Chronic NIV in heart failure patients: ASV, NIV and CPAP

Chronic NIV in heart failure patients: ASV, NIV and CPAP João C. Winck, Marta Drummond, Miguel Gonçalves and Tiago Pinto Sleep disordered breathing (SDB), including OSA and central sleep apnoea (CSA), is common and frequently undiagnosed in patients with congestive heart failure (CHF). The prevalence of SDB is estimated to be as high as 73% among those with stable CHF receiving optimised pharmacological therapy. The proportion of CSA and OSA is variable and the two conditions may coexist, associated with Cheyne Stokes respiration (CSR); sometimes, there is an overnight shift from OSA to CSA. CSR comprises a crescendo decrescendo pattern of VT followed by central apnoeas. OSA is characterised by periodic airway collapse during sleep, associated with increased respiratory effort, that causes repetitive episodes of oxygen desaturation and arousals. Key points Patients with congestive heart failure (CHF) can suffer from a mixture of central sleep apnoea (CSA), OSA and Cheyne Stokes respiration (CSR). The proportion of each of the components may vary with time, during the night and with different body positions. Sleep disordered breathing may significantly impact clinical outcomes in CHF. CPAP therapy may be used in patients with chronic heart failure and OSA, but is not generally effective in chronic heart failure patients with CSA/CSR. Early trials and a meta-analysis showed ASV benefited heart failure patients with CSA/CSR, but initial results from the Serve-HF multicentre RCT of ASV in chronic systolic heart failure patients with predominantly central sleep apnoea showed an excess of mortality in the ASV group compared with control. Consequently, ASV is no longer recommended in heart failure patients with CSA and ejection fraction <45%. From: ERS Practical European Handbook Respiratory Noninvasive Ventilation Society Publications (reader.erspublications.com) 211

There is evidence that central sleep apnoea with Cheyne Stokes respiration (CSA/ CSR) is an indicator of higher morbidity and mortality in CHF patients. Moreover, a recent meta-analysis showed that positive airway pressure modalities like ASV reduce all-cause mortality in patients with chronic heart failure with concomitant SDB. However, preliminary results from the Serve-HF (Treatment of Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure) study suggest that ASV may increase the risk of sudden death in systolic heart failure patients (those with left ventricular ejection fraction (LVEF) <45%), with predominantly central sleep apnoea, so it cannot currently be recommended in this situation. Management of SDB in CHF The first and most important step in the management of SDB in CHF should be optimisation of CHF treatment in accordance with published guidelines (i.e. diuretics, angiotensin-converting enzyme inhibitors and beta-blockers). Other conservative measures effective in OSA, e.g. weight reduction, avoiding a supine position during sleep and avoiding alcohol and sedatives before sleep, should also be applied. Therefore, treatment of heart failure in its own right is likely to improve SDB. The next step is to characterise the nature of SDB. At present, CPAP is recommended in patients with OSA or predominantly obstructive sleep apnoea (>5% obstructive events). Nocturnal CPAP in patients with OSA has been shown to improve LVEF and quality of life. Bilevel positive airway pressure ventilation may be more effective than CPAP in some cases, but there have been no long-term trials and care should be taken. It should be indicated for nonresponders to CPAP (as defined by the persistence of nocturnal hypoventilation or CSA with AHI 15 events h 1 on CPAP). This situation may occur in patients with comorbidities, such as in individuals with COPD and heart failure or those with OHS and heart failure. Bilevel positive airway pressure ventilation is probably particularly relevant for comorbid patients in whom nocturnal hypercapnia is present (figures 1 3). Notably, it is unlikely to have a role in patients with heart failure and CSA for whom episodic hypocapnia can be seen as a consequence of the hyperventilation component of CSR. Predominantly central sleep apnoea The Canadian Positive Airway Pressure Trial included patients with CSA and heart failure who were randomised to either CPAP or no CPAP. After 2 years of follow-up, the CPAP arm showed no benefit in terms of the primary outcome of transplant-free survival, although CSA, ejection fraction and exercise capacity were slightly enhanced. In fact, CPAP improves CSA/CSR in only 5% of cases; so it is suggested that CPAP may improve survival if titrated to achieve a therapeutic reduction in AHI, which is normally considered to be an AHI <15 events h 1. ASV is a new positive airway pressure technology that adjusts the delivered pressure support according to the ventilation of the patient. Since its introduction in 21, a series of trials have been published showing that, compared with the other positive airway pressure systems, ASV reduces AHI and systemic inflammation and improves LVEF and quality of life in CHF patients with CSA/CSR, but none of these studies was designed to examine long-term impact on mortality and morbidity. Two RCTs are currently underway to assess the impact of ASV on long-term outcomes of CHF patients with SDB. The first, Serve-HF, is a multicentre trial of ASV From: European Respiratory Society Publications (reader.erspublications.com) 212 ERS Practical Handbook Noninvasive Ventilation

