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Sleep Apnea and Heart Failure (2001-06-13)
 

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Sleep Apnea and Heart Failure (2001-06-13) Sleep Apnea and Heart Failure (2001-06-13) Presentation Transcript

  • Sleep Apnea in Heart Failure Update on Prevalence and Treatment Options
    • S. Javaheri, M.D., FCCP
    • Professor Emeritus of Medicine,
    • University of Cincinnati, College of Medicine
    • Medical Director, Sleepcare Diagnostics
    • Cincinnati, Ohio
    • Indianapolis,
    • 8/2007
  • Disclosures I am a consultant and/or have received grant and/or honoraria and/or travel expenses from: BI, Cardiac Concept, Cephalon, GSK, Respironics, Res Med, Sanofi-Aventis and Takeda
  • Obstructive Apnea Normal Airway Obstructed Airway
  • Polysomnographic Breathing Disorders Event Rib cage Obstructive apnea Abdomen Ribcage Airflow
  •  
  •  
  • Interaction Between Sleep and Heart Pathology Primary Secondary Sleep Apneas & Hypopneas Secondary Primary Cardiovascular Pathology
  • Polysomnographic Breathing Disorders Event Rib cage Abdomen Ribcage Airflow Central apnea
  •  
  • Hunter- Cheyne-Stokes Breathing in SHF
  • Survival % Months Javaheri et al, JAAC,2007 ( N=32 ) ( N=56 )
  • Prevalence of Sleep Apnea in Recent Prospective Studies of SHF Canada (07) (13) China (07) (12) Germany (07) (16) N Zealand (05) (11) US (06) (5) n % AHI ≥ 10/hr % β blockers % AHI ≥ 15/hr 80 10 80 30 % OSA % CSA 21 37 46 15 71 68 47 49 26 12 25 53 52 85 287 100 126 56 700 Country (y) (Ref) 90 28 43 203 54 80 37 17 102 Germany (07) (15) Germany (07) (19) 71 UK (07) (18) 78 38 15 55 53 33 19 85 33 19
  • Complex sleep apnea
    • The new kid on the block
    • or
    • the old guy in the background
  • Prevalence of Sleep Apnea in Prospective Studies of SHF
    • CPAP-resistant Central Sleep Apnea (CSA)
      • A large number of Patients with Systolic Heart failure
      • Patients with Atrial Fibrillation
      • Patients on Opioids
      • Neuromuscular Disease
    • CPAP-emergent CSA
      • Over-titration
      • Sleep Fragmentation ( Post-arousal )
      • S/P UPPP
    Complex Sleep Apnea CPAP-resistant CSA and CPAP-emergent CSA
  • Hunter- Cheyne-Stokes Breathing in SHF
  •  
  •  
  •  
  •  
  •  
  • Sleep Apnea & Hypopnea H/R  PCO 2 Arousals  Ppl  O 2 Delivery  RV Afterload  SVR/Others Changes in R&L Ventricular Preload & Afterload  Lung H 2 O Vasoconstriction Thrombosis Inflammation Organ Dysfunction Hypoxic & Hypercapnic Pulmonary Vasoconstriction Endothelial Dysfunction Syndrome Sympathetic Activation  Transmural P. of L&R ventricles, and Pulmonary Microvascular Bed SA/H: Mechanisms Contributing to Cardiovascular Disease
  • CSA as a Predictor of Mortality in SHF
    • N = 114 eligible
    • N = 100 Enrolled
