Visual interpretation of deep learning model in ECG classification: A comprehensive evaluation of feature attribution methods.

Feature attribution methods can visually highlight specific input regions containing influential aspects affecting a deep learning model's prediction. Recently, the use of feature attribution methods in electrocardiogram (ECG) classification has been sharply increasing, as they assist clinicians in understanding the model's decision-making process and assessing the model's reliability. However, a careful study to identify suitable methods for ECG datasets has been lacking, leading researchers to select methods without a thorough understanding of their appropriateness. In this work, we conduct a large-scale assessment by considering eleven popular feature attribution methods across five large ECG datasets using a model based on the ResNet-18 architecture. Our experiments include both automatic evaluations and human evaluations. Annotated datasets were utilized for automatic evaluations and three cardiac experts were involved for human evaluations. We found that Guided Grad-CAM, particularly when its absolute values are utilized, achieves the best performance. When Guided Grad-CAM was utilized as the feature attribution method, cardiac experts confirmed that it can identify diagnostically relevant electrophysiological characteristics, although its effectiveness varied across the 17 different diagnoses that we have investigated.

Classification of underlying paroxysmal supraventricular tachycardia types using deep learning of sinus rhythm electrocardiograms.

Background: Obtaining tachycardia electrocardiograms (ECGs) in patients with paroxysmal supraventricular tachycardia (PSVT) is often challenging. Sinus rhythm ECGs are of limited predictive value for PSVT types in patients without preexcitation. This study aimed to explore the classification of atrioventricular nodal reentry tachycardia (AVNRT) and concealed atrioventricular reentry tachycardia (AVRT) using sinus rhythm ECGs through deep learning. Methods: This retrospective study included patients diagnosed with either AVNRT or concealed AVRT, validated through electrophysiological studies. A modified ResNet-34 deep learning model, pre-trained on a public ECG database, was employed to classify sinus rhythm ECGs with underlying AVNRT or concealed AVRT. Various configurations were compared using ten-fold cross-validation on the training set, and the best-performing configuration was tested on the hold-out test set. Results: The study analyzed 833 patients with AVNRT and 346 with concealed AVRT. Among ECG features, the corrected QT intervals exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.602. The performance of the deep learning model significantly improved after pre-training, showing an AUROC of 0.726 compared to 0.668 without pre-training (p < 0.001). No significant difference was found in AUROC between 12-lead and precordial 6-lead ECGs (p = 0.265). On the test set, deep learning achieved modest performance in differentiating the two types of arrhythmias, with an AUROC of 0.708, an AUPRC of 0.875, an F1-score of 0.750, a sensitivity of 0.670, and a specificity of 0.649. Conclusion: The deep-learning classification of AVNRT and concealed AVRT using sinus rhythm ECGs is feasible, indicating potential for aiding in the non-invasive diagnosis of these arrhythmias.

Lifestyle risk behavior and atherosclerotic cardiovascular risk: An analysis using the Korea National Health and Nutrition Examination Survey.

BACKGROUND: Clustering lifestyle risk behaviors is important for predicting cardiovascular disease risk. However, it is unclear which behavior mediates other ones to influence cardiovascular disease risk. We aimed to assess the causal inference of each lifestyle risk behavior for the atherosclerotic cardiovascular disease (ASCVD) risk of the general population. METHODS: We performed a Bayesian network mediation analysis using data from the Korea National Health and Nutrition Examination Survey from 2014 to 2019. The main exposure was a combination of lifestyle risk behaviors including unhealthy weight, heavy alcohol consumption, inadequate sleep, physical inactivity, excessive sodium intake, and current smoking among subjects 40 to 79 years of age. The high risk of ASCVD (≥7.5% for the 10-year risk) was assessed using logistic regression, Bayesian networks, and structural equational models to examine the causal relationships between these six lifestyle risk behaviors. RESULTS: Among all participants, the most prevalent lifestyle risk behavior for those at high risk for ASCVD was excessive sodium intake (95.6%), followed by inadequate sleep (49.9%) and physical inactivity (43.8%). Older age (65-79 years) and male sex were directly associated with a high risk for ASCVD. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight indirectly mediated the effects of older age (8.2% of the older age) and male sex (39.9% of males) to high ASCVD risk. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight particularly mediated the high ASCVD risk sequentially. Heavy alcohol consumption and inadequate sleep were not directly associated with high ASCVD risk and did not indirectly mediate the effects of older age and males on the high ASCVD risk. CONCLUSION: Lifestyle risk behaviors mediated the atherosclerotic cardiovascular disease risk in a different manner. Especially, physical inactivity preceded current smoking, excessive sodium intake, and unhealthy weight in relation to high ASCVD risk, and this causal relationship was different according to age and sex. Therefore, tailored strategies according to specific target populations may be needed to effectively reduce the high ASCVD risk.

