Higher CHA2DS2-VASc Research Articles

Haemorrhagic risk in elderly patients with atrial fibrillation that develop low platelet count during direct oral anticoagulant treatment: insights from the ATHERO-AF study

Abstract Background Bleeding risk in atrial fibrillation (AF) patients is complex and dynamic. Among others, thrombocytopenia has been suggested as a bleeding risk factors. No data on thrombocytopenia occurring during direct oral anticoagulants (DOACs) therapy are available. Purpose We investigated the incidence rate of thrombocytopenia and major bleeding (MB) in AF patients on DOACs. We also investigated whether the addition of incident thrombocytopenia to the HAS-BLED score might increase its predictive value compared to baseline HAS-BLED calculation. Methods 955 AF patients from the prospective ongoing ATHERO-AF study followed for a mean of 38.4±26.6 months. All patients were on DOACs. Thrombocytopenia was defined by a platelet count <150 x109/L registered during follow-up visits. MB events were defined according to ISTH definition and were recorded at each follow-up visit. Patients with thrombocytopenia at baseline were excluded. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to bleeding risk. Results Mean age was 77.3±9.0 years and 40.1% were women. During a follow-up, 139 patients developed thrombocytopenia with an incidence rate of 0.8% per year. We recorded no difference between thrombin and factor Xa inhibitors. During follow-up, 179 bleedings occurred, of which 80 were major. Patients experiencing bleedings were more likely to suffer from arterial hypertension, heart failure, anaemia and had higher CHA2DS2-VASc and HAS-BLED scores. At multivariable Cox proportional hazards regression analysis, factors associated with MB were incident thrombocytopenia (HR 1.995, 95%CI 1.211-3.288), antiplatelet use (HR 2.716 95%CI 1.269-5.816) and age (HR 1.033, 95%CI 1.003-1.064). The addition of incident thrombocytopenia to the HAS-BLED score increased the predictive value of baseline HAS-BLED in patients without thrombocytopenia for MB events (AUC from 0.54 to 0.61, p=0.016). Conclusion Incident thrombocytopenia is associated with an increased risk of MB. The addition of incident thrombocytopenia to the baseline HAS-BLED score increased its predictive value, suggesting that continuous bleeding risk evaluation of AF patients may provide additional prognostic information compared to the baseline only.

Low rates of haemorrhagic stroke, not increased by age, renal/hepatic impairment, concomitant anti-platelet use and high CHA2DS2-VASc scores, in the 4-year follow-up of ETNA-AF-Europe

Abstract Background Balancing the risks of stroke and bleeding is necessary to optimise oral anticoagulation use in clinical practice. Concerns remain over the increased bleeding risk in patients receiving NOACs, and long-term safety data in this population are limited. Purpose To report annualised rates of haemorrhagic stroke in various sub-populations of patients with atrial fibrillation (AF) treated with edoxaban during the 4-year follow-up of ETNA-AF-Europe. Methods ETNA-AF-Europe, a post-authorisation, observational study conducted across 776 sites from 10 European countries, assessed the risks and benefits of edoxaban use in patients with AF. Here, we present the annualised event rates of haemorrhagic stroke during the 4-year follow-up, that occurred overall (on-/off-edoxaban) and on-edoxaban, including sub-populations stratified by age, renal impairment, hepatic impairment, chronic concomitant antiplatelet use and CHA2DS2-VASc score. Patient characteristics were collected at baseline and annualised event rates were reported for outcomes. Results A total of 13,164 patients were included in the full analysis set. Baseline characteristics are reported in Table 1. The overall and on-edoxaban annualised haemorrhagic stroke rates were low (number of events, % [95% confidence interval]: 36, 0.1 [0.05;0.11] and 31, 0.1 [0.05;0.10] respectively). The overall haemorrhagic stroke rates remained low in subgroups stratified by age (<65 years: 4, 0.1 [0.00;0.11]; ≥65–75 years: 13, 0.1 [0.04;0.13]; ≥75 years: 19, 0.1 [0.05;0.12]), renal impairment (yes: 23, 0.1 [0.05;0.13]; no: 12, 0.1 [0.03;0.11]), hepatic impairment (yes: 0, 0.0 [0.00;0.00]; no: 35, 0.1 [0.06;0.11]), concomitant antiplatelet use (yes: 2, 0.1 [0.00;0.16]; no: 34, 0.1 [0.05;0.11]) and CHA2DS2-VASc score (low [0–1]: 0, 0.0 [0.00;0.00]; moderate [2–4]: 28, 0.1 [0.06;0.12]; high [>4]: 7, 0.1 [0.03;0.18]) (Figure). Likewise, on-edoxaban haemorrhagic stroke rates were low irrespective of age (<65 years: 3, <0.1 [0.00;0.010; ≥65–75 years: 12, 0.1 [0.04;0.13]; ≥75 years: 16, 0.1 [0.04;0.12]); renal impairment (yes: 20, 0.1 [0.05;0.12]; no: 10, 0.1 [0.02;0.10]); hepatic impairment (yes: 0, 0.0 [0.00;0.00]; no: 30, 0.1 [0.05;0.11]); chronic concomitant antiplatelet use (yes: 2, 0.1 [0.00;0.18; no: 29, 0.1[0.05;0.10]) or CHA2DS2-VASc score (low [0–1]: 0, 0.0 [0.00;0.00]; moderate [2–4]: 25, 0.1 [0.05;0.12]; High [>4]: 6, 0.1 [0.02;0.17]) (Figure). Conclusions The overall and on-edoxaban annualised rates of haemorrhagic stroke were low and were not increased by non-modifiable risk factors such as age, renal/hepatic impairment, concomitant antiplatelet use and high CHA2DS2-VASc scores during the 4-year follow-up. The overall annualised rates on-edoxaban in ETNA-AF-Europe registry are quite comparable with incidence rates reported in the literature in age-stratified populations (incidence/100 person-years: 55-64 years: 0.06 [0.04-0.07]; 65-74 years: 0.1 [0.09-0.1]; 75-84 years 0.2 [0.1-0.2]).Baseline Characteristics

