Sleep Disordered Breathing and HH with Preserved Ejection Fraction: Pr Thibaud DAMY Heart Failure Unit Department of Cardiology CHU Mondor, Créteil, France
Definition of HF-PEF The diagnosis of HF-PEF requires four conditions to be satisfied: 1. Symptoms typical of HF 2. Signs typical of HF a 3. Normal or only mildly reduced LVEF and LV not dilated 4. Relevant structural heart disease (LV hypertrophy/la enlargement) and/or diastolic dysfunction ESC Guidelines, Eur Heart Journal 2012 Paulus W, Eur Heart Journal 2007
Paulus W, Eur Heart J 2007
Symptoms, signs, normal LVEF:HF-PEF? Non dilated LV Dilated LV AR - MR High-output Incorrect HF diagnosis Obesity Inaccurate LVEF measurement Increase IVS thickness AS Normal IVS thickness MS Right ventricular dysfunction TR HCM Infiltrative C Hypertensive C Pericardial disease Ischemia Restrictive CM PAH COPD Congenital disease
HF-PEF population CHARM -P I-PRESERVED PEP-CHF Mayo (Owan) ADHERE OPTIMIZE Age 67 72 76 74 74 75 Men 60 40 55 65 38 38 Hypertension 64 89 79 63 77 76 Diabetes 28 28 21 33 45 38 But sleep disordered breathing? AF 29 29 20 41 21 21 CAD 44 25 27 53 50 44 GFR 72 72 62 40 37 51 BMI 29 30 28 30 30 30 Elderly; Women>Men; high prevalence of comorbities
HF-PEF epidemiology 30 to 55% of Chronic HF patients Cleland JG, Euro- Heart Failure Survey, Eur Heart J 2003 Owan TE, N Engl J Med 2006 Proportion of HF-PEF increases over time 45% of acute decompensated HF have normal LVEF : ADHERE Owan TE, N Engl J Med 2006 Owan TE, N Engl J Med 2006
HF-PEF : no specific treatment Preserved CHARM-Added; 3023 67yrs old; 40% women; HTA : 64%; 39% NYHA III-IV Yusuf S, Lancet 2003 I-PRESERVED; N=4128 72yrs old; 60% women; HTA: 88%; 79% NYHA III/IV Massie N, N Engl J Med 2008 DIG-PEF; Digoxin; N=988; Ahmed A, Circulation 2006 PEP-CHF : Perindopril; N=846; ; Cleland JG, Eur Heart J2006 RELAX : Sildenafil; N=113; Redfield M, JAMA 2013
Survival in HF and mode of death Owan TE, N Engl J Med 2006 Traitement :de l IC à FEP : traitement des facteurs favorisants : HTA, diabète, activité physique Traitement de la cause Et les syndromes d apnées du sommeil?? Chan and Lam, Eur J Heart Fail 2013 NEJM 2006
A New paradigm for HF-PEF? Overweight/Obesity Diabetes Inflammation Endothelial dysfunction Inflammation Hypertension But sleep disordered breathing? Atrial F Aging Cardiac remodeling Diastolic dysfunction RV dysfunction Pulmonary hypertension HF-PEF Paulus W and Tschöpe C, J Am Coll Cardiol 2013
SAS risk factors and consequences Male sex Older age Obesity Risk Factors Menopause Fluid retention Smoking Risk Factors Heart failure Male, Elderly OSA Consequences CSA Stroke Diabetes Hypertension Heart failure Arrhythmias Sudden death Myocardial infarction CAD Jordan AS, The Lancet 2013; Sin DD, AM J RESPIR CRIT CARE MED 1999; White L, J Physiol 2013
Pathophysiology of SAS OSA CSA Somers, J Am Coll Cardiol, 2008; 52 : 686
Oxidative stress and SAS OSA (n=31) and Control (n=15) Cross over/ prospective randomized placebo/double blind (sham CPAP)/12 weeks Alonso-Fernandes et al, Thorax 2009.
OSA and Cardiac Remodelling Diastolic dysfunction Sleep Heart health Study 2058 patients Mean age 65 12, 58% women Usui et al, Sleep Medicine 2011 Chami et al, Circulation 2008; 117:2599-2607 Arias MA, Circulation 2005
OSA and pulmonary hypertension OSA IAH 44+/-29, cross over, 12 semaines de CPAP Arias, Eur Heart J 2006
Right ventricle, PVR and OSA RVEF PVR Wercules et al, Sleep Medicine 2012; May;13(5):510-6
OSA and sudden death Gami et al, NEJM 2005
OSA is associated with increased of HF in men Prospective longitudinal study of 1927 men and 2495 women free of heart failure and coronary artery disease at the time of the polysomnography and followed for a median of 8.7 years Gottliebd DJ, Circulation 2010
A New paradigm for HF-PEF? Overweight/Obesity Diabetes Aging Endothelial dysfunction Hypoxia Inflammation SAS Hypertension Atrial F RV dysfunction Pulmonary hypertension Cardiac remodeling Diastolic dysfunction HF-PEF Paulus W and Tschöpe C, J Am Coll Cardiol 2013
Relationship between AHI and change in left volume
What is the Prevalence of SAS in stable HF-PEF?
SAS prevalence in HF-PEF 20 patients with HF-PEF: LVEF>50% and with E/A<1. NYHA II-III, Age :65±6, 85% History of Hypertension, SBP :136±10mmHg; 65%Male AHI definition >10h -1 SDB :55% (n=11) AHI: 19.5±10.8 63% OSA 37% CSA. Chan et al, Chest 1997
SAS prevalence in HF-PEF 244 HF-PEF ESC Definition Right heart catheterism with (LVEDP>20mmHg) SDB: 69%; AHI >5/h : SDB: 48%: AHI>15/h SDB: 25%: AHI>30/h Bitter T, Eur J Heart F 2009 IAH< 5; 30,7% OSA; 39,8% CSA, 29,5% 96 104 44
SAS prevalence in HF-PEF 115 patients; 72% HF-REF and 38% HF-PEF = 42 patients, AHI 5/h 115 patients IC dont 38% avec IC-FEP CSA :18% 81% 80% OSA :62% HF-REF HF-PEF Herrscher T, J Cardiac Fail 2011; 17:420e425
FACE observatory The FACE study is a French prospective, multicentre, observational cohort that will provide, in routine practice, long-term data on 300 CHF patients eligible for ASV (PaceWave, AutoSet). 174 patients enrolled LVEF <50% 50% CSA+OSA CSA LVEF 50% Age, years 70 75* Men, % 91 86 BMI, kg/m² 28 28 HTA, % 69 70 Diabetes, % 43 30 AF, % 46 54 LVEF <50% AHI, H -1 38 44*
How should we treat them?
Adaptative servoventilation in HF-PEF with Cheyne-Stokes Respiration 60 patients with CSR, AHI>15/h and HFPEF defined accordingly to the ESC. ASV treatment for all. 21 rejected, withdrawn, non compliant 39 patients followed ASV. Follow-up :11.6±3months BASELINE ASV 39 Control 21 AHI 43.5 32.3 NA END OF FOLLOW-UP AHI 3.5* 19.3* NA NTproBNP, pg/ml 740 1480 0.10 LAD, mm 49.8 51.1 <0.01 E/e 17.9 21.7 0.03 VO2 peak ml/kg/min 17.9 15.2 <0.01 * : versus baseline Bitter et al, Eur Respir J 2010: 36; 385-392 p
36 patients with LVEF >50%; 80%men IAH >15 Prospective and randomized study: AutoSet CS vs no treatment Follow-up 6 months Combined Primary criteria Yoshihisa A, Eur J Heart Fail 2013
Change between baseline and 6 months ASV Non- ASV AHI, /h -30.2-8.2 <0.0001 NYHA -0.8 0.2 0.0001 Heart rate, bpm P -5.8-0.1 0.031 BNP, pg/ml -34.6 26.7 0.011 LVMi, g/m² -8.2 36.5 0.023 LAVi, g/m² -6.2 9.6 0.023 E/E -5.8 1.2 0.004 Cardiac death and worsening HF
Summary HF-PEF is frequent and no treatment has been shown to reduce mortality/morbidity in HF- PEF. Adequate treatment of comorbidities is recommended. They are pathophysiological relationships between SDB and HF-PEF.
Conclusion The Increase in the prevalence of HF-PEF over time AND the Stability in the rates of death underscore the importance of determining new concepts and new therapeutic strategies. SDB diagnosis and treatment should be one of these new concepts and strategies in HF-PEF.
OSA and HF-PEF interaction
Traitement des SAS centraux ds IC- FEP Bitter et al, Eur Respir J 2010: 36; 385-392
HCM and SAS prevalence IAH : 23+/-18 %SDB :80% (5/h) ; OSA : 75%; CSA : 25% IAH>15 : 44% Prinz C, Congest Heart Fail 2011; 17:19-24
Prevalence of HFPEF in patients with HF and Hypertension