Tommi Bo Lindhardt

Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study.

Study question What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation? Methods This Danish cohort study (1996-2012) included all patients with atrial fibrillation discharged from hospital after gastrointestinal bleeding while receiving antithrombotic treatment. Restarted treatment regimens were single or combined antithrombotic drugs with oral anticoagulation and antiplatelets. Follow-up started 90 days after discharge to avoid confounding from use of previously prescribed drugs on discharge. Risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding were estimated with competing risks models and time dependent multiple Cox regression models. Study answer and limitations 4602 patients (mean age 78 years) were included. Within two years, 39.9% (95% confidence interval 38.4% to 41.3%, n=1745) of the patients had died, 12.0% (11.0% to 13.0%, n=526) had experienced thromboembolism, 17.7% (16.5% to 18.8%, n=788) major bleeding, and 12.1% (11.1% to 13.1%, n=546) recurrent gastrointestinal bleeding. 27.1% (n=924) of patients did not resume antithrombotic treatment. Compared with non-resumption of treatment, a reduced risk of all cause mortality was found in association with restart of oral anticoagulation (hazard ratio 0.39, 95% confidence interval 0.34 to 0.46), an antiplatelet agent (0.76, 0.68 to 0.86), and oral anticoagulation plus an antiplatelet agent (0.41, 0.32 to 0.52), and a reduced risk of thromboembolism was found in association with restart of oral anticoagulation (0.41, 0.31 to 0.54), an antiplatelet agent (0.76, 0.61 to 0.95), and oral anticoagulation plus an antiplatelet agent (0.54, 0.36 to 0.82). Restarting oral anticoagulation alone was the only regimen with an increased risk of major bleeding (1.37, 1.06 to 1.77) compared with non-resumption of treatment; however, the difference in risk of recurrent gastrointestinal bleeding was not significant between patients who restarted an antithrombotic treatment regimen and those who did not resume treatment. What this study adds Among patients with atrial fibrillation who experience gastrointestinal bleeding while receiving antithrombotic treatment; subsequent restart of oral anticoagulation alone was associated with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding. Funding, competing interests, data sharing This study was supported by a grant from Boehringer-Ingelheim. Competing interests are available in the full paper on bmj.com. The authors have no additional data to share.

Risk of atrial fibrillation in diabetes mellitus: A nationwide cohort study.

Aim Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients with diabetes compared to the background population in Denmark. Methods and results Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background population and 253,374 (5%) in the diabetes group. Incidence rates of atrial fibrillation per 1000 person years were stratified in four age groups from 18 to 39, 40 to 64, 65 to 74 and 75 to 100 years giving incidence rates (95% confidence intervals) of 0.02 (0.02–0.02), 0.99 (0.98–1.01), 8.89 (8.81–8.98) and 20.0 (19.9–20.2) in the background population and 0.13 (0.09–0.20), 2.10 (2.00–2.20), 8.41 (8.10–8.74) and 20.1 (19.4–20.8) in the diabetes group, respectively. The adjusted incidence rate ratios in the diabetes group with the background population as reference were 2.34 (1.52–3.60), 1.52 (1.47–1.56), 1.20 (1.18–1.23) and 0.99 (0.97–1.01) in the four age groups, respectively. Conclusion Diabetes is an independent risk factor for developing atrial fibrillation/flutter, most pronounced in young diabetes patients. Routine screening for atrial fibrillation/flutter in diabetes patients might be beneficial and have therapeutic implications, especially in younger diabetes patients. Translational perspective Diabetes increases the risk of developing atrial fibrillation and especially young diabetes patients have a high relative risk. Increased focus on detecting atrial fibrillation in young diabetes patients might prove beneficial, and both anticoagulation treatment and anti-arrhythmic treatment strategies should be considered as soon as possible.

Cardioversion and Risk of Adverse Events with Dabigatran versus Warfarin-A Nationwide Cohort Study.

