Publications

Atrial fibrillation (AF) and chronic kidney disease are closely related, and any associated risk of stroke and thromboembolism due to AF is increased by concurrent renal dysfunction. The mechanism(s) for this include abnormalities in platelets and endothelial cells. We hypothesized relationships between levels of circulating platelet microparticles (PMPs, defined by CD42b), soluble P selectin (both reflecting platelet activation), soluble E-selectin (reflecting endothelial activation) and endothelial/platelet microparticles (EPMPs, defined by CD31) with progressive renal dysfunction. Blood samples were obtained from 160 anticoagulated AF patients. Microparticles were measured by flow cytometry, soluble E and P selectin levels by ELISA. Renal function was determined by estimated glomerular filtration rate (eGFR). EPMP levels demonstrated a linear increased trend across quartiles of eGFR (p = 0.034) and CKD stage (p < 0.001), and correlated with eGFR and serum creatinine (p < 0.01). PMPs, P-selectin and E-selectin levels were not significantly different across groupings of renal dysfunction, and no significant correlations with eGFR were evident (p = 0.186, p = 0.561, p = 0.746 respectively). Stepwise multivariable regression analysis demonstrated that worsening renal function was an independent predictor of EPMP levels (p < 0.001). In well-anticoagulated AF patients, there is potential relationship between endothelial function (as judged by elevated EPMP levels, with no change in PMPs) and renal function. Other markers of prothombotic state or cellular activation (PMP, P-selectin and E-selectin levels) were not significantly different across the various degree of renal dysfunction. Renal function must be addressed when measuring EPMP levels.

Peripheral arterial disease is prevalent in 11% of AF patients and related to various atherosclerotic risk factors. Even if PAD is associated with higher risk of all-cause death on univariate analysis, this risk was significantly lowered and was no longer evident after adjusting for the use of CV prevention drugs.

ABSTRACT Background and Objectives A key step in electrocardiogram (ECG) analysis is the detection of QRS complexes, particularly for arrhythmia detection. Telehealth ECGs present a new challenge for automated analysis as they are noisier than traditional clinical ECGs. The aim of this study was to identify the best-performing open-source QRS detector for use with telehealth ECGs. Methods The performance of 18 open-source QRS detectors was assessed on six datasets. These included four datasets of ECGs collected under supervision, and two datasets of telehealth ECGs collected without clinical supervision. The telehealth ECGs, consisting of single-lead ECGs recorded between the hands, included a novel dataset of 479 ECGs collected in the SAFER study of screening for atrial fibrillation (AF). Performance was assessed against manual annotations. Results A total of 12 QRS detectors performed well on ECGs collected under clinical supervision ( F 1 score ≥ 0.96). However, fewer performed well on telehealth ECGs: five performed well on the TELE ECG Database; six performed well on high-quality SAFER data; and performance was poorer on low-quality SAFER data (three QRS detectors achieved F 1 of 0.78-0.84). The presence of AF had little impact on performance. Conclusions The Neurokit and University of New South Wales QRS detectors performed best in this study. These performed sufficiently well on high-quality telehealth ECGs, but not on low-quality ECGs. This demonstrates the need to handle low-quality ECGs appropriately to ensure only ECGs which can be accurately analysed are used for clinical decision making.

<h3>Introduction</h3> Anticoagulation use in atrial fibrillation (AF) is common, but concurrent chronic kidney disease (CKD) reduces its efficacy and potentiates the risk of bleeding. Patients with AF have a higher incidence of renal impairment and the latter predisposes to incident AF. The co-existence of both conditions leads to a higher risk for thromboembolic-related adverse events but also a paradoxical increased haemorrhagic risk with devastating consequences for the individual. Assessing the effect of renal function on plasma clot properties in anticoagulated AF patients may help explain reasons behind this. <h3>Aim</h3> To observe how progressive renal dysfunction affects plasma clot properties in AF patients on warfarin. <h3>Methods</h3> We studied 192 patients with AF on warfarin and divided them in 4 groups based on estimated glomerular filtration rate (eGFR), eGFR&gt;90 (n=30), eGFR 60–89 (n=89), eGFR 30–59 (n=59) and eGFR&lt;30 (n=14). Plasma samples were obtained from patients using venepuncture and centrifuged to prepare platelet poor plasma. Assays were performed in 96-well polystyrene microtiter plates. Reagents were diluted in standard buffer (10 mM N-2-hydroxyethylpiperazine-N’-2-ethanesulphonic acid [HEPES], pH 7.4, 150 mM NaCl). Patient plasma samples (25 %) were incubated with tissue plasminogen activator (500 ng.mL-1) for 10 minutes at 37°C before the addition of CaCl2 (7.5 mM). Either PPP reagent (2.5 %), aPPT reagent (2.5 %), or thrombin (0.5 U.mL-1) were then added to initiate coagulation. Polymerisation of fibrin in plasma was monitored (ΔOD340 nm) using a Synergy H1 hybrid multi-mode plate reader, readings were taken in 12 second intervals for up to 60 minutes. <h3>Results</h3> Comparison between the 4 groups was performed using Kruskal-Wallis test with Dunn’s post-hoc analysis and Holm-Sidak adjustment. There was no statistical difference in optical density reflecting clot turbidity or rate of clot formation between the eGFR groups (table 1). Plasma clot lysis time was noted to be significantly prolonged in patients with worsening renal function with all 3 reagents used (PPP (p=0.03), APPT (p=0.02) and thrombin (p=0.03) respectively). Time for 50% of the clot to lyse was also significantly slower with worsening renal function with PPP (p=0.04) and thrombin (p=0.02) reagents suggesting modulation of warfarin action. <h3>Conclusion</h3> Worsening renal function in AF patients on warfarin leads to increased clot lysis time, hence leading to a potentially increased risk of thrombosis. <h3>Conflict of interest</h3> None

The increase of hypertension duration was associated with the increased risk of ischaemic stroke. However, this long-term effect of hypertension duration can be attenuated by long-term strict SBP control throughout the entire duration of hypertension.

Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.