    • N = 12 with OSA Excluded
    • N = 88
    • N = 88 : 32 with AHI <5 ; 56 with AHI ≥ 5/hr
    • Median F/U : 51 months
    • Javaheri et al , J Am Coll Cardiol (May, 2007)
  • Demographic and cardiovascular parameters in 88 heart failure patients without  and with central sleep apnea
    • Variable AHI<5/hr AHI ≥5/hr P  
    • Number 32 56 
    • Age, y 62 67 0.02
    • BMI, kg/m 2 28 26 0.09
    • SBP, mm Hg 127                119      0.06
    • DSP, mm Hg 72       70          0.09
    • Heart rate, n/min 78 80 0.48
  • SRBD in 88 heart failure patients without  and with central sleep apnea
    • Variable AHI<5/hr AHI ≥5/hr
    • AHI, n/hr 2 35
    • CAI, n/hr 0.6 23
    • OAI, n/hr 0.1 0.5
    • CAHI, n/hr 2 32
    • OAHI, n/hr 0.2 1
  • Cardiovascular parameters in 88 heart failure patients without  and with central sleep apnea
    • Variable AHI<5/hr AHI ≥5/hr P  
    • LVEF, % 27 22 0.006
    • RVEF, % 49 43 0.048
    • Atrial fibrillation,% 6 20 0.1   
    • NHYA Class I,% 25  9 0.09 
    • NHYA Class II, %           53           55 0.09 
    • NHYA Class III, %  22  36 0.09   
    •  
  • The Predictors of mortality in SHF
    • Three Variables, RVEF, AHI and DBP
    • Independently Correlated with Survival:
    • RVEF (HR=0.97, P=0.003)
    • AHI (HR=2.14, P=0.02)
    • DBP (HR=0.96, P=0.02)
  • 44 36 35 35 36 45 P=0.01 90 P=0.01 62 P=0.02 59 P=0.003 60 P=0.002 60 P=0.002 59 Median survival (months) AHI<5 VS ≥ 5 AHI<10 VS ≥ 10 AHI<15 VS ≥ 15 AHI<20 VS ≥ 20 AHI<25 VS ≥ 25 AHI<30 VS ≥ 30 ■ Less than the cutoff point ■ Greater or equal than the cutoff point 0 10 20 30 40 50 60 70 80 90 100 Javaheri et al, JAAC, 2007
  • Prevalence of Sleep apnea Stable Systolic Heart Failure Prospective Studies Variable Apnea-Hypopnea Index > 15/hr Central Sleep Apnea Obstructive Sleep Apnea Range, % 47 - 49 15 - 46 12 - 53
  • Prevalence of SRBD in Systolic Heart Failure
    • 100 out of 114 consecutive patients
      • 68% with AHI ≥ 5/h ; 49% with AHI ≥ 1 5/h
      • 56% CSA
      • 12% OSA
      • Javaheri, Ann Intern Med, 1995, Circulation 1998
      • and Int J cardiol 2006
  • Prevalence of Sleep Apnea in Prospective Studies of SHF AHI ≥ 5/hr AHI ≥ 10/hr AHI ≥1 5/hr Germany
  • Prevalence of Sleep Apnea in Prospective Studies of SHF Germany
  • Heart Failure in U.S.
    • 1.5–2% of population (5 million)
    • 6–10% of population >65 y old
    • 400,000–700,000 new cases annually
    • 20 million with asymptomatic cardiac impairment
    • 11 million physician office visits annually
    • 3.5 million hospitalizations annually
    • Leading cause of hospitalization in people >65 y
    • 250,000 deaths annually (direct and indirect)
    • $27 billion (annual cost), 2003
    • $8–15 billion per for hospitalization
  • Mortality Trends in Heart Failure U.S.