Aim Cardioversion can rapidly and effectively restore sinus rhythm in patients with persistent atrial fibrillation. Since 2011 dabigatran has been available as an alternative to warfarin to prevent thromboembolic events in patients with non-valvular atrial fibrillation undergoing cardioversion. We studied time to cardioversion, risk of adverse events, and risk of readmission with atrial fibrillation after cardioversion according to anticoagulation therapy. Methods and Results Through the nationwide Danish registries we included 1,230 oral anticoagulation naïve patients with first time non-valvular atrial fibrillation and first time cardioversion from 2011 to 2012; 37% in the dabigatran group (n = 456), and 63% in the warfarin group (n = 774). Median time to cardioversion was 4.0 (interquartile range [IQR] 2.9 to 6.5) and 6.9 (IQR 3.9 to 12.1) weeks in the dabigatran and warfarin groups respectively, and the adjusted odds ratio of cardioversion within the first 4 weeks was 2.3 (95% confidence interval [CI] 1.7 to 3.1) in favor of dabigatran. The cumulative incidence of composite endpoint of stroke, bleeding or death were 2.0% and 1.0% at 30 weeks in the warfarin and dabigatran groups respectively, with an adjusted hazard ratio of 1.33 (95% CI 0.33 to 5.42). Cumulative incidence of readmission with atrial fibrillation after 30 weeks were 9% and 11% in the warfarin and dabigatran groups, respectively, and an adjusted hazard ratio of 0.66 (95% CI 0.41 to 1.08). Conclusion Anticoagulation treatment with dabigatran allows shorter time to cardioversion for atrial fibrillation than warfarin, and appears to be an effective and safe alternative treatment strategy to warfarin.

Management and prognosis of atrial fibrillation in the diabetic patient

The global burden of atrial fibrillation and diabetes mellitus (diabetes) is considerable, and prevalence rates are increasing. Diabetes is associated with an increased risk of developing atrial fibrillation; however, diabetes also influences the management and prognosis of atrial fibrillation. In the following article, the authors describe the association between diabetes and atrial fibrillation; specifically, the significance of diabetes on the risk of atrial fibrillation, ischemic stroke and bleeding complications associated with anticoagulation. In addition, the authors evaluate the risks and outcomes of heart failure and the success rates of both ablation and cardioversion in atrial fibrillation patients with diabetes. Finally, this article describes the association of HbA1c levels with the management and prognosis of atrial fibrillation patients.

Monitoring of left ventricular ejection fraction with a miniature, nonimaging nuclear detector: accuracy and reliability over time with special reference to blood labeling.

BackgroundThe purpose of this study was to determine the accuracy of determinations of left ventricular ejection fraction (LVEF) by a nonimaging miniature nuclear detector system (Cardioscint) and to evaluate the feasibility of long-term LVEF monitoring in patients admitted to the coronary care unit, with special reference to the blood-labeling technique.Methods and ResultsCardioscint LVEF values were compared with measurements of LVEF by conventional gamma camera radionuclide ventriculography in 33 patients with a wide range of LVEF values. In 21 of the 33 patients, long-term monitoring was carried out for 1 to 4 hours (mean 186 minutes), with three different kits: one for in vivo and two for in vitro red blood cell labeling. The stability of the labeling was assessed by determination of the activity of blood samples taken during the first 24 hours after blood labeling. The agreement between Cardioscint LVEF and gamma camera LVEF was good with automatic background correction (r=0.82; regression equation y=1.04x+3.88) but poor with manual background correction (r=0.50; y=0.88x−0.55). The agreement was highest in patients without wall motion abnormalities. The long-term monitoring showed no difference between morning and afternoon Cardioscint LVEF values. Short-lasting fluctuations in LVEFs greater than 10EF units were observed in the majority of the patients. After 24 hours, the mean reduction in the physical decay-corrected count rate of the blood samples was most pronounced for the two in vitro blood-labeling kits (57%±9% and 41%±3%) and less for the in vivo blood-labeling kit (32%±26%). This “biologic decay” had a marked influence on the Cardioscint monitoring results, demanding frequent background correction.ConclusionA fairly accurate estimate of LVEF cn be obtained with the nonimaging Cardioscint system, and continuous bedside LVEF monitoring can proceed for hours with little inconvenience to the patients. Instability of the red blood cell labeling during long-term monitoring necessitates frequent background correction.

