Syndrome d apnées obstructives du sommeil dans les maladies coronaires : quelles conclusions tirer des grandes études prospectives?

Transcription

1 Syndrome d apnées obstructives du sommeil dans les maladies coronaires : quelles conclusions tirer des grandes études prospectives? Professor Atul PATHAK, MD, PhD. Head of Clinical Research Director Hypertension and Heart Failure unit Director of Hi-LAB Clinique Pasteur, Toulouse FRANCE

2 DRP Congrès cœur et sommeil à Marrakech : Mars 2018 Fondateur de l association i REST (innovation, recherche, enseignement sommeil transversal) Invitation par RESMED à participer à ce colloque Investigateur principal de l essai OSICAT (financé par AIR LIQUIDE, prestataire du sommeil) Soutien recherche ASD 2

3 Natural History of Coronary Artery Disease : OSA always behind! Facteur de risque Progression de l athérosclerose Maladie coronaire établie Complication CV de la maladie coronaire Complications annexes de la maladie coronaire (AVC, FA, AAA, ) 3

4 OSA, CAD : pathophysiology Cardio/ Vasc Atherome ICD : HTAP HTA Arythmie / Ischémie Dissection AAA

5 In middle-aged to older individuals (SHHS-ARIC study), OSA severity is independently associated with higher levels of hs-tnt, suggesting that subclinical myocardial injury may play a role in the association between OSA and risk of heart failure Rocca et al. Am J Respir Crit Care med 2013 In patients with coronary artery disease, moderate to severe OSA was Independently associated with a larger total atheroma volume (VH-IVUS) in the target coronary artery. Tan et al. Chest 2013 Prospective controlled study (Sleep Lab): Coronary plaque volume (computed tomographic angiography study) was significantly greater in the high-ahi group (mean plaque volume 2.6 ± 0.7 mm(2) versus 0.8 ± 0.2 mm(2); p=0.017) and, furthermore, correlated significantly with AHI (Spearman's r=0.433; p=0.019). Kent et al. Eur Respir J 2013

6 Importance du dépistage du SAHOS: Facteur de Risque établi J Am Coll Cardiol Feb 21; 69(7):

7 Y penser systématiquement, surtout quand la maladie coronaire se complique de dysfonction ventriculaire gauche dans toutes ses formes

8 Mort subite cardiaque et SAS (obstructive)

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10 Patient? CAD or Cerebrovascular disease, Moderate-to-severe OSA ( oxygen desaturation index (the number of times / hour that the blood oxygen saturation level drops by 4 percentage points from baseline) of at least 12, established with the use of ApneaLink, Patients excluded if severe daytime sleepiness (Epworth Sleepiness Scale score >15;) or at increased risk of an accident from falling asleep, if very severe hypoxemia (oxygen saturation <80% for >10% of recording time), or if Cheyne Stokes respiration

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16 Conclusion of SAVE In adults with cardiovascular disease and moderate-to-severe OSA, CPAP therapy : had no effect on the prevention of recurrent serious cardiovascular events significantly reduced sleepiness and other symptoms of obstructive sleep apnea and improved quality-of-life measures.

17 Limitation Asymptomatic patient : risk for low adherence Early motivation needed Participants in the SAVE study who were assigned to CPAP adhered to the treatment for a mean of 3.3 hours per night! The diagnosis and treatment of sleep apnea were not well established in clinical practice when the trial began.. This overall level of adherence to CPAP therapy exceeded the estimates in power calculations, but still have been insufficient to provide effect on CV outcomes.

18 Limitation For practical reasons a simple screening device (ApneaLink) rather than conventional standard test for OSA To reduce the risk of recruiting patients with predominantly central apnea rather than obstructive sleep apnea, we excluded patients with overt heart failure and patients in whom the nasal pressure signals showed a predominant pattern of Cheyne Stokes respiration.

