Adaptive Servo-Ventilation for Central Sleep Apnea in HF Patients
Despite advances in drug and device therapy, HF continues to be associated with high rates of recurrent hospitalization and increased mortality (~ 50% mortality within five years),1,2 which raises the possibility that a co-morbid condition such as sleep disordered breathing may be playing a pathophysiologic role. Congestive heart failure is the most commonly recognized cause of central sleep apnea (CSA), a sleep-related breathing disorder frequently associated with a periodic breathing pattern named Cheyne-Stokes respiration (CSR). In HF patients, it is estimated that up to 31-37 % of those with low left ventricular ejection fraction (<45%), and up to 29% of those with preserved ejection fraction (diastolic dysfunction) have CSA respectively.3-6 Most importantly, CSA associated with CSR (CSA-CSR) has been shown not only to be a marker of greater severity of heart failure, but may also an independent risk factor for adverse cardiovascular outcomes.7-9 Therefore, while not yet conclusively proven, addressing CSA-CSR may represent a unique opportunity to improve HF-related morbidity and mortality.
HF patients may exhibit a combination of obstructive sleep apnea (OSA) and CSA, or a pure form of either breathing disorder. In those patients with pure OSA, CPAP is still considered standard therapy, with demonstrated improvements in ejection fraction and sympathetic neural activity associated with its use.10, 11 CPAP may also be of benefit in those with mixed OSA and CSA. In HF-CSA patients, CPAP therapy improves the sleep-disordered breathing severity (SDB), reducing the number of obstructive and central respiratory events (AHI) by 21/h [95% CI: 17 to 25], improves the left ventricular ejection fraction (LVEF) by 6% [95% CI 2.4 to 10.5%], and reduces the sympathetic activity in comparison to usual medical care.10,12,13 However, the only largest randomized CPAP trial published to date (Canadian Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure Trial [CANPAP]), comparing CPAP therapy vs. usual medical care in HF-CSR patients, showed no survival benefits (dead and heart transplantation) in those patients without appropriate control of sleep-disordered breathing while on CPAP.10 As a result, new technologies based on feedback control systems devices (e.g., ASV) have emerged as alternative therapeutical option to CPAP in patients with HF-CSA, translating into better control of respiratory events of central origin (CSA) and better device use compliance in comparison to CPAP therapy.14
Assistive Device Therapy: Adaptive Servo Ventilator (ASV)
Several assistive devices modalities have been extensively studied in patients with CHF and CSA. These devices provide non-invasive positive airway pressure (PAP) to the patient via a nasal or oronasal interface. PAP may be provided as constant positive airway pressure (CPAP), bilevel positive airway pressure (BPAP), with or without back up respiratory rate (BPAP-S and BPAP-ST, respectively), or by servomechanism devices that attempt to modulate the patient's ventilation with various target ventilatory patterns. Among these latter devices are adaptive servo ventilator devices (ASV), a feedback control system targeting minute ventilation or peak respiratory flow, adding a component of ventilation that is anticyclic to the patient's own respiratory drive periodicity. ASV settings are generally adjusted to patients' breathing pattern during a polysomnographic study. The end expiratory pressure (EEP) is titrated to eliminate obstructive respiratory events, while the maximum and minimum inspiratory pre-set pressures would dynamically self-adjust (breath-by-breath) to normalize the breathing pattern with the help of a back-up respiration rate.
While there is limited long-term data available to evaluate the impact of ASV in HF patients with CSA, there is at this time sufficient amount of published data consistently demonstrating improvement in sleep-disordered breathing (SDB) severity (Apnea-hypopnea Index - AHI), left ventricular ejection fraction (LVEF), exercise capacity (6-minute walk distance), cardiopulmonary exercise testing, and quality of life up to one-year follow up.
In a parallel-nonrandomized trial comparing ASV vs. usual medical care in HF-CSA patients with stable EF <55% (NYHA II-III), improvement was noted in SDB severity (AHI, 36.6±15.8 to 4.7±3.3, P<0.01; AI, 22.8±11.6 to 0.8±1.3, P<0.01), and left ventricular ejection fraction (43.5 ± 6.4 to 53.3 ± 6.1% [P=0.002]) at one-month and six-month follow up.15,16 Salutatory effects were also reported in functional status, with increased daytime alertness at one-month, and improvement of NYHA functional class at seven-month follow up, associated with favorable changes in cardiopulmonary exercise tolerance parameters (VO2-ATOxygen consumption at anaerobic threshold or peak exercise, VO2 peak and six minutes walking distance).17,18
Even in cases of coexistence of obstructive sleep apnea (OSA), central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) in patients with (EF ≥ 20%, NYHA class II-III) and without heart failure (e.g., coronary artery disease, pulmonary hypertension), ASV reduced the central apnea hypopnea index and BNP levels significantly more effectively as compared with CPAP over a two-month and twelve-month follow up period.19-21 A similar improvement profile has also been shown in patients with diastolic HF-CSR on ASV, independently of the severity level of the SDB. 22,23 Even though two small observational studies of HF-CSA patients on ASV reported a decrease in the number of cardiac events (cardiac death and re-hospitalization) and cardiac related mortality (death from progression of HF, cardioembolic stroke, and fatal cardiac arrhythmias) at six-month and one-year follow up respectively, large randomized controlled studies are still missing in order to assess the long term impact of ASV on mortality and transplantation-free survival rates.16,24
There are also limited published studies with direct comparison of ASV with BPAP-ST, and oxygen supplementation. At one night study, ASV suppresses central sleep apnea and/or CSR (CSA-CSR) in heart failure and improves sleep quality better than CPAP or 2 L/min oxygen. In comparison to BPAP-ST, ASV performs better in CSR-CHF but equivalent to CPAP.25,26
In conclusion, congestive heart failure is a chronic, prevalent disease with high mortality rate at five years. The finding of CSA and CSR in HF patients is frequently associated with advanced cardiovascular disease and worse prognosis. Current data in the form of typically small observational studies report cardiopulmonary benefits from ASV implementation in HF patients with CSA. There is not only better control of central sleep apnea events in comparison to CPAP therapy, but there is also reported improvements in functional status (NYHA class) associated with increase in left ventricular ejection fraction (LVEF), exercise capacity (six-minute walk distance), and cardiopulmonary exercise testing over up to one year-follow up. Large scale randomized controlled trials are still needed to evaluate the impact of ASV devices in long term morbidity and mortality.13
- Go, A.S., et al., Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation 2013;127:e6-e245.
