Atrial fibrillation (AF) can cause a reduction in left ventricular ejection fraction (LVEF) that resolves rapidly upon restoration of sinus rhythm. We used artificial intelligence to understand (1) how often transient LVEF reduction during AF is from mismeasurement due to AF's beat-to-beat variability and (2) whether true transient AF-LVEF reduction has prognostic significance.

In this observational study, we analyzed all patients at a large academic center with a transthoracic echocardiogram in AF and subsequent transthoracic echocardiogram in sinus rhythm within 90 days. We classified patients by their clinically reported LVEFs: no AF-LVEF reduction, transient AF-LVEF reduction that recovered after conversion to sinus rhythm, or persistent AF-LVEF reduction that did not recover. We evaluated how automated multicycle AF-LVEF measurement using a validated artificial intelligence algorithm affected AF-LVEF and reclassified patients. We used Fine-Gray hazard modeling to analyze 1-year heart failure hospitalization risk.

In 810 patients (mean age 74.1 years, 34.3% female), 459 (56.7%) had no reduced AF-LVEF, 71 (8.8%) had transient AF-LVEF reduction, and 280 (34.6%) had persistent AF-LVEF reduction. In the group with transient AF-LVEF reduction, LVEF increased by 19.5% (95% CI, 12.0%-22.1%) upon conversion to sinus rhythm. AI reassessment increased AF-LVEF by 8.2% (95% CI, 6.0%-10.4%), reclassifying 20 (28.2%) patients as no longer having reduced AF-LVEF. The group with transient AF-LVEF reduction, as determined by AI, had significantly higher 1-year heart failure hospitalization risk (hazard ratio, 2.28 [95% CI, 1.23-4.21], P=0.003).

Artificial intelligence may decrease misdiagnosis of reduced LVEF during AF and more accurately identify true transient AF-LVEF reduction, a potentially high-risk phenotype.

Aim: Real-world evidence comparing healthcare resource utilization (HRU) and costs between ibrutinib and acalabrutinib, two Bruton's tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) is limited. Materials & methods: Commercial claims from IQVIA PharMetrics Plus and electronic medical records from Acentrus were used to separately evaluate HRU and costs in CLL/SLL patients initiating first-line (1L) single-agent ibrutinib or acalabrutinib on or after 21 November 2019 (index date). Imputed costs were used for Acentrus using previously published assumptions. Regression analyses adjusted for baseline characteristics were used to compare HRU and costs between ibrutinib and acalabrutinib during 1L therapy. Results: In IQVIA, 537 and 355 patients initiated 1L ibrutinib and acalabrutinib, respectively; in Acentrus, 710 and 373 patients initiated 1L ibrutinib and acalabrutinib, respectively. The mean duration of 1L (in years) was longer for ibrutinib (IQVIA: 1.2; Acentrus: 1.3) than acalabrutinib (IQVIA: 0.8; Acentrus: 0.9). The number of CLL/SLL-related outpatient visits were significantly lower for ibrutinib versus acalabrutinib (IQVIA: 0.86 vs 1.09 per-patient-per-month, rate ratio: 0.85, p = 0.018; Acentrus: 0.57 vs 0.74 per-patient-per-month, rate ratio: 0.80, p = 0.036). Using claims data for IQVIA and imputed costs for Acentrus, total all-cause costs (IQVIA: mean monthly cost difference [MMCD]: -$764, p = 0.279; Acentrus: MMCD: -$1355, p = 0.004) and CLL/SLL related costs (IQVIA: MMCD: -$649, p = 0.133; Acentrus: MMCD: -$1215, p = 0.004) were lower for ibrutinib versus acalabrutinib. Conclusion: In this large real-world study using a mix of claims data and imputed cost estimates, CLL/SLL patients treated with ibrutinib had longer duration of 1L, fewer days with CLL/SLL-related outpatient services and numerically lower all-cause and CLL/SLL-related costs versus acalabrutinib, showing that ibrutinib can be an optimal cost-effective option in 1L.

Safe and effective pharmacologic therapy for atrial fibrillation (AF) in heart failure (HF) is an unmet need. In AF clinical trials, the standard primary endpoint of time to first symptomatic AF event (TTFSE) has several disadvantages, which could theoretically be overcome by measurement of AF-specific symptoms burden during an entire follow-up period.

The authors sought to develop and validate a method of measuring symptom burden of AF in a HF population.

The authors constructed a patient-reported outcome instrument (AFSQ [Atrial Fibrillation Symptoms Questionnaire]) to function in the setting of AF/HF, and used it to measure symptoms throughout long-term follow-up. The AFSQ queries the presence of 10 new or worsening symptoms, equally divided between those associated with AF or HF. In a 267 patient AF/HF trial comparing 2 AF prevention treatments, the AFSQ was linked to electrocardiography documented AF to form a 2-component clinical outcome assessment (SxBAF) that was subjected to psychometric testing, anchor validation, and endpoint efficiency comparison to TTFSE.

SxBAF exhibited greater efficiency than time to first symptomatic event for treatment difference detection, resulting in smaller projected clinical trial sample sizes. SxBAF correlated well with device-detected AF burden (Spearman's ρ = 0.74; P < 0.0001), while permitting gradation in symptom severity. SxBAF also identified treatment group differences in cardiovascular serious adverse events and AF interventions and in recent-onset AF provided specificity for AF- or worsening HF-associated symptoms (P < 0.001 for each).

Measurement of symptoms burden throughout clinical trial follow-up is feasible in AF/HF and should be useful for evaluating patient-centered outcomes in AF prevention trials. (Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure [GENETIC-AF]; NCT01970501).

We assessed the CHA2DS2-VASc score for predicting hospital readmission risk and length of stay (LOS) in patients admitted with primary atrial fibrillation (AF).

This retrospective cohort study included patients with index admission for AF to Latakia's tertiary center (May 2021-November 2023). Patients were followed 90 days to assess readmission. CHA2DS2-VASc was correlated with 90-day readmission, inpatient all-cause mortality, and LOS during index admission.

In total, 717 patients were included; 320 (45%) were readmitted to the hospital within 90 days (58% men, 65% aged <65 years). Inpatient mortality was 4%; the median LOS was 2 days. There was an increase in the incident rate ratio (IRR) of LOS starting from a CHA2DS2-VASc of 2 (IRR: 2, 95% confidence interval [CI]: 1.7-2.2) to a score of >6 (IRR: 5, 95% CI: 1.8-10.7), compared with a score of 0. There was an incremental increase in the hazard ratio (HR) of readmission from a score of 1 (HR: 2.3, 95% CI: 1.3-4.1) to a score of >6 (HR: 41, 95% CI: 31-72) compared with a CHA2DS2-VASc of 0.

CHA2DS2-VASc could predict 90-day hospital readmission and LOS during the index admission in patients admitted with primary AF.

The association of haemoglobin A1c (HbA1c) variability with the risk of adverse outcomes in patients with atrial fibrillation (AF) prescribed anticoagulants remains unclear. This study aimed to evaluate the association of HbA1c variability with the risk of ischaemic stroke (IS)/systemic embolism (SE) and all-cause mortality among patients with non-valvular AF prescribed anticoagulants.

