title: Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.
abstract: BACKGROUND
  Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics.
  
  
  RESULTS
  Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05).
  
  
  CONCLUSIONS
  In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00756366.
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Allison B
authors.initials: AB
authors.lastname: Hall
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Maria C
authors.initials: MC
authors.lastname: Ziadi
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Judith A
authors.initials: JA
authors.lastname: Leech
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Shin-Yee
authors.initials: SY
authors.lastname: Chen
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Ian G
authors.initials: IG
authors.lastname: Burwash
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Jennifer
authors.initials: J
authors.lastname: Renaud
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Robert A
authors.initials: RA
authors.lastname: deKemp
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Haissam
authors.initials: H
authors.lastname: Haddad
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mielniczuk
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Yoshinaga
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Ann
authors.initials: A
authors.lastname: Guo
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Olga
authors.initials: O
authors.lastname: Walter
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Linda
authors.initials: L
authors.lastname: Garrard
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: Jean N
authors.initials: JN
authors.lastname: DaSilva
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.).
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
authors.affiliation: From the National Cardiac PET Center, Division of Cardiology, Department of Medicine (A.B.H., M.C.Z., S.C., I.G.B., J.R., R.A.d., H.H., L.M.M., K.Y., A.G., O.W., L.G., J.N.D., R.S.B.B.), and Cardiac Research Methods Center (L.C.), University of Ottawa Heart Institute, Ottawa, Canada; Diagnostico Medico Oronia, Non Invasive Cardiovascular Imaging Department, Rosario, Santa Fe, Argentina (M.C.Z.); Division of Respirology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada (J.A.L.); Department of Molecular Imaging, Hokkaido University Graduate School of Medicince, Sapporo, Japan (K.Y.); and Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Canada (J.S.F.). rbeanlands@ottawaheart.ca.
authors.forename: Rob S B
authors.initials: RS
authors.lastname: Beanlands
mesh_terms: D000328:Adult; D000368:Aged; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006321:Heart / Q000294:innervation* / Q000502:physiology; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D012890:Sleep / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D013318:Stroke Volume / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology
keywords: heart failure; imaging, diagnostic; metabolism; sleep; sympathetic nervous system