Treatment of central sleep apnea in patients with heart failure: Now and future

Table 1 Short term randomized control trial investigating the effects of continuous positive airway pressure treatment on cardiac functions in heart failure patients with central sleep apnea

Author, year	Duration	n	Design	Findings
Naughton, 1995[7]	1 mo	25	no-CSA vs CPAP vs CSA-control	Urine and plasma NE↓, LVEF↑, NYHA class↓
Naughton, 1995[8]	3 mo	29	no-CSA vs CPAP vs CSA-control	LVEF↑, improve symptoms
Granton, 1996[30]	3 mo	17	CPAP vs CSA-control	MIP↑, LVEF↑, improve symptoms
Tkacova, 1997[9]	3 mo	17	CPAP vs CSA-control	LVEF↑, Mitral regurgitant fraction↓, plasma ANP↓

RCT: Randomized control trial; CPAP: Continuous positive airway pressure; HF: Heart failure; CSA: Central sleep apnea; LVEF: Left ventricular ejection fraction; NYHA: New York Heart Association; NE: Norepinephrine; MIP: Maximal inspiratory pressure; ANP: Atrial natriuretic peptide.

Table 2 Short term randomized control trial investigating the effects of adaptive servo ventilation treatment on cardiac functions in heart failure patients with central sleep apnea

Author, year	Duration	n	Design	Findings
Pepperell, 2003[31]	1 mo	30	Therapeutic mv-ASV vs subtherapeutic mv-ASV	Plasma BNP↓, urinary metadrenaline↓
Philippe, 2006[11]	6 mo	25	CPAP vs mv-ASV	Significant increase in LVEF and improvement in QOL in ASV group
Fietze, 2008[32]	1.5 mo	37	bi-level PAP with standard S/T mode vs mv-ASV mode	LVEF increased more in the bi-level PAP group. Daytime blood pressure and heart rate did not change
Kasai, 2013[10]	3 mo	23	CPAP vs pf-ASV	LVEF increased more in the ASV group
O’Connor, 2017[21] (CAT-HF trial)1	6 mo	126	SDB-control vs mv-ASV	No significant cardiac improvement found

¹CAT-HF trial includes patients with predominant OSA in addition to predominant CSA (> 70% patients had predominant CSA). RCT: Randomized control trial; ASV: Adaptive servo ventilation; CPAP: Continuous positive airway pressure; HF: Heart failure; CSA: Central sleep apnea; OSA: Obstructive sleep apnea; LVEF: Left ventricular ejection fraction; QOL: Quality of life; S/T mode: Spontaneous/timed mode; SDB: Sleep disordered breathing; mv-ASV: Minute volume of ventilation-targeted ASV; pf-ASV: Peak-airflow triggered ASV.

Table 3 Long term randomized control trials investigating the effects of continuous positive airway pressure treatment on cardiovascular outcomes in heart failure patients with central sleep apnea

Author, year	Duration	n	Design	Findings
Sin, 2000[12]	2.2 yr (median)	66	No-CSA-control vs no-CSA-CPAP vs CSA-CPAP vs CSA-control	Mortality-cardiac transplantation rate↓ who complied with CPAP, LVEF↑ in CSA-CPAP group
Bradley, 2005[13] (CANPAP trial)	2 yr (mean)	258	CSA-control vs CPAP	Plasma NE↓, LVEF↑, distance in a 6-min walk test↑
Arzt, 2007[14] (Post hoc analysis of CANPAP trial)	23 mo (mean)	210	CSA-control vs CPAP	Patients whose AHI < 15 events/h by CPAP had significantly improved transplant-free survival and greater improvement in LVEF compared with control

RCT: Randomized control trial; CPAP: Continuous positive airway pressure; HF: Heart failure; CSA: Central sleep apnea; LVEF: Left ventricular ejection fraction; NE: Norepinephrine; AHI: Apnea hypopnea index.

Table 4 Long term randomized control trial investigating the effects of adaptive servo ventilation treatment on cardiovascular outcomes in heart failure patients with central sleep apnea

Author, year	Duration	n	Design	Findings
Cowie, 2015[15] (SERVE-HF trial)	31 mo (median)	1325	mv-ASV vs CSA-control	All-cause and cardiovascular mortality were both increased in ASV group

RCT: Randomized control trial; ASV: Adaptive servo ventilation; HF: Heart failure; CSA: Central sleep apnea; mv-ASV: Minute volume of ventilation-targeted ASV.