgical complications, postoperative atrial fibrillation or heart failure related symptoms. Given the generally high AF risk in patients undergoing cardiothoracic surgery, a strategy to preemptively resect the LAA may be feasible and safe.Figure 1 A & B

Cluster-specific risk factors for suboptimal thromboprophylaxis in contemporary European cohort of patients with atrial fibrillation: the EHRA-PATHS Project

Abstract Background Oral anticoagulation (OAC) is essential to optimal thromboprophylaxis in patients with atrial fibrillation (AF). Owing to bleeding risk concerns, OAC use may be challenging in clinically complex high-risk AF patients. Comorbidities might lead to suboptimal OAC use. We assessed cluster-specific risk factors for non-prescribing OAC in pre-defined AF clusters in contemporary European EHRA-PATHS AF cohort. Methods The EHRA-PATHS AF cohort was constructed using data from the three prospective EurObservational Research Programme (EORP) AF registries - General Pilot, General Long-term, and AF III registry. A two-step cluster analysis was performed. A hierarchical cluster analysis with 18 variables was used to identify the optimal number of clusters, followed by a K-means cluster analysis to determine variable cluster association. Cluster-specific risk factors for non-prescribing OAC were identified using univariate and multivariate logistic regression analyses. Results Of 18.799 patients, 2086 (11.1%) were not prescribed with OAC. Among the three clusters (see Table), OAC non-prescribing was significantly more prevalent in Cluster 1 (younger healthier AF patients) compared with Cluster 2 (Elderly with less comorbidity, mostly non-cardiovascular) or Cluster 3 (Elderly with more comorbidity, mostly cardiovascular), both P<0.001, with no significant difference between Clusters 2 and 3 (P=0.161). Cluster-specific multivariable risk factors for non-prescribing OAC are shown in Table. In all three clusters AF clinical type was significantly associated with OAC non-use. In Cluster 1, OAC non-use was less likely in the presence of CHA2DS2-VASc stroke risk factors, while bleeding risk factors were predominant multivariable predictors of OAC non-use among elderly (Clusters 2 and 3). Conclusion Our findings in a large contemporary European cohort suggest that different considerations prevail in treatment decision on OAC use in AF patients in clinical practice, depending on patient’s age and AF clinical type, as well as the presence and type of underlying comorbidities. Our findings could help in formulating targeted interventions to optimize stroke prevention in different subgroups of AF patients.

Clinical usefulness of digital twin guided virtual amiodarone test in patients with atrial fibrillation ablation

It would be clinically valuable if the efficacy of antiarrhythmic drugs could be simulated in advance. We developed a digital twin to predict amiodarone efficacy in high-risk atrial fibrillation (AF) patients post-ablation. Virtual left atrium models were created from computed tomography and electroanatomical maps to simulate AF and evaluate its response to varying amiodarone concentrations. As the amiodarone concentration increased in the virtual setting, action potential duration lengthened, peak upstroke velocities decreased, and virtual AF termination became more frequent. Patients were classified into effective (those with virtually terminated AF at therapeutic doses) and ineffective groups. The one-year clinical outcomes after AF ablation showed significantly better results in the effective group compared to the ineffective group, with AF recurrence rates of 20.8% vs. 45.1% (log-rank p = 0.031, adjusted hazard ratio, 0.37 [0.14-0.98]; p = 0.046). This study highlights the potential of a digital twin-guided approach in predicting amiodarone’s effectiveness and improving personalized AF management. Clinical Trial Registration Name: The Evaluation for Prognostic Factors After Catheter Ablation of Atrial Fibrillation: Cohort Study, Registration number: NCT02138695. The date of registration: 2014-05. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02138695.

Kidney function, uric acid, and risk of atrial fibrillation: experience from the AMORIS cohort