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

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

Incident thrombocytopenia and bleeding risk in elderly patients with atrial fibrillation on direct oral anticoagulants: insights from the ATHEROsclerosis in Atrial Fibrillation study

BackgroundThe bleeding risk of patients with atrial fibrillation (AF) changes over time. Most studies thus far evaluated only the baseline bleeding risk with discordant results. The impact of incident thrombocytopenia during direct oral anticoagulant (DOAC) therapy and its relation to bleeding has not been previously investigated. ObjectivesTo investigate the incidence rate of thrombocytopenia and major bleeding (MB) risk in AF patients on DOACs. MethodsProspective ongoing ATHEROsclerosis in Atrial Fibrillation study including patients with nonvalvular AF on DOACs. Incident thrombocytopenia was defined as a platelet count <150 × 109/L. MB events were recorded at each follow-up visit. Gray estimator for competing risk data was used. Estimates are expressed in terms of subdistributional hazard ratios (sHR) and relative 95% CI for MB. ResultsWe enrolled 957 AF patients treated with DOACs (mean age, 77.3 ± 9.0 years; 49.1% women). During a follow-up (median time to censoring 1330 days; 95% CI, 1246-1443), 139 patients developed thrombocytopenia (3.08 per 100 person-years; 95% CI, 2.27-3.89) with no difference between direct thrombin and factor Xa inhibitors. Overall, 179 bleedings occurred, of which 80 were major (3.17 per 100 person-years; 95% CI, 2.34-3.99). Patients sustaining bleedings were more frequently affected by arterial hypertension, heart failure, anemia and had higher CHA2DS2-VASc and HAS-BLED scores. On multivariable Cox analysis, independent risk factors for MB were incident thrombocytopenia (sHR, 12.77; 95% CI, 8.880-18.360; P < .001), and age (sHR, 1.030 per year; 95% CI, 1.010-1.040; P = .002). ConclusionPatients developing thrombocytopenia have an increased risk of MB. Dynamic evaluation of platelet count during follow-up may provide better prognostic value than baseline assessment only.

Clinical profile and outcomes in very elderly patients with atrial fibrillation anticoagulated with rivaroxaban: data from the EMIR study.

To analyze the clinical profile, adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation (AF), taking rivaroxaban in clinical practice. Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before being included. Data were analyzed according to age (≥ 80 vs. < 80 years) at baseline. Out of 1433 patients, 453 (31.6%) were octogenarians at baseline. Compared to younger patients, octogenarians had more comorbidities, higher CHA2DS2-VASc (4.5 ± 1.3 vs. 3.0 ± 1.4; P < 0.001) and HAS-BLED scores (2.0 ± 1.0 vs. 1.4 ± 1.0; P < 0.001). Overall, the dose of rivaroxaban was adequately prescribed in 83.4% of patients, but more frequently in the younger population (71.1% vs. 89.1%; P = 0.039). After a mean follow-up of 2.2 ± 0.6 years, annual rates of stroke + systemic embolism + transient ischemic attack, MACE, cardiovascular death and major bleeding were 1.03%, 1.24%, 1.03% and 1.75%, respectively, in octogenarian patients. Except for progressive heart failure death and major bleeding, rates of outcomes in octogenarians were similar compared to younger patients. In octogenarians, the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke, whereas previous coronary revascularization and heart failure with MACE, and higher HAS-BLED score with major bleeding. In clinical practice, around one third of patients taking rivaroxaban are octogenarians. These patients have many comorbidities and a high thromboembolic risk. Despite that, rates of adverse events remain low. Rivaroxaban is adequately prescribed in the majority of octogenarians.

Assessing adherence to treatment guidelines and complications among atrial fibrillation patients in the United Arab Emirates.