- McMurray JJ, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14:803-69.
- Javaheri, S., Sleep disorders in systolic heart failure: a prospective study of 100 male patients. The final report. Int J Cardiol 2006;106:21-8.
- MacDonald, M., et al., The current prevalence of sleep disordered breathing in congestive heart failure patients treated with beta-blockers. J Clin Sleep Med 2008;4:38-42.
- Bitter, T., et al., Sleep-disordered breathing in heart failure with normal left ventricular ejection fraction. Eur J Heart Fail 2009;11:602-8.
- Oldenburg, O., et al., Sleep-disordered breathing in patients with symptomatic heart failure: a contemporary study of prevalence in and characteristics of 700 patients. Eur J Heart Fail 2007;9:251-7.
- Hanly PJ, N.S. Zuberi-Khokhar. Increased mortality associated with Cheyne-Stokes respiration in patients with congestive heart failure. Am J Respir Crit Care Med 1996;153:272-6.
- Javaheri, S., et al., Sleep apnea testing and outcomes in a large cohort of Medicare beneficiaries with newly diagnosed heart failure. Am J Respir Crit Care Med 2011;183:539-46.
- Javaheri, S., Treatment of obstructive and central sleep apnoea in heart failure: Practical options. Eur Respir Rev 2007;16:183-188.
- Bradley, T.D., et al., Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005;353:2025-33.
- Mansfield, D.R., et al., Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med 2004;169:361-6.
- Naughton, M.T., et al., Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med 1995;152:473-9.
- Aurora, R.N., et al., The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an Evidence-Based Literature Review and Meta-Analyses. Sleep 2012;35:17-40.
- Kasai, T., et al., Effect of flow-triggered adaptive servo-ventilation compared with continuous positive airway pressure in patients with chronic heart failure with coexisting obstructive sleep apnea and Cheyne-Stokes respiration. Circ Heart Fail 2010;3:140-8.
- Koyama, T., et al., Beneficial effects of adaptive servo ventilation in patients with chronic heart failure. Circ J 2010;74:2118-24.
- Yoshihisa, A., et al., Adaptive servo ventilation improves cardiac dysfunction and prognosis in chronic heart failure patients with Cheyne-Stokes respiration. Int Heart J 2011;52:218-23.
- Pepperell, J.C.T., et al., A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure. Am J Respir Crit Care Med 2003;168:1109-14.
- Oldenburg, O., et al., Adaptive servoventilation improves cardiac function and respiratory stability. Clin Res Cardiol 2011;100:107-15.
- Randerath, W.J., et al., Long-term auto-servoventilation or constant positive pressure in heart failure and coexisting central with obstructive sleep apnea. Chest 2012;142:440-7.
- Randerath, W.J., et al., Adaptive servo-ventilation in patients with coexisting obstructive sleep apnoea/hypopnoea and Cheyne-Stokes respiration. Sleep Med 2008;9:823-30.
- Sharma, B.K., et al., Adaptive servoventilation for treatment of sleep-disordered breathing in heart failure: a systematic review and meta-analysis. Chest 2012;142:1211-21.
- Bitter, T., et al., Adaptive servoventilation in diastolic heart failure and Cheyne-Stokes respiration. Eur Resipr J 2010;36:385-92.
- Takama, N. and M. Kurabayashi, Effectiveness of adaptive servo-ventilation for treating heart failure regardless of the severity of sleep-disordered breathing. Circ J 2011;75:1164-9.
- Takama, N. and M. Kurabayashi, Effect of adaptive servo-ventilation on 1-year prognosis in heart failure patients. Circ J 2012;76:661-7.
- Teschler, H., et al., Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med 2001;164:614-9.
- Allam, J.S., et al., Efficacy of adaptive servoventilation in treatment of complex and central sleep apnea syndromes. Chest 2007;132:1839-46.
Keywords: Cheyne-Stokes Respiration, Comorbidity, Heart Failure, Hospitalization, Morbidity, Sleep Apnea Syndromes
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