    • Framingham Study (2002)
    • 59% in men and 43% in women
    • Olmsted Study (2004)
    • 43%
    • Worcester (2007)
    • 79%
  • Treatment of CSA in SHF (No Guidelines)
    • Promote sleep hygiene
    • Avoiding ETOH and benzodiazepines
    • Optimization of medical thereapy of CP functions
      •   lockers vs- melatonin secretion
    • Treatment algorithm for CSA
    • Treatment of RLS/PLM
  • Optimize Therapy: ACEI; ß-Blockers; Diuretics; Digoxin; CRT SRBD Eliminated Persistent SRBD Follow-up Clinically Consider Treatment Cardiac Transplantation Medications Theophylline Nocturnal Nasal Oxygen Acetazolamide APSSV HFV Medical Devices nCPAP Mandibular Advancement Cardiac Pacing
  • Optimize Therapy: ACEI; ß-Blockers; Diuretics; Digoxin SRBD Eliminated Persistent SRBD Follow-up Clinically Consider Treatment Cardiac Transplantation Medications Theophylline Nocturnal Nasal Oxygen Acetazolamide APSSV HFV Medical Devices nCPAP Mandibular Advancement Cardiac Pacing
  • Study Design-Inclusion Criteria • Subjects transplanted between 1995-1999 • At least 5 months post- transplant • 59 Eligible patients • 45 Participated (76%) • 14 Refused (24%) Javaheri et. al., EHJ, 2004
  • 21 1 7 0 5 4 7 5 10 15 20 0- 5 5- 10 10- 15 15- 20 20- 30 30- 40 40 47 % 53 % 51 % 36 % 36% 24% 16% AHI, no./hr N u m b e r o f S u b j e c t s Javaheri et. al., EHJ, 2004
  • Demographics and Physical Examination Findings in 45 Heart Transplant Subjects Without Sleep Disorders (Group I, n=15), With PLM (Group II, n=14) or With Sleep Related Breathing Disorders (Group III, n=16)
    • Variable
    • Age, y
    • Male/Female, n
    • Ht, cm
    • Wt, kg
    • Wt gain since
    • transplant, kg
    • BMI, kg/m 2
    • Neck size, cm
    Group II 55 12/2 179 • 90 9 28 • 42.4 Group I 58 13/2 176 85 4 27 41.1 Values are means ± SD; * p<0.05 when compared to Group I; • p<0.05 when compared to Group III. Group III 58 15/1 172 99* 16* 33* 43.9 p 0.7 — 0.03 0.045 0.03 <0.001 0.1
  • 10 20 30 40 50 60 80 Habitual Snoring Excessive Daytime Sleepiness Unrefreshed Sleep Restless Legs Syndrome Physical Component Scale Mental Component Scale P =0.02 P =0.002 P =0.03 P =0.04 P =0.01 P =0.7 * * * * Group I Group 2 Group 3 0 % % % % 70 Javaheri et. al., EHJ, 2004
  • Optimize Therapy: ACEI; ß-Blockers; Diuretics; Digoxin SRBD Eliminated Persistent SRBD Follow-up Clinically Consider Treatment Cardiac Transplantation Medications Theophylline Nocturnal Nasal Oxygen Acetazolamide APSSV HFV Medical Devices nCPAP Mandibular Advancement Cardiac Pacing
  • Apnea-Hypopnea Index (n/hr)
  • Effects of Supplemental Nasal O 2 on CSA in SHF • Decreases PB and central apneas • Improves hypnogram  Ar;  S 1 ;  S 2 • Improves exercise capacity • Decreases sympathetic activity  urinary norepinephrine  SMNA by microneurography • Increases LVEF • Improves Quality of life • Decreases BNP
  • Optimize Therapy: ACEI; ß-Blockers; Diuretics; Digoxin ,CRT SRBD Eliminated Persistent SRBD Follow-up Clinically Consider Treatment Cardiac Transplantation Medications Theophylline Nocturnal Nasal Oxygen Acetazolamide APSSV HFV Medical Devices nCPAP Mandibular Advancement Cardiac Pacing
  • Data of HF Patients Undergoing Theophylline Trial Placebo 15 15/0 66 175 88 ND Theo 15 15/0 66 175 88 11 Values are means; ND=not detectable Javaheri et al., NEJM, 1996, 335, 562-7 Baseline 15 15/0 66 175 89 ND Variable N Gender, M/F Age, y Ht, cm Wt, kg Theo, u g/ml
  • Periodic Breathing at Baseline, With Placebo and Theophylline in 15 HF Patients Placebo 37 26 2 2 17 Theo 18* 6* 2 1 8* Values are means; * p < 0.05 Javaheri et al., NEJM, 1996, 335, 562-7 Baseline 47 26 2 2 24 Variable AHI, n/h CAI, n/h OAI, n/h MAI, n/h DBArI, n/h