Atrial fibrillation (AF), a potential trigger for stroke development, is considered a modifiable condition that can halt complications, decrease mortality, and prevent morbidity. The CHA₂DS₂-VASc and HAS-BLED scores are categorized as risk assessment tools used to estimate the risk of thrombosis development and assess major bleeding among atrial fibrillation patients. Our study aims to assess the adherence to post-discharge treatment recommendations according to CHA₂DS₂-VASc score risk group and evaluate the impact of CHA₂DS₂-VASc score and HAS-BLED score risk categories on death, length of hospital stay, complications, and hospital readmission among United Arab Emirates (UAE) patients. This was a multicenter retrospective study conducted from November 2022 to April 2023 in the United Arab Emirates. Medical charts for AF patients were assessed for possible enrolment in the study. A total number of 400 patients were included with a mean age of 55 (±14.5) years. The majority were females (67.8%), and most had high CHA₂DS₂-VASc and HAS-BLED scores (60% and 57.3%, respectively). Our study showed that adherence to treatment recommendations upon discharge was 71.8%. The bivariate analysis showed that patients with a high CHA₂DS₂-VASc score had a significantly higher risk of death (p-value of 0.001), hospital readmission (p-value of 0.007), and complications (p-value of 0.044) vs. the low and moderate risk group with a p-value of <0.05. Furthermore, our findings showed that the risk of death (0.001), complications (0.057), and mean hospital stay (0.003) were significantly higher in the high HAS-BLED risk score compared to both the low- and moderate-risk categories. Hospital stay was significantly higher in CHA₂DS₂-VASc and HAS-BLED high-risk score categories compared to the low-risk score category with a p-value of <0.001. Our study concluded that the adherence to treatment guidelines in atrial fibrillation patients was high and showed that patients received the most effective and patient-centered treatment. In addition, our study concluded that the risk of complications and mortality was higher in high-risk category patients.

Oral anticoagulant treatment in atrial fibrillation: the AFIRMA real-world study using natural language processing and machine learning

IntroductionOral anticoagulation (OAC) is key in atrial fibrillation (AF) thromboprophylaxis, but Spain lacks substantial real-world evidence. We aimed to analyze the prevalence, clinical characteristics, and treatment patterns among patients with AF undertaking OAC, using natural language processing (NLP) and machine learning (ML). Materials and methodsThis retrospective study included AF patients on OAC from 15 Spanish hospitals (2014–2020). Using EHRead® (including NLP and ML), and SNOMED_CT, we extracted and analyzed patient demographics, comorbidities, and OAC treatment from electronic health records. AF prevalence was estimated, and a descriptive analysis was conducted. ResultsAmong 4,664,224 patients in our cohort, AF prevalence ranged from 1.9% to 2.9%. A total of 57,190 patients on OAC therapy were included, 80.7% receiving Vitamin K antagonists (VKA) and 19.3% Direct-acting OAC (DOAC). The median age was 78 and 76 years respectively, with males constituting 53% of the cohort. Comorbidities like hypertension (76.3%), diabetes (48.0%), heart failure (42.2%), and renal disease (18.7%) were common, and more frequent in VKA users. Over 50% had a high CHA2DS2-VASc score. The most frequent treatment switch was from DOAC to acenocoumarol (58.6% to 70.2%). In switches from VKA to DOAC, apixaban was the most chosen (35.2%). ConclusionsUtilizing NLP and ML to extract RWD, we established the most comprehensive Spanish cohort of AF patients with OAC to date. Analysis revealed a high AF prevalence, patient complexity, and a marked VKA preference over DOAC. Importantly, in VKA to DOAC transitions, apixaban was the favored option.

Phenotypes and outcomes in patients with atrial fibrillation: a global unsupervised cluster analysis from Phase II/III of the GLORIA-AF registry

Abstract Background Atrial fibrillation (AF) patients are characterized by a great clinical heterogeneity and complexity across the world. Usual classifications may not adequately characterize this population. Data-driven cluster analysis reveals different possible classifications of patients. Purpose To identify different clusters of AF patients who share similar clinical phenotypes and evaluate the association between identified clusters and clinical outcomes using cluster analysis. Methods An agglomerative hierarchical cluster analysis was performed in patients from phase II/III of the GLORIA-AF registry. Associations between clusters and a composite outcome composed of all-cause death, stroke and major bleeding were evaluated using Cox regression analyses. Results The study included 26,045 AF patients (mean±SD age 70.1±10; 44.8% female) with a median [IQR] follow-up of 3 years [2.3-3.1]. Five clusters were identified: Cluster 1 was composed of young males from North America with morbid obesity and cardiovascular (CV) risk factors; Cluster 2 included older Asian patients with lower body mass index (BMI), fewer CV risk factors, lower anticoagulation rate but the highest AF ablation rate; Cluster 3 identified European males with CV comorbidities and behavioral disorders (smoking, alcohol abuse); Cluster 4 was characterized by patients with the highest rate of permanent AF, cancer, anticoagulant therapy prescription ; Cluster 5 included older women from Europe with high CHA2DS2-VASc and HAS-BLED scores, the highest heart rate, lower BMI and high rate of previous stroke and transient ischemic attack. The incidence of the composite outcome increased a stepwise fashion among clusters from 3.2% patient-years (95% confidence interval (CI): 2.4-4.1) for Cluster 1 to 6% patient-years (95% CI: 5.6-6.4) for Cluster 5 (p&amp;lt;0.0001): Cluster 1 versus 2 hazard ratio (HR): 0.85 (95% CI 0.65–1.11); 2 versus 3 HR: 0.84 (95% CI 0.76–0.93); 3 versus 4 HR: 0.9 (95% CI 0.82–0.99) and 4 versus 5 HR: 0.82 (95% CI 0.74–0.91). Conclusion Cluster analysis identified five statistically-driven groups of AF patients, with distinct phenotype characteristics and associated with different risks for major clinical adverse events.Baseline characteristics.Dendrogram and Kaplan Meier-curves.

