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.

Changes in cognitive function and daytime sleepiness in patients with chronic heart failure and Cheyne-Stokes respiration with adaptive servo ventilation treatment.

STUDY OBJECTIVES: Cheyne - Stokes respiration (CSR) is prevalent in patients with chronic heart failure (CHF). Adaptive Servo Ventilation (ASV) alleviates CSR and improves objective sleep quality. We investigated the effects of ASV on neurocognitive function in the symptomatic phenotype of patients with CSR and CHF. METHODS: This case series included patients diagnosed with stable CHF (NYHA ≥ II) and CSR (N = 8). Sleep and neurocognitive function were assessed at baseline and after 1- and 6-months following initiation of ASV treatment. RESULTS: In CHF patients (n = 8, median age 78.0[64.5-80.8] years and BMI 30.0[27.0-31.5] kg/m2, median ejection fraction 30[24-45]%, Epworth Sleepiness Scale (ESS) score 11.5[9.0-15.0]), ASV markedly improved respiration during sleep (Apnea-Hypopnea Index (AHI) 44.1[39.0-51.5]n/h at baseline, 6.3[2.4-9.7]n/h at 6 months treatment, respectively, p < 0.01). The 6-min-walk test distance increased by treatment from (295.0[178.8-385.0] m to 356.0[203.8-495.0] m (p = 0.05)). Sleep structure was modified, and Stage 3 increased markedly from 6.4[1.7-20.1] % to 20.8[14.2-25.3] %, p < 0.02). Sleep latency in the Maintenance of Wakefulness Test increased from 12.0[6.0-30.0] min to 26.3[12.0-30.0] min, (p = 0.04). In the Attention Network Test, evaluating neurocognition, the number of lapses decreased from 6.0[1.0-44.0] to 2.0[0.3-8.0], (p = 0.05) and the overall number of responses to a preset stimulus increased after treatment (p = 0.04). CONCLUSIONS: ASV treatment in CHF patients with CSR may improve sleep quality, neurocognition and daytime performance.

The prevalence of sleep-disordered breathing and associated risk factors in patients with decompensated congestive heart failure in Mozambique.

STUDY OBJECTIVES: Sleep-disordered breathing (SDB) is common in patients with congestive heart failure and has important implications regarding symptoms and prognosis. However, the burden of SDB on those with heart failure has not been well characterized in developing countries, including Mozambique in sub-Saharan Africa. Diagnosing SDB in individuals with congestive heart failure is important because treatment of SDB may improve outcomes. METHODS: Between September 2014 and April 2017, patients hospitalized in a specialized cardiology unit in Maputo, Mozambique with decompensated congestive heart failure were recruited using convenience sampling. We determined the prevalence of SDB and associated risk factors. RESULTS: A total of 165 patients were recruited, of which 145 had evaluable sleep study data. The overall prevalence of SDB in patients with decompensated congestive heart failure was 72%, and of these 46% had Cheyne-Stokes respirations. Male sex, higher body mass index, and lower left ventricular ejection fraction were all associated with a higher likelihood of SDB and more severe SDB. Cheyne-Stokes respirations were associated with male sex, lower ejection fraction, and larger left atrial size. CONCLUSIONS: We conclude that in sub-Saharan Africa SDB is common in decompensated congestive heart failure and strongly predicted by demographic and echocardiographic parameters. This study highlights the need for the development of diagnostic tools and management strategies for patients with severe heart failure in resource-limited settings. CITATION: Lo S, Mbanze I, Orr JE, et al. The prevalence of sleep-disordered breathing and associated risk factors in patients with decompensated congestive heart failure in Mozambique. J Clin Sleep Med. 2023;19(6):1103-1110.

Prognostic Value of Cheyne-Stokes Respiration and Nutritional Status in Acute Decompensated Heart Failure.

