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Atrial fibrillation (AF) is the most common clinical arrhythmia, the incidence of which is rising. More than 15.9 million people in the USA will have AF by 2050.1 Current therapies for AF, antiarrhythmic drugs and catheter ablation, have significant limitations. Most current antiarrhythmic drugs target one or a few of the cardiomyocyte ion channels. Current drugs have considerable proarrhythmic and non-cardiac adverse effects. In the treatment of AF, a lack of a significant difference in the outcome of a rhythm control strategy using current antiarrhythmic drugs and a rate control strategy points to the limited efficacy of these drugs. Catheter ablation is based on creation of scar tissue in the heart in order to prevent focal discharges from propagating, or to block the re-entrant circuits of AF. Ablation has somewhat debatable long-term success in management of AF. In addition, catheter ablation of AF is an expensive treatment that probably cannot meet the growing demand for AF therapy and is associated with significant complications. A major reason for the limited success with the aforementioned therapies may be the fact that neither antiarrhythmic drugs nor catheter ablation addresses the upstream underlying pathophysiologies of AF. Current antiarrhythmic drugs block target ion channels, while the ion channel abnormality is often downregulated as a result of upstream signalling events. Similarly, catheter ablation provides an anatomically fixed treatment for focal discharges and re-entry circuits, while the reasons for those abnormal electrical activities remain unaddressed, and while the location of the arrhythmic substrates can change over time.
The pathophysiology of AF is complex and is not completely understood, but many studies suggest oxidative stress as …
Dr Dudley has applied for the following patents: (1) Method for Predicting Onset/Risk of Atrial Fibrillation, (2) Prevention of sudden death by modulation of Src family, (3) Modulating mitochondrial-reactive oxygen species to increase cardiac sodium channel current and mitigate sudden death, (4) Biomarkers for Prediction of Stroke Risk in Atrial Fibrillation, and (5) Mitochondrial antioxidants for prevention of sudden death by raising connexin43 levels.
Funding This work was funded by RO1 HL1024025, T32 HL072742, P01 HL058000, R01 HL106592, a VA MERIT grant, and an American Heart Association Midwest Affiliate Postdoctoral Fellowship # AHA10POST4450037.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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