Device flow Thorax Abdomen SpO 2 % 75 Pulse 1 beats min -1 5 Device leak 25 Pressure cmh 2 O -7.5 VT L 1.5 PtCO 2 mmhg 5 4 11:45 h 11:46 h 11:47 h 11:48 h 11:49 h 11:5 h 11:51 h 11:52 h 11:53 h 11:54 h Figure 1. Sleep study of a 64-year-old patient with chronic heart failure and nocturnal hypoventilation. Noninvasive bilevel positive airway pressure ventilation in spontaneoustimed titration mode was started to correct hypoventilation-related respiratory events and the patient started to present CSR. Although inspiratory and expiratory ventilatory settings were optimised and backup rate was adjusted, the patient maintained the same pathological respiratory pattern. versus standard therapy in systolic heart failure patients with ejection fraction <45% and AHI >15 events h 1 with events being predominantly central sleep apnoea. The second is Advent-HF, which is recruiting heart failure patients with OSA (AHI >15 events h 1 with >5% obstructive events) who are not sleepy (Epworth Sleepiness Scale score <1) and CSA (AHI >15 events h 1 with >5% CSA) with no preset criteria for sleepiness. Importantly, preliminary results from the Serve-HF trial suggest that ASV may increase the incidence of sudden death (despite controlling SDB and, in some patients, providing symptom relief). Pending full results and further evaluation, ASV cannot be recommended in patients with systolic heart failure and predominantly central sleep apnoea, and should be withdrawn in those that are using it. For further information see: Serve-HF ASV safety alert FAQs (www.resmed.com/us/ en/serve-hf.html#frequently-asked-questions). These results do not apply to patients with heart failure and CSA whose ejection fraction is >45%, or to heart failure patients with predominantly obstructive sleep apnoea. Further advice for management of SDB in heart failure should follow from sub-study analysis in the Serve-HF trial and from the Advent-HF trial, once completed. From: ERS Practical European Handbook Respiratory Noninvasive Ventilation Society Publications (reader.erspublications.com) 213

Device flow Thorax Abdomen SpO 2 % 75 Pulse 1 beats min -1 5 Device leak 2 Pressure cmh 2 O -1 VT L 1.5 PtCO 2 mmhg 5 4 11:52h 11:53 h 11:54 h 11:55 h 11:56 h 11:57 h 11:58 h 11:59 h 12: h 12:1 h Figure 2. In the same patient as figure 1, CSR events were not corrected with standard bilevel positive airway pressure ventilation mode. ASV was applied (from the vertical line) with an auto-backup rate. Maximum and minimum levels of EPAP were adjusted to assure the optimal patency of the upper airway and correct obstructive events. Maximum and minimum levels of pressure support were adjusted to the total correction of CSR events and patient comfort. If the maximal value of pressure support was achieved and the patient continued to present CSR, the level was increased by 2 cmh 2 O until total pattern correction. PtcCO 2 was monitored to evaluate safety/effectiveness of the ventilatory adjustments. After ASV was optimised, the algorithm corrected all the events and the dysfunctional respiratory pattern. Titration of positive airway pressure systems CPAP titration CPAP titration is started at 5 cmh 2 O. If obstructive apnoea hypopnea events persist, pressure is incremented in 1 cmh 2 O intervals to try and eliminate them. Bilevel positive airway pressure ventilation titration Kuzniar et al. (27) provide the following guidelines for bilevel positive airway pressure ventilation: Bilevel positive airway pressure ventilation titration is started with the EPAP set at or near the CPAP level which abolished any obstructive apnoeas, hypopneas and snoring. The IPAP is initially set 2 4 cmh 2 O above the EPAP. The EPAP is subsequently titrated to eliminate residual apnoeas, while the IPAP is increased to eliminate hypopnoeas and hypoventilation. From: European Respiratory Society Publications (reader.erspublications.com) 214 ERS Practical Handbook Noninvasive Ventilation