BackgroundUric acid closely relates to both kidney disease and atrial fibrillation (AF), yet the extent to which it influences the kidney-AF association remains uncertain. We examined the relationship between kidney function and risk of AF, accounting for uric acid levels.MethodsA total of 308,509 individuals in the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort were included and their serum creatinine and uric acid were measured during 1985–1996. Ten-year incident AF was identified via linkage with the national registers. Glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated with the 2009 Chronic Kidney Disease Epidemiology Collaboration equation. Hyperuricemia was defined as > 420 µmol/L for men and > 360 µmol/L for women.ResultsOver a mean follow-up of 9.4 years, 10,007 (3.2%) incident AF cases occurred. After adjusting for age, sex, cardiovascular diseases, total cholesterol, triglycerides, and glucose, individuals with low eGFR (< 30 and 30–59 ml/min/1.73 m2 ) had a higher risk of AF compared to those with normal eGFR (60–89) (hazard ratio (HR) = 1.72, 95% confidence interval (CI):1.29–2.30; HR = 1.10, 95% CI: 1.03–1.18, respectively). After further adjusting for uric acid levels, the association disappeared (HR = 0.97, 95% CI: 0.72–1.30; HR = 0.93, 95% CI: 0.86-1.00, respectively). When stratifying by hyperuricemia yes/no, eGFR < 30 ml/min/1.73 m2 was associated with higher AF risk in a small group of individuals without hyperuricemia (HR = 2.58, 95% CI: 1.64–4.07).ConclusionUric acid largely accounted for the relationship between eGFR and AF in this study. However, in individuals without hyperuricemia, eGFR in the lowest range (< 30 ml/min/1.73 m2) was still associated with increased risk of AF.

Risk of Stroke and Incident Atrial Fibrillation in Patients in Sinus Rhythm With Nonischemic Dilated Cardiomyopathy

Background: Non-ischemic dilated cardiomyopathy (NIDCM) is associated with an increased risk of atrial fibrillation (AF) and stroke, especially in patients with high CHA2DS2-VASc. We aimed to identify variables associated with incident AF or stroke using left atrial (LA) deformation analysis and its prognostic value added to CHA2DS2-VASc score. Patients with NIDCM and LVEF <50% in sinus rhythm were included between January 2015 and December 2019. LA volume index (LAVI) and atrial strain were used in combination with the CHA2DS2-VAS score to predict ischemic stroke or incident AF. Proportional hazards Cox regression was used to provide hazard ratios (HR). There were 338 patients included. After a median follow-up of 3.6 years, the endpoint occurred in 41 (12.1%) patients. LAVI outperformed other echocardiographic parameters, with significant improvement in risk reclassification compared to CHA2DS2-VASc alone (net reclassification index 0.6, increase in Harrell's C from 0.63 to 0.73, P=0.003) and remained significant after multivariate adjustment. LAVI was associated with both components of the endpoint separately. The best cutoff for LAVI was 44 ml/m2. LAVI ≥44ml/m2 increased the risk of the endpoint among those with CHA2DS2-VASc ≥3 (HR=6.0, 95%CI 2.6-13.5), but not in those with CHA2DS2-VASc <3 (HR=1.2, 95%CI 0.3-4.5). Competing risk analysis did not alter the results. In conclusion, LAVI might be used to assess the risk of incident AF or stroke in NIDCM. Patients with LAVI ≥44 ml/m2 and CHA2DS2-VASc ≥3 could be at high risk of AF and stroke and may benefit from more intensive surveillance.

Pathophysiological Mechanisms of Psychosis-Induced Atrial Fibrillation: The Links between Mental Disorder and Arrhythmia.

Atrial fibrillation (AF) is a common phenomenon of sustained arrhythmia leading to heart failure or stroke. Patients with mental disorders (MD), particularly schizophrenia and bipolar disorder, are at a high risk of AF triggered by the dysregulation of the autonomic nervous system, atrial stretch, oxidative stress, inflammation, and electrical or structural remodeling. Moreover, pathophysiological mechanisms underlying MD may also contribute to the genesis of AF. An overactivated hypothalamic-pituitary-adrenal axis, aberrant renin-angiotensin-aldosterone system, abnormal serotonin signaling, disturbed sleep, and genetic/epigenetic factors can adversely alter atrial electrophysiology and structural substrates, leading to the development of AF. In this review, we provide an update of our collective knowledge of the pathophysiological and molecular mechanisms that link MD and AF. Targeting the pathogenic mechanisms of MD-specific AF may facilitate the development of therapeutics that mitigate AF and cardiovascular mortality in this patient population.