Plasma apixaban concentrations and thrombin generation assay parameters in response to dose reduction for atrial fibrillation.

AIMS: To investigate plasma apixaban concentrations and thrombin generation assay (TGA) parameters across different apixaban doses in atrial fibrillation patients who had dose-reduction criteria for apixaban. METHODS: This observational study included 374 patients (mean age 75.6 ± 7.7 years, 54.8% female) with dose-reduction criteria for apixaban. The patients were divided into 3 groups: (i) on-label standard dose (5 mg twice daily, n = 166); (ii) on-label reduced dose (2.5 mg twice daily, n = 55); and (iii) off-label underdose (2.5 mg twice daily, n = 153). Apixaban concentrations determined via the anti-Xa assay and TGA parameters were compared at trough levels. RESULTS: The off-label underdose group exhibited significantly lower apixaban trough concentrations than the on-label reduced-dose and standard-dose groups (56.7 ± 42.9 vs. 83.7 ± 70.4 vs. 129.9 ± 101.8 ng/mL, all P < .001). Less than 70% of all patients fell within the expected range of apixaban concentrations. Proportions exceeding the upper limit of the expected range were significantly lower in the off-label underdose group (1.3%) than in the on-label reduced-dose (9.1%, P = .005) and standard-dose (12.7%, P < .001) groups. The TGA parameters showed the on-label standard-dose group displaying the lowest thrombogenic profiles. Lower creatinine clearance was the most significant predictor of higher apixaban concentrations. CONCLUSION: Off-label underdosed apixaban resulted in lower apixaban concentrations than both on-label standard and reduced-dose regimens. A considerable proportion of the patients exhibited apixaban concentrations outside the expected range, suggesting the potential benefits of plasma concentration monitoring. Further studies are needed to compare dosages directly, investigate the impact of plasma apixaban concentration monitoring and validate the current dose-reduction criteria.

Association between changes in renal function and clinical outcomes in anticoagulated atrial fibrillation patients with marginal renal function. A nationwide observational cohort study.

Background: Renal function is one of the crucial components for determining the dose and type of oral anticoagulants in atrial fibrillation (AF) patients, and is also closely associated with the risks of stroke and bleeding. This study aimed to assess renal function changes and their impact on clinical outcomes in anticoagulated AF patients with marginal renal function. Methods: From a Korean claims database, patients with AF on anticoagulants and a baseline eGFR of 45 to <60 ml/min/1.73 m2 were studied. Patients were grouped by changes in renal function over two years-maintained, improved (eGFR >60 ml/min/1.73 m2), or worsened (eGFR <45 ml/min/1.73 m2)-the study analyzed outcomes including ischemic stroke, major bleeding, end-stage renal disease (ESRD), all-cause death, and a composite of clinical outcomes. Results: A total of 5,126 patients were included in the study: 2,170 (42.3%) in the maintained group, 2,276 (44.4%) in the improved group, and 680 (13.1%) in the group with worsened renal function. The worsened group was older and had more prevalent comorbidities than other groups. After multivariable adjustment, the worsened group was associated with significantly higher risks of major bleeding (adjusted hazard ratio, 95% confidence interval; 1.46, 1.03-2.07, p = 0.035), ESRD (1.49, 1.24-1.80, p < 0.001), all-cause death (9.29, 4.92-17.6, p < 0.001), and the composite outcome (1.57, 1.36-1.83, p < 0.001). Conclusions: In anticoagulated AF patients with marginal renal function, a substantial proportion of patients experienced renal function decline below eGFR 45 ml/min/1.73 m2 within 2 years. Renal function decline was associated with higher risks of major bleeding, ESRD, all-cause death, and the composite outcome compared to those who maintained their baseline renal function.

Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: the ASPIRE (efficAcy and safety of aPixaban in rEal-world practice in Korean frail patients with atrial fibrillation) study.

Background: Data on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce. Objectives: We prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion. Methods: The multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose. Results: Of 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the "marginal zone," defined as age 75-80 years, weight 60-65 kg, and creatinine levels 1.2-1.5 mg/dL. Conclusions: In real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

Remimazolam-flumazenil provides fast recovery from general anesthesia compared to propofol during radiofrequency catheter ablation of atrial fibrillation.

The optimal anesthetic agent for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) and its impact on the recovery profiles remain uncertain. We compared the recovery and hemodynamic parameters between the remimazolam-flumazenil and propofol groups during RFCA. Patients were randomized into the remimazolam-flumazenil and propofol groups. The primary outcome measure was the time to eye opening following the discontinuation of anesthetic agents. Secondary outcomes included time to extubation, time to discharge from the operating room, intraprocedural hemodynamic variables and postoperative quality outcomes. Fifty-three patients were included in the final analysis (n = 26 in the remimazolam-flumazenil and n = 27 in the propofol group). The time to eye opening was significantly shorter in the remimazolam-flumazenil group compared to the propofol group (median [interquartile range]: 174 [157-216] vs. 353 [230-483] s, P < 0.001). The mean blood pressure and bispectral index were significantly higher in the remimazolam-flumazenil group compared to the propofol group (mean difference [95% CI], 7.2 [1.7-12.7] mmHg and 6 [3-8]; P = 0.011 and < 0.001, respectively), which were within target ranges in both groups. Other secondary outcomes were comparable between the groups. Consequently, remimazolam emerges as a promising anesthetic agent, characterized by rapid recovery and stable hemodynamics, during RFCA of AF.Trial registration: NCT05397886.

Perioperative Management in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Minor Bleeding Risk Procedure: Rationale and Protocol for the PERIXa Study.

Background: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks. Objective: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk. Methods: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events. Conclusion: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk. Trial Registration: Clinicaltrials.gov: NCT05801068.

Alcohol is neither a risk factor nor a protective factor for sudden cardiac death and/or fatal ventricular arrhythmia: A population-based study with genetic traits and alcohol consumption in the UK Biobank.

BACKGROUND: The association between alcohol consumption and the risk of sudden cardiac death and/or fatal ventricular arrhythmia remains controversial. OBJECTIVE: We analyzed the association between alcohol consumption, genetic traits for alcohol metabolism, and the risk of sudden cardiac death and/or fatal ventricular arrhythmia. METHODS: We identified 397,164 individuals enrolled between 2006 and 2010 from the UK Biobank database and followed them until 2021. Alcohol consumption was categorized as current nondrinkers (nondrinkers and ex-drinkers), mild drinkers, moderate drinkers, or heavy drinkers. Genetic traits of alcohol metabolism were stratified according to the polygenic risk score tertiles. The primary and secondary outcomes were a composite of sudden cardiac death and fatal ventricular arrhythmia as well as their individual components. RESULTS: During follow-up (median 12.5 years), 3543 cases (0.89%) of clinical outcomes occurred. Although mild, moderate, and heavy drinkers showed deceased risks of outcomes compared with current nondrinkers, there was no prognostic difference among nondrinkers, mild drinkers, moderate drinkers, and heavy drinkers. Ex-drinkers showed an increased risk in univariate analysis, but the significance was attenuated after adjusting covariates (hazard ratio 1.19; 95% confidence interval 0.94-1.50). As a continuous variable, alcohol consumption was not associated with clinical outcomes (hazard ratio 1.01; 95% confidence interval 0.99-1.02). Consistent with these findings, there was no association between genetic traits for alcohol metabolism and the risk of clinical outcomes. CONCLUSION: Alcohol consumption was neither a protective factor nor a risk factor for sudden cardiac death or fatal ventricular arrhythmia. Genetic traits of alcohol metabolism were not associated with the clinical prognosis.

