Chinese Medical Journal 2006;119(8):622-627
Efficacy of adaptive servoventilation in patients with congestive heart failure and Cheyne-Stokes respiration

ZHANG Xi-long,  YIN Kai-sheng,  LI Xin-li,  JIA En-zhi,  SU Mei

ZHANG Xi-long (Department of Respiratory Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China)

YIN Kai-sheng (Department of Respiratory Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China)

LI Xin-li (Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China)

JIA En-zhi (Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China)

SU Mei (Department of Respiratory Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China)

Correspondence to:ZHANG Xi-long,Department of Respiratory Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China (Tel: 86-25-83714511 ext 6723, 51919867. Fax:86-25-83724440. E-mail:zhangxil@jlonline. com)
Keywords
Cheyne-Stokes respiration; congestive heart failure; ventilation; oxygen therapy
Abstract

Background  Congestive heart failure (CHF) is associated with Cheyne-Stokes respiration (CSR), which may hasten CHF. Adaptive servoventilation (ASV) is a novel method of ventilatory support designed for removal of CSF in CHF patients. This study compares the efficacy of ASV in patients with CHF and CSR with the efficacy of oxygen therapy.
Methods  Fourteen patients with CHF and CSR were recruited. During sleep, nasal oxygen therapy and ASV treatment were each performed for two weeks. Comparison before and after each treatment was made for the following items: a) parameters of sleep respiration, sleep structure and quality; b) left ventricle ejection fraction (LVEF) and 6-minute walk distance.
Results  Compared with the baseline levels of apnoea hypopnoea index of 34.5±6.1 before treatment, the apnoea hypopnoea index significantly decreased following oxygen therapy to 27.8±8.2, P<0.05 and further reduced following ASV treatment to 6.5±0.8, P<0.01. The minimal pulse oxygen saturation markedly increased following oxygen therapy from a baseline of (84.3±2.6)% to (88.6±3.7)%, P<0.05 and further increased following ASV treatment (92.1±4.9)%, P<0.01. Stages I +II sleep as percentage of total sleep time decreased from (81.9±7.1)% to (78.4±6.7)% following oxygen therapy and further to (72.4±5.0)% following ASV treatment. Stages III +IV sleep as percentage of total sleep time decreased from (8.4±5.5)% to (6.0±3.0)% following oxygen therapy and but increased to (11.9±5.4)% following ASV treatment. The arousal index of 30.4±8.1 before treatment significantly decreased following oxygen therapy to 25.6±5.7, P<0.05 and further declined following ASV treatment to 18.2±6.1, P<0.01. No significant difference was shown in above percentages between day 14 of oxygen therapy and before treatment (P > 0.05). LVEF was significantly higher on day 14 of ASV treatment (37.2±4.1)% than on day 14 of oxygen therapy (33.2±5.1)% and before treatment (30.2±4.6)% (all P<0.05). Six-minute walk distance was the shortest before treatment (226±28) m, longer on day 14 of oxygen therapy (289±26) m, and the longest on day 14 of ASV treatment (341±27) m (all P < 0.01).
Conclusion
  ASV treatment is of better efficacy and greater clinical significance in improvement of CHF by eliminating CSR than oxygen therapy.

Approximately 40% of patients with congestive heart failure (CHF) experience Cheyne-Stokes respiration (CSR). Comparison between CHF patients with and without CSR has demonstrated that even though the left ventricle ejection fraction (LVEF) was similar at the beginning, those with CSR usually had a worse prognosis than those without CSR. The poor prognosis is associated with sleeping disordered breathing (SDB), intermittent hypoxemia and lower survival in CHF patients with CSR.1-4 Therefore, treatment for CSR may improve cardiac function and prognosis.

Adaptive servoventilation (ASV), delivered by Auto CS ventilator, is a novel ventilatory support specifically designed to normalize ventilation in CHF patients with CSR. With its automatic airway tracing feedback function, ASV can adaptively regulate the airway ventilation volume upon demand based on the variation of tidal volume throughout the period of CSR, and if necessary, automatically provide positive pressure ventilation during apnoea. Therefore, stable and regular breathing rate and tidal volume can be maintained so that nocturnal intermittent hypoxia, fluctuation of blood gas and fragmented sleep structure disappear, thus leading to a stable inner environment and improvement of cardiac function.5,6

By observing polysomnographic parameters and cardiac function, differences in efficacy between nasal oxygen therapy and ASV were made.

METHODS

Subjects
From October 2004 to May 2005, 14 patients (8 men, 6 women, aged 39 years to 58 years) with stable CHF and CSR, treated in Department of Cardiology and Sleep Centre of Department of Respiratory Medicine, were recruited. Their LVEF was (30.8± 4.3) %,nocturnal AHI 33.8±5.9 and body mass index 24.3±2.1. The causes of CHF were old myocardial infarction of coronary heart disease in 8 patients, dilated myocardiopathy in 3 patients and hypertensive myocardiopathy in 3 patients. Their cardiac function was New York Heart Association class III (NYHA III) in 10 patients and NYHA IV in 4 patients. All patients had been stable and on optimal medical therapy for at least two weeks before enrollment into this study.

