Apneas of Heart Failure and Phenotype-Guided Treatments: Part One: OSA

Abstract

Sleep-disordered breathing (SDB), including OSA and central sleep apnea, is highly prevalent in patients with heart failure (HF). Multiple studies have reported this high prevalence in asymptomatic as well as symptomatic patients with reduced left ventricular ejection fraction (HFrEF), as well as in those with HF with preserved ejection fraction. The acute pathobiologic consequences of OSA, including exaggerated sympathetic activity, oxidative stress, and inflammation, eventually could lead to progressive left ventricular dysfunction, repeated hospitalization, and excessive mortality. Large numbers of observational studies and a few small randomized controlled trials have shown improvement in various cardiovascular consequences of SDB with treatment. There are no long-term randomized controlled trials to show improved survival of patients with HF and treatment of OSA. One trial of positive airway pressure treatment of OSA included patients with HF and showed no improvement in clinical outcomes. However, any conclusions derived from this trial must take into account several important pitfalls that have been extensively discussed in the literature. With the role of positive airway pressure as the sole therapy for SDB in HF increasingly questioned, a critical examination of long-accepted concepts in this field is needed. The objective of this review was to incorporate recent advances in the field into a phenotype-based approach to the management of OSA in HF.

Keywords: Hunter-Cheyne-Stokes breathing; adaptive servo-ventilation; central sleep apnea; heart failure; noninvasive ventilation; oxygen; positive airway pressure.

Figure 1

Prevalence of moderate to severe sleep apnea (AHI ≥ 15 events per hour) in asymptomatic LVSD or LVDD, HFpEF or HFrEF, ADHF, and ACPE. ACPE = acute cardiogenic pulmonary edema; ADHF = acutely decompensated heart failure; AHI = apnea-hypopnea index; CSA = central sleep apnea; HFpEF = heart failure with preserved ejection fraction; HFrEF = heart failure with reduced ejection fraction; LVDD = left ventricular diastolic dysfunction; LVSD = left ventricular systolic dysfunction. Reprinted with permission of Elsevier from Javaheri et al.

Figure 2

Impact of sleep apnea on survival in heart failure (HF). Survival of patients with HF treated for sleep apnea (n = 258) and patients with HF not tested or treated for sleep apnea (n = 30,065). Kaplan-Meier survival curves adjusted according to age, sex, and Charlson Comorbidity Index. (Reprinted with permission of Am J Respir Crit Care Med. from Javaheri et al¹¹)

Figure 3

The various phenotypic/endotypic traits of OSA. (Courtesy of Dr David White, with permission.)

Figure 4

A conceptual approach to phenotype-guided treatment for OSA in patients with heart failure. PAP = positive airway pressure.