Olaf Oldenburg Novel pathophysiological concepts for the development and impact of sleep apnea in CHF. Sleep apnea the need to synchronize the heart, the lung and the brain. Heart Failure 2011 Gothenburg, Sweden 21 24 May 2011
Prevalence of Sleep Disordered Breathing in Chronic Heart Failure mild OSA AHI 6-14/h (n=118; 17%) no SDB AHI 5/h (n=169; 24%) moderate to severe OSA AHI 15/h (n=135; 19%) mild CSA AHI 6-14/h (n=55; 8%) moderate to severe CSA AHI 15/h (n=233; 32%) n = 700 NYHA II LVEF 40% Oldenburg et al, Eur J Heart Fail 2007; 9: 251-257
Cheyne-Stokes Respiration
Pathophysiology of Cheyne-Stokes Respiration in CHF Hyperventilation While Awake and Asleep n = 16 consecutive CHF patients LV-EF < 35% 9 with nocturnal CSR, 7 without Hanly P et al., Chest 1993; 104: 1079-1984
Pathophysiology of Cheyne-Stokes Respiration in CHF hyperventilation airflow arousals from sleep
Pathophysiology of Cheyne-Stokes Respiration in CHF Arousals Occur During Hyperventilation
Pathophysiology of Cheyne-Stokes Respiration in CHF hyperventilation airflow arousals from sleep pco 2 altered apnea threshold (CO 2 reserve)
Apnea Threshold CO 2 Reserve in CHF Patients Without vs. With CSA CHF patients with CSA have a relative small increase in eupnoeic P A, CO2 from wakefullness to NREM sleep, plus a reduced P A, CO2 from eupnea to the apneic threshold, the latter being due to an increased slope of the VA- PA, CO2 relationship below eupnea Xie A et al., Am J Respir Crit Care Med 2002; 165: 1245-1250
Hypocapnic Apneic Threshold CO 2 -Reserve: eupneic PET CO2 - PET CO2 -AT CSA < OSA < nosdb ventilatory control instability Dempsey JA., Exp Physiol 2004; 90: 13-24 Salloum A et al., Am J Respir Crit Care Med 2010; 181: 189-193
Pathophysiology of Cheyne-Stokes Respiration in CHF hyperventilation airflow pco 2 exceeds apnea threshold arousals from sleep pco 2 altered apnea threshold pco 2 falls below apnea threshold central apnea
Pathophysiology of Cheyne-Stokes Respriation in CHF increased central CO 2 receptor sensitivity hyperventilation airflow pco 2 exceeds apnea threshold arousals from sleep pco 2 altered apnea threshold pco 2 falls below apnea threshold central apnea
Hyperoxic Hypercapnic Ventilatory Response (HCVR)
Augmented Ventilatory Response to CO 2 Hyperoxic Hypercapnic Ventilatory Response (HCVR) Javaheri S, New Engl J Med 1999; 341: 949-954
Pathophysiology of Cheyne-Stokes Respriation in CHF Respiratory Control Center increased central CO 2 receptor sensitivity hyperventilation airflow pco 2 exceeds apnea threshold arousals from sleep pco 2 altered apnea threshold pco 2 falls below apnea threshold central apnea
Pathophysiology of Cheyne-Stokes Respriation in CHF Impaired feedback control: circulatory delay Respiratory Control Center increased central CO 2 receptor sensitivity hyperventilation airflow pco 2 exceeds apnea threshold arousals from sleep pco 2 altered apnea threshold pco 2 falls below apnea threshold central apnea
Cycle Length of CSR in Heart Failure Cycle length Apnoea lenght Ventilation length Circulatory Delay Wedewardt J et al., Sleep Med 2010; 11: 137-142
Cycle Length of CSR in Heart Failure Group 1 EF > 50% Group 2 EF 40 49% Group 3 EF 30 39% Group 4 EF 20 29% Group 5 EF < 20% AHI 37.2 ± 21.2 36.8 ± 13.8 34.9 ± 18.1 29.7 ± 10.5 30.7 ± 12.6 AI 19.0 ± 17.1 20.2 ± 13.1 17.8 ± 12.4 18.4 ± 12.4 21.8 ± 11.7 Mean S a O 2, % 94.1 ± 1.6 94.0 ± 1.9 93.1 ± 2.5 94.5 ± 1.8 93.3 ± 2.3 Minimum S a O 2, % 85.0 ± 3.5 84.7 ± 4.2 81.7 ± 5.9 84.2 ± 5.9 81.5 ± 5.4 Mean S a O 2 - desaturation, % 5.2 ± 0.9 c,d,g 5.5 ± 1.2 6.2 ± 1.4 6.5 ± 1.3 7.4 ± 2.3 Cycle length, sec 49.1 ± 17.4 b,c,d 58.9 ± 13.4 f,g 60.5 ± 10.5 h,i 73.9 ± 16.2 85.7 ± 23.1 Apnea length (AL), sec 20.6 ± 8.8 c,d 23.6 ± 6.0 g 22.2 ± 5.6 i 26.8 ± 8.2 31.1 ± 10.1 Ventilatory length (VL), sec 28.3 ± 10.0 b,c,d 35.3 ± 10.4 f,g 38.2 ± 8.0 h,i 47.3 ± 11.9 54.5 ± 16.5 Time to peak ventilation, sec 19.2 ± 5.2 a,b,c,d 25.4 ± 5.9 26.7 ± 6.0 28.1 ± 8.7 32.1 ± 10.5 VL : AL, ratio 1.45 ± 0.42 b,c,d 1.57 ± 0.51 1.82 ± 0.62 1.88 ± 0.60 1.89 ± 0.69 Circulatory delay, sec 29.0 ± 8.4 c,d 32.1 ± 8.6 g 33.6 ± 7.6 i 39.3 ± 13.9 j 49.3 ± 15.6 n =105 patients Wedewardt J et al., Sleep Med 2010; 11: 137-142