Patients newly diagnosed with AF from 2013 to 2018 were included. Variability in HbA1c, indexed by the coefficient of variation (CV), was determined for those with at least three HbA1c measurements available from the time of study enrolment to the end of follow-up. To evaluate whether prevalent diabetes would modify the relationship between HbA1c variability and outcomes, participants were divided into diabetes and non-diabetes groups. The study included 8790 patients (mean age 72.7% and 48.5% female). Over a median follow-up of 5.5 years (interquartile range 5.2, 5.8), the incident rate was 3.74 per 100 person-years for IS/SE and 4.89 for all-cause mortality in the diabetes group. The corresponding incident rates in the non-diabetes group were 2.41 and 2.42 per 100 person-years. In the diabetes group, after adjusting for covariates including mean HbA1c, greater HbA1c variability was significantly associated with increased risk of IS/SE [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.27-2.13) and all-cause mortality (HR = 1.24, 95% CI: 1.05-1.47) compared with the lowest CV tertile. A similar pattern was evident in the non-diabetes group (IS/SE: HR = 1.58, 95% CI: 1.23-2.02; all-cause mortality: HR = 1.35, 95% CI: 1.10-1.64).

Greater HbA1c variability was independently associated with increased risk of IS/SE and all-cause mortality among patients with AF, regardless of diabetic status.

Nonischemic 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 deformation analysis and its prognostic value added to CHA2DS2-VASc score. Patients with NIDCM and left ventricular ejection fraction <50% in sinus rhythm were included between January 2015 and December 2019. Left atrial 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 (HRs). There were 338 patients included. After a median follow-up of 3.6 years, the end point occurred in 41 patients (12.1%). LAVI outperformed other echocardiographic parameters, with a significant improvement in risk reclassification compared with 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 end point separately. The best cutoff for LAVI was 44 ml/m2. LAVI ≥44 ml/m2 increased the risk of the end point among those with CHA2DS2-VASc ≥3 (HR 6.0, 95% confidence interval 2.6 to 13.5) but not in those with CHA2DS2-VASc <3 (HR 1.2, 95% confidence interval 0.3 to 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.

We aim to assess the risk of thrombus-associated events (TAE) in patients with heart failure (HF) without atrial fibrillation (AF) and develop an effective scoring system for a risk stratification model.

This retrospective study included 450 patients (median age 64.0 years, interquartile range [55.0, 75.0]; 31.6% women) hospitalized for HF without AF and atrial flutter, but with a left ventricular ejection fraction (LVEF) ≤ 55% and New York Heart Association (NYHA) functional class of III-IV. A median follow-up of 47 months was conducted. In the present study, TAE during follow-up was independently associated with both all-cause death [hazard ratio (HR) 1.756, 95% confidence interval (CI) 1.324-2.328, P < 0.001] and readmission for HF (HR 1.574, 95% CI 1.122-2.208, P = 0.009) after adjustment for covariates. Hypertension (HR 1.573, 95% CI 1.018-2.429, P = 0.041), atrial arrhythmia excluding AF (AAexAF) (HR 2.041, 95% CI 1.066-3.908, P = 0.031), previous ischaemic stroke (HR 2.469, 95% CI 1.576-3.869, P < 0.001), and vascular disease (HR 1.658, 95% CI 1.074-2.562, P = 0.023) were independently associated with TAE. Age (HR 1.021, 95% CI 1.008-1.033, P = 0.001), previous ischaemic stroke (HR 1.685, 95% CI 1.248-2.274, P = 0.001), LVEF ([10, 25] vs. [40, 55]) HR 1.925, 95% CI 1.311-2.826, P = 0.001; (25, 40] vs. (40, 55] HR 1.084, 95% CI 0.825-1.424, P = 0.563), and creatinine clearance rate (Ccr) (HR 0.991, 95% CI 0.986-0.996, P = 0.001) were independently associated with composite events of TAE and death (TAE-D). CHA2DS2VASc modestly predicted 5-year TAE [area under the receiver operating characteristic curves (AUC) 0.660, P < 0.001 compared with 0.5] and TAE-D (AUC 0.639, P < 0.001 compared with 0.5). (C)ACE, formed by incorporating AAexAF, LVEF, and Ccr into CHA2DS2VASc, had higher AUC for predicting 5-year TAE (0.694 vs. 0.660, P = 0.018) and TAE-D (0.708 vs. 0.639, P < 0.001) compared with CHA2DS2VASc. In patients with HF with reduced ejection fraction (HFrEF), (C)ACE and (C)ACEN [formed by incorporating NYHA into (C)ACE] had higher AUC compared with CHA2DS2VASc in predicting 5-year TAE (0.700 and 0.707 vs. 0.649, P = 0.013 and 0.030, respectively) and TAE-D (0.712 and 0.713 vs. 0.622, P < 0.001 and <0.001, respectively). The AUC did not improve statistically from (C)ACE to (C)ACEN (0.700 vs. 0.707, P = 0.600 for TAE; 0.712 vs. 0.713, P = 0.917 for TAE-D).

In HF without AF, TAE during follow-up was associated with adverse prognoses. The independent risk factors of TAE or TAE-D improved CHA2DS2-VASc predictive ability, especially in patients with HFrEF. Our findings provide new evidence for TAE risk stratification in HF without AF, potentially guiding prophylactic anticoagulation.

It is not uncommon that atrial fibrillation (AF) coexists with left bundle branch block (LBBB). Whether LBBB is an independent predictor of poor prognosis in AF patients remains undetermined. This study aims to investigate the impact of LBBB on the AF-related outcomes in non-valvular AF patients.

The clinical data of AF patients were collected from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. The frequencies of acute arterial embolism events (AEE) and in-hospital cardiac death were compared between the non-LBBB and LBBB groups. And, their 1-year mortality was assessed through a survival analysis model. Additionally, the two groups were matched in a 1:2 ratio by a propensity score matching (PSM) method according to the CHA2DS2VASc score and AF type.

5051 patients diagnosed with non-valvular AF without apparent structural heart disease were enrolled in this study, among them, there were 65 with LBBB which had more AEE (13.8% vs 6.8%, p = 0.04). After PSM, with balanced CHA2DS2VASc score and AF type, LBBB was still related with AEE (13.8% vs 3.8%, p = 0.02) significantly, and it was also independent of heart failure (HF) (odds ratios (OR) 6.38, 95% confidence intervals (CI) [1.10, 36.93], p = 0.04). LBBB was also correlated with in-hospital cardiac death (OR 5.33, 95% CI [1.01, 28.28], p = 0.04). And, the LBBB patients had a lower 1-year survival rate in the subgroup of HF (67.6% vs 83.0%, p = 0.06).

The LBBB was an independent risk factor of AEE and related to in-hospital cardiac death and 1-year all-cause mortality in this non-valvular AF cohort from MIMIC-III.