Malnutrition frequently coexists with heart failure (HF), leading to series of negative consequences. Cheyne-Stokes respiration (CSR) is predominantly detected in patients with HF. However, the effect of CSR and malnutrition on the long-term prognosis of patients with acute decompensated HF (ADHF) remains unclear. We enrolled 162 patients with ADHF (median age, 62 years; 78.4% men). The presence of CSR was assessed using polysomnography and the controlling nutritional status score was assessed to evaluate the nutritional status. Patients were divided into four groups based on CSR and malnutrition. The primary outcome was all-cause mortality. In total, 44% of patients had CSR and 67% of patients had malnutrition. The all-cause mortality rate was 26 (16%) during the 35.9 months median follow-up period. CSR with malnutrition was associated with lower survival rates (log-rank p < 0.001). Age, hemoglobin, albumin, lymphocyte count, total cholesterol, triglyceride, low-density lipoprotein cholesterol, creatinine, estimated glomerular filtration rate, B-type natriuretic peptide, administration of loop diuretics, apnea-hypopnea index and central apnea-hypopnea index were significantly different among all groups (p < 0.05). CSR with malnutrition was independently associated with all-cause mortality. In conclusion, CSR with malnutrition is associated with a high risk of all-cause mortality in patients with ADHF.

The Association between Low CO2 Production and Central Sleep Apnea in Men with Heart Failure.

Rationale: Hunter-Cheyne-Stokes breathing with central sleep apnea (CSA) is prevalent in some patients with heart failure with reduced ejection fraction (HFrEF). Theoretical models of Hunter-Cheyne-Stokes breathing predict that a low metabolic rate (MR) predisposes one to CSA. Objectives: In this study, we examined the role of MR in the pathogenesis of CSA. Methods: A physiological study was conducted in a sleep laboratory at a U.S. Department of Veterans Affairs medical center. Patients were 28 consecutive male Veterans with stable HFrEF. After an adaptation night, polysomnography, left ventricular ejection fraction, pulmonary function tests, carbon dioxide production ([Formula: see text]), and arterial blood samples were obtained under strict standardized conditions. Physiological variables were then entered into regression models to examine the association with CSA. Results: Body mass index varied from 20 to 40 kg/m2, and [Formula: see text] ranged from 167 to 434 ml/min. In the final regression model, low [Formula: see text] and low body mass index were associated with CSA index. [Formula: see text] had the strongest association (95% confidence interval, -0.36 to -0.06; P = 0.007). Conclusions: In patients with HFrEF, a low MR and related low [Formula: see text], but not low oxygen consumption, were associated with CSA. Mechanistically, in the face of low MR and [Formula: see text], a given change in ventilation results in large swings in partial pressure of CO2, thus promoting CSA. To our knowledge, this is the first study in humans that shows this association.

Postural changes in lung volumes in patients with heart failure and Cheyne-Stokes respiration: Relationship with sleep apnea severity.

BACKGROUND AND AIM: It has been proposed that the increased severity of sleep apnea frequently observed in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) when sleeping in the supine compared to the lateral position, may be caused by the concomitant reduction in functional residual capacity (FRC). We assessed positional changes in FRC in patients with CSR and investigated the relationship between these changes in the laboratory and corresponding changes in CSR severity during sleep. METHODS: After a diagnostic polysomnography, 18 HF patients with dominant CSR and an apnea-hypopnea index (AHI)≥15 events/h underwent a standard pulmonary function test in the sitting position. Measurements were repeated in the supine, left lateral and right lateral. The latter two measurements were averaged to obtain a single lateral measurement. RESULTS: The FRC in the seated position was 3.0 ± 0.5 L (85 ± 13% of predicted), decreased to 2.3 ± 0.3 L (-21 ± 8%, p < 0.0001) in the supine position, and increased to 2.8 ± 0.4 L (+21 ± 12%, p < 0.0001) from the supine to the lateral position (-5±8% vs seated, p = 0.013). During sleep, the AHI and the apnea index (AI) decreased from 47 ± 15 events/h to 26 ± 12 events/h (-46 ± 20%, p < 0.0001) and from 29 ± 21 events/h to 12 ± 10 events/h (-61 ± 40%, p < 0.001) from the supine to the lateral position. Changes in the AI were significantly correlated with corresponding changes in FRC (ρ = -0.55, p = 0.032). CONCLUSION: In patients with HF and CSR, lying in the supine position causes a significant reduction in FRC in the context of a chronically reduced FRC. The negative correlation between postural changes in FRC and AI supports the hypothesis that the reduction in lung gas stores in the supine position may promote/exacerbate respiratory control instability.

Impact of transcatheter edge-to-edge mitral valve repair on central sleep apnoea.

