Ticagrelor Induced Cheyne-Stokes Respiration and Asystolic Ventricular Standstill: A Case Report.

Ticagrelor is a potent, direct-acting, and reversible P2Y12­adenosine diphosphate receptor blocker. It has a rapid onset of action and an intense and consistent platelet reactivity inhibition that has been demonstrated to be superior to clopidogrel in decreasing major adverse events in acute coronary syndrome (ACS). Although ticagrelor is well tolerated in ACS patients, it has side effects, such as dyspnea and bradyarrhythmia, as reported in the Platelet Inhibition and Patient Outcomes (PLATO) study. Furthermore, it was reported that ticagrelor's bradyarrhythmic potential was transient and not clinically significant beyond the acute initiation phase. Nor was there a difference in rates of syncope or need for pacemaker insertion during 30 days of follow-up. Here we report a case of ticagrelor associated with Cheyne-Stokes respiration and asystolic ventricular standstill in a patient with ACS who required resuscitation and insertion of a temporary pacemaker.

Cheyne-stokes respiration in children with heart failure.

Cheyne-Stokes respiration (CSA-CSR) is a form of central sleep apnea characterized by alternating periods of hyperventilation and central apneas or hypopneas. CSA-CSR develops following a cardiac insult resulting in a compensatory increase in sympathetic activity, which in susceptible patients causes hyperventilation and destabilizes respiratory control. The physiological changes that occur in CSA-CSR include hyperventilation, a reduced blood gas buffering capacity, and circulatory delay. In adults, 25% to 50% of patients with heart failure are reported to have CSA-CSR. The development of CSA-CSR in this group of patients is considered a poor prognostic sign. The prevalence, progression, and treatment outcomes of CSA-CSR in children remain unclear with only 11 children being described in the literature. The lack of data is possibly not due to the paucity of children with severe heart failure and CSA-CSR but because they may be under-recognized, compounded by the absence of routine polysomnographic assessment of children with moderate to severe heart failure. Building on much broader experience in the diagnosis and management of CSA-CSR in adult sleep medicine and our limited experience in a pediatric quaternary center, this paper will discuss the prevalence of CSA-CSR, its' treatment options, outcomes in children, and the potential future direction for research in this understudied area of pediatric sleep medicine.

Central Sleep Apnea with Cheyne-Stokes Breathing in Heart Failure - From Research to Clinical Practice and Beyond.

Characterized by periodic crescendo-decrescendo pattern of breathing alternating with central apneas, Central sleep apnea (CSA) with Cheyne-Stokes Breathing represents a highly prevalent, yet underdiagnosed comorbidity in chronic heart failure (CHF). A diverse body of evidence demonstrates increased morbidity and mortality in the presence of CSB. CSB has been described in both CHF patients with preserved and reduced ejection fraction, regardless of drug treatment. Risk factors for CSB are older age, male gender, high BMI, atrial fibrillation and hypocapnia.The pathophysiology of CSB has been explained by the loop gain theory, where a controller (the respiratory center) and a plant (the lungs) are operating in a reciprocal relationship (negative feedback) to regulate a key parameter (partial pressure of carbon dioxide (pCO2)). The temporal interaction between these elements is dependent on the circulatory delay. Increased chemosensitivity/chemoresponsiveness of the respiratory center and/or augmented ascending non- CO2 stimuli from the C-fibers in the lungs (interstitial pulmonary edema), overly efficient ventilation when breathing at low volumes and prolonged circulation time are involved. An alternative hypothesis of CSB being an adaptive response of the failing heart has its merits as well. The clinical manifestation of CSB is usually poor, lacking striking symptoms and complaints. Witnessed apneas and snoring are infrequently reported by the sleep partner. Sometimes patients may report poor sleep quality with frequent awakenings, paroxysmal nocturnal dyspnea and frequent urination at night. Standard instrumental and laboratory studies, performed in CHF patients, may present clues to the presence of CSB. Concentric remodeling of the left ventricle and dilated left atrium (echocardiography), high BNP and C-reactive protein levels, increased ventilation-carbon dioxide output (VEVCO2) and lower end-tidal CO2 (cardiopulmonary exercise testing), reduced diffusion capacity (pulmonary function testing) and hypocapnia (blood-gas analysis) may indicate the presence of CSB.CSB and cardiovascular disease are probably linked through bidirectional causality. Cyclic variations in heart rate, blood pressure, respiratory volume, partial pressure of arterial oxygen (pO2) and pCO2 lead to sympathetic-adrenal activation. The latter worsens ventricular energetism and survival of cardiomyocytes and exerts antiarhythmogenic effects. It causes cardiac remodeling, potentiating the progression and the lethal outcome in CHF patients. Several treatment modalities have been proposed in CSB. The most commonly used are continuous positive airway pressure (CPAP), adaptive servoventilation (ASV) and nocturnal home oxygen therapy (HOT). Novel therapies like nocturnal supplemental CO2 and phrenic nerve stimulation are being tested recently. The current treatment recommendations (by the American Academy of Sleep Medicine) are for CPAP and HOT as standard therapies, while ASV is an option only in patients with EF > 45%. BPAP (bilevel device) remains an option only when there is no adequate response to previous modes of treatment. Acetazolamide and theophylline are options only after failing the above modalities and if accompanied by a close follow-up.

Monitoring mandibular movements to detect Cheyne-Stokes Breathing.

BACKGROUND: The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with "sharp" large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM patterns. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. METHODS: In 573 consecutive patients attending an in-laboratory PSG for suspected sleep disordered breathing (SDB), MM signals were acquired using magnetometry and scored manually while blinded from the PSG signal. Data analysis aimed to verify the concordance between the CSB identified by PSG and the presence of LPM or SPM. The data were randomly divided into training and validation sets (985 5-min segments/set) and concordance was evaluated using 2 classification models. RESULTS: In PSG, 22 patients (mean age ± SD: 65.9 ± 15.0 with a sex ratio M/F of 17/5) had CSB (mean central apnea hourly indice ± SD: 17.5 ± 6.2) from a total of 573 patients with suspected SDB. When tested on independent subset, the classification of CSB based on LPM and SPM is highly accurate (Balanced-accuracy = 0.922, sensitivity = 0.922, specificity = 0.921 and error-rate = 0.078). Logistic models based odds-ratios for CSB in presence of SPM or LPM were 172.43 (95% CI: 88.23-365.04; p < 0.001) and 186.79 (95% CI: 100.48-379.93; p < 0.001), respectively. CONCLUSION: CSB in patients with sleep disordered breathing could be accurately identified by a simple magnetometer device recording mandibular movements.

Long-Term Experience with First-Generation Implantable Neurostimulation Device in Central Sleep Apnea Treatment.

BACKGROUND: Sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) are associated with shorter survival in patients with heart failure. A novel treatment method for this patient group is unilateral phrenic nerve stimulation by the remede® system (Respicardia Inc., Minnetonka, MN, USA), a transvenously implantable neurostimulation device, which has recently been studied in a large randomized, controlled trial. Previous literature has shown efficacy and safety of the treatment with this first-generation device, but hardly any data are available on long-term clinical parameters, the remede® device's battery lifetime, device exchangeability, lead position stability, surgical accessibility, and manageability. METHODS: We performed remede® device replacements in consecutive patients for battery depletion, and documented clinical parameters, longevity, operation procedure, complications, and difficulties. RESULTS: All patients were on neurostimulation treatment by phrenic nerve neurostimulation when device replacement became necessary. Apnea-hypopnea index (from 45 ± 4/h to 9 ± 4/h), oxygen-desaturation index (from 35 ± 7/h to 7 ± 6/h), and time spent with oxygen saturation of <90% (T < 90% from 5 ± 7% to 0 ± 0%) were improved and improvements remained constant throughout the 4-year follow-up. Mean battery life was 4.2 ± 0.2 years and mean replacement procedure time was 25 ± 5.1 minutes. Apart from conventional X-ray documentation of stable lead positions in a long-term setting, no radiation or contrast dye usage was needed and no major complications occurred. In addition, clinical exercise capacity and sleepiness symptoms improved. CONCLUSIONS: Novel remede® device shows sustained therapy efficacy and safety in terms of stable lead positions over 4 years. Long-term phrenic nerve neurostimulation therapy for central SDB/CSR appears feasible in a clinical routine setting.

A retrospective analysis of cardiovascular outcomes in patients treated with ASV.

OBJECTIVES: The effect of long-term adaptive servo-ventilation (ASV) on cardiovascular mortality and admission rates in patients with chronic heart failure (CHF) and Cheyne-Stokes respiration (CSR) has not been much studied. The aim of this study was primarily to investigate whether ASV therapy significantly reduced these parameters. DESIGN: We included 75 CHF patients on optimal medication and CSR ≥25% of sleeping time, in New York Heart Association (NYHA) classes II-IV and left ventricular ejection fraction (LVEF) ≤ 45%. Thirty-one patients were treated with ASV for >3-18 months and 44 patients served as a control group. RESULTS: Seven deaths (16%) in the control group and one death (3%) in the ASV treatment group had cardiovascular etiology. There was no significant difference between the two groups regarding cardiovascular death (log rank p = 0.07; HR 0.18 (95% CI 0.02-1.44), p = 0.11) and combined cardiovascular death or readmissions, but there was a trend toward better outcome regarding cardiovascular event-free survival (log rank p = 0.06; HR 0.53 (95% CI 0.27-1.05). CONCLUSIONS: In CHF patients with CSR, 18 months ASV treatment did not significantly affect cardiovascular death or combined cardiovascular death or hospital admissions. But there was a trend toward better combined outcome.

ECG-derived Cheyne-Stokes respiration and periodic breathing in healthy and hospitalized populations.

BACKGROUND: Cheyne-Stokes respiration (CSR) has been investigated primarily in outpatients with heart failure. In this study we compare CSR and periodic breathing (PB) between healthy and cardiac groups. METHODS: We compared CSR and PB, measured during 24 hr of continuous 12-lead electrocardiographic (ECG) Holter recording, in a group of 90 hospitalized patients presenting to the emergency department with symptoms suggestive of acute coronary syndrome (ACS) to a group of 100 healthy ambulatory participants. We also examined CSR and PB in the 90 patients presenting with ACS symptoms, divided into a group of 39 (43%) with confirmed ACS, and 51 (57%) with a cardiac diagnosis but non-ACS. SuperECG software was used to derive respiration and then calculate CSR and PB episodes from the ECG Holter data. Regression analyses were used to analyze the data. We hypothesized SuperECG software would differentiate between the groups by detecting less CSR and PB in the healthy group than the group of patients presenting to the emergency department with ACS symptoms. RESULTS: Hospitalized patients with suspected ACS had 7.3 times more CSR episodes and 1.6 times more PB episodes than healthy ambulatory participants. Patients with confirmed ACS had 6.0 times more CSR episodes and 1.3 times more PB episodes than cardiac non-ACS patients. CONCLUSION: Continuous 12-lead ECG derived CSR and PB appear to differentiate between healthy participants and hospitalized patients.

Cheyne-stokes respiration during wakefulness in patients with chronic heart failure.

PURPOSE: Cheyne-Stokes respiration (CSR) during sleep has been studied extensively in patients with chronic heart failure (CHF). Prevalence and prognostic significance of CSR during wakefulness in CHF, however, are largely unknown. METHODS: CSR during wakefulness with an apnea-hypopnea cut-off ≥5/h and moderate to severe CSR with an apnea-hypopnea cutoff ≥15/h were analyzed using polysomnographic recordings in 267 patients with stable CHF with reduced left ventricular (LV) ejection fraction at our institution. Primary endpoint during follow-up was heart transplant-free survival. RESULTS: Fifty of 267 patients (19%) had CSR during wakefulness and 73 of 267 patients (27%) had CSR during sleep. CSR during wakefulness was associated with advanced age, atrial fibrillation, decreased LV ejection fraction, increased LV end-diastolic diameter, brain natriuretic peptide, New York Heart Failure class, and CSR during sleep. During 43 months mean follow-up, 67 patients (25%) died and 4 patients (1%) underwent heart transplantation. Multivariate Cox analysis identified age, male gender, chronic kidney disease, and LV ejection fraction as predictors of reduced transplant-free survival. CSR during wakefulness with an apnea-hypopnea cutoff ≥5/h as well as moderate to severe CSR while awake using an apnea-hypopnea cutoff ≥15/h did not predict reduced transplant-free survival independently from confounding factors. CONCLUSION: CSR during wakefulness appears to be a marker of heart failure severity.

Cerebral Hemodynamic Effects of Cheyne-Stokes Respiration in a Patient with Stroke.

INTRODUCTION: Cheyne-Stokes respiration (CSR) and central sleep apnea (CSA) are common in patients with heart failure and/or stroke. We aim to describe the cerebrovascular effects of CSR during the acute phase of stroke in a heart failure patient. CASE REPORT: A 74-year-old male with previous dilated cardiomyopathy had sudden onset of right hemiparesis and aphasia. A transcranial Doppler was performed with continuous measurement of blood pressure (BP) (Finometer) and end-tidal CO2 (nasal capnography). Offline analysis of hemodynamic data disclosed relatively large periodic oscillations of both cerebral blood flow velocity and BP related to the CSR breathing pattern. Derivate variables from the cerebrovascular resistance were calculated (critical closing pressure and resistance-area product), demonstrating that there may be a myogenic impairment of cerebral blood flow (CBF) control in the affected hemisphere of this subgroup of patient. CONCLUSION: There is an impairment of CBF regulation in the affected hemisphere of the patient with ischemic stroke and CSR, highlighting the role of cerebral hemodynamic monitoring in this scenario.

Heterogenous haemodynamic effects of adaptive servoventilation therapy in sleeping patients with heart failure and Cheyne-Stokes respiration compared to healthy volunteers.

This study investigated the haemodynamic effects of adaptive servoventilation (ASV) in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) versus healthy controls. Twenty-seven HF patients with CSR and 15 volunteers were ventilated for 1 h using a new ASV device (PaceWave™). Haemodynamics were continuously and non-invasively recorded at baseline, during ASV and after ventilation. Prior to the actual study, a small validation study was performed to validate non-invasive measurement of Stroke volume index (SVI). Non-invasive measurement of SVI showed a marginal overall difference of -0.03 ± 0.41 L/min/m(2) compared to the current gold standard (Thermodilution-based measurement). Stroke volume index (SVI) increased during ASV in HF patients (29.7 ± 5 to 30.4 ± 6 to 28.7 ± 5 mL/m(2), p < 0.05) and decreased slightly in volunteers (50.7 ± 12 to 48.6 ± 11 to 47.9 ± 12 mL/m(2)). Simultaneously, 1 h of ASV was associated with a trend towards an increase in parasympathetic nervous activity (PNA) in HF patients and a trend towards an increase in sympathetic nervous activity (SNA) in healthy volunteers. Blood pressure (BP) and total peripheral resistance response increased significantly in both groups, despite marked inter-individual variation. Effects were independent of vigilance. Predictors of increased SVI during ASV in HF patients included preserved right ventricular function, normal resting BP, non-ischaemic HF aetiology, mitral regurgitation and increased left ventricular filling pressures. This study confirms favourable haemodynamic effects of ASV in HF patients with CSR presenting with mitral regurgitation and/or increased left ventricular filling pressures, but also identified a number of new predictors. This might be mediated by a shift towards more parasympathetic nervous activity in those patients.

Pathophysiology of central sleep apneas.

The transition from wake to sleep is accompanied by a host of physiologic changes, which result in major alterations in respiratory control and may result in sleep-related breathing disorders. The central sleep apneas are a group of sleep-related breathing disorders that are characterized by recurrent episodes of airflow reduction or cessation due to a temporary reduction or absence of central respiratory drive. The fundamental hallmark of central sleep apnea (CSA) disorders is the presence of ventilatory control instability; however, additional mechanisms play a role in one or more specific manifestations of CSA. CSA may manifest during conditions of eucapnia/hypocapnia or chronic hypercapnia, which is a useful clinical classification that lends understanding to the underlying pathophysiology and potential therapies. In this review, an overview of normal breathing physiology is provided, followed by a discussion of pathophysiologic mechanisms that promote CSA and the mechanisms that are specific to different manifestations of CSA.

Tissue Doppler Imaging predicts central sleep apnea in patients with chronic heart failure: data from the Daunia Registry.

BACKGROUND: Tissue Doppler imaging (TDI) is used to improve risk stratification in patients with chronic heart failure (CHF). So far, few studies have used this method to investigate the characteristics of subjects with CHF and Cheyne-Stokes breathing (CSB). The aim of this study was therefore to evaluate whether TDI assessment may predict the presence of CSB in patients with CHF. MATERIALS AND METHODS: A total of 41 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and nocturnal polygraphy to evaluate the presence of sleep apnea and CSB. Conventional echocardiography and TDI parameters were calculated. We have also quantified by TDI a combined index (EAS index) of diastolic and systolic performance: E'/(A' × S'). RESULTS: Subjects with evidence of CSB (N = 8) were characterized by lower values of A' (5·03 ± 2·64 vs. 7·88 ± 2·64 cm/s, P < 0·01). A' and EAS index values were related to Cheyne-Stokes episode rates (r = -0·49 and 0·52, P < 0·05 and <0·01 respectively), EAS index values also with the number of episodes of central apnea (r = 0·39, P < 0·05). A' values predicted the presence of CSB at poly-somnography examination with an OR 0·62 (95% CI 0·40-0·96, P < 0·05) even after correction for age and gender. CONCLUSIONS: Tissue Doppler imaging values (A') are associated with the presence of sleep apnea at nocturnal polygraphy.

Performance of conventional and enhanced adaptive servoventilation (ASV) in heart failure patients with central sleep apnea who have adapted to conventional ASV.

PURPOSE: Adaptive servo-ventilation (ASV) is a positive pressure ventilator support system to normalize ventilation in patients with Cheyne-Stokes respiration (CSR). The latest generation enhanced ASV device (PaceWave; ResMed) has a new feature--auto-adjustment of EPAP. This study tested the hypothesis that enhanced ASV with auto-adjustment of EPAP (PaceWave) is non-inferior to conventional ASV (AutoSetCS). METHODS: This prospective, randomized, crossover, single-center study enrolled adult patients with stable heart failure (HF) and moderate-to-severe sleep-disordered breathing (SDB) who had been receiving conventional ASV therapy for at least 4 weeks. Patients received conventional ASV for one night and enhanced ASV on another night. Support settings for the two ASV devices were similar, with fixed expiratory positive airway pressure (EPAP) set to between 4 and 10 cm H2O and variable EPAP set to between 4 and 15 cm H2O. Full polysomnography was performed during ASV therapy on both nights. Endpoints were the number of nocturnal respiratory events and oxygen desaturations, and changes in blood pressure (BP). RESULTS: Levels of EPAP were comparable during the use of enhanced and conventional ASV, but minimum and maximum inspiratory pressure support values were significantly higher with the PaceWave device. All measures of apnea and hypopnea, and oxygen saturation, were significantly improved during ASV therapy with either device. There were no significant changes in BP or heart rate. CONCLUSIONS: Enhanced ASV is non-inferior to ASV with fixed EPAP in patients with chronic HF and CSR, with a trend towards better control of respiratory events.

Implications of revised AASM rules on scoring apneic and hypopneic respiratory events in patients with heart failure with nocturnal Cheyne-Stokes respiration.

STUDY OBJECTIVES: This study investigated the implications of the revised scoring rules of the American Academy of Sleep Medicine (AASM) in patients with heart failure (HF) with Cheyne-Stokes respiration (CSR). METHODS: Ninety-one patients (NYHA ≥II, LVEF ≤45 %; age 73.6 ± 11.3 years old; 81 male subjects) with documented CSR underwent 8 h of cardiorespiratory polygraphy recordings. Those were analyzed by a single scorer strictly applying the 2007 recommended, 2007 alternative, and the 2012 scoring rules. RESULTS: Compared with the AASM 2007 recommended rules, apnea-hypopnea index (AHI) and hypopnea index (HI) increased significantly when the 2007 alternative and 2012 rules were applied (AHI 34.1 ± 13.5/h vs 37.6 ± 13.2/h vs 38.3 ± 13.2/h, respectively; HI 10.2 ± 9.4/h vs 13.7 ± 10.7/h vs 14.4 ± 11.0/h, respectively; all p < 0.001). Duration of CSR increased significantly with the alternate versus recommended 2007 rules (182.2 ± 117.0 vs 170.1 ± 115.0 min; p ≤ 0.001); there was a significant decrease in CSR duration for the 2012 versus 2007 alternative rules (182.2 ± 117.0 vs 166.7 ± 115.4 min; p ≤ 0.001). CONCLUSION: AHI was higher using the AASM 2012 scoring rules due to a less strict definition of hypopnea. Data on the prognostic effects of CSR in patients with HF and the benefits of treatment are mostly based on the AASM 2007 recommended rules, so differences between these and the newer version need to be taken into account.

[SLEEP DISORDERED BREATHING AND EPILEPSY: RELATIONSHIPS AND THERAPEUTIC CONSIDERATIONS]. / AZ ALVÁSFÜGGO LÉGZÉSZAVAROK ÉS EPILEPSZIA: KAPCSOLÓDÁSI PONTOK ÉS TERÁPIÁS MEGFONTOLÁSOK.