The recent rise of artificial intelligence represents a revolutionary way of improving current medical practices, including cardiovascular (CV) assessment scores. Retinal vascular alterations may reflect systemic processes such as the presence of CV risk factors. The value of swept-source retinal optical coherence tomography-angiography (SS OCT-A) imaging is significantly enhanced by image analysis tools that provide rapid and accurate quantification of vascular features. We report on the interest of using machine-learning (ML) and deep-learning (DL) models for CV assessment from SS OCT-A microvasculature imaging. We assessed the accuracy of ML and DL algorithms in predicting the CHA2DS2-VASc neurocardiovascular score based on SS OCT-A retinal images of patients from the open-source RASTA dataset. The ML and DL models were trained on data from 491 patients. The ML models tested here achieved good performance with area under the curve (AUC) values ranging from 0.71 to 0.96. According to a classification into two neurocardiovascular risk groups, the EfficientNetV2-B3, a well suited DL model for retinal OCT-A images, predicted risk correctly in 68% of cases, with a mean absolute error (MAE) of approximately 0.697. Our models enable a confident prediction of the CHA2DS2-VASc score from SS OCT-A imaging, which could be a useful tool contributing to the assessment of neurocardiovascular profiles in the future.

Despite clear associations between arrhythmia burden and cardiovascular risk, clinical risk scores that predict cardiovascular events do not incorporate individual-level arrhythmia characteristics from long-term continuous monitoring (LTCM).

This study evaluated the performance of risk models that use data from LTCM and patient claims for prediction of heart failure (HF) and ischemic stroke.

We retrospectively analyzed features extracted from up to 14 days of LTCM electrocardiogram (ECG) data linked to patient-level claims data for 320,974 Medicare beneficiaries who underwent ZioXT ambulatory monitoring. We created predictive models for HF hospitalization, stroke hospitalization, and new-onset HF within 1 year using LASSO Cox regression for variable selection among ambulatory ECG variables and components of the CHA2DS2-VASc score.

A model that included components of the CHA2DS2-VASc and all ambulatory ECG variables had greater discrimination for HF hospitalization (C-statistic 0.85, 95% CI: 0.84-0.86) than the CHA2DS2-VASc (C-statistic 0.73, 95% CI: 0.72-0.74), but performed similarly to the CHA2DS2-VASc for prediction of stroke hospitalization (C-statistic 0.75 [95% CI: 0.74-0.77] vs 0.71 [95% CI: 0.70-0.72], respectively). Atrial fibrillation was associated with greater risk in the most predictive models (HF hospitalization, HR: 1.53 [95% CI: 1.35-1.72]; stroke hospitalization, HR: 1.58 [95% CI: 1.30-1.93]), and premature ventricular couplets were associated with greater risk of HF hospitalization (HR: 1.54, 95% CI: 1.43-1.65).

The CHA2DS2-VASc performed modestly for prediction of stroke and HF events; predictive ability improved significantly with addition of LTCM ECG covariates. The presence of atrial fibrillation and ventricular ectopy on 14-day LTCM were strongly associated with HF events.

The impact of comorbidity burden on outcomes of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in patients with heart failure and preserved ejection fraction (HFpEF) remains unclear.

The purpose of this study was to evaluate how comorbidity burden influences the association between RFCA and cardiovascular outcomes in AF patients with HFpEF.

AF patients with HFpEF from the prospective China-AF cohort, recruited between August 2011 and December 2020, were categorized into 2 groups based CHA2DS2-VASc score: low comorbidity burden (score ≤4) and high comorbidity burden (score >4). The associations between RFCA and cardiovascular outcomes and interaction effects of comorbidity burden on these associations were assessed.

Among 1700 patients with median follow-up of 65.9 months, those in the low comorbidity burden group who received RFCA had a lower risk of composite events (cardiovascular death and ischemic stroke/transient ischemic attack [TIA]) (adjusted hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.21-0.59] and all-cause death (adjusted HR 0.31, 95% CI 0.17-0.54) compared to those without RFCA. However, significant associations were not observed in the high comorbidity burden group. The differences between low and high comorbidity burden groups were significant, with interaction effects noted between comorbidity burden and RFCA for cardiovascular death (Pinteraction = 0.045) and ischemic stroke/TIA (Pinteraction = 0.010). RFCA was associated with a reduced risk of AF recurrence in both comorbidity burden groups.

RFCA for AF is associated with reduced AF recurrence and improved cardiovascular outcomes in patients with HFpEF. However, these benefits may be limited for patients with a CHA2DS2-VASc score >4 (high comorbidity burden).

Patients with atrial fibrillation (AF) suffer a higher risk of death, and it is necessary to develop prediction tools for mortality risk in critically ill patients with AF. This study aimed to develop a novel predictive nomogram of in-hospital mortality after 48 h in the coronary care unit (CCU) for patients with AF.

We collected information on CCU patients with AF from the "Medical Information Mart for Intensive Care-III" database and developed a nomogram model for predicting the all-cause mortality risk after 48 h in the hospital. Key variables were selected by univariate logistic and least absolute shrinkage and selection operator regression. The independent predictors with p < 0.05 were screened out by multivariate logistic regression. A predictive nomogram was constructed using these independent predictors, and the model calibration and discrimination were evaluated.

This study finally enrolled 1248 CCU patients with AF, and the in-hospital mortality was 17% (209/1248). The predictive nomogram was constructed by 13 selected independent predictors, including age, smoking status, acute kidney injury, chronic obstructive pulmonary disease, ventricular arrhythmia, shock, urea, red cell distribution width, leucocytosis, continuous renal replacement therapy, continuous positive airway pressure, anticoagulation, and heart rate. The area under the curve of the nomogram was 0.803 (95% confidence interval 0.771-0.835). The nomogram was verified to have good accuracy and calibration.

This study developed a novel nomogram containing age, acute kidney injury, and heart rate that can be a good predictor of potential in-hospital mortality after 48 h in CCU patients with AF.

The CHA2DS2-VASc [congestive heart failure, hypertension, age (≥75 years earns 2 points, 65-74 years earns 1 point), diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism (2 points), vascular disease (eg, prior myocardial infarction, peripheral artery disease), and female sex category] score has demonstrated potential as a prognostic indicator for adverse outcomes in patients with heart failure (HF). This systematic review and meta-analysis aimed to assess the predictive accuracy of the CHA2DS2-VASc score in determining the occurrence of stroke and mortality in HF patients. We did a thorough search of electronic databases until December 2023. Included studies examined the correlation between the CHA2DS2-VASc score and the likelihood of stroke or death in patients with HF. The meta-analysis showed a substantial correlation between elevated CHA2DS2-VASc scores and heightened risks of both stroke and mortality in HF patients. Patients with CHA2DS2-VASc scores ≥4 had a greater stroke risk than those with scores <4 (odds ratio, 0.38, 95% confidence interval, 0.33-0.43, P < 0.00001). Similarly, patients with CHA2DS2-VASc scores ≥4 had a higher mortality risk (OR, 0.49, 95% confidence interval, 0.30-0.80, P = 0.05). The CHA2DS2-VASc score is a useful predictive tool for identifying HF patients who are at a high risk of both stroke and mortality. Additional investigation is necessary to confirm these findings and examine the incorporation of the CHA2DS2-VASc score into risk assessment algorithms for tailored patient management.