Device flow Thorax Abdomen SpO 2 % 75 Pulse 1 beats min -1 5 Device leak 25 Pressure cmh 2 O -2-15 VT L 1.5 PtCO 2 mmhg 5 4 16:4 h 16:6 h 16:8 h 16:1 h 16:12 h 16:14 h 16:16 h 16:18 h 16:2 h 16:22 h 16:24 h 16:26 h 16:28 h 16:3 h 16:32 h Figure 3. Algorithm of ASV working to correct CSR, by increasing and decreasing the levels of pressure support. The IPAP and/or EPAP are adjusted by 1 cmh 2 O at 1- to 2-min intervals while trying to maintain an IPAP EPAP difference of at least 2 3 cmh 2 O until stable sleep and breathing is achieved. Maximum IPAP and EPAP should be no greater than 2 and 15 cmh 2 O, respectively. For bilevel positive airway pressure ventilation in spontaneous-timed mode, the respiratory backup rate is set at or slightly below the patient s spontaneous awake respiratory rate (usually 1 14 breaths min 1 ). Further reading Artzt M, et al. (27). Suppression of central sleep apnea by continuous positive pressure airway pressure and transplant-free survival in heart failure: a post hoc analysis of the Canadian Continuous Positive Airway Pressure for patients with central sleep apnea and heart failure trial (CANPAP). Circulation; 115: 3173 318. Aurora RN, et al. (212). The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and metaanalyses. Sleep; 35: 17 4. Bradley TD, et al. (25). Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med; 353: 225 233. From: ERS Practical European Handbook Respiratory Noninvasive Ventilation Society Publications (reader.erspublications.com) 215

Ferreira S, et al. (21). Prevalence and characteristics of sleep apnoea in patients with stable heart failure: results from a heart failure clinic. BMC Pulm Med; 1:9. DOI: 1.1186/1471-2466-1-9. Franklin KA, et al. (1997). Reversal of central sleep apnea with oxygen. Chest; 111: 163 166. Kaneko Y, et al. (23). Cardiovascular effects of continuous positive airway pressure in patinents with heart failure and obstructive sleep apnoea. N Engl J Med; 348: 1233 1241. Kuzniar TJ, et al. (27). Moving beyond empiric continuous positive airway pressure (CPAP) trials for central sleep apnea: a multi-modality titration study. Sleep Breath; 11: 259 266. Mansfield DR, et al. (24). Controlled trial of continuous positive airway pressure in obstructive sleep apnoea and heart failure. Am J Respir Crit Care Med; 169: 361 366. Nakamura S, et al. (215). Impact of sleep-disordered breathing and efficacy of positive airway pressure on mortality in patients with chronic heart failure and sleep-disordered breathing: a meta-analysis. Clin Res Cardiol; 14: 28 216. Pasquina P, et al. (212). What does built-in software of home ventilators tell us? An observational study of 15 patients on home ventilation. Respiration; 83: 293 299. Roebuck T, et al. (24). Increased long-term mortality in heart failure due to sleep apnoea is not yet proven. Eur Respir J; 23: 735 74. Sharma BK, et al. (211). Sleep disordered breathing in patients with heart failure: pathophysiology and management. Curr Treat Options Cardiovasc Med; 13: 56 516. Sharma BK, et al. (212). Adaptive servoventilation for treatment of sleepdisordered breathing in heart failure: a systematic review and meta-analysis. Chest; 142: 1211 1221. Teschler H, et al. (21). Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med; 164: 614 619. From: European Respiratory Society Publications (reader.erspublications.com) 216 ERS Practical Handbook Noninvasive Ventilation