Background: Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism. Objectives: To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Methods: All patients admitted with first-time AF in Denmark from 1997 to 2006 and their present and subsequent use of antithyroid medication were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies. Patients with previous thyroid disease or any thyroid medication were excluded. Development of hyperthyroidism was assessed by treatment initiation of methimazole or propylthiouracil within a 10 year period. Every patient was matched with ten controls in the background population by sex and age and the risk of hyperthyroidism was analyzed by multivariate Cox proportional-hazard models. Results: A total of 139,521 patients with new-onset AF were included (mean age 73.5 ...
Background —Studies have suggested that ACE inhibitors have an antiarrhythmic effect on ventricular arrhythmias. Whether they have an effect on atrial fibrillation is unknown. Methods and Results —We investigated the effect of ACE inhibition with trandolapril on the incidence of atrial fibrillation in patients with reduced left ventricular function secondary to acute myocardial infarction. The patients in this study were those who qualified for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study, a randomized double-blind placebo-controlled study and who had sinus rhythm on the ECG obtained at randomization. Patients who fulfilled the criteria for inclusion were randomized to treatment with the ACE inhibitor trandolapril or placebo and were followed up for 2 to 4 years. Development and time to occurrence of atrial fibrillation in one 12-lead ECG recorded at the outpatient visits was the primary end point of this investigation. Of the 1749 patients included in the TRACE study, 1577 had sinus rhythm on the ECG recorded at randomization. Of these patients, 790 were randomized to trandolapril treatment and 787 to placebo treatment. The groups differed only slightly with respect to baseline characteristics. A total of 64 patients developed atrial fibrillation during the 2- to 4-year follow-up period. Significantly more patients developed atrial fibrillation in the placebo group than in the trandolapril group, 5.3% (n=42) versus 2.8% (n=22), respectively, P <0.05. Cox multivariable regression analysis, adjusting for important baseline characteristics, revealed that trandolapril treatment significantly reduced the risk of developing atrial fibrillation (RR, 0.45; 95% CI, 0.26 to 0.76; P <0.01). Conclusions —The results from the present study demonstrate that trandolapril treatment reduces the incidence of atrial fibrillation in patients with left ventricular dysfunction after acute myocardial infarction.
OBJECTIVE: To determine whether there was a relation between plasma resistance to activated protein C and the coagulation activation induced during thrombolysis with 100 mg alteplase in 25 patients with acute ischaemic heart disease. METHODS: Blood samples were collected before (t = 0 h), during (t = 2.25 h), and after (t = 4 h, t = 12 h, and t = 24 h) thrombolysis to examine the relation between baseline activated protein C resistance ratio and markers of coagulation activation-that is, thrombinantithrombin III-complexes and prothrombin fragment 1 + 2 generated during thrombolysis. RESULTS: There was a negative correlation between activated protein C resistance ratio and area under the curve of thrombin-antithrombin III-complexes (rs = - 0.60; P < 0.003) and there was a trend to a negative correlation between activated protein C resistance ratio and area under the curve of prothrombin fragment 1 + 2 (rs = - 0.37; P = 0.07). This accorded with the negative correlation between activated protein C resistance ratio and the peak value of thrombin-antithrombin III-complexes (rs = - 0.55; P < 0.005) and between activated protein C resistance ratio and the peak value of prothrombin fragment 1 + 2 (rs = - 0.42; P < 0.04). Components of the protein C/S system or known inhibitors of activated protein C may influence the activated protein C resistance ratio. There were no associations between the activated protein C resistance ratio and protein C, protein C inhibitor, or plasminogen activator inhibitor type-1, whereas there was a trend to a negative correlation between activated protein C resistance ratio and protein S. CONCLUSIONS: The results indicate that plasma resistance to activated protein C may be one of the main mechanisms regulating the activation of coagulation induced by thrombolysis. This study suggests that it may be possible to single out individuals with a high risk of reocclusion before the start of thrombolytic therapy.
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Mortality, and especially morbidity caused by AF, are major and growing health problems in the western world. AF is strongly associated with arterial hypertension, congestive heart failure, valvular heart disease, ischaemic heart disease, and with prevalence increasing with age. A variety of drugs have been used to terminate or prevent AF but, as many antiarrhythmic agents have the potential life-threatening pro-arrhythmia, safety problems remain. Dofetilide (Tikosyn®, Pfizer), a new Vaughan Williams class III antiarrhythmic agent, has been developed and approved for the treatment of AF. In contrast to most antiarrhythmic agents, the development programme included two safety studies in high-risk patients. Dofetilide is effective and safe when an elaborate procedure for dosing is implemented. Along with amiodarone and β-blockers, dofetilide is the only antiarrhythmic drug, which is recommended by guidelines for the treatment of AF in a wide range of patients.