The importance of the sleep related breathing disorders (obstructive sleep apnea syndrome, central sleep apnea, and Cheyne-Stokes breathing) in the pathophysiology crebro- and cardiovascular disorders is well known. The relationship of sleep related breathing abnormalities and epilepsy is also important but underestimated in the daily practice. The relation is bidirectional. The breathing abnormalities in sleep may play important role in generating epileptic seizure, but the adverse effect of seizure and antiepileptic therapy (generation of apneas and hypopneas) may worsen the seizure control. The effect of new therapies (vagal nerve and deep brain stimulation) on the sleep architecture and sleep disordered breathing must be examined and discussed. Here we present a brief case of epileptic patient with deep brain stimulation therapy on sleep as well. The examination of the sleep related breathing abnormalities in epilepsy patient may help improve the effectiveness of antiepileptic therapy.

Validation of blood pressure monitoring using pulse transit time in heart failure patients with Cheyne-Stokes respiration undergoing adaptive servoventilation therapy.

PURPOSE: Using pulse transit time (PTT) and an ECG appears to be a promising alternative for invasive or noninvasive monitoring of blood pressure (BP). This study assessed the validity of PTT for BP monitoring in clinical practice. METHODS: Twenty-nine patients with chronic heart failure (HF; 27 male, 70.5 ± 9.9 years) and nocturnal Cheyne-Stokes respiration were noninvasively ventilated for one hour using adaptive servoventilation (ASV) therapy (PaceWave, ResMed). BP was measured using two devices (oscillometrically via Task Force Monitor, CNSystems and PTT via SOMNOscreen, Somnomedics) at least every 7 min for 30 min before, during, and after ASV. RESULTS: Mean systolic BP was 118.1 ± 14.4 mmHg vs. 115.9 ± 14.1 mmHg for oscillometric method vs PTT, respectively. Corresponding values for diastolic BP were 72.3 ± 10.3 mmHg and 69.4 ± 11.1 mmHg. While clinically comparable, differences between the two methods were statistically significant (p < 0.05). The difference between the two methods showed an increasing trend over time. A total of 18.5 % of PTT-based measurements could not be analyzed. The direction of a change in BP was opposite for PTT vs oscillometry for 17.0 % and 32.8 % of systolic and diastolic BP measurements, respectively. CONCLUSIONS: When monitoring BP in HF patients, overall BP monitoring using PTT is comparable to oscillometry for a period of 2 h (including a 1-h ASV phase). However, PTT shows a tendency to underestimate BP over time and during ASV.

Treatment of Cheyne-Stokes respiration reduces arrhythmic events in chronic heart failure.

OBJECTIVE: This study aimed to investigate whether adequate treatment of Cheyne-Stokes respiration (CSR) reduces the risk of arrhythmic events in patients with chronic heart failure (CHF). METHODS: A cohort of 403 registry patients with CHF (LVEF≤45%, NYHA-class≥2) and implanted cardioverter-defibrillator devices (ICD) was studied. They underwent overnight polygraphy, with 221 having mild or no CSR (apnea-hypopnea index [AHI]<15/h), and 182 having moderate to severe CSR (AHI>15/h). Latter ones were offered therapy with adaptive servoventilation (ASV), which 96 patients accepted and 86 rejected. During follow-up (21± 15 months) defibrillator therapies were recorded in addition to clinical and physiologic measures of heart failure severity. RESULTS: Event-free survival from (a) appropriate cardioverter-defibrillator therapies and (b) appropriately monitored ventricular arrhythmias was shorter in the untreated CSR group compared to the treated CSR and the no CSR group. Stepwise Cox proportional hazard regression analysis showed untreated CSR (a: hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.46-2.72, P < 0.001; b: HR 2.19, 95%CI 1.42-3.37, P < 0.001), but not treated CSR (a: HR 1.06, 95%CI 0.74-1.50; P = 0.77; b: HR 1.21, 95%CI 0.75-1.93, P = 0.43) was an independent risk factor. The treated CSR group showed improvements in cardiac function and respiratory stability compared to the untreated CSR group. CONCLUSION: This study demonstrates a decrease of appropriate defibrillator therapies by ASV treated CSR in patients with CHF and ICD. A reduced exposure to hyperventilation, hypoxia, and improvement in indices of CHF severity and neurohumoral disarrangements are potential causative mechanisms.