The CHA2DS2 -VASc score is a vital clinical tool for evaluating thromboembolic risk in patients with atrial fibrillation (AF). This study investigated the efficacy of the CHA2DS2 -VASc score in a cohort of 737 heterogeneous patients (mean age: 63 years) receiving care in cardiac intensive care units (CICUs), with a creatinine-based estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 upon admission and discharge. Incident chronic kidney disease (CKD) was defined as the emergence of a new-onset eGFR<60 mL/min/1.73 m2, accompanied by a decline of >5 mL/min/1.73 m2 compared to that at discharge. The primary endpoint was the incidence of CKD, and the secondary endpoints included all-cause mortality, cardiovascular events, and progression to end-stage kidney disease. In this cohort, 210 (28 %) patients developed CKD. Multivariate analyses revealed that CHA2DS2 -VASc score was a significant independent predictor of incident CKD, regardless of the presence of AF. Integration of CHA2DS2 -VASc scores with eGFR enhanced the predictive accuracy of incident CKD, as evidenced by the improved C-index, net reclassification improvement, and integrated discrimination improvement values (all p < 0.05). Over the 12-month follow-up period, a composite endpoint was observed in 61 patients (8.3 %), with elevated CHA2DS2 -VASc scores being independently associated with this endpoint. In conclusion, CHA2DS2-VASc scores have emerged as robust predictors of both CKD incidence and adverse outcomes. Their inclusion substantially refined the 12-month risk stratification of patients with preserved renal function hospitalized in the CICUs.

The accuracy of available prediction tools for clinical outcomes in patients with atrial fibrillation (AF) remains modest. Machine Learning (ML) has been used to predict outcomes in the AF population, but not in a population entirely on anticoagulant therapy.

Different supervised ML models were applied to predict all-cause death, cardiovascular (CV) death, major bleeding and stroke in anticoagulated patients with AF, processing data from the multicenter START-2 Register.

11078 AF patients (male n = 6029, 54.3%) were enrolled with a median follow-up period of 1.5 years [IQR 1.0-2.6]. Patients on Vitamin K Antagonists (VKA) were 5135 (46.4%) and 5943 (53.6%) were on Direct Oral Anticoagulants (DOAC). Using Multi-Gate Mixture of Experts, a cross-validated AUC of 0.779 ± 0.016 and 0.745 ± 0.022 were obtained, respectively, for the prediction of all-cause death and CV-death in the overall population. The best ML model outperformed CHA2DSVA2SC and HAS-BLED for all-cause death prediction (p < 0.001 for both). When compared to HAS-BLED, Gradient Boosting improved major bleeding prediction in DOACs patients (0.711 vs. 0.586, p < 0.001). A very low number of events during follow-up (52) resulted in a suboptimal ischemic stroke prediction (best AUC of 0.606 ± 0.117 in overall population). Body mass index, age, renal function, platelet count and hemoglobin levels resulted the most important variables for ML prediction.

In AF patients, ML models showed good discriminative ability to predict all-cause death, regardless of the type of anticoagulation strategy, and major bleeding on DOAC therapy, outperforming CHA2DS2VASC and the HAS-BLED scores for risk prediction in these populations.

CHA2DS2-VASc score-related differences have been reported in atrial fibrotic remodeling and prognosis of atrial fibrillation (AF) patients after ablation. There are currently no data on the efficacy of low voltage zone (LVZ)-guided ablation in persistent AF patients according to CHA2DS2-VASc score. We assessed in a cohort of persistent AF patients the extent of LVZ, the regional distribution of LA voltage and the outcome of LA voltage-guided substrate ablation in addition to PVI according to CHA2DS2-VASc score.

138 consecutive persistent AF patients undergoing a first voltage-guided catheter ablation were enrolled. 58 patients with CHAD2DS2-VASc score ≥ 3 and 80 patients with CHAD2DS2-VASc score ≤ 2 were included. LA voltage maps were obtained using 3D-electroanatomical mapping system in sinus rhythm. LVZ was defined as < 0.5 mV.

In the high CHAD2DS2-VASc score group, LA voltage was lower (1.5 [1.1-2.5] vs. 2.3 [1.5-2.8] mV, p = 0.02) and LVZs were more frequently identified (40% vs. 18%), p < 0.01). Female with CHA2DS2-VASc score ≥ 3 (p = 0.031), LA indexed volume (p = 0.009) and P-wave duration ≥ 150 ms (p = 0.001) were predictors of LVZ. After a 36-month follow-up, atrial arrhythmia-free survival was similar between the two groups (logrank test, P = 0.676).

AF patients with CHAD2DS2-VASc score ≥ 3 display more LA substrate remodeling with lower voltage and more LVZs compared with those with CHAD2DS2-VASc score ≤ 2. Despite this atrial remodeling, they had similar and favorable 36 months results after one single procedure. Unlike male with CHAD2DS2-VASc score ≥ 3, female with CHAD2DS2-VASc score ≥ 3 was predictor of LVZ occurrence.

Subclinical, device-detected atrial fibrillation (AF) is frequently recorded by pacemakers and other implanted cardiac rhythm devices. Patients with device-detected AF have an elevated risk of stroke, but a lower risk of stroke than similar patients with clinical AF captured with surface electrocardiogram. Two randomized clinical trials (NOAH-AFNET 6 and ARTESiA) have tested a direct oral anticoagulant (DOAC) against aspirin or placebo. A study-level meta-analysis of the two trials found that treatment with a DOAC resulted in a 32% reduction in ischaemic stroke and a 62% increase in major bleeding; the results of the two trials were consistent. The annualized rate of stroke in the control arms was ∼1%. Several factors point towards overall net benefit from DOAC treatment for patients with device-detected AF. Strokes in ARTESiA were frequently fatal or disabling and bleeds were rarely lethal. The higher absolute rates of major bleeding compared with ischaemic stroke while on treatment with a DOAC in the two trials are consistent with the ratio of bleeds to strokes seen in the pivotal DOAC vs. warfarin trials in patients with clinical AF. Prior research has concluded that patients place a higher emphasis on stroke prevention than on bleeding. Further research is needed to identify the characteristics that will help identify patients with device-detected AF who will receive the greatest benefit from DOAC treatment.

This study aimed to explore the relationship between the trajectory of the triglyceride-glucose (TyG) index and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with atrial fibrillation (AF).This prospective study included 1979 patients with AF, who were initially selected from the Kailuan study. Patients of AF were split into four groups according to the value of TyG index. The clinical endpoint was MACCE, including myocardial infarction and ischemic stroke. Cox proportional hazard models were employed to examine the hazard ratio (HR) and 95% confidence interval (CI) for MACCE in various trajectory groups.The mean age of all patients with AF was 67.65 ± 11.15 years, and 1752 (88.53%) were male. Over a median follow-up duration of 5.31 years, in total 227 MACCE were recorded. MACCE cumulative incidence in Quartile 4 (26.96%) was significantly higher than those in other quartiles (P = 0.023). Multivariate Cox proportional hazards regression analysis showed that a higher TyG index (Quartile 4) was significantly and positively linked to MACCE in patients with AF (P = 0.023, HR: 2.103; 95% CI: 1.107-3.994).The evaluated TyG index is significantly associated with an increased risk of MACCE in patients with AF.

