Fetal cardiomyocyte phenotype, ketone body metabolism, and mitochondrial dysfunction in the pathology of atrial fibrilla
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Fetal cardiomyocyte phenotype, ketone body metabolism, and mitochondrial dysfunction in the pathology of atrial fibrillation Sean M. Brown1 · Nicholas K. Larsen1 · Finosh G. Thankam2 · Devendra K Agrawal2 Received: 29 July 2020 / Accepted: 6 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Atrial fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice. Even though hypertension, congestive heart failure, pulmonary disease, and coronary artery disease are the potential risk factors for AF, the underlying molecular pathology is largely unknown. The reversion of the mature cardiomyocytes to fetal phenotype, impaired ketone body metabolism, mitochondrial dysfunction, and the cellular effect of reactive oxygen species (ROS) are the major underlying biochemical events associated with the molecular pathology of AF. On this background, the present manuscript sheds light into these biochemical events in regard to the metabolic derangements in cardiomyocyte leading to AF, especially with respect to structural, contractile, and electrophysiological properties. In addition, the article critically reviews the current understanding, potential demerits, and translational strategies in the management of AF. Keywords Atrial fibrillation · Cardiomyocyte metabolism · Cardiomyocyte · Cardiac metabolism · Arrhythmias
Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice and represents a substantial financial burden [1]. AF is characterized by the electrocardiographic (ECG) features consisting of an “irregularly irregular,” non-repetitive R-R interval and non-distinct P waves. Hypertension, congestive heart failure, pulmonary disease, and coronary artery disease are the potential risk factors for AF. Patients are often asymptomatic; however, they may present with symptoms of shortness of breath, heart palpitations, angina, and fatigue. Untreated AF results in reduced cardiac output and thromboembolic events, such as stroke and atrial appendage thrombus formation [2–4]. Initial management consists of strategies that control the rate and/or rhythm including ß-blockers, calcium channel blockers, or antiarrhythmic drugs. In addition, due to the increased risk of thrombus, anti-coagulation is often used. * Devendra K Agrawal [email protected] 1
Creighton University School of Medicine, Omaha, NE 68178, USA
Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA 91766, USA
2
For patients with persistent or refractory AF, radiofrequency catheter ablation has shown higher efficacy rates when compared to antiarrhythmic drugs [5]. Epidemiologically, AF is increasing in the general population, with an additional increase of prevalence in men and with increasing age [6–8]. In general, the pathophysiology of AF consists of three stages: initiation of the arrhythmia, maintenance of the arrhythmia, and progression of the disease to longer lasting forms [9, 1
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