BETWEEN SCYLLA AND CHARYBDIS: MULTIPLE LEFT ATRIAL THROMBI DESPITE ORAL ANTICOAGULATION AND ANTIPLATELET THERAPY IN A PATIENT CANDIDATE FOR LEFT ATRIAL APPENDAGE OCCLUSION

Abstract Introduction Left atrial (LA) thrombosis usually occurs in patients affected by atrial fibrillation (AF), generally involving the left atrial appendage (LAA). We present the unexpected echocardiographic finding of multiple LA thrombi despite an adequate antithrombotic strategy. Case Presentation A 76–year–old lady underwent transesophageal echocardiographic examination (TOE) to assess eligibility for percutaneous LAA occlusion (LAAO) procedure due to high bleeding risk. Her medical history included AF and a recent percutaneous coronary revascularization; therefore, her antithrombotic therapy included apixaban 2.5 mg bid and clopidogrel 75 mg od. The TOE showed LA structural and functional remodeling with spontaneous echo contrast and multiple thrombi involving the LAA (one [12 x 9 mm] overflowing the orifice and attached to the Coumadin Ridge and the second [12 x 7 mm] attached and arising from the tunnel of patent foramen ovale). Mitral valve stenosis was excluded (Fig.1). Due to TOE findings, the patient was not considered eligible for percutaneous LAAO. Due to the concomitant very high thromboembolic risk, despite the previous intracranial bleeding, we decided to stop apixaban and to start parenteral anticoagulation for 3 weeks with low–molecular weight heparin (100 UI/kg bid) followed by the switch to a vitamin k antagonist (VKA). We also prescribed a hematological evaluation to exclude a hypercoagulability disorder. Our patient’s daughter was a carrier of a mutation in both the methylenetetrahydrofolatereductase and Thrombin genes. A TOE after 30 days showed the persistence of LA thrombi, although with significantly reduced size and mobility (Fig.2). The follow–up was clinically uneventful. We suggested to continue anticoagulation therapy with VKA, and we planned a new TOE after 4 weeks. Discussion Although proper anticoagulation decreases cardioembolic risk in patients with AF, atrial thrombosis may occur due to LA remodeling, high CHA2DS2–VASc score and other factors, including hypercoagulability disorders. The presence of multiple LA thrombi represents a challenge for clinicians, especially in case of concomitant high thromboembolic and bleeding risk. However, the best treatment strategies for these extreme conditions are not defined, so far. Therefore, the therapeutic choice is often tailored to the single patient and based on the clinical judgment, bearing in mind that avoiding Charybdis means passing to close to Scylla and vice versa.

Scalable Approach to Consumer Wearable Postmarket Surveillance: Development and Validation Study.

With the capability to render prediagnoses, consumer wearables have the potential to affect subsequent diagnoses and the level of care in the health care delivery setting. Despite this, postmarket surveillance of consumer wearables has been hindered by the lack of codified terms in electronic health records (EHRs) to capture wearable use. We sought to develop a weak supervision-based approach to demonstrate the feasibility and efficacy of EHR-based postmarket surveillance on consumer wearables that render atrial fibrillation (AF) prediagnoses. We applied data programming, where labeling heuristics are expressed as code-based labeling functions, to detect incidents of AF prediagnoses. A labeler model was then derived from the predictions of the labeling functions using the Snorkel framework. The labeler model was applied to clinical notes to probabilistically label them, and the labeled notes were then used as a training set to fine-tune a classifier called Clinical-Longformer. The resulting classifier identified patients with an AF prediagnosis. A retrospective cohort study was conducted, where the baseline characteristics and subsequent care patterns of patients identified by the classifier were compared against those who did not receive a prediagnosis. The labeler model derived from the labeling functions showed high accuracy (0.92; F1-score=0.77) on the training set. The classifier trained on the probabilistically labeled notes accurately identified patients with an AF prediagnosis (0.95; F1-score=0.83). The cohort study conducted using the constructed system carried enough statistical power to verify the key findings of the Apple Heart Study, which enrolled a much larger number of participants, where patients who received a prediagnosis tended to be older, male, and White with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, sex category) scores (P<.001). We also made a novel discovery that patients with a prediagnosis were more likely to use anticoagulants (525/1037, 50.63% vs 5936/16,560, 35.85%) and have an eventual AF diagnosis (305/1037, 29.41% vs 262/16,560, 1.58%). At the index diagnosis, the existence of a prediagnosis did not distinguish patients based on clinical characteristics, but did correlate with anticoagulant prescription (P=.004 for apixaban and P=.01 for rivaroxaban). Our work establishes the feasibility and efficacy of an EHR-based surveillance system for consumer wearables that render AF prediagnoses. Further work is necessary to generalize these findings for patient populations at other sites.