Atrial fibrillation (AF) often escapes detection, given its frequent paroxysmal and asymptomatic presentation. Deep learning of transthoracic echocardiograms (TTEs), which have structural information, could help identify occult AF. We created a two-stage deep learning algorithm using a video-based convolutional neural network model that (1) distinguished whether TTEs were in sinus rhythm or AF and then (2) predicted which of the TTEs in sinus rhythm were in patients who had experienced AF within 90 days. Our model, trained on 111,319 TTE videos, distinguished TTEs in AF from those in sinus rhythm with high accuracy in a held-out test cohort (AUC 0.96 (0.95-0.96), AUPRC 0.91 (0.90-0.92)). Among TTEs in sinus rhythm, the model predicted the presence of concurrent paroxysmal AF (AUC 0.74 (0.71-0.77), AUPRC 0.19 (0.16-0.23)). Model discrimination remained similar in an external cohort of 10,203 TTEs (AUC of 0.69 (0.67-0.70), AUPRC 0.34 (0.31-0.36)). Performance held across patients who were women (AUC 0.76 (0.72-0.81)), older than 65 years (0.73 (0.69-0.76)), or had a CHA2DS2VASc ≥2 (0.73 (0.79-0.77)). The model performed better than using clinical risk factors (AUC 0.64 (0.62-0.67)), TTE measurements (0.64 (0.62-0.67)), left atrial size (0.63 (0.62-0.64)), or CHA2DS2VASc (0.61 (0.60-0.62)). An ensemble model in a cohort subset combining the TTE model with an electrocardiogram (ECGs) deep learning model performed better than using the ECG model alone (AUC 0.81 vs. 0.79, p = 0.01). Deep learning using TTEs can predict patients with active or occult AF and could be used for opportunistic AF screening that could lead to earlier treatment.

Patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post hoc analysis of the A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER-HF) trial we evaluated how a previously validated risk model consisting of 3 variables (history of prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide level) would perform, compared with plasma d-dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban.

Stroke risk and treatment effect were computed across risk score and plasma d-dimer tertiles. Risk score was available in 58% of the COMMANDER-HF population (n = 2928). Over a median follow-up of 512 days (range 342-747 days), 60 patients experienced a stroke (14.6 per 1000 patient-years). The risk model did not identify patients at higher risk of stroke and showed a low overall prognostic performance (C-index = 0.53). The effect of rivaroxaban on stroke was homogeneous across risk score tertiles (P-interaction = .67). Among patients in whom the risk score was estimated, d-dimer was available in 2343 (80%). d-dimer had an acceptable discrimination performance for stroke prediction (C-index = 0.66) and higher plasma d-dimer concentrations were associated with higher rates of stroke (ie, tertile 3 vs tertile 1, hazard ratio 3.65, 95% confidence interval 1.59-8.39, P = .002). Treatment with low-dose rivaroxaban reduced the incidence of stroke in patients at highest risk by d-dimer levels (ie, >515 ng/mL, hazard ratio 0.42, 95% confidence interval 0.18-0.95, P-interaction = .074), without any safety concerns.

In our analysis, plasma d-dimer concentrations performed better than a previously described 3-variable risk score for stroke prediction in patients with heart failure with reduced ejection fraction, a recent clinical worsening and sinus rhythm as enrolled in the COMMANDER-HF trial. In these patients, a raised plasma d-dimer concentration identified patients who might benefit most from rivaroxaban.

This nationwide routine data analysis evaluates if oral anticoagulant (OAC) use in patients with heart failure (HF) and atrial fibrillation (AF) leads to a lower mortality and reduced readmission rate. Superiority of new oral anticoagulants (NOACs), compared to vitamin K antagonists (VKA), was analyzed for these endpoints.

Anonymous data of patients with a health insurance at the Allgemeine Ortskrankenkasse and a claims record for hospitalization with the main diagnosis of HF and secondary diagnosis of AF (2017-2019) were included. A hospital stay in the previous year was an exclusion criterion. Mortality and readmission for all-cause and stroke/intracranial bleeding (ICB) were analyzed 91-365 days after the index hospitalization. Kaplan-Meier survival curves and multivariable Cox regression models were used to evaluate the impact of medication on outcome.

180,316 cases were included [81 years (IQR 76-86), 55.6% female, CHA2DS2-VASc score ≥ 2 (96.81%)]. In 80.6%, OACs were prescribed (VKA: 21.7%; direct factor Xa inhibitors (FXaI): 60.0%; direct thrombin inhibitors (DTI): 3.4%; with multiple prescriptions per patient included). Mortality rate was 19.1%, readmission rate was 29.9% and stroke/ICB occurred in 1.9%. Risk of death was lower with any OAC (HR 0.77, 95% CI [0.75-0.79]) but without significant differences in OAC type (VKA: HR 0.73, [0.71-0.76]; FXaI: HR 0.77, [0.75-0.78]; DTI: HR 0.71, [0.66-0.77]). The total readmission rate (HR 0.97, [0.94 to 0.99]) and readmission for stroke/ICB (HR 0.71, [0.65-0.77]) was lower with OAC.

Nationwide data confirm a reduction in mortality and readmission rate in HF-AF patients taking OACs, without NOAC superiority.

The presence of both atrial fibrillation (AF) and heart failure (HF) increases the risk of an ischemic cerebrovascular event (CVE) by roughly fivefold. The HATCH score is a score used to predict new-onset AF. Although there are some differences, it contains risk factors similar to the CHA2DS2-VASc score. Our study aimed to investigate the relationship between the HATCH score and ischemic CVE. This retrospective study obtained data from 1719 HF patients between 2015 and 2022. About 673 patients with AF were included in the study. In the univariate and multivariate Cox regressions, we found that CHA2DS2-VASc and HATCH scores were independent predictors of ischemic CVE (p = 0.001 and < p = 0.001, respectively). The ROC analysis, AUC for the CHA2DS2-VASc score was 0.884 (95% CI 0.828-0.940, Collapse

Stroke is a leading cause of death and disability in the United States and worldwide, necessitating comprehensive efforts to optimize stroke risk factor management. Health disparities in stroke incidence, prevalence, and risk factor management persist among various race/ethnic, geographic, and socioeconomic populations and negatively impact stroke outcomes. This review highlights existing literature and guidelines for stroke risk factor management, emphasizing health disparities among certain populations. Moreover, stroke risk factors for special groups, including the young, the very elderly, and pregnant/peripartum women are outlined. Strategies for stroke risk factor improvement at every level of the health care system are discussed, from the individual patient to providers, health care systems, and policymakers. Improving stroke risk factor management in the context of the social determinants of health, and with the goal of eliminating inequities and disparities in stroke prevention strategies, are critical steps to reducing the burden of stroke and equitably improving public health.

No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder.

To develop an individual-level prediction tool for risk of return to use in opioid use disorder.

