Atrial Fibrillation - assessment of arrhythmia mechanism and novel interventional therapies
There are three ongoing projects evaluating non-pharmacological treatment strategies for AF:
- The CAPTAF (Catheter Ablation compared with Pharmacological Therapy for Atrial Fibrillation) study, a Nordic multicenter, randomised study comparing the efficacy and safety of pulmonary vein isolation versus antiarrhythmic drugs as a treatment strategy in AF with regard to quality of life as primary end-point.
- In substudies of our completed national SWEDMAF trial, we have e.g. evaluated the effects of the concomitant epicardial catheter based Maze surgery on heart function and further analyzed the effects on patient’s quality of life.
- The RAMCOR (Randomised AF ablation study using Cryo Or Radiofrequency energy) have included 60 % of patients with paroxysmal AF, scheduled for pulmonary vein isolation with either cryo-balloon ablation or radiofrequency ablation, using a novel circular ablation catheter. Endpoints studied include AF burden, quality of life, atrial function and procedure related variables.
There are also studies assessing AF mechanism, including analyses of various surgical techniques, which lesion sets are associated with the highest AF elimination rate and the role of vagal denervation for elimination of AF. Other projects evaluate the role of inflammation and pre-thrombotic state for the initiation and perpetuation of atrial fibrillation
Molecular investigation of Inherited Cardiac Arrhythmogenic Syndromes - The MICAS project.
Some inherited heart diseases unfold symptom-free or without abnormal findings on examination and may remain undiagnosed until sudden cardiac death (SCD) occurs. Diagnostic tests and risk stratification tools are lacking. This translational project aims to identify i) novel genetic mutations in inherited heart diseases associated with increased risk of SCD and ii) genetic and phenotype risk markers for life-threatening ventricular arrhythmias, with the goal to develop a quick screening test for these conditions. Genetic assays to screen for mutations in the genes coding for desmoplakin, plakophyllin, plakoglobulin and novel mutations are being developed and found mutations will be compared with clinical findings (phenotypes) to create risk markers for life threatening ventricular arrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and other inherited heart diseases, suitable for screening and risk stratification. The genetic analysis will be performed on samples from SCD victims, patients and their relatives using Sanger sequencing and/or a screening assay of all exons in these genes. Novel mutations identified in dogs with ARVC will be searched for in selected patients. The projects are all in collaboration with Marie Allen, Gen. Path. Department, and Kerstin Lindahl Toh, with co-workers, at Broad Institute and BMC.
During 2010 we have started to analyze the most common gene in ARVC: the plakophilin 2 (PKP2) gene, covering about 45% of ARVC affected individuals. In a pilot study, all 14 exons of PKP2 gene were screened for mutations by bi-directional Sanger sequencing. So far, we have identified pathogenic mutations in 14 of 66 (21%) patients from the cardiology clinic with suspected ARVC.