Correction: Three-Day Monitoring of Adhesive Single-Lead Electrocardiogram Patch for Premature Ventricular Complex: Prospective Study for Diagnosis Validation and Evaluation of Burden Fluctuation.

[This corrects the article DOI: 10.2196/46098.].

Association between types of antihypertensive medication and the risk of atrial fibrillation: a nationwide population study.

Background: Patients with hypertension are at a high risk of atrial fibrillation (AF). Recent research has indicated the varying effects of antihypertensive medications on developing AF. Objectives: We investigated the relationship between different types of antihypertensive medications and the risk of AF occurrence. Methods: We analyzed data from 113,582 subjects with national health screening examinations between 2009 and 2014. The study population was categorized according to antihypertensive medication type. The primary outcome was the incidence of AF. Results: Among 113,582 subjects (mean age 59.4 ± 12.0 years, 46.7% men), 93,557 received monotherapy [angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), beta-blockers, calcium channel blockers (CCB), or diuretics], while 34,590 received combination therapy (ARB/beta-blockers, ARB/CCB, ARB/diuretics, or ARB/CCB/diuretics). During a mean follow-up duration of 7.6 ± 2.1 years, 3.9% of patients were newly diagnosed with AF. In monotherapy, ACEi and CCB had similar AF risks as ARB, while beta-blockers and diuretics showed higher AF risks than ARB. In combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers had the highest compared to ARB/CCB. Among the specific ARBs, the AF risk varied insignificantly, except for telmisartan and candesartan. Conclusions: In hypertensive patients receiving monotherapy, ACEi and CCB showed a similar AF risk as ARBs, while beta-blockers and diuretics were associated with a higher risk. Among those receiving combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers showed the highest risk. Various types of ARBs have different associations with AF risk.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry.

AIMS: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS AND RESULTS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, P = 0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Three-Day Monitoring of Adhesive Single-Lead Electrocardiogram Patch for Premature Ventricular Complex: Prospective Study for Diagnosis Validation and Evaluation of Burden Fluctuation.

BACKGROUND: Wearable electrocardiogram (ECG) monitoring devices are used worldwide. However, data on the diagnostic yield of an adhesive single-lead ECG patch (SEP) to detect premature ventricular complex (PVC) and the optimal duration of wearing an SEP for PVC burden assessment are limited. OBJECTIVE: We aimed to validate the diagnostic yield of an SEP (mobiCARE MC-100, Seers Technology) for PVC detection and evaluate the PVC burden variation recorded by the SEP over a 3-day monitoring period. METHODS: This is a prospective study of patients with documented PVC on a 12-lead ECG. Patients underwent simultaneous ECG monitoring with the 24-hour Holter monitor and SEP on the first day. On the subsequent second and third days, ECG monitoring was continued using only SEP, and a 3-day extended monitoring was completed. The diagnostic yield of SEP for PVC detection was evaluated by comparison with the results obtained on the first day of Holter monitoring. The PVC burden monitored by SEP for 3 days was used to assess the daily and 6-hour PVC burden variations. The number of patients additionally identified to reach PVC thresholds of 10%, 15%, and 20% during the 3-day extended monitoring by SEP and the clinical factors associated with the higher PVC burden variations were explored. RESULTS: The recruited data of 134 monitored patients (mean age, 54.6 years; males, 45/134, 33.6%) were analyzed. The median daily PVC burden of these patients was 2.4% (IQR 0.2%-10.9%), as measured by the Holter monitor, and 3.3% (IQR 0.3%-11.7%), as measured in the 3-day monitoring by SEP. The daily PVC burden detected on the first day of SEP was in agreement with that of the Holter monitor: the mean difference was -0.07%, with 95% limits of agreement of -1.44% to 1.30%. A higher PVC burden on the first day was correlated with a higher daily (R2=0.34) and 6-hour burden variation (R2=0.48). Three-day monitoring by SEP identified 29% (12/42), 18% (10/56), and 7% (4/60) more patients reaching 10%, 15%, and 20% of daily PVC burden, respectively. Younger age was additionally associated with the identification of clinically significant PVC burden during the extended monitoring period (P=.02). CONCLUSIONS: We found that the mobiCARE MC-100 SEP accurately detects PVC with comparable diagnostic yield to the 24-hour Holter monitor. Performing 3-day PVC monitoring with SEP, especially among younger patients, may offer a pragmatic alternative for identifying more individuals exceeding the clinically significant PVC burden threshold.

Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study.

BACKGROUND: Diabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration. METHODS: Patients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015-2016 were grouped by DM duration: new onset and < 5, 5-9, and ≥ 10 years. Physical activity was classified into four levels: 0, < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (MET)-min/week, with the primary outcome being new-onset AF. RESULTS: The study enrolled 2,392,486 patients (aged 59.3 ± 12.0 years, 39.8% female) with an average follow-up of 3.9 ± 0.8 years and mean DM duration of 5.3 ± 5.1 years. Greater physical activity was associated with a lower AF risk. Lowering of incident AF risk varied with different amounts of physical activity in relation to known DM duration. Among patients with new-onset DM, DM duration < 5 years and 5-9 years and 1,000-1,499 MET-min/week exhibited the lowest AF risk. Physical activity ≥ 1,500 MET-min/week was associated with the lowest incident AF risk in patients with DM duration ≥ 10 years (by 15%), followed DM duration of 5-9 years (12%) and < 5 years (9%) (p-for-interaction = 0.002). CONCLUSIONS: Longer DM duration was associated with a high risk of incident AF, while increased physical activity generally reduced AF risk. Engaging in > 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.

Accelerometer-derived physical activity and the risk of death, heart failure, and stroke in patients with atrial fibrillation: a prospective study from UK Biobank.

OBJECTIVE: Data on cardiovascular outcomes according to objectively measured physical activity (PA) in patients with atrial fibrillation (AF) are scarce. This study explored the associations between PA derived from wrist-worn accelerometers and the risk of death, incident heart failure (HF), and incident stroke in patients with AF. METHODS: From 37 990 patients with AF in UK Biobank, 2324 patients with accelerometer data were included. Weekly moderate-to-vigorous PA (MVPA) duration was computed from accelerometer data. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, incident HF, and incident stroke. Restricted cubic splines estimated the dose-response associations between MVPA duration and the outcomes. The adjusted HRs (aHRs) of the outcomes according to adherence to PA standard guidelines (performing MVPA≥150 min/week) were also evaluated. RESULTS: The mean age was 66.9±6.2 years and 64.9% were male. During a median follow-up of 6.7 years, there were 181 all-cause deaths, 62 cardiovascular deaths, 225 cases of incident HF, and 91 cases of incident stroke; the overall incidence rate per 1000 patient-years was 11.76, 4.03, 15.16 and 5.99, respectively. There was a linear inverse dose-response relationship between MVPA (≥108 min/week) and all-cause mortality. Performing MVPA for 105-590 min/week was associated with a lower risk of HF than those with no measurable MVPA. The risk of stroke and cardiovascular mortality was not associated with MVPA. Performing guideline-adherent MVPA was related to a 30% lower risk of all-cause mortality (aHR: 0.70 (0.50-0.98), p=0.04) and 33% lower risk of HF (aHR 0.67 (0.49-0.93), p=0.02). CONCLUSION: In patients with AF, accelerometer-derived PA data supports lower risks of all-cause mortality and HF according to a greater level of MVPA and adherence to PA guidelines. Regular MVPA should be encouraged in patients with AF as a part of integrated management.