The Comparison of the Effectiveness of Dapagliflozin and Empagliflozin in the Prevention of Cardiovascular Outcomes in Patients With Type 2 Diabetes: A Network Meta-Analysis.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular diseases, prompting research into treatments that can mitigate this risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly dapagliflozin and empagliflozin, have shown promising cardiovascular benefits in T2DM patients. This meta-analysis aimed to directly compare the cardiovascular outcomes of these two drugs. To achieve this, we conducted a comprehensive literature search across multiple databases up to August 5, 2024, including both randomized controlled trials (RCTs) and observational studies. The primary outcomes of interest were major adverse cardiovascular events (MACE), atrial fibrillation (AF), cardiovascular mortality, myocardial infarction (MI), and hospitalization for heart failure (HF). Twelve studies met the inclusion criteria for this meta-analysis. The pooled analysis revealed several key findings. Notably, dapagliflozin demonstrated superior efficacy in preventing atrial fibrillation compared to empagliflozin. However, no significant differences were observed between the two drugs in terms of MACE, cardiovascular mortality, hospitalization for heart failure (HHF), or myocardial infarction. When compared to placebo, both dapagliflozin and empagliflozin showed greater effectiveness in preventing adverse cardiovascular outcomes in T2DM patients.These results reinforce the cardiovascular benefits of both dapagliflozin and empagliflozin in patients with T2DM. The comparable efficacy in most outcomes suggests that clinicians have flexibility in prescribing either of these SGLT2 inhibitors. However, the lower risk of atrial fibrillation associated with dapagliflozin may be a crucial factor in treatment decisions, especially for patients with a history of or at high risk for atrial fibrillation.

Identifying a Heterogeneous Effect of Atrial Fibrillation Screening in Older Adults: A Secondary Analysis of the VITAL-AF Trial.

One-time atrial fibrillation (AF) screening trials have produced mixed results; however, it is unclear if there is a subset for whom screening is effective. Identifying such a subgroup would support targeted screening. We conducted a secondary analysis of VITAL-AF, a randomized trial of one-time, single-lead ECG screening during primary care visits. We tested two approaches to identify a subgroup where screening is effective. First, we developed an effect-based model using a T-learner. Specifically, we separately predicted the likelihood of AF diagnosis under screening and usual care conditions; the difference in probabilities was the predicted screening effect. Second, we used a validated AF risk model to test for a heterogeneous screening effect. We used interaction testing to determine if observed AF diagnosis rates in the screening and usual care groups differed when stratified by decile of the predicted screening effect and predicted AF risk. Baseline characteristics were similar between the screening (n=15187) and usual care (n=15078) groups (mean age 74 years, 59% female). In the effect-based analysis, in the highest decile of predicted screening effectiveness (n=3026), AF diagnosis rates were higher in the screening group (6.50 vs. 3.06 per 100 person-years, rate difference 3.45, 95%CI 1.62 to 5.28). In this group, the mean age was 84 years and 68% were female. The risk-based analysis did not identify a subgroup where screening was more effective. Predicted screening effectiveness and predicted baseline AF risk were poorly correlated (Spearman coefficient 0.13). In a secondary analysis of the VITAL-AF trial, we identified a small subgroup where one-time screening was associated with increased AF diagnoses using an effect-based approach. In this study, predicted AF risk was a poor proxy for predicted screening effectiveness. These data caution against the assumption that high AF risk is necessarily correlated with high screening effectiveness.

Adulthood weight changes, body mass index in youth, genetic susceptibility and risk of atrial fibrillation: a population-based cohort study

BackgroundEpidemiological evidence on weight change and atrial fibrillation (AF) remains limited and inconsistent. Previous studies on body mass index (BMI) in youth and AF rarely considered subsequent BMI. This study aimed to assess the associations of AF with weight change and BMI in youth, as well as modified effect by genetic susceptibility of AF.MethodsThe study included 21,761 individuals (mean age 57.8 years) from the Malmö Diet and Cancer cohort. Weight information was obtained at three time points, including recalled weight at age 20 years, measured weight at baseline (middle adulthood), and reported weight at 5-year follow-up examination (late middle adulthood). A weighted genetic risk score of AF was created using 134 variants.ResultsDuring a median follow-up of 23.2 years, a total of 4038 participants developed AF. The association between weight change from early to middle adulthood and AF risk was modified by sex (Pinteraction = 0.004); weight loss was associated with a lower AF risk in females, but not in males. Conversely, weight gain was positively associated with AF risk in a linear manner in females, whereas increased AF risk appeared only when weight gain exceeded a threshold in males. Participants with weight gain of > 5 kg from middle to late middle adulthood had a 19% higher risk of AF relative to those with stable weight, whereas weight loss showed a null association. Compared to individuals with a lower BMI at age 20 years, those with a BMI above 25 kg/m2 had an increased risk of AF (HR = 1.14; 95% CI: 1.02–1.28), after controlling for baseline BMI; this association was more pronounced in males or those with a lower genetic risk of AF.ConclusionsWeight gain in middle adulthood was associated with higher AF risk. Weight loss from early to middle adulthood, but not from middle to late middle adulthood, was associated with a lower risk of AF only in females. Higher BMI in youth was associated with an increased risk of AF, particularly among males or those with a lower genetic risk of AF.