This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016. The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities.

All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone.

Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment.

The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84).

The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.

Quantitative changes in retinal microvasculature are associated with subclinical cardiac alterations and clinical cardiovascular diseases (i.e., heart failure and coronary artery disease). Nonetheless, very little is known about the retinal vascular and structural changes in patients with atrial fibrillation (AF). Our study aims to characterize the microvasculature and structure of the retina in AF patients and explore their differences in different types of AF (paroxysmal and sustained AF).

This cross-sectional study was conducted at the Departments of Neurology and Cardiology in West China Hospital, Chengdu, China. Individuals aged 40 years or older with a diagnosis of AF were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 40 years or older and without a history of AF, ocular abnormalities/disease, or any significant systemic illness were recruited. The retinal vascular and structural parameters were assessed using swept-source optical coherence tomography (SS-OCT)/SS-OCT angiography. Echocardiographic data of left atrium (LA) diameter were collected in patients with AF at the time of inclusion.

A total of 242 eyes of 125 participants [71 men (56.8%); mean (SD) age, 61.98 (8.73) years] with AF and 219 eyes of 111 control participants [53 men (47.7%); mean (SD) age, 62.31 (6.47) years] were analyzed. In our AF cohort, 71 patients with paroxysmal AF and 54 patients with sustained AF (i.e., persistent/permanent AF) were included. Decreased retinal microvascular perfusion (β coefficient = -0.08; 95% CI, -0.14 to -0.03) and densities (β coefficient = -1.86; 95% CI, -3.11 to -0.60) in superficial vascular plexus (SVC) were found in the eyes of the participants with AF. In regard to retinal structures, thinner ganglion cell-inner plexiform layer (GCIPL; β coefficient = -2.34; 95% CI, -4.32 to -0.36) and retinal nerve fiber layer (RNFL) thicknesses (β coefficient = -0.63; 95% CI, -2.09 to -0.18) were observed in the eyes of the participants with AF. The retinal parameters did not significantly differ between paroxysmal and sustained AF (all P > 0.05). However, significant interactions were observed between LA diameter and AF subtypes with the perfusion and densities in SVC (P < 0.05).

This study found that individuals with AF had decreased retinal vascular densities and perfusion in SVC, as well as thinner GCIPL and RNFL thickness compared with age- and sex-matched control participants. The differences of the retinal microvasculature in SVC between paroxysmal and sustained AF depend on the LA diameter. Given our findings, further longitudinal studies with our participants are of interest to investigate the natural history of retinal microvascular and structural changes in individuals across the clinical process of AF and AF subtypes.

Heart failure (HF) is a major disease in our society that often presents with multiple comorbidities with mutual interaction and aggravation. The comorbidity of HF and stroke is a high risk condition that requires particular attention to ensure early detection of complications, efficient diagnostic workup, close monitoring, and consequent treatment of the patient. The bi-directional interaction between the heart and the brain is inherent in the pathophysiology of HF where HF may be causal for acute cerebral injury, and - in turn - acute cerebral injury may induce or aggravate HF via imbalanced neural and neurovegetative control of cardiovascular regulation. The present document represents the consensus view of the ESC Council on Stroke, the Heart Failure Association and the ESC Working Group on Thrombosis to summarize current insights on pathophysiological interactions of the heart and the brain in the comorbidity of HF and stroke. Principal aspects of diagnostic workup, pathophysiological mechanisms, complications, clinical management in acute conditions and in long-term care of patients with the comorbidity are presented and state-of-the-art clinical management and current evidence from clinical trials is discussed. Beside the physicians perspective, also the patients values and preferences are taken into account. Interdisciplinary cooperation of cardiologists, stroke specialists, other specialists and primary care physicians is pivotal to ensure optimal treatment in acute events and in continued long-term treatment of these patients. Key consensus statements are presented in a concise overview on mechanistic insights, diagnostic workup, prevention and treatment to inform clinical acute and continued care of patients with the comorbidity of HF and stroke.

This study aims to assess the risk of direct oral anticoagulant (DOAC) discontinuation among Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) who reach the Medicare coverage gap stratified by low-income subsidy (LIS) status and the impact of DOAC discontinuation on rates of stroke and systemic embolism (SE) among beneficiaries with increased out-of-pocket (OOP) costs due to not receiving LIS.

In this retrospective cohort study, Medicare claims data (2015-2020) were used to identify beneficiaries with NVAF who initiated rivaroxaban or apixaban and entered the coverage gap during ≥ 1 year. DOAC discontinuation rates during the coverage gap were stratified by receipt of Medicare Part D Low-Income Subsidy (LIS), a proxy for not experiencing increased OOP costs. Among non-LIS beneficiaries, incidence rates of stroke and SE during the subsequent 12 months were compared between beneficiaries who did and did not discontinue DOAC in the coverage gap.

Among 303,695 beneficiaries, mean age was 77.3 years, and 28% received LIS. After adjusting for baseline differences, non-LIS beneficiaries (N = 218,838) had 78% higher risk of discontinuing DOAC during the coverage gap vs. LIS recipients (adjusted hazard ratio [aHR], 1.78; 95% CI [1.73, 1.82]). Among non-LIS beneficiaries, DOAC discontinuation during coverage gap (N = 91,397; 34%) was associated with 14% higher risk of experiencing stroke and SE during the subsequent 12 months (aHR, 1.14; 95% CI [1.08, 1.20]).

Increased OOP costs during Medicare coverage gap were associated with higher risk of DOAC discontinuation, which in turn was associated with higher risk of stroke and SE among beneficiaries with NVAF.

The aim of this study was to evaluate the correlation between P-wave indexes, echocardiographic parameters, and CHA2DS2-VASc score in patients without atrial fibrillation and valvular disease.

This retrospective cross-sectional study included patients of a tertiary hospital with no history of atrial fibrillation, atrial flutter, or valve disease and collected data from June 2021 to May 2022. The exclusion criteria were as follows: unavailable medical records, pacemaker carriers, absence of echocardiogram report, or uninterpretable ECG. Clinical, electrocardiographic [i.e., P-wave duration, amplitude, dispersion, variability, maximum, minimum, and P-wave voltage in lead I, Morris index, PR interval, P/PR ratio, and P-wave peak time], and echocardiographic data [i.e., left atrium and left ventricle size, left ventricle ejection fraction, left ventricle mass, and left ventricle indexed mass] from 272 patients were analyzed.

PR interval (RHO=0.13, p=0.032), left atrium (RHO=0.301, p<0.001) and left ventricle diameter (RHO=0.197, p=0.001), left ventricle mass (RHO=0.261, p<0.001), and left ventricle indexed mass (RHO=0.340, p<0.001) were positively associated with CHA2DS2-VASc score, whereas P-wave amplitude (RHO=-0.141, p=0.02), P-wave voltage in lead I (RHO=-0.191, p=0.002), and left ventricle ejection fraction (RHO=-0.344, p<0.001) were negatively associated with the same score. The presence of the Morris index was associated with high CHA2DS2-VASc (p=0.022).