Patients with atrial fibrillation and permanent pacemaker: Temporal changes in patient characteristics and pharmacotherapy

Background The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM). Methods Through Danish nationwide registries, patients with NVAF and a PPM were identified from 2001 to 2012. Changes in concomitant pharmacotherapy and comorbidities were tested using the Cochran–Armitage trend test and linear regression. Patients with NVAF were identified to calculate the proportional amount of PPM implants. Results A total of 12,231 NVAF patients with a PPM were included in the study, 55.6% of which were men. Median age was 78 years (interquartile range 70–84). From 2001 to 2012, the number of NVAF patients with a PPM increased from 850 to 1344, while the number of NVAF patients increased from 67,478 to 127,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p <0.001). Diabetes mellitus increased from 7.2% to 16.8% (p <0.001). Heart failure (HF) decreased from 36.7% to 29.3% (p = 0.010) and ischemic heart disease (IHD) decreased from 32.4% to 26.1% (p <0.001). Beta-blocker use increased from 38.1% to 58.0% (p <0.001), while digoxin and anti-arrhythmic drug use decreased over time. Conclusion From 2001 to 2012, the absolute number of NVAF patients with a PPM increased while the proportional amount decreased. The number of NVAF patients receiving a PPM within one year of AF diagnosis decreased. The prevalence of DM increased, while the prevalence of HF and IHD was high but decreasing. The use of beta-blockers increased markedly, while use of digoxin and anti-arrhythmic drugs decreased over time.

Risk of Ischemic Stroke, Hemorrhagic Stroke, Bleeding, and Death in Patients Switching from Vitamin K Antagonist to Dabigatran after an Ablation.

Background Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation. Methods Through the Danish nationwide registries, patients with non-valvular atrial fibrillation undergoing ablation were identified, in the period between August 22nd 2011 and December 31st 2015. The risk of ischemic stroke, hemorrhagic stroke, bleeding, and death, related to switching from VKA to dabigatran was examined using a multivariable Poisson regression model, where Incidence rate ratios (IRR) were estimated using VKA as reference. Results In total, 4,236 patients were included in the study cohort. The minority (n = 470, 11%) switched to dabigatran in the follow up period leaving the majority (n = 3,766, 89%) in VKA treatment. The patients in the dabigatran group were older, were more often males, and had higher CHA2DS2-VASc, and HAS-BLED scores. The incident rates of bleeding and death were almost twice as high in the dabigatran group compared with the VKA group. When adjusting for the individual components included in the CHA2DS2-VASc and HAS-BLED scores, the multivariable Poisson analyses yielded a non-significant IRR (95%CI) of 1.64 (0.72–3.75) for bleeding and of 1.41 (0.66–3.00) for death associated with the dabigatran group, compared to the VKA group. A significant increased risk of bleeding was found in the 110mg bid group with an IRR (95%CI) of 4.49(1.40–14.5). Conclusion Shifting from VKA to dabigatran after ablation was associated with twice as high incidence of bleeding compared to the incidence in patients staying in VKA treatment. The only significant increased risk found in the adjusted analyses was for bleeding with 110mg bid dabigatran and not for 150mg bid. Since there was no dose-response for bleeding, the switch from VKA to dabigatran in itself was not a risk factor for bleeding.

Risk of ischemic stroke, hemorrhagic stroke, bleeding, and death in patients switching from warfarin to dabigatran after an ablation

Successful reperfusion is associated with lower levels of markers of myocardial damage and dysfunction in ST-elevation but not in non-ST-elevation myocardial infarction : insights from the PLATO trialBackground: Carbohydrate antigen 125 (CA125) is a mucin produced by serosal cells in response to mechanical and inflammatory stimuli. CA125 has emerged as prognostic biomarker in heart failure (HF) and correlates with markers of fluid overload, echocardiographic parameters and prognosis in HF patients. In patients with acute coronary syndrome (ACS), elevated CA125 is correlated with a higher risk of in-hospital HF. The relationship between CA125 and long-term prognosis in ACS patients has not previously been assessed. Purpose: The purpose of our study was to investigate if CA125 measured at the time of an acute coronary event is related to cardiac remodeling during the first year of follow-up and long-term risk for HF and death Methods: We measured CA125 in plasma within 24 hours of the acute event in 523 patients with acute myocardial infarction or unstable angina admitted to the Coronary Care Unit. Routine echocardiograms were performed in all participants. The primary outcomes were hospitalization with a diagnosis of heart failure or death during follow-up, identified through data from the Swedish Hospital Discharge Register and the Swedish Cause of Death Register. In a subgroup of 109 patients aged 75 years or above we assessed the relationships between baseline CA125 and echocardiographical parameters of cardiac structure and function at 1 year after the index ACS. Results: The median follow-up period was 27.3 months for incident HF and 39.5 months for mortality. In Cox proportional hazards models we found an adjusted hazard ratio of 1.51 (95% CI 1.08-2.12; p (Less)