Remission of Paroxysmal Atrial Fibrillation with Iron Reduction in Hemophilia A.

Abstract 5100

Two male first cousins with mild hemophilia A had symptomatic electrocardiographically documented paroxysmal atrial fibrillation for several years that had become resistant to pharmacologic suppression. Both had baseline factor VIII levels of 12 to 15% and experienced bleeding requiring coagulation factor infusion therapy in response to trauma and surgical procedures. Radiofrequency ablation of ectopic electrical foci was considered in both cases but deferred because anticoagulation required to prevent thromboembolic complications of radiofrequency ablation carried an unacceptably high risk of bleeding. Iron accumulation with aging has been implicated in the pathogenesis of cardiovascular disease in general and arrhythmias in particular. Uncompensated iron-catalyzed oxygen free radical formation accounts for such toxicity. Remission of arrhythmias has been reported with iron reduction therapy in patients with iron overload disorders. Effects of iron reduction on arrhythmias in settings other than iron overload syndromes are unknown. Body iron stores as assessed by serum ferritin levels were elevated in both men (389 and 305 ng/ml respectively) but neither had the C282Y or H63D genes for hemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was performed and was followed by sustained remission of PAF in both cases. These findings suggest that iron reduction with maintenance of ferritin levels below about 100 ng/ml may be effective treatment for arrhythmias apart from the classic iron overload syndromes. Effects of primary prevention of iron accumulation over time and reduction of existing elevated iron stores deserve further study in patients with bleeding disorders in whom standard treatment of diseases of aging may be costly and carry high risk. The efficacy, safety, simplicity and cost effectiveness of iron reduction therapy commends application of this investigational approach to disease prevention and treatment in the general population.