19 External validity a multicenter study conducted in Spain that compared CPAP with usual care in 725 patients with obstructive sleep apnea without CV disease (limited power? )

20 From: Effect of Continuous Positive Airway Pressure on the Incidence of Hypertension and Cardiovascular Events in Nonsleepy Patients With Obstructive Sleep ApneaA Randomized Controlled Trial JAMA. 2012;307(20): doi: /jama

21 From: Effect of Continuous Positive Airway Pressure on the Incidence of Hypertension and Cardiovascular Events in Nonsleepy Patients With Obstructive Sleep ApneaA Randomized Controlled Trial JAMA. 2012;307(20): doi: /jama

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24 Qui sont les adhérents?

25 External validity a multicenter study conducted in Spain that compared CPAP with usual care in 725 patients with obstructive sleep apnea without CV disease (limited power? ) a single-center study involving 224 patients with OSA and CAD who had just undergone revascularization showed no difference in composite cardiovascular end points in adjusted analyses, both studies reported better outcomes among patients who were adherent to CPAP therapy ( 4 hours per night) than among patients who did not receive CPAP or who used CPAP less than 4 hours per night. A third study involving 140 patients with recent ischemic stroke showed no effect of CPAP on event-free survival over 2 years.

26 Morbi Mortalité CV? J Am Coll Cardiol Feb 21; 69(7):

27 Luyster et al. Clinical Cardiology. 2017;1 6.

28 Luyster et al. Clinical Cardiology. 2017;1 6.

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30 Plus le pronostic est sévère même aux Soins Intensifs plus la prevalence augmente Chest Aug 16. pii: S (17)31396-X. doi: /j.chest

31 Chest Aug 16. pii: S (17)31396-X. doi: /j.chest

32 Chest Aug 16. pii: S (17)31396-X. doi: /j.chest

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36 Rôle de la consultation d annonce Donc Patient coronariens symptomatiques Compliqués Adhérents, précocement Retirent un bénéfice

37 Beyond classical management Alternative or additional approaches

38 Role central du SNS : nouvelle cible pour la prise en charge du SAS en cardiologie? J Am Coll Cardiol Feb 21; 69(7):

39 CAD Bloquer la gachette

40 Carotid Chemoreceptors Julian F.R. Paton et al. Hypertension. 2013;61:5-13

41 Carotid chemoreceptors and chemoreflex physiology Hypoxia Hypercapnia Decrease ph Hypoglycemia Decrease blood flow Lungs Ventilation Julian F.R. Paton et al. Hypertension. 2013;61:5-13

42 Mechanism of action: Carotid Body Ablation Narkiewicz et al. JACC Basic Transl Sci Aug 29;1(5):

43 Narkiewicz et al. JACC Basic Transl Sci Aug 29;1(5):

44 Future of Carotid Body Ablation Future direction : An ongoing uncontrolled observational study will assess the feasibility of unilateral endovascular CB ablation in a larger cohort of patients with RHTN. The targeted trial enrolment is set at 50 patients and is expected to report its findings in early 2017 (clinicaltrials.gov: NCT ). Possible to identify responders Possibly amenable to endovascular approach Carotid Body Ablation with a transvenous ultrasound imaging and ablation catheter

45 Bloquer le SNS et les consequences CAD

46 Barostimulateur carotidien

47 Intended to Inhibit Sympathetic Activity Acute Muscle Sympathetic Nerve Activity After 3 Months of Therapy 250 ABP [mmhg] OFF ON OFF ON OFF MSNA [%] Time [mins] Heusser et al., Hypertens 2010, 55(3):

48 Bloquer le SNS et les consequences

49 Physiopathologie de la denervation renale

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51 Potentialisation CPAP et Denervation Renale Circ J May 25;80(6):

52 Intérêt des antagonistes aux récepteurs des mineralocorticoïdes J Hum Hypertens Sep 21. doi: /jhh

53 Intérêt du bosentan Placebo Bosentan Placebo Bosentan

54 Quand évoquer des troubles du sommeil chez le coronarien? Tout le temps: C est un FDR Devant une progression de la maladie (restenose, angor) Apparition de complications (dysfonction VG, FA, TV, AVC) Suspicion clinique ou par PMK

55 Chez le coronarien Evoquer le SAOS Qualifier (dépistage et diagnostic) Prendre en charge Le plus tôt possible Chez les plus symptomatiques Ou ceux dont le risque est élevé