Inclusion/exclusion criteria
Inclusion criteria were as follows: adult patients with stable congestive cardiac failure already known to have predominant CSR on polysomnography (PSG) and giving written informed consent. Exclusion criteria were as follows: patients with more than 10 obstructive events per hour of sleep, unstable angina, myocardial infarction or acute pulmonary oedema within the previous 4 months, history of stroke, patients with tachycardiac atrial fibrillation refractory to drug therapy and poor compliance to ASV treatment.

Polysomnography examination
A Compumedics somnography (S-series, Compumedic Corp., Australia) was used to conduct tests and record the results during the sleep. A respiratory event was considered as CSR when PSG revealed a waxing and waning pattern of ventilation with an arousal at peak ventilation, followed by a period of apnoea with absence of respiratory effort. The major PSG parameters investigated were apnoea hypopnoea index (AHI), minimal pulse oxygen saturation (miniSpO2), arousal index, total sleep time (TST), total recording time (TRT), sleep efficiency (TST/TRT%), stages I + II /TST(%) and stages III + IV sleep /TST (%), and rapid eye movement (REM) sleep / TST(%).

LVEF and 6-minute walk test
Two dimensional, echocardiographic images (HP-SONOS5500 Echocardiography, USA.) were acquired from the parasternal long and short axis, apical long axis, apical four chamber views by an echocardiographer who was blind to the patient’s treatment assignment. The left ventricular end diastolic and end systolic dimensions were determined and LVEF was calculated according to a modification of Simpson’s method.7 In addition, all patients were tested for their 6-minute walk distance to test their exercising capacity. The 6-minute walk test was always administered in a 30-metre long hospital corridor by the same trained person. We measured the distance covered by the patient when walking at a brisk pace for 6 minutes.

Oxygen therapy and ASV treatment
On the nasal oxygen nights, patients received nasal oxygen at 2 L/min through nasal cannulae. The adaptive servoventilator with a high gain integral controller (Autoset CS; ResMed Corp., Sydney, Australia) provided the patients with servocontrolled ventilation. Therapeutic ASV was set to expiratory pressure 5 cmH2O, inspiratory pressure support between 3 cmH2O and 10 cmH2O, backup respiratory rate 15 breaths per minute. Subtherapeutic ASV was delivered from an identical machine, adapted to deliver a minimal 1.75 cmH2O pressure with little pressure support ventilation (minimum, 0.75 cmH2O; maximum, 2.75 cmH2O). To avoid confounding experimental effects, oxygen therapy was not used during the period of ASV treatment.


Experimental design
Oxygen therapy was performed for the first two weeks. Following oxygen therapy, there was an interval of two weeks during which neither oxygen therapy nor ASV treatment was given. ASV treatment began immediately following the interval and lasted for another two weeks. Night PSG examination was done one day before oxygen therapy and one day before ASV treatment. On the last day (day 14) of oxygen and ASV therapies, night PSG test was repeated. During the investigation, all patients were kept on routine pharmacological therapy as they had done just before the study. On the same day as the PSG examinations, all patients were tested for their LVEF and 6-minutes walk distance.

Statistical analysis
Data for all parameters were approximately normal (Gaussian) and expressed as mean±standard deviation (SD). All data were recorded by computer and SPSS 10.0 software was used for statistical analysis. Paired samples t test was used for comparison between two different conditions as shown in Table 1. Analysis of variance was used for comparison among three different conditions expressed in Table 2, in which multiple comparison between two conditions was performed with L-S-D method. P< 0.05 was considered statistically significant.


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Table 1. Comparison of parameters one day before each therapy (n = 14) (mean ± SD)

RESULTS

Comparison of parameters one day beforeeach therapy
There was no significant difference for any parameter between one day before oxygen therapy and one day before ASV therapy (Table 1): after oxygen therapy all parameters reversed to their respective levels before oxygen therapy. Therefore, the mean values of parameters one day before two therapies were taken as baseline values prior to treatment for comparing with those on day 14 of oxygen therapy and ASV treatment.

Sleep breathing parameters
Compared with the baseline level before treatment, the AHI significantly decreased by day 14 of oxygen therapy (P<0.05) and reduced further by day 14 of ASV (P<0.01). On the other hand, the miniSpO2 increased by day 14 of oxygen therapy (P<0.05) and increased further by day 14 of ASV (P<0.01). A significant difference was also detected between day 14 of oxygen therapy and ASV treatment in both AHI (P<0.01) and miniSpO2 (P<0.05) (Table 2).


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Table 2. Changes of sleep breathing and structure, cardiac function before and after each therapy(n = 14) (mean ± SD)

Parameters associated with quality of sleep
Compared with before treatment, arousal index significantly decreased by day 14 of oxygen therapy (P<0.05) and declined further by day 14 of ASV (P<0.01) with a noticeable difference between day 14 of oxygen therapy and day 14 of ASV treatment (P<0.05). Compared with before treatment, sleeping stages I + II /TST (%) was significantly lower while stages III + IV/TST (%) was significantly higher than day 14 of ASV treatment. No statistical difference was shown between the above percentages on day 14 of oxygen therapy and before treatment (P>0.05). No significant difference in REM sleep/TST (%) between before treatment and either treatment was found. Compared with before treatment, TST/TRT(%) was not statistically higher on day 14 of oxygen therapy but was significantly higher on day14 of ASV (P<0.05) with no statistical difference between day 14 of oxygen therapy and ASV treatment (Table 2).

