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J Physiol. 2016 Jul 15;594(14):3963-80. doi: 10.1113/JP271992. Epub 2016 Jun 12.

Arrhythmogenic and metabolic remodelling of failing human heart.

Author information

1
Department of Biomedical Engineering, The George Washington University, Washington, DC, USA.

Abstract

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.

PMID:
27019074
PMCID:
PMC4945707
DOI:
10.1113/JP271992
[Indexed for MEDLINE]
Free PMC Article

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