  • Optimize Therapy: ACEI; ß-Blockers; Diuretics; Digoxin;CRT SRBD Eliminated Persistent SRBD Follow-up Clinically Consider Treatment Cardiac Transplantation Medications Theophylline Nocturnal Nasal Oxygen Acetazolamide APSSV HFV Medical Devices nCPAP Mandibular Advancement Cardiac Pacing
  • Demographics and Cardiovascular Findings in 12 SHF Patients with Central Sleep Apnea Treated with Acetazolamide
    • Variable
    • Patients, n
    • Age, y
    • BMI, kg/m 2
    • SBP, mm Hg
    • DBP, mm Hg
    • LVEF, %
    Placebo 12 66 26 113 69 21 ACTZ 12 66 26 108 69 20 Values are means. Javaheri, AJRCCM, 2006 Baseline 12 66 26 110 67 19 p ---- 0.9 1.0 0.8 0.9 0.5
  • Variable AHI, n/h CAI, n/h Placebo 57 49 ACTZ 34* † 23* † Disordered Breathing Events of 12 SHF Patients with Central Sleep Apnea Treated with Acetazolamide Baseline 55 44 p 0.002 0.004 * p < 0.05 versus baseline † = p < 0.05 versus placebo
  • Patients’ Perception of Their Sleep Quality and Daytime Symptoms Comparing Acetazolamide with Placebo Variable Sleep quality Waking up refreshed Daytime fatigue Fall asleep unintentionally Javaheri, Am J Respir Crit Care Med,2006 Acetazolamide Improved Improved Improved Decreased p 0.003 0.007 0.02 0.002
  •  
    • The Canadian Continuous Positive Airway Pressure for Patients with CSA and Heart Failure trial tested the hypothesis that CPAP would improve the survival rate without heart transplantation of patients who have CSA and heart failure
    Background Continuous Positive Airway Pressure for Central Sleep Apnea and Heart Failure Bradley TD et al., N Engl J Med 2005;353:2025-33.
    • After medical therapy was optimized, 258 patients who had heart failure , were randomly assigned to receive CPAP (128) or no CPAP (130)
    • CAHI = 40/hr , LVEF = 25%, age = 63 yr
    • Patients were followed for a mean of two yr
    Methods Continuous Positive Airway Pressure for Central Sleep Apnea and Heart Failure Bradley TD et al., N Engl J Med 2005
  • Effect of CPAP on the Frequency of Episodes of Apnea and Hypopnea Bradley TD et al., N Engl J Med 2005 P<0.001 Control group CPAP group Time from Randomization (mo) Episodes of Apnea and Hypopnea (no. per hr of sleep) 50 40 30 20 10 0 0 3 24
  • Bradley TD et al., N Engl J Med 2005 Heart-Transplantation-Free Survival Transplantation-free Survival (%) Time from Enrollment (mo) Control group (32 events) CPAP group (32 events) P=0.54 100 80 60 40 20 0 0 12 24 36 48 60
  • Potential Mechanisms of CPAP Failure
    • Hemodynamic Consequences:
      • Effects on RV Function, LV Stroke Volume, BP and CBF. Hemodynamic Effects of Atrial Fibrillation
    • Nonresponsive Patients
      • Importance of Hpocapnia and Failure of PAP Devices to Correct it
      • Javaheri, JCSM, 2006
  • The Predictors of mortality in SHF
    • N = 88; 32 with AHI <5; 56 with AHI ≥ 5/hr
    • Mean AHI 2/hr vs. 32/hr (CAI = 23/hr)
    • Median F/U : 51 months
    • RVEF (HR=0.97,P=0.003), AHI (HR=2.14,P=0.01) and DBP (HR=0.96,P=0.02) independently correlated with survival
  •  
  • CVD mortality in the elderly The lower the DBP the worse
    • CV effects of SBP and DBP depend on the age
    • In the Fram study, there was a gradual transition from DBP to SBP as the more important predictor of CV mortality
    • After age 60 yr, the risk of CHD correlated positively with SBP and negatively with DBP
    • After age 60 yr, the lower DBP was associated with a worsening CV prognosis
    • Franklin et al, Circulation, 2001
  • The risk with aggressively lowering blood pressure in HTN patients with CAD
    • Low DBP and Mortality; Post hoc analysis of INVEST
    • N = 22576 patients with CAD, CHF (I,II) and HTN
    • The risk for the primary outcome, all-cause death and MI, but not stroke, progressively increased with low diastolic blood pressure.