Psychosocial Stressors at Work and Atrial Fibrillation Incidence: An 18-Year Prospective Study.

Psychosocial stressors at work, defined by the job strain and effort-reward imbalance at work (ERI) models, were shown to increase coronary heart disease risk. No previous study has examined the adverse effect of psychosocial stressors at work from both models on atrial fibrillation (AF) incidence. The objective of this study was to examine the separate and combined effect of psychosocial stressors at work from the job strain and ERI models on AF incidence in a prospective cohort study. A total of 5926 white-collar workers (3021 women and 2905 men) free of cardiovascular disease at baseline were followed for an average of 18 years. Job strain (high psychological demands combined with low decision latitude) and ERI were assessed using validated instruments. AF events were identified in medical databases with universal coverage. Hazard ratios (HRs) with 95% CIs were estimated using Cox regression models, controlling for socioeconomic characteristics and lifestyle-related and clinical risk factors. A total of 186 AF incident events were identified over 18 years. Workers exposed to job strain (HR, 1.83 [95% CI, 1.14-2.92]) and ERI (HR, 1.44 [95% CI, 1.05-1.98]) had a higher risk of AF in fully adjusted models. Combined exposure to job strain and ERI was associated with a 2-fold AF risk increase (HR, 1.97 [95% CI, 1.26-3.07]). Psychosocial stressors at work from the job strain and ERI models are associated with an increased risk of AF, separately and in combination. Workplace prevention strategies targeting these psychosocial stressors at work may be effective to reduce the burden associated with AF.

Titin truncating variants, cardiovascular risk factors and the risk of atrial fibrillation and heart failure.

High-proportion spliced-in (hiPSI) titin truncating variant (TTNtv) carriers have a higher risk of atrial fibrillation and heart failure1. However, the role of cardiovascular risk factors in modifying the risk of atrial fibrillation and heart failure attributed to hiPSI TTNtv carriers is unknown. Here, we investigate the role of cardiovascular risk, quantified using the pooled cohort equations (PCEs), in influencing the hazard of outcomes attributed to hiPSI TTNtvs among UK Biobank participants without baseline cardiovascular disease. The cohort was stratified based on hiPSI TTNtv carrier status and cardiovascular risk (low: <5%, intermediate: 5.0-7.5% and high: >7.5%). The primary outcome was a composite of atrial fibrillation, heart failure or death. TTNtv noncarriers with low cardiovascular risk were used as the reference group for all analyses. Among 179,752 participants (median age: 56 (49, 62) years; 57.5% female), the risk of the primary outcome was lower in hiPSI TTNtv carriers with low cardiovascular risk (adjusted hazard ratio: 2.23 (95% confidence interval: 1.62-3.07)) than those with high cardiovascular risk (adjusted hazard ratio: 8.21 (95% confidence interval: 6.63-10.18)). A favorable cardiovascular risk factor profile may partially offset the risk of clinical outcomes among hiPSI TTNtv carriers.

Parity, infertility, age at first birth and risk of atrial fibrillation: data from the HUNT study.

Although parity, infertility, and age at first birth are important for later development of cardiovascular disease, research on their association with atrial fibrillation (AF) is limited. We linked data from the population-based HUNT study, the Medical Birth Registry of Norway (MBRN) and validated medical records from local hospitals. A total of 24,015 women aged 45 years or older were followed for verified incident AF. Parity and age at first birth were retrieved from the MBRN or from self-reported questionnaires in the HUNT. History of infertility was self-reported on the HUNT questionnaire. Cox-proportional hazard models were used to calculate hazard ratios (HR) for the multivariable-adjusted associations of parity, infertility, and age at first birth with risk of AF. During a median follow-up of 12.8 years, 1,448 (6.0%) participants developed AF. Women with higher parity (four or more births vs. two births) were at 21% higher risk of AF (HR 1.21, 95% confidence interval (CI), 1.05-1.39). History of infertility was also associated with risk of AF (HR 1.20, 95% CI, 1.02-1.42). Among parous women, younger age at first birth (<20 years vs. 20-29 years) was associated with a 20% higher risk of AF (HR 1.20, 95% CI, 1.03-1.40). Women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF among women over 45 years old.