Publications

<h3>Introduction</h3> Left ventricular thrombus (LVT) is encountered in patients with poor ventricular function or following acute myocardial infarction (AMI). Furthermore, incorporating oral anticoagulants into dual antiplatelet therapy for AMI adds complexity. While conventional guidance favours vitamin K antagonists (VKAs), emerging evidence suggests favourable outcomes with direct oral anticoagulants (DOACs). <h3>Purpose</h3> To assess the safety and efficacy of DOACs versus VKAs in managing LVT among patients with and without recent acute coronary syndrome (ACS). <h3>Methods</h3> This was a retrospective observational study conducted within TriNetX, a global federated health research network with access to electronic medical records (EMRs) from participating health care organizations including academic medical centres and community hospitals covering approximately 70 million individuals, mainly in the United States. The search was conducted on 26th Februrary 2024 with a study cohort comprising patients with LV thrombus treated with either DOAC or VKA between 1st December 2013 to 1st December 2023. Subgroup analyses were conducted for patients with ACS within one month and those without ACS within a month of treatment. Cohort data were subject to propensity score matching (PSM) for age, gender, ethnicities, medical and drug history. Outcomes of interest was (1) all cause death, (2) stroke, (3) systemic embolism and (4) intracranial or gastrointestinal bleeding. Risk analysis and Kaplan-Meier survival analysis were computed for each subgroup at 90 days since the indexed event. <h3>Results</h3> Following PSM, a total of 39,770 patients were included and 14,302 were in the ACS group with 7151 on DOACs and 7151 on VKAs (mean age 61.6 SD 16.5 vs 61.4 SD 16.1 years, 33.9% vs 34% female) and 24,162 in the non-ACS group with 12081 on DOACs vs 12081 on VKAs (mean age 62.2 SD 14.4 vs 62.4 SD 14.0 years; 29.3% vs 28.9% female). DOAC treatment exhibited favourable outcomes for stroke, bleeding, and systemic embolism (p&lt;0.05) compared to VKA in the overall cohort (table 1). In the ACS group, DOAC was linked to a reduced risk of stroke and systemic embolism (p&lt;0.05) with borderline reduction in bleeding (p=0.066). In the non-ACS group, DOAC was associated with a decreased risk of stroke and bleeding (p&lt;0.05) but not systemic embolism (p=0.113). Across all groups, there were no disparities in relation to causes of mortality. <h3>Conclusion</h3> DOACs demonstrated better safety and efficacy outcomes when compared to VKAs in LVT treatment. DOAC utilisation within the ACS context was associated with a lower risk of embolic complications with a trend for reduced bleeding risks. <h3>Conflict of Interest</h3> none

Monocytes derive from bone marrow and circulate in the blood. They phagocytose, produce cytokines and present antigens. Individual monocyte subsets play distinct roles in the pathogenesis of cardiovascular disease, but their implications in gestational hypertensive disease are unclear. Our objective was to examine the difference in monocyte subsets between pregnant women with or without previous hypertension in pregnancy. Women were enrolled in a prospective observational study in which monoclonal antibodies against cell surface receptors were used to detect monocytes in the peripheral blood by flow cytometry. We compared 17 pregnant women with previous hypertension in pregnancy (Group 1) and 42 pregnant women without previous gestational hypertensive disease (Group 2) with 27 healthy, non-pregnant controls (Group 3). The pregnant women were studied at 13 ± 1 weeks gestation. Monocyte subsets were quantified by flow cytometry: Mon1 (CD14++CD16-CCR2+), Mon2 (CD14++CD16+CCR2+), Mon3 (CD14+CD16+CCR2-), their aggregates with platelets and expression of the surface markers. The groups were well-matched for age, body mass index and ethnicity (P > 0.05 for all). Mon1 counts were higher in women with a history of gestational hypertension or preeclampsia compared to other groups (Group 1 = 441 per µl (376-512); Group 2 = 357 (309-457); Group 3 = 323 (277-397); P < 0.001). Mon3 was higher in both groups of pregnant women compared to non-pregnant controls (Group 1 = 51 (38-62); Group 2 = 38 (29-58); Group 3 = 26 (20-40), P = 0.002). Increased monocytes in women with a previous hypertensive pregnancy generates a hypothesis that these cells may link hypertension in pregnancy, chronic inflammation and future cardiovascular risk.

