Oral anticoagulation treatment in atrial fibrillation - To bleed or not to bleed, that is the question

Background: Oral antigoagulation treatment (OAT) with warfarin have a narrow therapeutic window and patients exhibit a highly variable doseresponse that is attributable to genetic, disease-related,and environmental factors as well as prescription and nonprescription drugs, dietary vitamin K and alcohol. The effect of warfarin treatement on blood coagulation is measured using international normalized ratio (INR). Monitoring and tight control of anticoagulation treatment reduces the risk of both thrombosis and bleeding. The time in therapeutic range (TTR) has been validated as a quality indicator of the anticoagulation treatment given, correlating inversely to complication frequencies. The Swedish national quality registry for atrial fibrillation and anticoagulation (AuriculA) was founded in 2006 and has by August 2011 enrolled 68,000 patients, close to 40 % of all patients on anticoagulation in Sweden. Patients with end stage renal disease are at high risk for both bleeding and thrombosis and even a moderate decrease in glomerular filtration rate (GFR) is associated with thromboembolic and bleeding complications. Impaired kidney function has also been shown to be associated with a greater need of warfarin dose adjustment, poor TTR, and an increased risk of bleeding in patients taking warfarin. New anticoagulants, most of them eliminated by renal route, can be administered in a fix dose, have few drug and no dietary interactions, has been shown to be at least inferior and in some cases superior to OAT with warfarin. Methods: The Anticoagulation Clinic in Malmö participates in AuriculA, and uses this registry for prospective follow-up and as a tool for OAT dosage. This thesis has utilized data from AuriculA for epidemilogical analysis of impaired kidney function, using two equations for estimated glomerular filtration rate (eGFR), TTR, and the correlation of these two markers to major bleeding and thrombo-embolic events. Results: In Paper I, TTR in 18391 patients in the whole Swedish AuriculA population was 76.2%. Compared to recent prospective randomized trials of warfarin treatment, TTR in the AuriculA population was higher. Adherence to treatment, as measured by TTR, was higher in elderly patients with a significant correlation with increasing age. In 4273 patients from two centers in AuriculA the frequency of major bleedings and venous/arterial thromboembolism were 2.6 % and 1.7 % and for atrial fibrillation (AF), 2.6 % and 1.4 %, per treatment year respectively. In Paper II, the fraction of 2603 AF patients on warfarin with eGFR 3.0 (p<0.001 for both). There was no correlation between age, eGFR and thromboembolic events. The prevalence of eGFR <45ml/min/1.73m2 was 52% in patients aged ≥75 years with major bleeding. eGFR levels <30 ml/min/1.73m2 were particularly associated with high risk of bleeding in elderly patients. No correlation between eGFR and thromboembolic events was seen. In Paper IV, 397 patients on OAT with warfarin, there was a positive correlation between results from the point-of-care device (POC) CoaguChek XS and the Owren-type PT assay for INR measurement (r=0.94;p<0.001) and concordance of 88.2%. In patients with 152 double samples analyzed with the CoaguChek XS, a positive correlation of 0.99 was seen; p<0.001. Conclusions: The quality of OAT with warfarin in Sweden is high and comparable to prospective randomized trials of warfarin treatment. Complications were low, probably due to the organization of anticoagulation treatment in Sweden, although the AuriculA dosing algorithm could have contibuted by keeping dosing regimens consistent over all centers. The POC-device CoaguChek XS presents reproducible results, highly comparable with Owren PT at therapeutic levels of INR, offering a more convenient method of monitoring, compared to regular venous INR measurement in patients on OAT with warfarin. Severe renal impairment is common among AF patients on OAT with warfarin, especially at higher ages, indicating one important difference between a ‘real world’ clinical population and those of randomized controlled trials of new oral anticoagulant drugs, where patients with severe renal failure (eGFR <30 ml/min/1.73 m2) were excluded. Given the strong correlation between eGFR and major bleeding events in patients on anticoagulation treatment demonstrated in Paper III, caution is advised in the upcoming era of new oral anticoagulants with elimination by renal route. Monitoring of renal function should be implemented in clinical practice for AF patients treated with new anticoagulants eliminated by the kidneys and registries like AuriculA can be used for prospective follow-up of these patients

Referring physicians underestimate the extent of abnormalities in final reports from myocardial perfusion imaging