Cycle Length of CSR in Heart Failure Circulation time (circulatory delay): increases with more impaired LV function might alter physiological feedback mechanisms dyssynchronizes the heart, the lung, and the brain Wedewardt J et al., Sleep Med 2010; 11: 137-142
Pathophysiology of Cheyne-Stokes Respriation in CHF Many other factors: age, gender, hypoxia, sympathetic tone, peripheral chemoreceptor sensitivity, TLCO etc. Impaired feedback control: circulatory delay hyperventilation Respiratory Control Center increased central CO 2 receptor sensitivity airflow pco 2 exceeds apnea threshold arousals from sleep pco 2 altered apnea threshold pco 2 falls below apnea threshold central apnea
Ventilatory Response Episodic hypoxia Chowdhuri S et al., J Appl Physiol 2010;108:369-377
Pathophysiology of SDB in CHF The Fluid Shift Concept PCWP CSR OSA Neck edema
Pathophysiology of Cheyne-Stokes Respiration in CHF PCWP and pco 2 n = 11 CHF patients hemodynamic measurements LV-EF < 35% NYHA II + III Relationship between carbon dioxide tension in arterial blood (Pa, CO2) and pulmonary capillary wedge pressure (PCWP) at baseline conditions in 11 CHF patients. r=0.80; p=0.003 Lorenzi-Filho G et al., Eur Respir J 2002; 19: 37-40
Pathophysiology of Cheyne-Stokes Respiration in CHF Cardiac Function and PCWP are Associated with CSA CSA-patients: n=61, NYHA II, LV-EF 40%, simultaneous right and left cardiac catheterisation; AHI: 30 ± 15/h; PCWP: 21 ± 9mmHg; CI: 1.9 ± 0.5 l/min/m 2 Oldenburg et al, Sleep Med 2010; 10: 726-730
Pathophysiology of Cheyne-Stokes Respiration in CHF nosdb OSA CSA Age, years 48.3 ± 13 64.3 ± 13 59.2 ± 11 LV-EF, % 32.0 ± 6.7 32.8 ± 4.6 31.9 ± 6.2 AHI, h -1 1.2 ± 1.7 27.1 ± 28.3 32.1 ± 19 HCVR, l/min/mmhg 1.6 ± 0.6 2.2 ± 0.6 5.6 ± 6.5 PCWP mean baseline, mmhg post-angio, mmhg significance Blood gas analysis ph baseline ph post-angio po 2 baseline, mmhg po 2 post-angio, mmhg S a O 2 baseline, % S a O 2, post-angio, % BE baseline, mmhg BE post-angio, mmhg 14.2 ± 9.5 17.4 ± 9.3 p < 0.05 7.436 ± 0.03 7.422 ± 0.04 79.3 ± 12.1 93.5 ± 20.9 96.1 ± 2.2 97.5 ± 2.0 2.3 ± 1.8 1.3 ± 1.4 22.8 ± 10.0 25.4 ± 11.3 p < 0.01 7.444 ± 0.04 7.430 ± 0.04 83.8 ± 13.0 78.4 ± 14.1 96.6 ± 1.5 95.7 ± 1.8 2.5 ± 1.8 2.0 ± 1.8 20.3 ± 6.6 22.9 ± 7.9 p = 0.01 7.438 ± 0.03 7.438 ± 0.05 81.6 ± 14.3 96.1 ± 22.7* 96.2 ± 1.8 96.9 ± 3.3 0.6 ± 2.1 0.2 ± 2.1 Simultaneous left and right heart catheterizations 29 consecutive patients with symptomatic compensated CHF (NYHA II; LV-EF 40%). PCWP and arterial pco 2 were measured at baseline and after angiography to increase intravascular volume. Oldenburg O et al., Circulation 2008 (Abstract)
Pathophysiology of Cheyne-Stokes Respiration in CHF Acute Increase in PCWP Causes Hyperventilation Arterial pco 2 at baseline and after increasing PCWP by left ventricular angio- and/or aortography in CHF patients without SDB (green), with OSA (blue) and CSA (red). Oldenburg O et al., Circulation 2008 (Abstract)
Pathophysiology of Cheyne-Stokes Respriation in CHF J receptor stimulation PCWP Fluid Shift CHF Many other factors: age, gender, hypoxia, sympathetic tone, peripheral chemoreceptor sensitivity, TLCO etc. Impaired feedback control: circulatory delay hyperventilation Respiratory Control Center increased central CO 2 receptor sensitivity airflow pco 2 exceeds apnea threshold arousals from sleep pco 2 altered apnea threshold pco 2 falls below apnea threshold central apnea
