(obstructive sleep apnea; OSA) (central sleep apnea; CSA) CSA. OSA CPAP (continuous positive airway pressure) CSA controversial

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1 (2016 ) (obstructive sleep apnea; OSA) (central sleep apnea; CSA) CSA OSA CPAP (continuous positive airway pressure) CSAcontroversial Heart failure, sleep apnea, positive airway pressure, adaptive servo ventilation, hemodynamics 47 76% 1-4) (obstructive sleep apnea; OSA) OSA (central sleep apnea; CSA) OSA CSA 5) OSA CSA 6) CSA adaptive servo-ventilation (ASV) CSA SEE-HF ASV negative study 7) OSA CSA OSA CSA 10 30%10 3% 8) (apnea-hypopea index; AHI) 1 AHI < 5/h 5/h AHI < 15/h 15/h AHI < 30/h AHI 30/h 3070 AHI 5/hOSA 34% 17% AHI 15/h 13% 6% 9) AHI 11/h OSA 17

2 ) OSA AHI 15/h 12 32% 2-4,11) AHI BMI 12) OSA 13) Marin JMOSA 2.87OSA 14) OSA 15) 16) MACE (major adverse cardiac events) 17) 18) OSA transmural pressure 19) OSA 20) OSA OSA 20) (Figure 1) OSA 21) Arousal OSA Fluctua ng thoracic pressure Hypoxia Hypercapnia Airway collapse Hypoxia Sympathe c ac va on Vagal tone Rostral fluid shi at night Pharyngeal muscular drive Oxida ve stress A erload RAAS Blood pressure Heart rate VO 2 Peripheral edema Cheyne-Stokes respira on Endothelial dysfunc on Le ventricular remodeling CAD Fluid reten on Heart failure Figure 1. Relationship between obstructive sleep apnea (OSA) and heart failure (modified from reference 67) Schematic representation of the mutual interactions between OSA and heart failure. CAD = coronary artery disease; RAAS = renin-angiotensin-aldosterone system; VO 2 = oxygen consumption rate. 18

3 volume overload 22) OSA OSA OSA 22) OSA OSA OSA 23) OSA CPAP (continuous positive airway pressure) 24,25) CSA 1% 26) AHI 15/h 15 37% 2,3,11) CO 2 2) CSA (pulmonary capillary wedge pressure; PCWP) (cardiac index; CI) CSA 27) CSA 28) β CRT (cardiac resynchronization therapy) CSA 29-31) (PaCO 2 ) PaCO 2 CSA 32) CSA PaCO ) PaCO 2 CO 2 35,36) CSA OSA 37,38) 39) 40) (Figure 2) CSA CPAP CANPAP trialcpap SDB (sleep disordered breathing) EF 41) CPAP SDB (AHI 15/h ) responder CSA 42) CSA adaptive servo ventilation (ASV) CPAP BIPAP (biphasic positive airway pressure) HOT (home oxygen therapy) CSA 43) CSA ASV CPAP 43) EF NT-pro BNP 44-47) 48-50) 51-55) ASV SAIVOR- C ASV 56) CSA (EF 45%) ASV SEE-HFprimary end point death from any cause lifesaving cardiovascular intervention ASV 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 57) EF ASVClass III (Level B) EF ASV adverse effect CAT-HF study 58) SEE-HF entry 19

4 Arousal CSA Apnea threshold PaO 2 and PaCO 2 oscilla on Respiratory center altera ons PaCO 2 Sympathe c ac va on Vagal tone Cardiovascular sympathe c neuron cyclic ac va on Ven latory rate RAAS Blood pressure Heart rate VO 2 oscilla on PaCO 2 sensi vity Rostral fluid shi at night Fluid reten on Le ventricular remodeling Heart failure Peripheral edema Pulmonary conges on Figure 2. Relationship between central sleep apnea (CSA) and heart failure (modified from reference 67) Schematic representation of the mutual interactions between CSA and heart failure. PaCO 2 = arterial partial pressure of CO 2 ; PaO 2 = arterial partial pressure of O 2 ; RAAS = renin-angiotensin-aldosterone system; VO2 = oxygen consumption rate. ASV ASV CSA 59) 60) AHI 49.9 ± 15.1/h 27.5 ±18.3/h, CAI (central apnea index) 28.2 ± 15.0/h 6.0 ± 9.2/h 12 (p < 0.001) QOL 41 5 (10.6%) 1 CSA SEE-HF CPAP 5 cmh 2 O PCWP 12 cmh 2 O High PCWPCI PCWP < 12 cmh 2 O low PCWP CI 61) diastolic ventricular interaction 62) Frank-Starling (Figure 3) ASV 63-66) (low PCWP) CI 65) SEE-HF EF 45% AHI 15/h CSA CSA AHI < 10/h 20

5 A Before treatment A er treatment B Figure 3. Diastolic ventricular interaction (Modified from reference 61) Schematic representation of changes in ventricular volumes after preload reduction by diuretics or vasodilators or positive airway pressure A: Normal subjects. B: Direct diastolic ventricular interaction in heart failure patients with pericardial constraint. = right ventricle; = left ventricle. SEE-HF ASV ICD (implantable cardioverter defibrillator) ASV ICD (HR 0.71, p = 0.08) 6 ASV 48 CSA ASV 6 (fluid shift) CSA OSA 66) CSA OSA fluid shift fluid shift CSACSA ASV 1 1) Javaheri S, Parker TJ, Liming JD, et al. Circulation 1998; 97: ) Sin DD, Fitzgerald F, Parker JD, et al. Am J Respir Crit Care Med 1999; 160: ) Javaheri S. Int J Cardiol 2006; 106: ) Vazir A, Hastings PC, Dayer M, et al. Eur J Heart Fail 2007; 9: ) Tkacova R, Niroumand M, Lorenzi-Filho G, et al. Circulation 2001; 103:

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7 Heart Failure and Sleep Apnea Yosuke Nishihata, M.D., Ph.D. Department of Cardiology, Cardiovascular Center, St. Luke s International Hospital Abstract Obstructive sleep apnea (OSA) and central sleep apnea (CSA) are more common in heart failure patients than in general population. OSA causes sympathetic nervous activation, atherosclerosis, left ventricular hypertrophy, and myocardial remodeling, contributing to the progression of heart failure. The prevalence of CSA increases with heart failure severity, and CSA is known as the poor prognostic factor of heart failure. The efficacy of positive airway pressure (PAP) treatment for OSA has been reported and established. On the other hand, it is controversial whether PAP treatment including adaptive servo ventilation for heart failure with CSA is effective or not. We should consider the mechanisms of the PAP efficacy and the conditions of heart failure. This review summarizes and discusses the influences of both OSA and CSA to heart failure, and the mechanisms and the effects of PAP treatment for heart failure patients. Key words Heart failure, sleep apnea, positive airway pressure, adaptive servo ventilation, hemodynamics 23