Background The true frequency of AF in patients with cryptogenic stroke or TIA is not well defined. The aim was to estimate the frequency and burden of AF in patients with apparent cryptogenic minor stroke or TIA by long term monitoring providing complete data on arrhythmia occurrence. Methods Patients with minor stroke or DWI-positive TIA were included if stroke causation remained unknown during standardized work up including 24 hours telemetry. A Reveal XT®, an atrial fibrillation sensitive loop-recorder, was implanted subcutaneously allowing continuous monitoring for up to 3 years. Arrhythmia episodes were adjudicated by senior consultant cardiologist. Endpoints include episodes of AF, time and burden of AF. A total of 84 patients were included and had a minimum of three months of monitoring before final analysis. Five patients were explanted due to local infections or discomfort. (fig.2) Results In 13 patients (15.5 %) AF was documented by long term monitoring. The mean burden of AF was 2 hours pr day monitored, varying from less than a minute to 17 hours pr day monitored. (median 20 minutes pr day monitored) Kaplan Meier (fig.1) presents time from stroke onset to first AF event, mean time was 106,0 days (SD 47,9 days) Time from stroke onset to implantation was at a median of 56 days. (Mean 80 days, SD 74,9). Logistic regression analysis including all elements of CHADS2VAS found increasing risk of AF with an OR = 1.096 (p=0.015) with increasing age in years. CHADS 2 VAS score was 4.14 in the AF group vs. 3.24 (p=0.03). Conclusion Paroxysmal AF is frequent and brief in patients with cryptogenic stroke. Long term monitoring resulted in change of treatment in one out of 6 patients in this cohort.
Objectives To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients. Design Population based cohort study of general practice patients identified by linkage of nationwide registries at the individual level. Setting Primary care patients in the city of Copenhagen. Subjects Registry data for 586 460 adults who had their thyroid function evaluated for the first time by their general practitioner during 2000-10 and who were without previously recorded thyroid disease or atrial fibrillation. Main outcome measure Poisson regression models used to estimate risk of atrial fibrillation by thyroid function. Results Of the 586 460 individuals in the study population (mean (SD) age 50.2 (16.9) years, 39% men), 562 461 (96.0%) were euthyroid, 1670 (0.3%) had overt hypothyroidism, 12 087 (2.0%) had subclinical hypothyroidism, 3966 (0.7%) had overt hyperthyroidism, and 6276 (1.0%) had subclinical hyperthyroidism. Compared with the euthyroid individuals, the risk of atrial fibrillation increased with decreasing levels of thyroid stimulating hormone (TSH) from high normal euthyroidism (incidence rate ratio 1.12 (95% CI 1.03 to 1.21)) to subclinical hyperthyroidism with reduced TSH (1.16 (0.99 to 1.36)) and subclinical hyperthyroidism with supressed TSH (1.41 (1.25 to 1.59)). Both overt and subclinical hypothyroidism were associated with a lower risk of atrial fibrillation. Conclusion The risk of atrial fibrillation was closely associated with thyroid activity, with a low risk in overt hypothyroidism, high risk in hyperthyroidism, and a TSH level dependent association with risk of atrial fibrillation across the spectrum of subclinical thyroid disease.
Background In patients with left ventricular dysfunction, atrial fibrillation and flutter (AF and AFl, respectively) are common arrhythmias associated with increased morbidity and mortality. The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm, which might reduce mortality and hospitalizations. Methods and Results In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies, 506 patients were in AF-AFl at baseline. Over the course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%) placebo-treated patients. In these patients, the probability of maintaining sinus rhythm for 1 year was 79% with dofetilide versus 42% with placebo ( P <0.001). Dofetilide had no effect on all-cause mortality, but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality (risk ratio [RR], 0.44; 95% CI, 0.30 to 0.64; P <0.0001). In addition, dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P ≤0.005) or congestive heart failure (RR, 0.69; 95% CI, 0.51 to 0.93; P ≤0.02) rehospitalization. Conclusions Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease. The present study suggests that restoration of sinus rhythm is associated with improved survival.