Prolonged PR interval, Morris index, increased left atrium diameter, left ventricle diameter, left ventricle mass, and left ventricle indexed mass values as well as lower P-wave amplitude, P-wave voltage in lead I, and left ventricle ejection fraction values were correlated with higher CHA2DS2-VASc scores.

Up to 25% of embolic strokes occur in individuals without atrial fibrillation (AF) or other identifiable mechanisms.

This study aims to assess whether left atrial (LA) blood flow characteristics are associated with embolic brain infarcts, independently of AF.

The authors recruited 134 patients: 44 with a history of ischemic stroke and 90 with no history of stroke but CHA2DS2VASc score ≥1. Cardiac magnetic resonance (CMR) evaluated cardiac function and LA 4-dimensional flow parameters, including velocity and vorticity (a measure of rotational flow), and brain magnetic resonance imaging (MRI) was performed to detect large noncortical or cortical infarcts (LNCCIs) (likely embolic), or nonembolic lacunar infarcts.

Patients (41% female; age 70 ± 9 years) had moderate stroke risk (median CHA2DS2VASc = 3, Q1-Q3: 2-4). Sixty-eight (51%) had diagnosed AF, of whom 58 (43%) were in AF during CMR. Thirty-nine (29%) had ≥1 LNCCI, 20 (15%) had ≥1 lacunar infarct without LNCCI, and 75 (56%) had no infarct. Lower LA vorticity was significantly associated with prevalent LNCCIs after adjustment for AF during CMR, history of AF, CHA2DS2VASc score, LA emptying fraction, LA indexed maximum volume, left ventricular ejection fraction, and indexed left ventricular mass (OR: 2.06 [95% CI: 1.08-3.92 per SD]; P = 0.027). By contrast, LA flow peak velocity was not significantly associated with LNCCIs (P = 0.21). No LA parameter was associated with lacunar infarcts (all P > 0.05).

Reduced LA flow vorticity is significantly and independently associated with embolic brain infarcts. Imaging LA flow characteristics may aid identification of individuals who would benefit from anticoagulation for embolic stroke prevention, regardless of heart rhythm.

Isolated sinus node dysfunction (ISND) is a sinus node dysfunction without atrial fibrillation. A high risk of ischaemic stroke (IS) has been reported in ISND populations. However, current guidelines do not recommend anticoagulation in ISND management. P-wave indicates ISND-related atrial remodelling. P-wave indices and the CHA2DS2-VASc score may contribute to risk stratification for ISND-related IS.

In this multi-centre longitudinal cohort, ISND patients were divided into development (n = 1185) and external validation (n = 988) cohorts. Ischaemic stroke prediction capacity of the P-combined score was assessed with regard to discrimination, calibration, and clinical effectiveness. The cut-off value of the score was confirmed by using a restricted cubic spline curve. One hundred and twenty-four (10.46%) ISND patients developed IS [1.63%/year; 95% confidence interval (CI): 1.49-1.78%/year] after a median 3.02-year follow-up in the development cohort. The P-wave terminal force in electrocardiogram-lead V1 (PTFV1) was the only significantly abnormal P-wave index (adjusted hazard ratio: 2.56; 95% CI: 1.72-3.80). Therefore, we incorporated the PTFV1 with the CHA2DS2-VASc score to generate a P-combined score. For a 5-year IS risk, the P-combined score improved Harrell's C-statistic (95% CI) from 0.678 (0.618-0.738) to 0.716 (0.657-0.774) and 0.747 (0.677-0.816) to 0.808 (0.747-0.868) in the development and validation cohorts, respectively, along with calibration and decision curve analyses. The cut-off value of the score was 3 in the development cohort and well-discriminated in the validation cohort.

Chinese ISND patients have a higher IS risk than the general population. Compared with the CHA2DS2-VASc score, the PTFV1-combined CHA2DS2-VASc score shows a better risk-stratification capacity for ISND-related IS.

COMMANDER-HF was a randomised trial comparing rivaroxaban 2.5 mg two times a day to placebo, in addition to antiplatelet therapy, in patients hospitalised for worsening heart failure with coronary artery disease and sinus rhythm. Patients with diabetes are at increased risk of cardiovascular events and therefore have more to gain.

In this post-hoc analysis, we evaluated the efficacy and safety of rivaroxaban in patients with (n=2052) and without diabetes (n=2970). The primary outcome was the composite of cardiovascular death, myocardial infarction (MI) or ischaemic stroke. HRs and 95% CIs with interaction analyses were used to describe event-rates and treatment effects. Patients with diabetes had a higher prevalence of cardiovascular comorbidities (eg, hypertension, obesity) and increased incidence of cardiovascular events. Adjusted HRs for events in people with versus without diabetes were 1.34 (95% CI 1.19 to 1.50) for the primary outcome, 1.21 (95% CI 0.84 to 1.75) for stroke, 1.51 (95% CI 1.14 to 1.99) for MI, 1.17 (95% CI 1.05 to 1.31) for heart failure hospitalisation and 1.06 (95% CI 0.56 to 2.01) for major bleeding. Rivaroxaban had no significant effect on event-rates in patients with and without diabetes (all interaction p values >0.05). Low-dose rivaroxaban was associated with an overall reduction in ischaemic stroke (HR 0.66; 95% CI 0.47 to 0.95), with no apparent subgroup interaction according to diabetes status (p-int=0.93).

In COMMANDER-HF a diagnosis of diabetes conferred higher rates of cardiovascular events that, with exception of ischaemic stroke, was not substantially reduced by rivaroxaban. Rivaroxaban was associated with reduced risk of ischaemic stroke for patients with and without diabetes.

NCT01877915; Post-results.

The impact of adherence to oral anticoagulation has not been reported in terms of absolute risk, which would enhance patients' understanding and treatment adherence.

This retrospective cohort study analysed data from the National Health Insurance Database of Korea, from January 2010 to December 2018, on 84 227 patients with non-valvular atrial fibrillation (NVAF). The participants were analysed according to their overall adherence to oral anticoagulants (OACs) and further divided into four groups: non-vitamin K antagonist oral anticoagulant (NOAC) adherent, vitamin K antagonist (VKA) adherent, NOAC non-adherent, and VKA non-adherent. The incidence of ischaemic stroke, major bleeding, and death was compared between the four groups using risk difference, number needed to treat and number needed to harm. Among the participants, 50 178 were adherent to (OACs), while 34 049 were non-adherent. The incidence of major bleeding was higher in the adherent group (4.49%; 95% confidence interval, 4.11-4.85%) than in the non-adherent group (3.61%; 3.16-4.06%), and the incidence of ischaemic stroke was higher in the non-adherent group (7.68%; 7.08-8.33%) than in the adherent group (5.61%; 5.17-6.07%). In terms of risk difference, adherence to OACs increased the risk of major bleeding by 0.87% and decreased the risk of ischaemic stroke by 2.08%. This finding suggests that one additional major bleeding event occurred for every 115 adherent patients, and one additional ischaemic stroke event was prevented for every 48 adherent patients.

The benefits of OAC adherence in NVAF patients for ischaemic stroke prevention exceeding the risk of bleeding are shown more clearly in terms of absolute risk.

