Genetic aspects of atrial fibrillation

Atrial fibrillation (AF) occurs predominantly in the elderly and is commonly associated with underlying cardiac diseases. A significant number of patients, however, have early onset AF that is not associated with any underlying disease. At present, it is unknown how often this form of AF is familial and how frequently familial AF is due to genetic causes. Recent data suggest that familial AF occurs more frequently than previously recognized. Also, in AF in the setting of underlying diseases, it is suggested that some form of genetic control may be present. Understanding the molecular mechanisms underlying AF may provide insight into the pathogenesis of AF and eventually may lead to improved, patient-tailored rhythm control strategies. (C) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved

Favorable long-term outcome of maze surgery in patients with lone atrial fibrillation

Background. Rhythm control is indicated for patients suffering from symptomatic atrial fibrillation (AF), but remains difficult to establish. We investigated the long-term outcome of Cox maze III surgery in patients with symptomatic lone AF refractory to antiarrhythmic drug therapy. Methods. Patients with a history of symptomatic paroxysmal or persistent AF refractory for at least two class I or III antiarrhythmic drugs and without structural heart disease or bradyarrhythmias were included. All patients underwent Cox maze III surgery. Complete success was defined as the absence of AF without antiarrhythmic drugs beyond 3 months after the procedure, and partial success as the absence of AF with antiarrhythmic drug use. Results. A total of 29 patients were included (27 male), with a mean age of 48 +/- 6 years. At the time of surgery, 11 patients (38%) had persistent AF. After a mean follow-up of 4.8 +/- 2.4 years, 79% of patients had complete success, and 2 patients (7%) were free of AF with antiarrhythmic drugs. At the end of follow-up, left ventricular fractional shortening was significantly improved (from 31% +/- 10% to 39% +/- 8%, p = 0.002), left atrial size was unchanged, exercise capacity was within normal ranges, and quality of life was comparable with that of healthy controls. Severe complications included reoperations for postoperative bleeding (n = 3), pericardial effusion (n = 1), and mediastinitis (n = 1). In 2 patients, a pacemaker was implanted postoperatively because of sinus node dysfunction. Conclusions. Cox maze III surgery is a highly effective therapy for drug-refractory lone AF, and therefore remains an alternative to transvenous pulmonary vein ablation

External validation and updating of prediction models of bleeding risk in patients with cancer receiving anticoagulants

Objective Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with cancer are lacking. The aim of this study is to predict bleeding risk in anticoagulated patients with cancer.Methods We performed a study using the routine healthcare database of the Julius General Practitioners’ Network. Five bleeding risk models were selected for external validation. Patients with a new cancer episode during anticoagulant treatment or those initiating anticoagulation during active cancer were included. The outcome was the composite of major bleeding and clinically relevant non-major (CRNM) bleeding. Next, we internally validated an updated bleeding risk model accounting for the competing risk of death.Results The validation cohort consisted of 1304 patients with cancer, mean age 74.0±10.9 years, 52.2% males. In total 215 (16.5%) patients developed a first major or CRNM bleeding during a mean follow-up of 1.5 years (incidence rate; 11.0 per 100 person-years (95% CI 9.6 to 12.5)). The c-statistics of all selected bleeding risk models were low, around 0.56. Internal validation of an updated model accounting for death as competing risk showed a slightly improved c-statistic of 0.61 (95% CI 0.54 to 0.70). On updating, only age and a history of bleeding appeared to contribute to the prediction of bleeding risk.Conclusions Existing bleeding risk models cannot accurately differentiate bleeding risk between patients. Future studies may use our updated model as a starting point for further development of bleeding risk models in patients with cancer

Right atrial overdrive pacing for prevention of symptomatic refractory atrial fibrillation

Aims Our aim was to investigate whether right atrial. overdrive pacing is effective for the prevention of atrial. fibrillation (AF) in patients without bradyarrhythmias. Methods and results Patients with symptomatic paroxysmal or persistent AF refractory to at least two Class I or III antiarrhythmic drugs and without bradyarrhythmias were included. Successful therapy was defined as the combination of (a) a reduction of AF burden with or without AAD use > 75%, (b) total AF burden Conclusion Right atrial overdrive pacing in combination with antiarrhythmic drugs seems an attractive treatment option in drug refractory symptomatic AF patients

Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation

AIMS: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. METHODS AND RESULTS: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73 m(2), 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m(2), 0.96-1.00). CONCLUSION: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets