Sleep Apnea and chronic Heart Failure

Transcription

1 ESC CONGRESS 2012 Sleep Apnea and chronic Heart Failure Prof. Dr. med. Michael Arzt Schlafmedizinisches Zentrum Klinik und Poliklinik für Innere Medizin II Universitätsklinikum Regensburg

2 Conflicts of Interest Universitätsklinikum Regensburg Research Support: - ResMed GmbH & Co. KG - Philips Home Healthcare Solutions - Sanofi Aventis - Bayer - Deutsche Stiftung für Herzforschung Holder of donated professorship of the freestate of bavaria: - Philips Home Healthcare Solutions - ResMed GmbH & Co. KG Lecture and consulting fees: - Philips Home Healthcare Solutions - ResMed GmbH & Co. KG - AstraZeneca - Covidien

3 1 - Interactions between SA and CHF?? obstructive SA Heart failure central SA?

4 Universitätsklinikum Regensburg 2 Implications of treatment of sleep apnea CPAP?? obstructive SA Heart failure central SA? CPAP/Adaptive Servoventilation

5 LV massindex (g/m²) Universitätsklinikum Regensburg How obstructive SA can contribute to CHF - nocturnal cardiac afterload, BP, myocardial hypertrophy night 100 p = 0.004* n=45 n= n.s.* 70 0 Normotensive Hypertensive Dippers Hypertensive Non-Dippers Davies et al., Thorax 2000 Verdecci et al. Circulation 1990 *adjusted for age, sex, heigh, and daytime systolic and diastolic BP

6 Increase cardiac afterload Obstructive SAinduced negative thoracic pressure swings CPAP-treated Obstructive SA Obstructive SA Pes syst -1 Pes syst -5 BP syst 115 BP syst 132 LV transmural P syst 115 (-1) = 116 mmhg Tkacova et al. Circulation LV transmural P syst 132 (-5) = 137 mmhg

7 How obstructive SA can contribute to CHF - myocardial hypertrophy Shivalkar et al., JACC 2006

8 How obstructive SA can contribute to CHF - myocardial infarction Jessup and Brozena New Engl J Med Obstructive SA risk for CAD and myocardial infarction n=264 n=235 n=372 modified from Marin et al. Lancet 2005

9 How obstructive SA can contribute to CHF - myocardial infarction Jessup and Brozena New Engl J Med Obstructive SA risk for CAD and myocardial infarction 2. Obstructive SA expansion of infarct/impair cardiac remodelling

10 Infarct size <5 days and 12 weeks after (posterior) myocardial infarction without SA RCA OSA (-) baseline RCA OSA (-) 12 weeks Area at risk 38% LVM Infarct size15% LVM Area at risk 0% LVM Infarct size 6% LVM

11 Infarct size <5 days and 12 weeks after (posterior) myocardial infarction with SA RCA OSA (+) baseline Infarct size 14% LVM RCA OSA (+) 12 weeks Area at risk 36% LVM Infarct size 14% LVM Area at risk 0% LVM

12 1 - Interactions between SA and CHF Left ventricular hypertrophy and impaired remodelling: cardiac afterload - arterial hypertension, non-dipping - negative intrathoracic pressure myocardial energy depletion Coronary artery disease and myocardial infarction: atherosclerosis N=4422 Gottlieb et al. Circulation 2010 platelet activation? obstructive SA Heart failure central SA?

13 Heart failure can cause central SA Medical therapy (e.g. diuretics): PCWP CO 2 Chemosensitivity Ventilatory drive Solin et al, Circulation 1999

14 Prognostic significance of obstructive and central SA in CHF Obstructive SA Central SA Hazardratio 2.8 (95% CI ) adjusted for age, NYHA and LVEF Wang et al. J Am Coll Cardiol Hazardratio 2.0 (95% CI ) adjusted for age, NYHA, cause of CHF and diabetes Jilek and Krenn et al. Eur. J Heart Failure 2007

15 Prognostic significance of SA in CHF - malignant ventricular arrhythmias requiring cardioverterdefibrillator therapies Bitter et al. Eur Heart J 2010

16 Universitätsklinikum Regensburg 2 Implications of treatment of sleep apnea Left ventricular hypertrophy and impaired remodelling: cardiac afterload - arterial hypertension, non-dipping - negative intrathoracic pressure myocardial energy depletion Coronary artery disease and myocardial infarction: atherosclerosis platelet activation Ventilatory control instability hyperventilation and hypocapnia chemosensitivity for CO 2 circulatory delay CPAP? obstructive SA Heart failure CPAP/ Adaptive Servoventilation central SA? sympathetic nervous system activity ventricular arrythmias

