Sleep-Disordered Breathing and Cardiac Arrhythmias in Adults: Mechanistic Insights and Clinical Implications: A Scientific Statement From the American Heart Association

Abstract

Sleep-disordered breathing (SDB), characterized by specific underlying physiological mechanisms, comprises obstructive and central pathophysiology, affects nearly 1 billion individuals worldwide, and is associated with excessive cardiopulmonary morbidity. Strong evidence implicates SDB in cardiac arrhythmogenesis. Immediate consequences of SDB include autonomic nervous system fluctuations, recurrent hypoxia, alterations in carbon dioxide/acid-base status, disrupted sleep architecture, and accompanying increases in negative intrathoracic pressures directly affecting cardiac function. Day-night patterning and circadian biology of SDB-induced pathophysiological sequelae collectively influence the structural and electrophysiological cardiac substrate, thereby creating an ideal milieu for arrhythmogenic propensity. Cohort studies support strong associations of SDB and cardiac arrhythmia, with evidence that discrete respiratory events trigger atrial and ventricular arrhythmic events. Observational studies suggest that SDB treatment reduces atrial fibrillation recurrence after rhythm control interventions. However, high-level evidence from clinical trials that supports a role for SDB intervention on rhythm control is not available. The goals of this scientific statement are to increase knowledge and awareness of the existing science relating SDB to cardiac arrhythmias (atrial fibrillation, ventricular tachyarrhythmias, sudden cardiac death, and bradyarrhythmias), synthesizing data relevant for clinical practice and identifying current knowledge gaps, presenting best practice consensus statements, and prioritizing future scientific directions. Key opportunities identified that are specific to cardiac arrhythmia include optimizing SDB screening, characterizing SDB predictive metrics and underlying pathophysiology, elucidating sex-specific and background-related influences in SDB, assessing the role of mobile health innovations, and prioritizing the conduct of rigorous and adequately powered clinical trials.

Keywords: AHA Scientific Statements; arrhythmia; atrial fibrillation; autonomic; hypoxia; sleep apnea.

Figure 1.. Multilayered pathophysiology and temporality of sleep-disordered breathing and cardiac arrhythmia.

Immediate, subacute, and chronic sleep-disordered breathing (SDB) pathophysiology contributing to cardiac arrhythmogenesis. SDB includes obstructive sleep apnea (OSA) characterized by upper airway collapse and central sleep apnea (CSA) with abnormalities in hypoxic ventilatory mechanisms (carotid chemoreceptors) and carbon dioxide chemosensitivity (medullary chemoreception). Immediate SDB effects include autonomic nervous system fluctuations, repetitive intermittent hypoxia and carbon dioxide alterations, intrathoracic pressure alterations, and circadian variability. Acute and subacute SDB influences over days to weeks lead to repetitive direct cardiac mechanical influences, resulting in atrial distention, increased left ventricular (LV) pressure and transmural gradient, and increased venous return, as well as electrophysiological alterations, including reduced atrial effective refractory period (AERP), dynamic QT prolongation, electromechanical window (EMW) shortening, increased delayed afterdepolarizations (DADs), and early afterdepolarizations (EADs), as well as increased systemic inflammation and oxidative stress. Chronic SDB influences include cardiac structural and electrophysiological remodeling, with data supporting Ca/calmodulin–dependent protein kinase II (CaMKII)–dependent phosphorylation, connexin dysregulation, increased fibrosis, and a potential role of metabolic dysregulation and epicardial fat secretome. Over time, with increasing age, these SDB-induced pathophysiological effects on the cardiac substrate enhance arrhythmia vulnerability. LA indicates left atrial. Reprinted with permission from the Cleveland Clinic Center for Medical Art & Photography. Copyright © 2022. All rights reserved.

Figure 2.. Patient-centric, integrated stepped care model of SDB and cardiac arrhythmia.

A multidisciplinary team–based care approach in a patient-centered model leveraging technology to support sleep-disordered breathing (SDB) diagnostics and management in people with cardiac arrhythmia incorporating the following steps can be considered: initiation of (1) guideline-directed therapy, (2) SDB screening, (3) SDB diagnostics as indicated, (4) SDB treatment as indicated, and (5) cardiac arrhythmia risk factor and SDB management with the goal of follow-up to reduced cardiac arrhythmia–related morbidity and maintain sinus rhythm in atrial fibrillation (AF), as well as (6) teaching and self-care support. App indicates application; CSA, central sleep apnea; EMR, electronic medical record; HSAT, home sleep apnea testing; NABS, Neck Circumference/Age/Body Mass Index/Snoring; NC, neck circumference; OSA, obstructive sleep apnea; PAP, positive airway pressure; PSG, polysomnogram; STOP-BANG, Snoring/Tiredness/Observed Apnea/Pressure (High Blood Pressure)/Body Mass Index/Age/Neck Circumference/Gender; and VTA, ventricular tachyarrhythmia. *Please refer to Table 3 for reference to sources for guideline recommendations for cardiac arrhythmia management. Reprinted with permission from the Cleveland Clinic Center for Medical Art & Photography. Copyright © 2022. All rights reserved.