Arrhythmogenic and metabolic remodelling of failing human heart

• Published in: The Journal of physiology Vol. 594; no. 14; pp. 3963 - 3980
• Main Authors: Gloschat, C. R., Koppel, A. C., Aras, K. K., Brennan, J. A., Holzem, K. M., Efimov, I. R.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 15.07.2016; John Wiley and Sons Inc
• Subjects: Animals; Arrhythmias, Cardiac - physiopathology; Cardiovascular Physiology; Heart; Heart - physiology; Heart - physiopathology; Heart Failure - physiopathology; Humans; Special section reviews: Cardiac autonomic control in health and disease; Topical Review
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP271992

Heart failure (HF) is a major cause of morbidity and mortality worldwide. The global burden of HF continues to rise, with prevalence rates estimated at 1–2% and incidence approaching 5–10 per 1000 persons annually. The complex pathophysiology of HF impacts virtually all aspects of normal cardiac function – from structure and mechanics to metabolism and electrophysiology – leading to impaired mechanical contraction and sudden cardiac death. Pharmacotherapy and device therapy are the primary methods of treating HF, but neither is able to stop or reverse disease progression. Thus, there is an acute need to translate basic research into improved HF therapy. Animal model investigations are a critical component of HF research. However, the translation from cellular and animal models to the bedside is hampered by significant differences between species and among physiological scales. Our studies over the last 8 years show that hypotheses generated in animal models need to be validated in human in vitro models. Importantly, however, human heart investigations can establish translational platforms for safety and efficacy studies before embarking on costly and risky clinical trials. This review summarizes recent developments in human HF investigations of electrophysiology remodelling, metabolic remodelling, and β‐adrenergic remodelling and discusses promising new technologies for HF research. Cardiovascular science pendulum swings between reductionist and integrative approaches (left to right): single isolated myocyte labelled with a membrane fluorescent marker (Di‐4‐ANEPPS); human ventricular myocardium is primarily composed of myocytes (red, a‐actinin) coupled with connexin 43 (green), and fibroblasts (vimentin, blue); isolated human heart; electrocardiography in patient (1925, Thomas Lewis).