Figures
- FIGURE 1
Illustration of the pathophysiological approach to treatment of sleep disordered breathing. Continuous positive airway pressure or expiratory positive airway pressure stabilise the obstructive component of the upper airways; variable pressure support or mandatory breaths counterbalance the overshoot and undershoot of ventilation due to brainstem disturbances; and reduction in tidal volume and minute ventilation require mechanical ventilation.
- FIGURE 2
The respiratory system is composed of three components, which have been described as a loop gain. Imbalance of the loop gain may lead to a vicious circle of overshoot and undershoot of the ventilation: any inadequate increase of the ventilation induces hypocapnia; hypocapnia dampens the carbon dioxide-sensitive chemoreceptors, leading to a dampening of the inspiratory impulses of the brain stem. As a consequence, minute ventilation (generated from the plant gain) is reduced, leading to hypoxia; hypoxia stimulates the chemoreceptors and consecutively respiratory drive.
- FIGURE 3
The figure shows the approaches of various treatment options on the loop gain. Oxygen (O2) supply increases the alveolar O2 concentration and avoids hypoxic stimulation of the chemoreceptors. In addition, it may influence myocardial function. Carbon dioxide (CO2) plays a major role in the pathophysiology of periodic breathing. The application of CO2 by rebreathing or external supply elevates the arterial CO2 tension above the apnoea threshold and impedes central apnoeas. Drugs may influence respiratory drive in the brainstem. Some pharmaceutical influences on arousability, sleep stages and sleep efficiency can stabilise respiration or shift sleep stages from non-rapid eye movement (REM) stages I and II to slow-wave or REM sleep. CPAP: continuous positive airway pressure; BIPAP: bilevel positive airway pressure.
Tables
- TABLE 1
Studies on adaptive servoventilation since the publication of SERVE-HF
Study/authors, year [reference] Design Population Intervention Primary outcome Median follow-up Results FACE study, 2016 [50] Prospective multicentre observational cohort
France
Up to January 31, 2013CHF with reduced LVEF (HFrEF <40%), mid-range (HFmrEF 40–49%), preserved (HFpEF >50%) 361 CHF patients with CSA eligible for ASV therapy (n=258) versus controls# (n=133) refused/not compliant with ASV (<3 h per night)
(ResMed, AutoSet CS) 66% compliant to ASV therapyAll-cause death, hospitalisation for worsening heart failure, heart transplant or ventricular assist device 21.6 months ASV improved prognosis in HFmEF in non-ischaemic heart failure; trend to increase in event rate in HFmrEF in ischaemic heart disease; improved prognosis in HFpEF CHF with severe desaturations CAT-HF study, 2017 [51] Prospective, randomised, controlled, multicentre clinical trial
United States and Germany
2013–2015Hospitalised heart failure (HFrEF >45% or HFpEF ≥45%) and SDB (OSA or CSA) with AHI ≥15 events·h−1 via polygraphy 126 out of 215 patients assigned on ASV plus optimised medical therapy (n=65) versus optimised medical therapy alone (control) (n=61) Composite global rank score (death, CV hospitalisations, and percentage changes in 6-min walk distance)
Secondary end-points: sleep apnoea parameters, functional capacity, cardiovascular and all-cause death, days alive and out of the hospital, biomarkers, QoL, sleep parameters, imaging parameters and NYHA functional class6 months Neutral
No improvement in 6-month cardiovascular outcomes; however, a positive effect of ASV in patients with HFpEF
Study was stopped after publication of SERVE-HFImamura et al., 2016 [52] Case–control study
Tokyo, Japan
2008–2014Heart failure NYHA III or IV (71% NYHA IV, LVEF 33±17%) with ASV irrespective of SDB 85 patients receiving ASV 1 month versus guideline-directed medical therapies
(AutoSet-CS; ResMed, Sydney, Australia) with full face mask (ResMed)All-cause mortality and cardiac deaths 2-year follow-up Continued ASV significantly lowered all-cause mortality and cardiac death rate Hetland et al., 2016 [53] Retrospective observational study
Østfold, Norway
2007–2012Heart failure NYHA class II–IV, LVEF ≤45%; CSR pattern ≥25% of sleeping time and dominant central sleeping pattern via polygraphy 75 patients treated with ASV (n=31 with ASV for >3–18 months versus n=44 control)
(AutoSet-CS)Mortality and hospital admission of any cause and number of days in hospital in total 18 months ASV did not significantly affect CV death or combined CV death or hospital admissions after 18 months; trend toward better CV event-free survival for ASV usage Bordier and Lataste, 2019 [54] Retrospective study
2006–2018Patient from the sleep unit of the CV department treated with ASV for sleep apnoea (C/M/O apnoeas via PG) 32 patients with ASV
8 deathsCV mortality Survival CV deaths not predominant
No relationship between sleep apnoea or ASV and deathMansukhani et al., 2019 [55] Population-based study, using the Rochester Epidemiology Project database CSA (AHI 41.6±26.5 events·h−1), with ASV therapy (65% ≥4 h per night on ≥70% nights in their first month), and had ≥1 month of clinical data before and after ASV initiation 309 CSA patients under ASV versus healthcare utilisation Rates of hospitalisations, emergency department visits, outpatient visits and medications prescribed per year (mean±sd) 2 years pre- and post-ASV initiation ASV did not change healthcare utilisation ADVENT-HF trial, recruiting [56] Multicentre, multinational, randomised, parallel-group, open-label trial
CanadaChronic HFrEF (≤45%) and SDB (OSA or CSA) with AHI ≥15 events·h−1 via PSG Estimated n>800, still recruiting 524 patients (31% CSA, 69% OSA) randomised until February 2018 on medical therapy alone or ASV (AutoSet-CS) with nasal mask All-cause mortality, first hospitalisation for CV diseases, new-onset atrial fibrillation/flutter requiring anticoagulation but not hospitalisation or implantable cardioverter-defibrillator shock not requiring hospitalisation Every 6 months Awaited ASV studies with mortality as primary outcome. The table summarises the results of additional studies on ASV in heart failure and CSA. Methodologies incompletely describe the types of masks and ASV devices used, sleep study, algorithm of titration and compliance to the device. Only one study (FACE) stratified patients in relation to the severity of HFrEF. CHF: chronic heart failure; LVEF: left ventricular ejection fraction; HFrEF: heart failure with reduced ejection fraction; HFmrEF: heart failure with mid-range ejection fraction; HFpEF: heart failure with preserved ejection fraction; CSA: central sleep apnoea; ASV: adaptive servoventilation; SDB: sleep disordered breathing; OSA: obstructive sleep apnoea; AHI: apnoea–hypopnoea index; CV: cardiovascular; QoL: quality of life; NYHA: New York Heart Association; CSR: Cheyne–Stokes respiration.
