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Background: The 4S‐AF classification scheme comprises of four domains (stroke risk [St], symptoms [Sy], severity of atrial fibrillation (AF) burden [Sb] and substrate [Su]), which has been recommended in the 2020 ESC guidelines to characterize and evaluate patients with AF. Objectives: We aimed to determine whether the 4S‐AF scheme would be useful for AF characterization and provides prognostic information in a large contemporary prospective Asian registry conducted by the Asia Pacific Heart Rhythm Society (APHRS). Methods: Among 4666 patients enrolled in APHRS registry, 3586 of them whose data about left atrial (LA) dimension and European Heart Rhythm Association (EHRA) symptom score were available have constituted as the study population. The 4S‐AF score was calculated as the sum of each domain with a maximum score of 9. The clinical endpoint was defined as the 1‐year composite risk of any thromboembolic event, ischaemic stroke, heart failure, acute coronary syndrome, significant coronary artery disease requiring coronary intervention and all‐cause mortality. Results: Based on the 4S‐AF domains, 86.7% were 'non‐low risk' for stroke; 94.3% had EHRA Class I‐II, 48.5% were newly diagnosed or paroxysmal AF; and only 8.4% had no cardiovascular risk factors or LA enlargement. The risk of clinical events was higher in patients who were 'non‐low risk' for stroke (aOR 2.175, 95% CI 1.060–4.461), with permanent AF (aOR 1.579, 95% CI 1.106–2.225) and increasing points for substrate (aORs 2.376–4.968 from score 2 to 4). When compared to the first tertile of 4S‐AF score (0–3 points), patients in the second tertile (4–5 points) had approximately 2.5‐fold increase in adverse events (OR 2.478, 95% CI 1.678–3.661, p <.001), while those in the third tertile (6–9 points), had a 3.5‐fold increase (OR 3.484, 95% CI 2.322–5.226, p <.001), both without significant differences between the 5 participating countries (p for interaction >.05). If all 4S‐AF domains were appropriately treated, this was associated with a lower risk of composite clinical outcomes (aOR 0.384, p <.001; p for interaction for different countries =.234). Conclusions: Categorization according to the 4S‐AF scheme can be related to the risk of the composite adverse event rate in Asian AF patients, and appropriate treatments based on the 4S‐AF scheme resulted in better clinical outcomes. These observations support the characterization and management according to the 4S‐AF scheme in Asian patients. [ABSTRACT FROM AUTHOR]

Background: Ceramide is involved in regulating metabolism and energy expenditure, and its abnormal myocardial accumulation may contribute to heart injury or lipotoxic cardiomyopathy. Whether ceramide can modulate the electrophysiology of pulmonary veins (PVs) remains unknown. Materials and methods: We used conventional microelectrodes to measure the electrical activity of isolated rabbit PV tissue preparations before and after treatment with various concentrations of ceramide with or without H2O2 (2 mM), MitoQ, wortmannin or 740 YP. A whole‐cell patch clamp and fluorescence imaging were used to record the ionic currents, calcium (Ca2+) transients, and intracellular reactive oxygen species (ROS) and sodium (Na+) in isolated single PV cardiomyocytes before and after ceramide (1 μM) treatment. Results: Ceramide (0.1, 0.3, 1 and 3 μM) reduced the beating rate of PV tissues. Furthermore, ceramide (1 μM) suppressed the 2 mM H2O2‐induced faster PV beating rate, triggered activities and burst firings, which were further reduced by MitoQ. In the presence of wortmannin, ceramide did not change the PV beating rate. The H2O2‐induced faster PV beating rate could be counteracted by MitoQ or wortmannin with no additive effect from the ceramide. Ceramide inhibited pPI3K. Ceramide reduced Ca2+ transients, sarcoplasmic reticulum Ca2+ contents, L‐type Ca2+ currents, Na+ currents, late Na+ currents, Na+‐hydrogen exchange currents, and intracellular ROS and Na+ in PV cardiomyocytes, but did not change Na+‐Ca2+ exchange currents. Conclusion: C2 ceramide may exert the distinctive electrophysiological effect of modulating PV activities, which may be affected by PI3K pathway–mediated oxidative stress, and might play a role in the pathogenesis of PV arrhythmogenesis. [ABSTRACT FROM AUTHOR]

Background Atrial fibrillation ( AF) is the most common sustained arrhythmia, and pulmonary veins ( PVs) play a critical role in triggering AF. Angiotensin (Ang)-(1-7) regulates calcium (Ca2+) homoeostasis and also plays a critical role in cardiovascular pathophysiology. However, the role of Ang-(1-7) in PV arrhythmogenesis remains unclear. Materials and methods Conventional microelectrodes, whole-cell patch-clamp and the fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca2+ in isolated rabbit PV preparations and in single isolated PV cardiomyocytes, before and after administration of Ang-(1-7). Results Ang (1-7) concentration dependently (0.1, 1, 10 and 100 nmol/L) decreased PV spontaneous electrical activity. Ang-(1-7) (100 nmol/L) decreased the late sodium (Na+), L-type Ca2+ and Na+-Ca2+ exchanger currents, but did not affect the voltage-dependent Na+ current in PV cardiomyocytes. In addition, Ang-(1-7) decreased intracellular Ca2+ transient and sarcoplasmic reticulum Ca2+ content in PV cardiomyocytes. A779 (a Mas receptor blocker, 3 μmol/L), L- NAME (a NO synthesis inhibitor, 100 μmol/L) or wortmannin (a specific PI3K inhibitor, 10 nmol/L) attenuated the effects of Ang-(1-7) (100 nmol/L) on PV spontaneous electric activity. Conclusion Ang-(1-7) regulates PV electrophysiological characteristics and Ca2+ homoeostasis via Mas/ PI3K/ eNOS signalling pathway. [ABSTRACT FROM AUTHOR]