    • Excessive reduction in diastolic pressure should be avoided in patients with CAD who are being treated for hypertension.
    • Messerli et al, AIM, 2006
  • Transplant-free survival in HF patients according to effect of CPAP on CSA CPAP responders * (AHI at 3 months < 15/hr, n = 57) CPAP non-responders (AHI at 3 months  15/hr, n = 43) 0 6 12 18 24 30 36 42 48 54 60 Time from enrollment (months) Control 0 20 40 60 80 100 Transplant-free survival (%) *versus control: HR=0.36, p=0.040
  • Optimize Therapy: ACEI; ß-Blockers; Diuretics; Digoxin SRBD Eliminated Persistent SRBD Follow-up Clinically Consider Treatment Cardiac Transplantation Medications Theophylline Nocturnal Nasal Oxygen Acetazolamide APSSV HFV Medical Devices nCPAP Mandibular Advancement Cardiac Pacing
  • APSSV in CSA (mean values) AHI ArI PtCO 2 45* 67* 32 28* 32* 37* 6 17 34 27* 32* 35 15* 18 35 (n/hr) (n/hr) (mm Hg) Baseline O 2 2l/min CPAP 8-11 Bilevel IP:11-15 EP: 5-6 APSSV  PI:4-10 EP: 4-6 *Significant vs. APSSV. Teschler et al., AJRCCM, 2001
  •  
  • Studies with ASV in SHF
    • a
    Szollosi Phillips Pepperell* Teschler n Age (Y) LVEF % (2006) (2001) (2006) (2003) Baseline AHI n/hr 14 8 <10 5 Duration nights 30 47 47 25 ASV AHI n/hr 67 69 64 71 32 NR 29 30 1 1 180 30 10 14 12 15 Kasai (2006) 6 63 72 38 1 4
  • CPAP vs. APSSV in Patients on Opioids Baseline PSG CPAP Final Setting ADAPT Final Settings AHI OAI CAI AHI OAI CAI AHI OAI CAI 1 74 45 29 101 0.0 101 6 0.0 0.0 2 17 0.5 3 27 0.0 22 12 0.0 0.0 3 44 4 3 61 0.0 56 1 0.0 0.0 4 83 1 60 34 0.0 33 5 0.0 0.0
  • Prevalence of Sleep Apnea in Recent Prospective Studies of SHF Canada (07) (13) China (07) (12) Germany (07) (16) N Zealand (05) (11) US (06) (5) n % AHI ≥ 10/hr % β blockers % AHI ≥ 15/hr 80 10 80 30 % OSA % CSA 21 37 46 15 71 68 47 49 26 12 25 53 52 85 287 100 126 56 700 Country (y) (Ref) 90 28 43 203 54 80 37 17 102 Germany (07) (15) Germany (07) (19) 71 UK (07) (18) 78 38 15 55 53 33 19 85 33 19
  • OSA as a Cause of Mortality in SHF (Wang, JAAC, 2007 ) N=37 N=113
  • Treatment of OSA in CHF
    • Promote sleep hygiene
    • Avoid ETOH , benzodiazepines and Viagra
    • Weight loss
    • Positive airway pressure devices CPAP, bilevel
    • Mandibular advancement devices
    • Upper airway procedures
    • Nocturnal use of supplemental oxygen
  • Effects of CPAP on Systolic Heart Failure in OSA
    • 24 patients with systolic HF and OSA (AHI ~40/h) were randomized to CPAP (n = 12) or a control group (n = 12)
    • LVEF increased significantly following one month of CPAP therapy (25% to 34%)
    • LVEF did not change significantly in the control group
    Kaneko Y et al. N Engl J Med . 2003;348:1233. CPAP = continuous positive airway pressure HF = heart failure LVEF = left ventricular ejection fraction
