Arrhythmogenic mechanisms of obstructive sleep apnea in heart failure patients.

Abstract

Heart failure (HF) affects 23 million people worldwide and results in 300000 annual deaths. It is associated with many comorbidities, such as obstructive sleep apnea (OSA), and risk factors for both conditions overlap. Eleven percent of HF patients have OSA and 7.7% of OSA patients have left ventricular ejection fraction <50% with arrhythmias being a significant comorbidity in HF and OSA patients. Forty percent of HF patients develop atrial fibrillation (AF) and 30%-50% of deaths from cardiac causes in HF patients are from sudden cardiac death. OSA is prevalent in 32%-49% of patients with AF and there is a dose-dependent relationship between OSA severity and resistance to anti-arrhythmic therapies. HF and OSA lead to various downstream arrhythmogenic mechanisms, including metabolic derangement, remodeling, inflammation, and autonomic imbalance. (1) Metabolic derangement and production of reactive oxidative species increase late Na+ currents, decrease outward K+ currents and downregulate connexin-43 and cell-cell coupling. (2) remodeling also features downregulated K+ currents in addition to decreased Na+/K+ ATPase currents, altered Ca2+ homeostasis, and increased density of If current. (3) Chronic inflammation leads to downregulation of both Nav1.5 channels and K+ channels, altered Ca2+ homeostasis and reduced cellular coupling from alterations of connexin expression. (4) Autonomic imbalance causes arrhythmias by evoking triggered activity through increased Ca2+ transients and reduction of excitation wavefront wavelength. Thus, consideration of these multiple pathophysiological pathways (1-4) will enable the development of novel therapeutic strategies that can be targeted against arrhythmias in the context of complex disease, such as the comorbidities of HF and OSA.

• Authors: Karan R Chadda, Ibrahim T Fazmin, Shiraz Ahmad, Haseeb Valli, Charlotte E Edling, Christopher L-H Huang, Kamalan Jeevaratnam
• Journal: Sleep (Sleep) Vol. 41 Issue 9 (09 01 2018) ISSN: 1550-9109 [Electronic] United States
• PMID: 30016501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Connexin 43
• GJA1 protein, human

Topics

• Atrial Fibrillation (epidemiology, metabolism, physiopathology)
• Comorbidity
• Connexin 43 (metabolism)
• Death, Sudden, Cardiac (epidemiology)
• Heart Failure (epidemiology, metabolism, physiopathology)
• Humans
• Risk Factors
• Sleep Apnea, Obstructive (epidemiology, metabolism, physiopathology)
• Ventricular Function, Left (physiology)