title: What Is the Arrhythmic Substrate in Viral Myocarditis? Insights from Clinical and Animal Studies.
abstract: Sudden cardiac death (SCD) remains an unsolved problem in the twenty-first century. It is often due to rapid onset, ventricular arrhythmias caused by a number of different clinical conditions. A proportion of SCD patients have identifiable diseases such as cardiomyopathies, but for others, the causes are unknown. Viral myocarditis is becoming increasingly recognized as a contributor to unexplained mortality, and is thought to be a major cause of SCD in the first two decades of life. Myocardial inflammation, ion channel dysfunction, electrophysiological, and structural remodeling may play important roles in generating life-threatening arrhythmias. The aim of this review article is to examine the electrophysiology of action potential conduction and repolarization and the mechanisms by which their derangements lead to triggered and reentrant arrhythmogenesis. By synthesizing experimental evidence from pre-clinical and clinical studies, a framework of how host (inflammation), and viral (altered cellular signaling) factors can induce ion electrophysiological and structural remodeling is illustrated. Current pharmacological options are mainly supportive, which may be accompanied by mechanical circulatory support. Heart transplantation is the only curative option in the worst case scenario. Future strategies for the management of viral myocarditis are discussed.
authors: Li Ka Shing Faculty of Medicine, School of Biomedical Sciences, University of Hong KongHong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong KongHong Kong, China.
authors: Gary
authors: G
authors: Tse
authors: Faculty of Medicine, Imperial College London London, UK.
authors: Jie M
authors: JM
authors: Yeo
authors: Department of Psychology, School of Biological Sciences, University of Cambridge Cambridge, UK.
authors: Yin Wah
authors: YW
authors: Chan
authors: Li Ka Shing Faculty of Medicine, School of Biomedical Sciences, University of Hong Kong Hong Kong, China.
authors: Eric T H Lai
authors: ET
authors: Lai
authors: Department of Medicine and Therapeutics, The Chinese University of Hong KongHong Kong, China; Department of Epidemiology and Preventive Medicine, Monash UniversityMelbourne, VIC, Australia.
authors: Bryan P
authors: BP
authors: Yan
keywords: cardiac arrhythmia; conduction; mouse model; repolarization; viral myocarditis; viral-induced cardiomyopathy