  • A controlled study of mild to moderate OSA (AHI~25, low SaO 2 ~78%) with CPAP (9cm H 2 O) for 3 months in SHF Variables N AHI, n/hr LVEF UNE ESS SF36 CHF? Control 21 21  18  1.5%  2  1 No change No change CPAP 19 25  3  5% (P=0.04)  10 (P=0.04)  3 (P=0.01) Improved Improved No change in BP, Dyspnea, VO 2 , NYHA, BMI or Meds Mansfield et al, Am J Respir Crit Care Med, 2004
  • CPAP Improves Cardiac Efficiency
    • Open study of 7 HF /OSA compared to 5 HF/No OSA
    • Yoshinaga et al; JAAC, 2007
    SHF/OSA LVEF BMI AHI Age 61 37 31 38 SHF/No OSA 62 30 27 3 % Kg/m 2 /hr yrs
    • 2D-ECHO and “C acetate PET (K mono) baseline
    • and 6 W
    • K mono = Monoexponential function fit to myocardial clearance
    • (rate of oxidative metabolism reflecting MVO 2 )
    • Myocardial efficiency: LV WMI = SVI *SBP/K mono)
    • Yoshinaga et al; JAAC, 2007
    Long-term CPAP Improves Cardiac Efficiency
  • CPAP Improves Cardiac Efficiency
    • Yoshinaga et al; JAAC, 2007
    SVI Heart rate SHF/No OSA SHF/OSA (CPAP) 59 37 141 60 42 129 SBP 58 38 141 42 121 55 WMI LVEF 38 7.1 0.047 43 8.2 0.039 Kmono 43* 8.2* 0.04* 7.0 0.036 44 Base line Base line 6 wk 6 wk 38 43*
  • Effects of CPAP on LVEF in OSA/SHF AHI, n / h Duration CPAP titration LVEF, % n Mansfield Kaneko Smith Yoshinaga 6W 30 38 yes 3.5 19 7 3M 35 21 23 yes NR 36 6W 38 6.2 Compliance, h 40 12 4W 25 yes 5.6 Auto Change in LVEF, % N0 5 5 9
  • Treatment of OSA in CHF
    • Promote sleep hygiene.
    • Avoid ETOH and benzodiazepines.
    • Weight loss.
    • Positive airway pressure devices, CPAP, bilevel.
    • Mandibular advancement devices.
    • Upper airway procedures.
    • Nocturnal use of supplemental oxygen.
    • Pacing does not improve OSA .
  •  
  • HR /min 64 75 Pacing Does Not Improve OSA Baseline Pacing AHI /hr 43 50 CAI /hr 1 2 Minimum SaO 2 % 83 84 n=15; BMI=28 kg/m 2 ;  LVEF=64 % (5<56 %) Pepin et al, ERJ;2005
  • Treatment of OSA in CHF
    • Promote sleep hygiene.
    • Avoid ETOH and benzodiazepines.
    • Weight loss.
    • Positive airway pressure devices, CPAP, bilevel.
    • Mandibular advancement devices.
    • Upper airway procedures.
    • Nocturnal use of supplemental oxygen.
  • Heart Failure in U.S.
    • 1.5–2% of population (5 million)
    • 6–10% of population >65 y old
    • 400,000–700,000 new cases annually
    • 20 million with asymptomatic cardiac impairment
    • 11 million physician office visits annually
    • 3.5 million hospitalizations annually
    • Leading cause of hospitalization in people >65 y
    • 250,000 deaths annually (direct and indirect)
    • $27 billion (annual cost), 2003
    • $8–15 billion per for hospitalization