Incidence and Predictors of Worsening Renal Function in Edoxaban-Treated Atrial Fibrillation Patients Within ETNA-AF-Europe Registry

BackgroundManaging patients with atrial fibrillation (AF) and worsening renal function (WRF) remains a clinical challenge due to the need of dose adjustment of non-vitamin K antagonist oral anticoagulants. ObjectivesTo determine the incidence of WRF in patients with AF treated with edoxaban, the association of WRF with clinical outcomes, and predictors of WRF and clinical outcomes in these patients. MethodsThis is a subanalysis of the Edoxaban Treatment in routiNe clinical prActice for patients with non-valvular Atrial Fibrillation in Europe study (NCT02944019), an observational study of edoxaban-treated patients with AF. WRF was defined as a ≥25% reduction in creatinine clearance between baseline and 2 years. ResultsOf the 9,054 patients included (69% of the total 13,133 enrolled), most did not experience WRF (90.3%) during the first 2 years of follow-up. WRF occurred in 9.7% of patients. Patients with WRF had significantly higher rates of all-cause death (3.88%/y vs 1.88%/y; P < 0.0001), cardiovascular death (2.09%/y vs 0.92%/y; P < 0.0001), and major bleeding (1.51%/y vs 0.98%/y; P = 0.0463) compared with those without WRF. Rates of intracranial hemorrhage (0.18%/y vs 0.18%/y) and of any stroke/systemic embolic events were low (0.90%/y vs 0.69%/y; P = 0.3161) in both subgroups. The strongest predictors of WRF were a high CHA2DS2-VASc score, high baseline creatinine clearance, low body weight, and older age. Most predictors of WRF were also predictors of clinical outcomes. ConclusionsWRF occurred in approximately 10% of edoxaban-treated AF patients. Rates of death and major bleeding were significantly higher in patients with WRF than without. Stroke events were low in both subgroups.

Unveiling the Hidden Stroke Threat in Patients With Atrial Fibrillation and Primary Hyperparathyroidism

Recent American College of Cardiology (ACC), American Heart Association (AHA), American College of Clinical Pharmacy (ACCP), and Heart Rhythm Society (HRS) guidelines suggest that patients with atrial fibrillation (AF) at intermediate to low annual risk of ischemic stroke can benefit from consideration of factors that might modify their risk of stroke. The role of nontraditional risk factors, such as primary hyperparathyroidism (PHPT), remains unexplored. In our study, we investigated the potential association between PHPT and the risk of ischemic stroke in patients with AF. Using data from the Nationwide Inpatient Sample Database, a retrospective cohort study focused on the adult population with AF, we stratified the participants based on PHPT presence. Demographic information, co-morbidities, and hospitalization details were extracted using International Classification of Diseases, Tenth revision codes. Propensity score matching was applied, encompassing over 20 confounding variables, including the risk factors outlined in the CHA2DS2-VASc (Congestive heart failure (C), Hypertension (H), Age ≥75 years (A₂), Diabetes Mellitus (D), Stroke/Transient Ischemic Attack (TIA)/Thromboembolism (S₂), Vascular disease (V), Age 65-74 years (A), Sex category [female] (Sc)) score. Multivariate logistic regression analysis was performed after matching to assess the independent impact of PHPT as an ischemic stroke risk factor. A total of 2,051 of the identified 395,249 patients with AF had PHPT. The PHPT group had an average age of 74 years and consisted of more women (66.1% vs 53.0%). After matching, it was observed that the PHPT group had longer hospital stays (5 vs 4 days) and higher hospitalization charges ($45,126 vs $36,644). This group exhibited higher rates of ischemic stroke (6.0% vs 4.4%) and mortality (6.3% vs 4.9%). The adjusted outcomes showed a 1.4-fold increased risk for ischemic stroke and a 1.32-fold increased risk for mortality in the PHPT cohort. The subgroup analysis showed a higher incidence of mortality in men with a high CHA2DS2-VASc score. In conclusion, this study highlights a marked association between PHPT and ischemic stroke in patients with AF, independent of the conventional CHA2DS2-VASc score. The potential mechanisms implicated include vascular changes, cardiac dysfunction, and coagulation cascade alterations. The presence of PHPT should be taken into consideration when deciding the assessment of thromboembolic risk.

The CHA2DS2-Vasc Score's Role as A Standalone Predictor for Suboptimal Reperfusion and Short-Term Mortality Post Primary PCI in Individuals Diagnosed with Acute ST-Segment Elevation Myocardial Infarction