LVEF and 6-minute walk test
LVEF was significantly higher on day 14 of ASV than before treatment and on day 14 of oxygen therapy (all P<0.05), while no significant difference was detected between LVEF before treatment and on day 14 of oxygen therapy. Six-minute walk distance was the shortest before treatment and the longest on day 14 of ASV. There were significant differences between before treatment, on day 14 of oxygen therapy and ASV treatment (all P<0.01) (Table 2). All patients were kept in stable CHF throughout our study.

DISCUSSION

CSR is sleep apnoea with a cyclical pattern of periods of hyperventilation with waxing/waning tidal volume alternating with period of hyponea/apnea. CSR during sleep is common in CHF patients and is believed to be the most prevalent form of sleep disordered breathing (SDB) in patients with severe left ventricular dysfunction.8 In our study, CSR was the predominant SDB in all patients investigated.

Traditional routine treatment for CHF usually focuses on the pharmacological therapy of diuretics, digoxin, vasodilators and so on. The effects of SDB on CHF are often neglected. Recent research has suggested that CSR could accelerate the progression of CHF by causing repetitive hypoxaemia and arousal, increased afterload, enhanced sympathetic activity and oscillations in heart rate and blood pressure.9-11 Arousals and hypoxaemia during sleep resulting from CSR can alter quality of life and contribute to fragmented sleep and paroxysmal nocturnal dyspnea.12 Continuous hyperventilation and associated increase in work of breathing during CSR also increase the requirement upon cardiac output significantly. So far, CSR has been considered as an independent predictor of poor prognosis of CHF.13 Some studies have proved that prolonged treatment for CSR with continuous positive airway pressure (CPAP) can benefit CHF patients not only by improvement in sleep quality and daytime sleepiness, but also increase in cardiac output and function, as well as decrease in mortality and morbidity.14

The effects of positive airway pressure treatment for CSR in CHF patients are as follows:14-16 this treatment can (1) stabilize upper airway, (2) increase end expiratory pulmonary volume and alveolar pressure, (3) assist inspiratory muscles and (4) decrease the pressure gradient, inner diameter of left ventricle and fraction of mitral regurgitation. With these mechanisms, cardiac function can be improved and hypoxemia, delayed blood circulating time, increased noradrenalin level and associated cardiac arrhythmia may all be lessened.

Nevertheless, continuous positive airway pressure (CPAP) treatment often produces dissatisfactory compliance and intolerance from patients, which prevents them from receiving long lasting treatment.17 Moreover, the efficacy of CPAP might be shown in only some patients. In view of this, a different positive airway pressure treatment is needed to overcome the shortcomings of current CPAP treatment.

The newly designed ventilator from Auto CS has successfully displayed its advantages over ordinary CPAP and bilevel ventilators. It can reduce CSR and improve sleep quality more efficiently and effectively than other types of positive airway support ventilators. It is comfortable for CHF patients and thus more likely to encourage compliance.6 Except for two patients who were excluded from our study because of intolerance to ASV treatment, the remaining 14 patients showed good compliance with ASV treatment which was tolerated well throughout the study.

This study revealed that returning abnormally increased AHI and decreased miniSpO2 prior to treatment towards normal range was achieved more effectively during ASV treatment than during oxygen therapy. Moreover, all patients showed a good compliance with Auto CS ventilator with few side effects to ASV treatment. A definite effectiveness for correcting SDB was revealed by ASV treatment. Monitoring of sleep structure and quality also showed it better than oxygen therapy: the best efficacy during ASV therapy was obtained with a significant decrease in arousal index and shallow sleep, as well as an increase in slow wave sleep. These suggested that Auto CS ventilator treatment improved sleep quality very efficiently in CHF patients with CSR.

A significant increase in LVEF was found during ASV treatment, but not during oxygen therapy. In addition, 6-minute walk test, an indirect test of cardiac function and life quality, demonstrated that the walk distance was not only significantly longer during both oxygen therapy and ASV treatment than that before treatment, but also strikingly longer during ASV treatment than during oxygen therapy. These results suggested that cardiac function and life quality could be clearly improved by ASV treatment.

Oxygen therapy has long been regarded as an effective treatment of CHF patients with CSR.18,19 But some researches indicated that oxygen therapy should be used with caution due to reduced cardiac output and the paradoxical worsening of CSR.20

The present study demonstrated that ASV delivered by Auto CS ventilator could provide significantly better treatment of CHF patients with CSR than oxygen therapy. By effectively eliminating CSR, ASV treatment is a significant improvement in the treatment of CHF. As this is a clinical study with a small sample, confirmation of our findings with a large sample is needed.

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  1. Jiangsu Committee of Science and Technology,BZ2003048;