Atrial fibrillation (AF) significantly increases the risk of stroke and, therefore, stroke prevention is an essential component of the management for patients with AF. This requires formal assessment of the individual risk of stroke to determine if the patient is eligible for oral anticoagulation (OAC), and if so, their risk of bleeding on OAC, before a treatment decision regarding stroke prevention is made. Risk of stroke is not homogenous; it depends on the presence or absence of risk factors. A plethora of stroke and bleeding risk factors has been identified, including common and less-well established clinical risk factors, plus imaging, urine, and blood biomarkers. Consequently, there are several stroke and bleeding risk stratification scores available and this article provides an overview of them, the risk factors included and how they are scored, and provides a critical appraisal of them. The review also discusses the debate regarding whether female sex is a risk factor or a risk modifier, and highlights the dynamic nature of both stroke and bleeding risk and the need to re-assess these risks periodically to ensure treatment is optimal to reduce the risk of adverse outcomes. This review also summarizes the recommended stroke and bleeding risk stratification scores from all current major international guidelines.

KEY POINTS: Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay. In the presence of β-adrenergic stimulation, RyR-mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase. Two forms of Ca leak have been studied, Ca-sensitising (induced by caffeine) and non-sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient. Only Ca-sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine. Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca-sensitising and non-sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca(2+)]i with fluo-3 in voltage-clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non-sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca(2+)]i , increased diastolic [Ca(2+)]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l(-1)) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the biphasic decay was replaced by slow decay. We conclude that, in the presence of adrenergic stimulation, Ca leak can produce biphasic decay; the slow phase results from the leak opposing Ca uptake by SERCA. The degree of leak determines whether decay of Ca waves, biphasic or monophasic, occurs.

Full adherence to the ABC_stroke pathway based on the current guidelines was evident in only 6.2 % of our ischaemic stroke cohort but was independently associated with lower risks of stroke recurrence, major cardiovascular events and mortality. This highlights a potential opportunity to improve clinical outcomes post-stroke with a holistic or integrated care management approach.

Abstract Background In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4), early rhythm control was associated with better clinical outcomes for patients with atrial fibrillation (AF). However, the intervention arm had more structured and regular followup, and whether the better outcomes of patients assigned to rhythm control were solely due to “early” intervention or because of more regular and structured follow up was unclear. Purpose We aimed to investigate whether the findings of the EAST trial are applicable to the “real world” clinical setting, where a less structured management protocol is operated. Methods From 2001 to 2016, 301,064 newly-diagnosed AF patients were identified from Taiwan National Health Insurance Research Database. Among these patients, 62,649 AF patients receiving antiarrhythmic drugs or catheter ablation within 1 year after AF being diagnosed (similar to the timing definition of the EAST-AFNET 4 trial) were categorized as the early rhythm control group, and the remaining 238,415 patients were defined as usual care group. Risk of clinical events were compared between 2 groups. Results Compared to usual care, early rhythm control was associated with a lower adjusted risk of ischemic stroke (aHR 0.771, 95CI 0.751–0.792; p&amp;lt;0.001), heart failure (aHR 0.851, 95% CI 0.806–0.891; p&amp;lt;0.001), acute myocardial infarction (aHR 0.915, 95% CI 0.877–0.955; p&amp;lt;0.001), mortality (aHR 0.794, 95% CI 0.782–0.806; p&amp;lt;0.001) and composite adverse events (aHR 0.823, 95% CI 0.813–0.834; p&amp;lt;0.001) (Figure). Compared to usual care, the lower risks of ischemic stroke (aHR 0.746, 95% CI 0.717–0.775), heart failure (aHR 0.819, 95% CI 0.798–0.841), mortality (aHR 0.777, 95% CI 0.759–0.795) and composite adverse events (aHR 0.802, 95% CI 0.787–0.818) associated with early rhythm control were even more evident when performed early (&amp;lt;3 months) than later periods (3–6 months, 7–9 months and 10–12 months; pint &amp;lt;0.001). Principal results were generally consistent for majority of subgroups studied and among the cohort after the propensity matching. Conclusions In this nationwide cohort study, early rhythm control therapy was associated with a lower risk of adverse events than usual care among patients with early AF. Outcomes were even better with earlier (&amp;lt;3 months) intervention. Funding Acknowledgement Type of funding sources: None.