Background: The CHA2DS2-VASc score is an established clinical prediction tool for assessing stroke risk in patients with atrial fibrillation. However, its potential utility in predicting outcomes following primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) has not been extensively explored. The no-reflow phenomenon and in-hospital mortality are critical endpoints in the management of STEMI patients undergoing PCI. Objective: This study aimed to evaluate the independent predictive value of the CHA2DS2-VASc score for suboptimal reperfusion and short-term mortality in patients with acute STEMI undergoing primary PCI. Methods: In a prospective cohort study involving 116 patients with confirmed STEMI at the National Institute of Cardiovascular Diseases in Karachi, participants were categorized based on their CHA2DS2-VASc score into low (&lt;3) and high (≥3) risk groups. Primary PCI was performed following standard treatment protocols, and variables such as initial TIMI flow, thrombus grade, and lesion complexity were documented. Statistical analysis, including multivariate regression, was conducted using SPSS Version 25. Results: Patients with a high CHA2DS2-VASc score (≥3) exhibited a significantly increased risk of no-reflow (p-value range 0.00-0.03) and in-hospital mortality (11.1%) compared to those with a low score (&lt;3; 1.3% mortality). Other significant findings included an association between high CHA2DS2-VASc scores and larger stent lengths (28.75±5.67 mm), smaller stent diameters (2.69±0.6 mm), higher creatinine levels (1.00±0.202 mg/dL), and increased incidence of diabetes mellitus (36.1%). The odds ratio for mortality associated with a high CHA2DS2-VASc score was 1.58 (95% CI: 1.14–2.13, p-value &lt; 0.00). Conclusion: The CHA2DS2-VASc score is a significant independent predictor of both no-reflow post-PCI and short-term in-hospital mortality in STEMI patients. These findings suggest the score's potential role in the pre-PCI risk stratification, which could guide clinical decision-making and potentially improve patient outcomes.

Abstract 138: Cost-Effectiveness of Insertable Cardiac Monitors to Identify Atrial Fibrillation After Stroke Attributed to Large-Artery or Small-Vessel Disease

Introduction: Identification of atrial fibrillation (AF) in patients with stroke is critical for secondary stroke prevention with guideline-recommended oral anticoagulation (OAC). The randomized STROKE AF trial evaluating patients with ischemic stroke attributed to large-artery or small-vessel disease (LAD/SVD) found that insertable cardiac monitors (ICMs) were more likely to detect AF than standard of care (SoC) using intermittent external ECG monitors. However, the cost-effectiveness of ICMs in this population is not known. This study aimed to evaluate the cost-effectiveness of ICMs to detect new AF in patients with LAD/SVD stroke in the U.S. Methods: Using patient data from STROKE AF (N=492, median CHA 2 DS 2 -VASc=5.0), a lifetime Markov model was developed to assess the cost-effectiveness of ICM vs. SoC from a payer perspective. SoC was based on the frequency of ECG/Holter monitoring observed in the trial. AF detection was assumed to result in a switch from aspirin to OAC, unless precluded by prior bleeds. Lifetime risks of stroke and bleeding events were based on underlying presence of AF and the safety and efficacy of the treatment received. Future costs/effects were discounted at 3% annually to adjust to present values. Sensitivity analyses were conducted to assess uncertainty. Results: ICM was associated with a gain of 0.17 quality-adjusted life years (QALYs) versus SoC (6.63 vs. 6.46), driven by higher incidence of OAC and consequent reduction in lifetime ischemic strokes, with 53 fewer strokes projected per 1,000 patients. Total lifetime per-patient costs were $65,989 and $59,703 in the ICM and SoC arms, respectively. The incremental cost-effectiveness ratio was $37,760 per QALY gained compared to SoC (under the $50,000/QALY threshold considered highly cost-effective in the U.S.). Cost-effectiveness improved further in the subset with CHA 2 DS 2 -VASc≥6. In the patients at highest risk of AF detection (left atrial enlargement, heart failure, obesity, or prolonged QRS), the cost/QALY was $22,016. Conclusions: ICMs are likely to be cost-effective in the U.S. for the diagnosis of AF in the population with stroke attributed to LVD or SVD. This strategy was most cost-effective in patients with high CHA 2 DS 2 -VASc scores and those at greatest risk of AF.

Wearable dynamic electrocardiogram monitor-based screening for atrial fibrillation in the community-dwelling elderly population

BackgroundAtrial fibrillation (AF) is a major public health problem with high rates of morbidity, disability and mortality, especially in the elderly population. This study explored the diagnosis and treatment status of AF in adults aged ≥65 years in the community through wearable dynamic electrocardiogram (ECG) monitoring. MethodsWe conducted a cross-sectional study in 4 random communities within the Qingpu district of Shanghai, China. Between January 1, 2020 and June 30, 2022, the ECGs of 3852 adults aged 65 years or older were examined through wearable dynamic ECG monitoring. Data from 3839 participants were ultimately analyzed. Multivariate logistic regression was used to determine the independent predictors of AF. ResultsWearable dynamic ECG monitoring detected AF in 360 elderly people, 78 of whom were diagnosed with AF for the first time. Multivariate logistic regression analysis revealed that snoring, renal dysfunction, coronary heart disease and high CHA2DS2-VASc score were independent risk factors for AF. Among patients with unknown AF, 68 (87.20 %) met the criteria for anticoagulant therapy based on the CHA2DS2-VASc score. Only 4 (5.88 %) patients were taking anticoagulants. Of the patients with a clear history of AF, 249 (84.98 %) needed an anticoagulant strategy, but only 18 (7.23 %) took oral anticoagulants. ConclusionMany elderly people have silent AF, and wearable dynamic ECG monitoring can be used to screen for AF effectively.