Neuroticism and the Risk of Atrial Fibrillation: An Observational Epidemiologic and Mendelian Randomization Study.

Background: The association between neuroticism and atrial fibrillation (AF) remains unknown. Objectives: This study aimed to assess the epidemiological and causal relationships between neuroticism and AF. Methods: Individuals without AF history were selected From the UK Biobank nationwide prospective cohort study. Participants were divided into 2 groups (high and low) based on the median summary score from a self-questionnaire of 12 neurotic behavior domains. The 10-year AF risk was compared between the neuroticism score groups using inverse probability of treatment weighting. The causal relationship between neuroticism and AF was evaluated using a 2-sample summary-level Mendelian randomization with the inverse variance-weighted method. Results: Of 394,834 participants (mean age 56.3 ± 8.1 years, 45.9% male), AF occurred in 23,509 (6.0%) during a 10-year follow-up. The risk of incident AF significantly increased in the high neuroticism score group (score ≥4) (inverse probability of treatment weighting-adjusted HR: 1.05; 95% CI: 1.02-1.09; P = 0.005) compared with the low neuroticism group. In the subgroup analysis, younger age, lower body mass index, or nonsmoker/ex-smoker participants were particularly susceptible to increased AF risk due to high neuroticism scores. A Mendelian randomization analysis showed a significant causal relationship between an increase in neuroticism score and increased risk of AF (OR by inverse variance-weighted method 1.06; 95% CI: 1.02-1.11; P = 0.007) without evidence of reverse causality. Conclusions: There was a significant longitudinal and causal relationship between neuroticism and AF. An integrated care including active mental health screening and management may benefit in high-risk populations.

Reduction of Upper Gastrointestinal Bleeding Risk With Proton Pump Inhibitor Therapy in Asian Patients With Atrial Fibrillation Receiving Direct Oral Anticoagulant: A Nationwide Population-based Cohort Study.

BACKGROUND & AIMS: In patients with atrial fibrillation (AF) receiving direct oral anticoagulant (DOAC), upper gastrointestinal bleeding (UGIB) is a serious complication. There are limited data on the benefit of preventive proton pump inhibitor (PPI) use to reduce the risk of UGIB in DOAC users. METHODS: We included patients with AF receiving DOAC from 2015 to 2020 based on the Korean Health Insurance Review and Assessment database. The propensity score (PS) weighting method was used to compare patients with PPI use and those without PPI use. The primary outcome was hospitalization for UGIB. Weighted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 165,624 patients were included (mean age: 72.2 ± 10.8 years; mean CHA2DS2-VASc score: 4.3 ± 1.8; mean HAS-BLED score: 3.3 ± 1.2). Among them, 99,868 and 65,756 were in the non-PPI group and PPI group, respectively. During a median follow-up of 1.5 years, the PPI group was associated with lower risks of hospitalization for UGIB and UGIB requiring red blood cell transfusion than non-PPI group (weighted HR, 0.825; 95% CI, 0.761-0.894 and 0.798; 95% CI, 0.717-0.887, respectively, both P < .001). The benefits of PPI on the risk of hospitalization for UGIB were greater in those with older age (≥75 years), higher HAS-BLED score (≥3), prior GIB history, and concomitant use of antiplatelet agent (all P-for-interaction < .1). Low-dose PPI was consistently associated with a lower risk of significant UGIB by 43.6-49.3% (P < .001). CONCLUSIONS: In this large Asian cohort of patients with AF on DOAC, PPI co-therapy is beneficial for reducing the risk of hospitalization for UGIB, particularly in high-risk patients.

Association between antithrombotic therapy after stroke in patients with atrial fibrillation and the risk of net clinical outcome: an observational cohort study.

