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Aims The 4S-AF classification scheme comprises of four domains: stroke risk (St), symptoms (Sy), severity of atrial fibrillation (AF) burden (Sb), and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and compare outcomes in AF patients according to the 4S-AF-led decision-making process. Methods and results  Atrial fibrillation patients from 250 centres across 27 European countries were included. A 4S-AF score was calculated as the sum of each domain with a maximum score of 9. Of 6321 patients, 8.4% had low (St), 47.5% EHRA I (Sy), 40.5% newly diagnosed or paroxysmal AF (Sb), and 5.1% no cardiovascular risk factors or left atrial enlargement (Su). Median follow-up was 24 months. Using multivariable Cox regression analysis, independent predictors of all-cause mortality were (St) [adjusted hazard ratio (aHR) 8.21, 95% confidence interval (CI): 2.60–25.9], (Sb) (aHR 1.21, 95% CI: 1.08–1.35), and (Su) (aHR 1.27, 95% CI: 1.14–1.41). For CV mortality and any thromboembolic event, only (Su) (aHR 1.73, 95% CI: 1.45–2.06) and (Sy) (aHR 1.29, 95% CI: 1.00–1.66) were statistically significant, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Higher 4S-AF score was related to a significant increase in all-cause mortality, CV mortality, any thromboembolic event, and ischaemic stroke but not major bleeding. Treatment of all 4S-AF domains was associated with an independent decrease in all-cause mortality (aHR 0.71, 95% CI: 0.55–0.92). For each 4S-AF domain left untreated, the risk of all-cause mortality increased substantially (aHR 1.35, 95% CI: 1.16–1.56). Conclusion  Implementation of the novel 4S-AF scheme is feasible, and treatment decisions based on this scheme improve mortality rates in AF.

Background Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Acute coronary syndrome occurs when the heart muscle does not receive adequate oxygen and nutrients in a timely manner. Acute coronary syndromes are primarily due to atherosclerosis of the coronary arteries, i.e., coronary heart disease. Nitric oxide (NO) is synthesised from L-arginine in endothelial cells by the constitutive calcium-calmodulindependent enzyme, nitric oxide synthase (NOS), which mediates endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) is predominantly expressed in endothelial cells. Three NOS isoforms have been detected in different tissue: (1) neuronal NOS (nNOS) (NOS1), (2) eNOS (NOS2), and (3) inducible NOS (iNOS) (NOS3). These isoforms are encoded by three different genes. NOS3 is located on chromosome 7q35-36 and contains 26 exons. Previous studies have suggested that NOS3 polymorphisms may be associated with acute coronary syndromes. Therefore, the aim of the study was to examine the associations between NOS3 rs1799983 (894G/T) and rs2070744 (-786T/C) polymor-phisms and unstable angina. This study included 246 patients with unstable angina, as confirmed by coronary angiography. We also included 189 healthy controls who were also assessed by this technique. There were no significant differences in genotype distributions of NOS3 rs1799983 and rs2070744 polymorphisms in patients with unstable angina and healthy controls in both univariate and multivariate analyses. In patients with the NOS3 rs1799983 TT genotype, we observed a higher BMI (TT vs. GT + GG, p = 0.068), and in patients with the NOS3 rs2070744 TT genotype, we observed a higher waist circumference (TT vs. TC + CC, p = 0.023; TT vs. CC, p = 0.0053). These data suggest a lack of association between the NOS3 rs1799983 and rs2070744 polymorphisms and unstable angina in our patient population. However, these polymorphisms may be associated with some obesity parameters, rs1799983 in females and rs2070744 in males.

Background Frailty is a medical syndrome characterised by reduced physiological reserve and increased vulnerability to stressors. Data regarding the relationship between frailty and atrial fibrillation (AF) are still inconsistent. Objectives We aim to perform a comprehensive evaluation of frailty in a large European cohort of AF patients. Methods A 40-item frailty index (FI) was built according to the accumulation of deficits model in the AF patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Association of baseline characteristics, clinical management, quality of life, healthcare resources use and risk of outcomes with frailty was examined. Results Among 10,177 patients [mean age (standard deviation) 69.0 (11.4) years, 4,103 (40.3%) females], 6,066 (59.6%) were pre-frail and 2,172 (21.3%) were frail, whereas only 1,939 (19.1%) were considered robust. Baseline thromboembolic and bleeding risks were independently associated with increasing FI. Frail patients with AF were less likely to be treated with oral anticoagulants (OACs) (odds ratio 0.70, 95% confidence interval 0.55–0.89), especially with non-vitamin K antagonist OACs and managed with a rhythm control strategy, compared with robust patients. Increasing frailty was associated with a higher risk for all outcomes examined, with a non-linear exponential relationship. The use of OAC was associated with a lower risk of outcomes, except in patients with very/extremely high frailty. Conclusions In this large cohort of AF patients, there was a high burden of frailty, influencing clinical management and risk of adverse outcomes. The clinical benefit of OAC is maintained in patients with high frailty, but not in very high/extremely frail ones.

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Background:The management of patients with atrial fibrillation (AF) and malignancy is challenging given the paucity of evidence supporting their appropriate clinical management.

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