Short summary

An evaluation of the atrial fibrillation clinic at Odense University Hospital. Paitiens enrolled in long-term treatment between 1st of January 2013 and 31st of December 2015 will be invited to join an extra outpatient control. Here, their current medical treatment will be controlled with the current guidelines for treatment of atrial fibrillation. 

Rationale

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting more men and elderly, and associated with significant morbidity and mortality due to thromboembolic complications and heart failure, leading to hospitalisations, and impaired quality of life. Therefore, atrial fibrillation has a major impact on healthcare systems, which is likely to increase in an ageing population.

Although AF might be completely asymptomatic, about two thirds of the patients experience symptoms. Besides oral anticoagulation treatment for stroke prevention the management of AF largely focusses on symptom control and improvement of quality of life. Restoring and maintaining sinus rhythm (SR) is an integral part of AF management. Although there is a clear association between AF and death, stroke, and other cardiovascular events, there is currently no scientific evidence that rhythm control aiming at maintaining SR is superior to rate control in terms of the reduction of mortality and morbidity. Therefore, current guidelines on the management of AF recommend rhythm control therapy to improve symptoms in patients, who remain symptomatic despite adequate rate control therapy.

Rhythm control includes cardioversion, either electrical or pharmacological, to restore SR and treatment with antiarrhythmic drugs (AAD) or ablation to maintain SR. Current guidelines on the management of AF still recommend AADs as first-line treatment for rhythm control, while catheter ablation is recommended as second-line therapy, when AAD therapy has failed or is not tolerated. Only in selected patients with paroxysmal AF, catheter ablation may be used as firstline treatment.

Several AADs are available for rhythm control in AF, which have been tested in a number of clinical trials. A recent meta-analysis found a significant reduction of AF recurrences on AADs compared to control. Moreover, amiodarone was more effective in reducing AF recurrences than class Ic AADs or dronedarone and sotalol. On the other hand, there might be adverse drug reactions, which also differ in their extent in terms of pro-arrhythmia, e.g. torsade des pointes tachycardia, and other side-effects. This has led to the current guideline recommendation that, when a decision is made to initiate long-term AAD therapy, this needs to balance the patient's symptom burden, possible adverse drug reactions, and patient preferences. When one AAD fails to control AF, another trial might be done with a second AAD. Dependent on underlying conditions, the choice of ADDs is limited, e.g. only amiodarone can be used in patients with heart failure and reduced left ventricular function. Current guidelines outline several general principles, which should be taken into account when initiating AAD therapy.

Over the years there have been changes regarding the preference of rhythm versus rate control in AF. It has been shown that the guidelines for antiarrhythmic drugs are not always followed. For patients with hearts failure this is especially important, since several drugs can have serious adverse side-effects in these patients.

The primary objective is to evaluate the success of treatment with AADs in AF patients at OUH.

A recent study has shown that the expression of the homeodomain-2 transmission factor PITX2 might influence the effectivity of the antiarrhythmic drug (AAD) Flecainide, a Na+-channel blocker, in the individual patient. PITX2 modulates the atrial resting membrane potential, and atria with less PITX2 have a greater effect from Flecainide. It is not yet possible to detect different values in blood samples, but the hope is that it will be possible in the future. Markers for the expression of PITX2, and perhaps other genes, will be a great help towards individualized treatment.  

Description of the cohort

Patients with documented AF who initiated treatment with class Ic AAD (flecainide, propafenon) or class III AAD (amiodarone, dronedarone, sotalol) between January 1st, 2013 and December 31st, 2015 will receive a letter where they are invited to join the research project.
Patients initiating treatment during hospitalization for ablation therapy or patients undergoing an ablation therapy less than 3 months after start of treatment will be excluded. 

Data and biological material

Blood samples will be taken at the outpatent control. These include the normal bloodsamples taken during a normal outpatient control and two 10ml samples that will be stored and sent to a biobank at the Institute of Cardiovascular Sciences, University of Birmingham, UK for future research in the PITX2 gene.
Information about previous treatment, procedures and comorbidities will be accessed from the patients journals and Odense Pharmacoepidemiological Database (OPED). 

Collaborating researchers and departments

Department of Cardiology, Odense University Hospital

• Professor Axel Brandes, MD, DMSc FESC

• Kenneth Bruun Pedersen, MD