Obstructive Sleep Apnea in Heart Failure
Obstructive Sleep Apnea Fluid Shift Theory Inclusion: n = 6 consecutive men (>18 years) sedentary lifestyle ( 10h/day sitting) OSA with AHI 15/h Exclusion: BMI 30 kg/m 2 Prescribed medication (incl. diuretics) Redolfi S et al., Respir Physil Neurobil 2011; 175: 390-393
Increase in Neck Circumference In obstructive- and central-dominant groups, there were inverse exponential relationships between overnight changes in neck circumferences and leg fluid volume (LFV). Yumino D et al.; Circulation 2010; 121: 1598-1605
Reversal of Peripheral Oedema and AHI Relationship between change in LFV and AHI in the obstructive- and central-dominant groups. The open circles and solid line represent the relationship between the AHI and the change in LFV in the obstructivedominant group [y=2.4 * e (-0.011 * x) ]. The closed circles and dashed line represents the relationship between the AHI and the change in LFV in the central-dominant group [y=5.1*e (-0.004 * x) ]. The slopes of these curves differed significantly (p<0.001). Demonstration of a progressively greater reduction in LFV from patients with mild to no sleep apnea (M-NSA) (AHI < 15/h; n=19) to OSA (AHI 15/h; n=17). Yumino D et al.; Circulation 2010; 121: 1598-1605
Reversal of Peripheral Oedema and PtCCO 2 In obstructive-dominant group, there was no significant correlation between mean Pt CCO2 during sleep and overnight change in LFV (n=32; A). However, in the central-dominant group, there was a significant correlation between mean sleep Pt CCO2 and the overnight change in LFV (n=20; B). Yumino D et al.; Circulation 2010; 121: 1598-1605
Effects of CPAP on OSA, Leg Fluid Volume and Neck Circumference Effect of CPAP on OSA, overnight changes in LFV, and neck circumference. The AHI shown is the AHI during the entire polysomnogram at all CPAP levels. At the optimum CPAP levels, the AHI was 8.2 ± 2.8/h. Data are mean ± SE. Yumino D et al.; Circulation 2010; 121: 1598-1605
New Data on the Impact of Sleep Disordered Breathing in Chronic Heart Failure
Sleep Apnea Testing and Outcome (Medicare) RM 782 Kaplan-Meier survival curves for the tested, diagnosed and treated subjects vs not tested and not treated subjects, adjusted by age, gender, and Charlson Comorbidity Index, 2004-2005 Javaheri S et al., Am J Respir Crit Care Med 2011; 183: 539-546
Sleep Apnea Testing and Outcome (Medicare) RM 782 Kaplan-Meier survival curves for tested, diagnosed and treated subjectes vs. tested, diagnosed and not treated subjects, adjusted by age, gender, and Charlson Comorbidity Index, 2004-2005 Javaheri S et al., Am J Respir Crit Care Med 2011; 183: 539-546
Prognosic Impact of Sleep-Disordered Breathing in Heart Failure RM 795 Severe SDB: AHI 22.5/h. Unadjusted Cox proportional hazard analysis. Jilek C et al., Eur J Heart Failure 2011; 13: 68-75
RM 791 Appropriate ICD-Therapies in CHF Patients n=82 n=87 n=86 AHI cut-off 5 h -1 CSA: HR 3.24 [CI: 1.86 5.64; p<0.001] OSA: HR 2.07 [CI:1.14 3.77; p=0.02] Bitter T et al., Eur Heart J 2011; 32: 61-74
Appropriate ICD-Therapies in CHF Patients with Moderate to Severe SDB n=68 n=44 n=143 RM 791 AHI cut-off 15 h -1 CSA: HR 3.41 [CI: 2.10 5.54; p<0.001] OSA: HR 2.10 [CI:1.17 3.78; p=0.01] Bitter T et al., Eur Heart J 2011; 32: 61-74
Sleep Disordered Breathing Prognosis in Long-Term Cardiac Resynchronization Survival % nosdb OSA CSA Months Oldenburg O et al., Europace 2011
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