Abstract WMP102: Risk Factors for MACE and Major Bleeding in Patients With Atrial Fibrillation Undergoing Elective Surgery: Insights From the BRIDGE Randomized Trial

Introduction: Atrial fibrillation (AF) patients undergoing elective procedures are at risk for Major Adverse Cardiovascular Events (MACE) and major bleeding. This study aimed to identify risk factors to guide risk stratification and perioperative management. Methods: We performed a post-hoc analysis of the BRIDGE randomized trial. Patients who were randomized into the study with outcome follow-ups were included in the analysis. The primary outcome was MACE (stroke, myocardial infarction, and cardiovascular death) and clinically symptomatic major bleeding. Statistical techniques included standard univariate analysis, logistic stepwise regression, and Cox regression models with Schoenfeld residual test to validate proportional hazard assumption. Additional interaction analyses were performed to assess interactions between low-molecular-weight heparin bridge therapy with identified risk factors. Results: A total of 1,813 participants met inclusion criteria: mean age 71.6±8.8, 73.3% male. MACE occurred in 25 (1.4%) individuals, with pre-procedure clopidogrel use (adjusted hazard ratio [aHR] 7.73, 95% CI 2.63-22.72, p&lt;0.001) and high CHA 2 DS 2 -VASc score (≥ 5; aHR 2.89, 95% CI 1.26-6.63, p=0.012) identified as risk factors. Major bleeding occurred in 41 (2.3%) individuals, with bridge therapy (aHR 2.53, 95% CI 1.29-4.96, p=0.007), history of renal disease (aHR 3.12, 95% CI 1.56-6.24, p=0.001), post-procedure aspirin use (aHR 3.02, 95% CI 1.61-5.68, p=0.001), post-procedure NSAID use (aHR 3.90, 95% CI 1.20-12.70, p=0.024), and major surgery (aHR 2.17, 95% CI 1.05-4.46, p=0.036) identified as risk factors. The interactions between above risk factors and bridge therapy for MACE and major bleeding outcomes were not significant (p&gt;0.05). Conclusion: The importance of perioperative assessment in AF patients is underscored by our findings, which identify distinct predictors for MACE and major bleeding. Guided by these insights, clinicians may generally avoid bridging and concomitant post-operative aspirin and NSAID use, thereby optimizing perioperative management to minimize the risk of adverse outcomes.

Embolic stroke of undetermined source - ESUS: a new challenge for the cardiologist

Embolic stroke of undetermined source (ESUS) is a new clinical entity which requires an accurate diagnostic work-up. The involvement of the cardiologist in this challenge is of paramount importance as in many cases an occult cardioembolic source is detectable. In the absence of subclinical atrial fibrillation detectable by prolonged ECG monitoring, potential causes of ESUS include atrial cardiomyopathy, left ventricular dysfunction or heart failure, aortic plaques and patent foramen ovale. The assessment of a causal relationship between these cardiac abnormalities and ESUS is often a difficult challenge and the randomized clinical trials performed so far failed to demonstrate a superiority of direct oral anticoagulants (DOAC) over aspirin. In selected individual patients with heart failure in sinus rhythm with high CHA2DS2-VASc score, or aortic plaques with thrombotic component, oral anticoagulation with DOAC might be considered even in the absence of evidence from randomized clinical trials.

Right atrial wall inflammation detected by 18F-FDG PET/CT may be significantly associated with persistent atrial fibrillation: a prospective case-control study

AimAtrial fibrillation (AF) is a progressive disease from paroxysmal to persistent, and persistent AF (PerAF) had worse prognosis. AF has potential link with inflammation, but it is not clear whether PerAF or paroxysmal AF (ParAF) is more closely related to inflammation. On the basis of inhibiting myocardial physiological uptake, 18F-fluorodeoxyglucosepositron emission tomography/computed tomography (18F-FDG PET/CT) is an established imaging modality to detect cardiac inflammation. We aimed to decipher the association between AF and atrial inflammatory activity by 18F-FDG PET/CT.MethodsThirty-five PerAF patients were compared to age and sex matched ParAF group with baseline 18F-FDG PET/CT scans prior to radiofrequency catheter ablation (RFCA) in the prospective case-control study. High-fat and low-carbohydrate diet and prolonged fast (HFLC+Fast) was applied to all AF patients before PET/CT. Then 22 AF patients with positive right atrial (RA) wall FDG uptake (HFLC+Fast) were randomly selected and underwent HFLC+Fast+heparin the next day. The CHA2DS2-VASc score was calculated to evaluate the risk of stroke. Clinical data, ECG, echocardiography, and atrial 18F-FDG uptake were compared.ResultsPerAF patients had significantly higher probability of RA wall positive FDG uptake and higher SUVmax than ParAF group [91.4% VS. 28.6%, P < 0.001; SUVmax: 4.10(3.20–4.90) VS. 2.60(2.40–3.10), P < 0.001]. Multivariate logistic regression analyses demonstrated that RA wall SUVmax was the independent influencing factor of PerAF (OR = 1.80, 95%CI 1.02–3.18, P = 0.04). In 22 AF patients with RA wall positive FDG uptake (HFLC+Fast), the “HFLC+Fast+Heparin” method did not significantly change RA wall FDG uptake evaluated by either quantitative analysis or visual analysis. High CHA2DS2-VASc score group had higher RA wall 18F-FDG uptake [3.35 (2.70, 4.50) vs, 2.8 (2.4, 3.1) P = 0.01].ConclusionsRA wall FDG positive uptake was present mainly in PerAF. A higher RA wall 18F-FDG uptake was an independent influencing factor of PerAF. RA wall FDG uptake based on 18F-FDG PET/CT may indicate pathological inflammation.Trial registrationhttp://www.chictr.org.cn, ChiCTR2000038288.