BACKGROUND: It is important that referring physicians and other treating clinicians properly understand the final reports from diagnostic tests. The aim of the study was to investigate whether referring physicians interpret a final report for a myocardial perfusion scintigraphy (MPS) test in the same way that the reading nuclear medicine physician intended. METHODS: After viewing final reports containing only typical clinical verbiage and images, physicians in nuclear medicine and referring physicians (physicians in cardiology, internal medicine, and general practitioners) independently classified 60 MPS tests for the presence versus absence of ischemia/infarction according to objective grades of 1–5 (1 = No ischemia/infarction, 2 = Probably no ischemia/infarction 3 = Equivocal, 4 = Probable ischemia/infarction, and 5 = Certain ischemia/infarction). When ischemia and/or infarction were thought to be present in the left ventricle, all physicians were also asked to mark the involved segments based on the 17-segment model. RESULTS: There was good diagnostic agreement between physicians in nuclear medicine and referring physicians when assessing the general presence versus absence of both ischemia and infarction (median squared kappa coefficient of 0.92 for both). However, when using the 17-segment model, compared to the physicians in nuclear medicine, 12 of 23 referring physicians underestimated the extent of ischemic area while 6 underestimated and 1 overestimated the extent of infarcted area. CONCLUSIONS: Whereas referring physicians gain a good understanding of the general presence versus absence of ischemia and infarction from MPS test reports, they often underestimate the extent of any ischemic or infarcted areas. This may have adverse clinical consequences and thus the language in final reports from MPS tests might be further improved and standardized

Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation: the 8th AFNET/EHRA consensus conference

Aims Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy.Methods and results This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework.Conclusions Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.</p

Bleeding complications related to warfarin treatment: a descriptive register study from the anticoagulation clinic at Helsingborg Hospital

The most common indication for treatment with warfarin is the prevention of ischemic stroke in patients with atrial fibrillation. Time in therapeutic range (TTR) is an important tool to evaluate the quality of anticoagulation treatment. The aim of this study was to investigate the quality of treatment and the incidence of bleeding complications in patients on warfarin treatment treated by the anticoagulation clinic in Helsingborg. This is the first study that has specifically focused on the spontaneous reporting of bleeding complications in a real-world population. A total of 4,400 patients with a total of 8,394 patient years were registered, in the database Journalia AVK, during the time period November 1, 2007 to November 1, 2010. The mean age was 72 years. TTR was 73.3 % for the whole population. 421 patients suffered from haemorrhagic events. The frequency of major and fatal bleedings and intracranial haemorrhage (ICH) were 1.6, 0.2 and 0.5 % per patient-year, respectively. A correlation between age and severe bleeding (major, fatal and ICH) (p = 0.003) was seen, but no correlation between gender and severe bleeding (p = 0.27). In 60 out of 455 bleeding events the complication had been reported to the anticoagulation clinic. At the anticoagulation clinic in Helsingborg the quality of warfarin treatment is good compared to previous results described in the literature, with regards to bleeding complications and efficacy. However, in our study, we confirm that the spontaneous reporting of bleeding complications related to warfarin is inadequate, and that review of patient records is needed to assure proper follow-up

Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain.

The genomic response following brain ischemia is very complex and involves activation of both protective and detrimental signaling pathways. Immediate early genes (IEGs) represent the first wave of gene expression following ischemia and are induced in extensive regions of the ischemic brain including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated the spatial and temporal activation pattern for these genes during the first 24 h of reperfusion following 2-h occlusion of the middle cerebral artery. Neuritin showed a persistent activation in frontal-cingulate cortex while Arc displayed a biphasic response. Also, in dentate gyrus, activation was observed at 0–6 h of reperfusion for Neuritin and 0–12 h of reperfusion for Arc while BDNF was induced 0–9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part of long-term synaptic responses of ischemic brain tissue

Skåne Emergency Department Assessment of Patient Load (SEAL)-A Model to Estimate Crowding Based on Workload in Swedish Emergency Departments.

Emergency department (ED) crowding is an increasing problem in many countries. The purpose of this study was to develop a quantitative model that estimates the degree of crowding based on workload in Swedish EDs.At five different EDs, the head nurse and physician assessed the workload on a scale from 1 to 6 at randomized time points during a three week period in 2013. Based on these assessments, a regression model was created using data from the computerized patient log system to estimate the level of crowding based on workload. The final model was prospectively validated at the two EDs with the largest census.Workload assessments and data on 14 variables in the patient log system were collected at 233 time points. The variables Patient hours, Occupancy, Time waiting for the physician and Fraction of high priority (acuity) patients all correlated significantly with the workload assessments. A regression model based on these four variables correlated well with the assessed workload in the initial dataset (r2 = 0.509, p < 0.001) and with the assessments in both EDs during validation (r2 = 0.641; p < 0.001 and r2 = 0.624; p < 0.001).It is possible to estimate the level of crowding based on workload in Swedish EDs using data from the patient log system. Our model may be applicable to EDs with different sizes and characteristics, and may be used for continuous monitoring of ED workload. Before widespread use, additional validation of the model is needed

Concomitant use of dronedarone with dabigatran in patients with atrial fibrillation in clinical practice.

Dronedarone is a strong P-glycoprotein inhibitor with a potential to increase bioavailability of dabigatran. We sought to measure and report plasma concentrations of dabigatran in patients with atrial fibrillation (AF) on concomitant dronedarone treatment