Sleep-Disordered Breathing in Heart Failure　― A Therapeutic Dilemma ―

Abstract

for their deployment can be advocated (Table). However, the promise of observational studies and randomized trials of small size and duration describing a beneficial effect of treating SDB in HF via positive airway pressure (PAP) was not realized in 2 recent randomized outcome-driven trials: SAVE, which evaluated the cardiovascular effect of treating OSA in a cohort without HF, 7 and SERVE-HF, which reported the results of a strategy of random allocation of minute-ventilation-triggered adaptive servo-ventilation (ASV) for HF patients with CSA. 3 Consequently, equipoise remains as to whether either OSA or CSA, once detected in a HF patient with reduced left ventricular ejection fraction (LVEF), should be therapeutically suppressed. The threefold purpose of this review was to: (1) summarize current knowledge concerning the prevalence, pathophysiology, and prognostic implications of SDB in HF in support of treatment; (2) examine and reflect upon the results of randomized controlled trials evaluating the effect of treating OSA or CSA on cardiovascular endpoints and mortality; and (3) illustrate how ADVENT-HF, a randomized controlled trial designed to determine the effect of treating HF patients with either CSA or nonsleepy OSA using a peak-airflow triggered ASV algorithm, could resolve the present clinical equipoise concerning the treatment of one or both forms of SDB.A fundamental and as yet unresolved question for the heart failure (HF) community is whether coexisting obstructive (OSA) or central sleep apnea (CSA) should be specific targets of therapy. For individuals without HF, the principal clinical indication to treat sleep apnea is to improve quality of life (QOL) and avert accidental injury or death by alleviating daytime hypersomnolence. However, this indication does not pertain to the majority of patients with reduced left ventricular systolic function and sleep-disordered breathing (SDB) as they are not burdened by excess daytime sleepiness. 1-3 In such individuals, the impetus to diagnosis and treatment is the hypothesis that attenuation or abolition of SDB will modify beneficially the natural history of HF.OSA and CSA interrupt breathing by different mechanisms but impose qualitatively similar autonomic, chemical, mechanical, and inflammatory burdens on the heart and circulation. 4-6 Because contemporary evidence-based drug and device HF therapies have little or no mitigating effect on the acute consequences of such stimuli or on the long-term structural and functional adaptations they induce within the atria and ventricles, the brain and the peripheral vasculature, there is a sound mechanistic rationale for targeting SDB to reduce cardiovascular event rates and prolong life. Importantly, effective treatment is presently available for both OSA and CSA and cogent reasons Sleep-disordered breathing (SDB) occurs in approximately 50% of patients with reduced left ventricular ejection fraction receiving contemporary heart failure (HF) therapies. Obstructive (OSA) and central sleep apneas (CSA) interrupt brea...

The 2021 Carl Ludwig Lecture. Unsympathetic autonomic regulation in heart failure: patient-inspired insights

“…The principal risk factors for central sleep apnea (CSA) were male gender, atrial fibrillation, age > 60 years, and hypocapnia (PCO2 < 38 mmHg). Subsequently, similar prevalences, based on lower or higher diagnostic thresholds, were documented in German, British, Japanese and American heart failure cohorts (60). Longitudinal studies revealed 453 the prognostic importance of concurrent sleep apnea: in our patients with ischemic cardiomyopathy but no or only mild sleep apnea, 3-year survival was approximately 83%, whereas if moderate to severe sleep apnea was diagnosed and treatment declined, 3-year survival was approximately 48% (adjusted hazard ratio P=0.04) (61).…”

“…Our subsequent long-term trial of treating heart failure patients with co-existing CSA was neutral (78), principally because in ~40% enrolled, conventional CPAP failed to suppress apnea (79). We are now exploring, in a multinational randomized clinical trial, the impact of long-term adaptive servo-ventilation therapy on survival and cardiovascular hospitalization of patients with heart failure and either OSA or CSA (60,80).…”

Relationship of stroke volume to different patterns of Cheyne-Stokes respiration in heart failure

“…It will be possible to test prospectively whether responses to ASV therapy differ between the positive and negative forms of CSR-CSA in the setting of the ADVENT-HF trial [11,35]. This randomized trial is examining the effects of peak flow triggered ASV on morbidity, mortality and cardiac structure and function [36] in HFrEF patients with either CSR-CSA or OSA. Reduction in LV workload is a mainstay of HFrEF therapy.…”

Sleep Disordered Breathing and Cardiovascular Diseases

“…Further studies are needed to determine whether managing SDB improves the prognosis of patients with SDB. Several studies in patients with CAD 106) or HF 107, 108) are ongoing and their results are expected.…”