The optimal approach to prevent stroke and systemic embolism in patients with advanced chronic kidney disease (CKD) and atrial fibrillation remains unresolved. We conducted a narrative review to explore areas of uncertainty and opportunities for future research. First, the relationship between atrial fibrillation and stroke is more complex in patients with advanced CKD than in the general population. The currently employed risk stratification tools do not adequately discriminate between patients deriving a net benefit and those suffering a net harm from oral anticoagulation. Anticoagulation initiation should probably be more restrictive than is currently advocated by official guidelines. Recent evidence reveals that the superior benefit-risk profile of non-vitamin K antagonist oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) observed in the general population and in moderate CKD can be extended to advanced CKD. The NOACs yield better protection against stroke, cause less major bleeding, are associated with less acute kidney injury and a slower decline of CKD, and are associated with a lower incidence of cardiovascular events than VKAs. The VKAs may be harmful in CKD patients, in particular in patients with a high bleeding risk and labile international normalized ratio. The better safety and efficacy of NOACs as opposed to VKAs may be particularly evident in advanced CKD as a result of better on-target anticoagulation with NOACs, harmful off-target vascular effects of VKAs, and beneficial off-target vascular effects of NOACs. The intrinsic vasculoprotective effects of NOACs are supported by animal experimental evidence as well as by findings of large clinical trials and may result in use of NOACs beyond their anticoagulant properties.

During the last decade, the CHA₂DS₂-VASc score has been used for stratifying the mortality risk in both atrial fibrillation (AF) and non-AF patients. However, no previous study considered this score as a prognostic indicator in non-AF patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). All consecutive non-AF patients with mild-to-moderate IPF, diagnosed between January 2016 and December 2018 at our Institution, entered this study. All patients underwent physical examination, blood tests, spirometry, high-resolution computed tomography and transthoracic echocardiography. CHA₂DS₂-VASc score, Gender-Age-Physiology (GAP) index and Charlson Comorbidity Index (CCI) were determined in all patients. Primary endpoint was all-cause mortality, while the secondary endpoint was the composite of all-cause mortality and rehospitalizations for all causes over mid-term follow-up. 103 consecutive IPF patients (70.7 ± 7.3 yrs, 79.6% males) were retrospectively analyzed. At the basal evaluation, CHA₂DS₂-VASc score, GAP index and CCI were 3.7 ± 1.6, 3.6 ± 1.2 and 5.5 ± 2.3, respectively. Mean follow-up was 3.5 ± 1.3 yrs. During the follow-up period, 29 patients died and 43 were re-hospitalized (44.2% due to cardiopulmonary causes). On multivariate Cox regression analysis, CHA₂DS₂-VASc score (HR 2.15, 95% CI 1.59-2.91) and left ventricular ejection fraction (LVEF) (HR 0.91, 95% CI 0.86-0.97) were independently associated with all-cause mortality in IPF patients. CHA₂DS₂-VASc score (HR 1.66, 95% CI 1.39-1.99) and LVEF (HR 0.94, 95% CI 0.90-0.98) also predicted the secondary endpoint in the same study group. CHA₂DS₂-VASc score > 4 was the optimal cut-off for predicting both outcomes. At mid-term follow-up, a CHA₂DS₂-VASc score > 4 predicts an increased risk of all-cause mortality and rehospitalizations for all causes in non-AF patients with mild-to-moderate IPF.

Drug-induced prolongation of the corrected QT interval (QTc) increases the risk for Torsades de Pointes (TdP) and sudden cardiac death. Medication effects on the QTc have been studied in controlled settings but may not be well evaluated in real-world settings where medication effects may be modulated by patient demographics and comorbidities as well as the usage of other concomitant medications.

We demonstrate a new, high-throughput method leveraging electronic health records (EHRs) and the Surescripts pharmacy database to monitor real-world QTc-prolonging medication and potential interacting effects from demographics and comorbidities.

We included all outpatient electrocardiograms (ECGs) from September 2008 to December 2019 at a large academic medical system, which were in sinus rhythm with a heart rate of 40-100 beats per minute, QRS duration of <120 milliseconds, and QTc of 300-700 milliseconds, determined using the Bazett formula. We used prescription information from the Surescripts pharmacy database and EHR medication lists to classify whether a patient was on a medication during an ECG. Negative control ECGs were obtained from patients not currently on the medication but who had been or would be on that medication within 1 year. We calculated the difference in mean QTc between ECGs of patients who are on and those who are off a medication and made comparisons to known medication TdP risks per the CredibleMeds.org database. Using linear regression analysis, we studied the interaction of patient-level demographics or comorbidities on medication-related QTc prolongation.

We analyzed the effects of 272 medications on 310,335 ECGs from 159,397 individuals. Medications associated with the greatest QTc prolongation were dofetilide (mean QTc difference 21.52, 95% CI 10.58-32.70 milliseconds), mexiletine (mean QTc difference 18.56, 95% CI 7.70-29.27 milliseconds), amiodarone (mean QTc difference 14.96, 95% CI 13.52-16.33 milliseconds), rifaximin (mean QTc difference 14.50, 95% CI 12.12-17.13 milliseconds), and sotalol (mean QTc difference 10.73, 95% CI 7.09-14.37 milliseconds). Several top QT prolonging medications such as rifaximin, lactulose, cinacalcet, and lenalidomide were not previously known but have plausible mechanistic explanations. Significant interactions were observed between demographics or comorbidities and QTc prolongation with many medications, such as coronary disease and amiodarone.

We demonstrate a new, high-throughput technique for monitoring real-world effects of QTc-prolonging medications from readily accessible clinical data. Using this approach, we confirmed known medications for QTc prolongation and identified potential new associations and demographic or comorbidity interactions that could supplement findings in curated databases. Our single-center results would benefit from additional verification in future multisite studies that incorporate larger numbers of patients and ECGs along with more precise medication adherence and comorbidity data.

The CHA2DS2-VASc score, a system which has been initially recommended for the assessment of thromboembolic risk in patients with atrial fibrillation (AF), arouses attention in the field of adverse coronary events. The purpose of this study was to explore the predictive value of preprocedural CHA2DS2-VASc score on ISR in patients after drug-eluting stent (DES) implantation.

To further investigate the relationship between CHA2DS2-VASc scores and ISR after DES, a retrospective study of DES was carried on. Additionally, the preoperative variables for the ISR and control groups were contrasted. Predictive factors were chosen using the optimal subset regression. We validate the model using internal validation. The prediction model was evaluated using the receiver operator characteristic (ROC) analysis.

We used a 3:7 ratio to create an experimental group and a validation group, and then ran a stepwise regression with the data from each of the two groups. The results showed that CHA2DS2-VASc score was an independent risk factor for ISR in both the experimental (p = 0.0139) and validation groups (p = 0.0014), and both had significant predictive value for ISR. The area of the ROC curve was greater than 0.5 in both groups (AUC = 0.78, 0.719, respectively) indicating that the model fit was good in both groups.

The CHA2DS2-VASc score is a reliable predictor of in-stent restenosis (ISR) after DES implantation.