AIMS: Data on the optimal use of antithrombotic drugs and associated clinical outcomes in patients with atrial fibrillation (AF) and acute ischaemic stroke (IS) are limited. We investigated the prescription patterns of antithrombotics in community practice and long-term clinical prognosis according to early post-stroke antithrombotic therapy in patients with AF and acute IS. METHODS AND RESULTS: Patients with AF who were admitted for acute IS at a single tertiary hospital in 2010-2020 were retrospectively reviewed. Clinical profiles including the aetiology of stroke and prescription patterns of antithrombotics were identified. The net clinical outcome (NCO)-the composite of recurrent stroke, any bleeding, hospitalization or emergency department visits for cardiovascular (CV) events, and death-was compared according to the antithrombotic therapy at the first outpatient clinic visit [oral anticoagulation (OAC) alone vs. antiplatelet (APT) alone vs. OAC/APT(s)] following discharge. A total of 918 patients with AF and acute IS (mean age, 72.6 years; male, 59.3%; mean CHA2DS2-VASc score 3.3) were analysed. One-third (33.9%, n = 310) of patients were simultaneously diagnosed with AF and IS. The most common aetiology of IS was cardioembolism (71.2%), followed by undetermined aetiology (19.8%) and large artery atherosclerosis (6.0%). OAC, APT(s), and concomitant OAC and APT(s) were prescribed in 33.4%, 11.1%, and 53.4% of patients during admission that changed to 67.0%, 9.1%, and 21.7% at the first outpatient clinic, and were mostly continued up to one year after IS. Non-prescription of OAC was observed in 11.3% of post-stroke patients with AF. During a median follow-up of 2.1 years, the overall incidence rate of NCO per 100 patient-year (PY) was 20.14. APT(s) monotherapy presented the highest cumulative risk of NCO (adjusted hazard ratio 1.47, 95% confidence interval 1.08-2.00, P = 0.015; with reference to OAC monotherapy) mainly driven by the highest rates of recurrent stroke and any bleeding. OAC/APT(s) combination therapy was associated with a 1.62-fold significantly higher risk of recurrent stroke (P = 0.040) and marginally higher risk of any bleeding than OAC monotherapy. CONCLUSION: Approximately one-third of acute IS in AF have a distinctive mechanism from cardioembolism. Although APT was frequently prescribed in post-stroke patients with AF, no additive clinical benefit was observed. Adherence to OAC treatment is essential to prevent further CV adverse events in patients with AF and IS.

Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study.

BACKGROUND AND AIMS: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. METHODS: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. RESULTS: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). CONCLUSIONS: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.

Differential effect of left ventricular unloading according to the aetiology of cardiogenic shock.

AIMS: Evidence for the effectiveness of left ventricular (LV) unloading in patients who received venoaterial extracorporeal membrane oxygenation (VA-ECMO) for acute myocardial infarction (AMI) or non-AMI induced cardiogenic shock (CS) is limited. The aim of the present study was to compare the effect of LV unloading in AMI-induced and non-AMI-induced CS. METHODS AND RESULTS: This is a single-centre retrospective observational study of patients with CS undergoing VA-ECMO from January 2011 to March 2019. Patients were classified as AMI-induced and non-AMI-induced CS. The association of LV unloading with 90-day mortality in both groups was analysed using Cox proportional hazard regression analysis. RESULTS: Of the 128 CS patients, 71 (55.5%) patients received VA-ECMO due to AMI-induced CS, and the remaining 57 (44.5%) received VA-ECMO due to non-AMI-induced CS. The modality of LV unloading was predominantly with IABP (94.5%). In the AMI-induced CS group, LV unloading did not reduce 90-day mortality (adjusted hazard ratio 1.96, 95% confidence interval 0.90-4.27, P = 0.089). However, in the non-AMI-induced CS group, LV unloading combined with VA-ECMO significantly reduced 90-day mortality (adjusted hazard ratio 0.37, 95% confidence interval 0.14-0.96, P = 0.041; P for interaction = 0.029) as compared with those who received VA-ECMO alone. CONCLUSIONS: LV unloading with VA-ECMO may reduce 90-day mortality compared with VA-ECMO alone in patients with non-AMI-induced CS, but not in AMI-induced CS.