Patients with AF and dementia are undertreated for their AF and cardiovascular comorbidities: results from the GARFIELD-AF registry

Abstract Background Oral anticoagulation (OAC) is key in preventing stroke in patients with atrial fibrillation (AF). However, patients with AF and dementia pose practical therapeutic challenges, such as compliance and haemorrhagic complications, resulting in possible underuse of cardiovascular (CV) treatment. Purpose The aim of this study is two-fold: a) to determine whether AF patients with dementia are undertreated for stroke prevention with OAC and for their CV comorbidities and b) to assess the risks and benefits of OAC in AF patients with dementia. Methods Analyses were conducted in newly diagnosed AF patients enrolled in GARFIELD-AF, the largest multinational prospective AF registry. Medical history of dementia was recorded at enrolment. Guideline-directed medical therapy (GDMT), defined according to ESC guidelines, was explored for coronary artery disease (CAD), diabetes, heart failure (HF), hypertension, and peripheral vascular disease (PVD). Propensity score weighting was applied to obtain estimates of OAC effect on all-cause mortality and stroke within two-year follow-up. Major bleeding occurrence is simply reported due to the low number of events. Results The study comprised 764 (1.5%) AF patients with dementia and 50,966 (98.5%) without dementia. Patients with dementia were more often female (58% vs 44%), older (median age 82 vs 71) and had higher prevalence of comorbidities, resulting in higher CHA2DS2-VASc (excl. sex; median 5.0 vs 3.0) and HAS-BLED score (median 2.0 vs 1.0) compared to patients without dementia. The proportion anticoagulated was lower among those with dementia (60% vs 70%), with fewer patients receiving VKA (27% vs 42%) (Fig. 1). Despite the increase in NOAC use among patients with dementia (17% in 2010-2013 vs 48% in 2015-2016), 35% remained non-anticoagulated in 2015-2016. Appropriate GDMT was lower among patients with dementia for the five considered comorbidities combined (35% vs 45%), with substantial differences observed for HF (35% vs 50%), CAD (27% vs 39%) and PVD (36% vs 48%) compared to patients without dementia. In patients with dementia, OAC usage was associated with lower all-cause mortality (HR 0.69; 95% CI 0.48-1.00). In contrast to patients without dementia, no evidence of a stroke risk reduction with OAC was observed among patients with dementia (HR 1.10; 95% CI 0.50-2.43) (Fig. 2). This finding might be explained by the higher proportion of patients with dementia receiving a reduced NOAC dose (73% vs 39% of NOAC receivers) and their lower VKA quality control (37% vs 46%, defined as time in therapeutic range &amp;gt;65%). Seven (1.6%) and eight (2.7%) major bleeding events occurred among patients with dementia who were on or not on OAC, respectively. Conclusions Despite their high risk of stroke, patients with AF and dementia are often undertreated for their AF and CV comorbidities. Our results support the use of OAC and should help inform treatment decisions in this vulnerable population.

Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF.

Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs. Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF). We evaluated 1890 patients with AF receiving DOACs (apixaban 55%, dabigatran 7%, and rivaroxaban 38%). Inappropriate dosing was noted in 18% of the population. Patients with appropriate dosing had less comorbidities: younger age (75 ± 10 vs. 82 ± 8 years old, P < 0.0001), reduced chronic renal failure (26 vs. 61%, P < 0.0001), and lower CHA2DS2VASc and HASBLED scores (3 ± 2 vs. 4 ± 3, P < 0.0001; 2 ±1 vs. 2 ± 2, P < 0.0001), respectively. In multivariate analysis, older age (P < 0.0001) and a higher CHA2DS2VASc score (P = 0.0056) were independently associated with inappropriate DOAC dosing. Among 472 patients (27%) treated with low-dose rivaroxaban or apixaban, 46% were inappropriately underdosed. Patients inappropriately underdosed were younger (82.3 ± 8.4 vs. 85.9 ± 5.9 years, P < 0.0001) with less chronic renal disease (47 vs. 98%, P < 0.0001). However, these patients had higher rates of prior haemorrhagic events (18 vs. 10%, P = 0.01), clopidogrel use (11 vs. 3%, P = 0.0002), and apixaban prescription (74 vs. 50%, P < 0.0001). Within this large registry, DOACs were associated with inappropriate dosing in 18% of cases. Independent predictors of inappropriate dosing were high CHA2DS2VASc scores and older age. Moreover, 46% of patients treated with low-dose DOACs were inappropriately underdosed and more frequently in patients treated with apixaban.