17 1. Principal of SA treatment in CHF - treatment of heart failure Effect of Heart transplantation on SA and Ventilation LVEF, % AHI, /h 28 7 CSR, %TST Cyclelength, sec Mansfield et al. Chest 2003

18 Prevalence of SA in chronic heart failure n(f)= 5605 (1189) CHF patients, LVEF 45%, NYHA II-IV, on optimal medication n=403 n=845 n=1552 n=1249 n=337 n=450 n=367 n=117 n=190 n=95 The prevalence of SDB (AHI 15/h) was 37% in women, 49% in men and 47% overall H. Woehrle, M. Arzt, O. Oldenburg, E. Erdmann, H. Teschler, A. Graml, K. Wegscheider for the SchlaHF-Investigators 2012 Tuesday 8:45 Reykjavik Village 5

19 Prävalenz (%) Universitätsklinikum Regensburg Different types of SA require different therapies! N=1067 CHF with SA* CPAP % OSA CSA 49% 51% CPAP/ Adaptive Servoventilation (ASV) 18% 21% Adaptive Servoventilation (ASV) 29% OSA OSA+CSA CSA+OSA CSA %cahi/ahi 0-19% 20-49% 50-80% % M. Arzt, I. Schulz, O. Oldenburg, E. Erdmann, H. Teschler, A. Graml, K. Wegscheider, H. Woehrle for the SchlaHF-Investigators 2012

20 Treatment of Obstructive SA is indicated in all Patients with SA-related symptoms! Continous Positive Airway Pressure provides - Open upper airway Sullivan et al., Lancet Restoration of sleep! - Symptom relief in the majority of the patients

21 Effects of CPAP in obstructive SA and CHF LV ejection fraction, % 29±2 30±2 % Control 25±3 34±2 % CPAP Kaneko et al. New Engl J Med 2003 Ventricular ectopic beats Blood pressure Sympathetic activity Ryan et al. Thorax 2005 Kaneko et al. New Engl J Med 2003 Usui K, J Am Coll Cardiol Quality of life Mansfield et al. Am J Resp Crit Care Med 2003

22 Transplantation-free Survival (%) Universitätsklinikum Regensburg Effects of CPAP in central SA and CHF - Phase III: Transplant-free survival in the CANPAP trial CPAP group (32 events) 60 P= (HR = 1.5, P = 0.02) (HR = 0.66, P = 0.057) Control group (32 events) CANPAP Time from Enrollment (mo) No. at Risk CPAP Control Bradley et al., NEJM 2005

23 Transplantfree Survival (%) Universitätsklinikum Regensburg CPAP-response in central SA and CHF - Phase III: Transplant-free survival in the CANPAP trial 100 CPAP responder* (AHI at 3 Mo < 15/hr) CPAP non-responder (AHI at 3 Mo 15/hr) Control CANPAP 20 0 *versus Controls:HR=0.37, p=0.043 (not adjusteed) HR=0.35, p=0.034 (adjusted: age and AHI) Time after Randomization (Mo) Arzt et al., Circulation 2007

24 One night of treatment of Central SA in CHF Teschler et al., Am J Resp Crit Care Med 2001

25 Effect of treatment of severe SA in CHF with PAP on survival an observational study 48% CPAP 13% BIPAP 39% Auto Servoventilation PP 70% risk reduction ITT 22% risk reducton n=184 Jilek and Krenn et al. Eur J Heart Failure 2011

26 Summary and Conclusion I SA contributes to the progression of heart failure, and is a risk factor for poor prognosis in CHF patients In patients with CHF on current heart failure therapy the prevalence of SA (AHI 15/h) is 47%. SA + a SA-related symptom justifies treatment of SA with positive airway pressure for symptom relief.

27 Perspective Universitätsklinikum Regensburg Gaps in evidence: does treatment of SA prevent/improve CHF ESC Guidelines for diagnosis and treatment of acute and chronic heart failure 2012 Jessup et al. New Engl J Med 2003

28 Phase III trials: treatment of SA in CHF with Adaptive Servoventilation Patients Key Outcomes Serve HF n=1260 (adapt.) Long-term Recruitment >1100 CHF + CSA Progression CHF Survival ADVENT-HF n=860 Long-term Recruitment >100 CHF +OSA/CSA Progression CHF Survival Secondary Outcomes: Symptom burdon, quality of life

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30 Prof. Dr. med. Michael Arzt, Center of Sleep Medicine Department of Internal Medicine II, Division of Respirology Universitätsklinikum Regensburg