AIMS: Sleep-disordered breathing (SDB) and its subtype central sleep apnoea (CSA) are highly prevalent in patients with heart failure and associated with worse prognosis. Whereas pharmacological therapy of heart failure has been shown to ameliorate CSA, results from previous studies on the effect of mitral regurgitation therapy on SDB are contradicting. The aim of this study was to assess the impact of transcatheter edge-to-edge mitral valve repair (TEER) on prevalence and severity of CSA. METHODS AND RESULTS: We enrolled 47 patients undergoing TEER for symptomatic mitral regurgitation in a prospective study. Secondary mitral regurgitation and left ventricular ejection fraction < 50% were present in 79% and 68% of patients, respectively. Respiratory polygraphy was performed before TEER in a compensated condition and four weeks after the procedure. 34 patients completed the follow-up. At baseline, 19 (56%) patients showed moderate-to-severe SDB, of whom 13 (68%) were classified as CSA. Both apnoea-hypopnoea index and percentage of recorded time spent in Cheyne-Stokes respiration strongly decreased from baseline to follow-up (median [IQR] 16 [7-30] vs. 7 [4-15] /h, p = 0.007; 6 [0-34] vs. 0 [0-8] %, p = 0.008). Median relative reduction of central apnoea index was 75% (p = 0.023), while obstructive apnoea index did not change significantly. Increase in stroke volume after TEER and high systolic pulmonary artery pressure at baseline predicted a > 50% reduction of both Apnoea-hypopnoea index and Cheyne-Stokes respiration. CONCLUSION: TEER is associated with a significant short-term reduction of CSA and Cheyne-Stokes respiration in high-risk patients, strengthening its value as an effective treatment option for advanced heart failure.

Treatment of Cheyne-Stokes Respiration in Heart Failure with Adaptive Servo-Ventilation: An Integrative Model.

The SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) multicenter trial found a small but significant increase in all-cause and cardiovascular mortality in patients assigned to adaptive servo-ventilation (ASV) versus guideline-based medical treatment. To better understand the physiological underpinnings of this clinical outcome, we employ an integrative computer model to simulate congestive heart failure with Cheyne-Stokes respiration (CHF-CSR) in subjects with a broad spectrum of underlying pathogenetic mechanisms, as well as to determine the in silico changes in cardiopulmonary and autonomic physiology resulting from ASV. Our simulation results demonstrate that while the elimination of CSR through ASV can partially restore cardiorespiratory and autonomic physiology toward normality in the vast majority of CHF phenotypes, the degree of restoration can be highly variable, depending on the combination of CHF mechanisms in play. The group with the lowest left ventricular ejection fraction (LVEF) appears to be most vulnerable to the potentially adverse effects of ASV, but the level of pulmonary capillary wedge pressure (PCWP) plays an important role in determining the nature of these effects.

Detection of Cheyne-Stokes Breathing using a transformer-based neural network.

Annotation of sleep disordered breathing, including Cheyne-Stokes Breathing (CSB), is an expensive and time-consuming process for the clinician. To solve the problem, this paper presents a deep learning-based algorithm for automatic sample-wise detection of CSB in nocturnal polysomnographic (PSG) recordings. 523 PSG recordings were retrieved from four different sleep cohorts and subsequently scored for CSB by three certified sleep technicians. The data was pre-processed and 16 time domain features were extracted and passed into a neural network inspired by the transformer unit. Finally, the network output was post-processed to achieve physiologically meaningful predictions. The algorithm reached a F1-score of 0.76, close to the certified sleep technicians showing that it is possible to automatically detect CSB with the proposed model. The algorithm had difficulties distinguishing between severe obstructive sleep apnea and CSB but this was not dissimilar to technician performance. In conclusion, the proposed algorithm showed promising results and a confirmation of the performance could make it relevant as a screening tool in a clinical setting.

Cardiorespiratory Phase Synchronization in Elderly Patients with Periodic and non-Periodic Breathing Patterns.

Cardiorespiratory Phase Synchronization (CRPS) is the manifestation of the non-linear coupling between the cardiac and the respiratory systems, different to the Respiratory Sinus Arrythmia (RSA). This takes place when the heartbeats occur at the same relative phase of the breathing, during a succession of respiratory cycles. In this study, we investigated the CRPS in 45 elderly patients admitted to the semi-critical unit of a hospital. The patients were classified according to their respiratory state as non-Periodic Breathing (nPB), Periodic Breathing (PB) and Cheyne-Stokes Respiration (CSR). The phase synchrogram between the electrocardiographic and respiratory signals was computed using the Hilbert transform technique. A continuous measure of the CRPS was obtained from the synchrogram, and was characterized by the average duration of synchronized epochs (A vgDurSync), the percentage of synchronized time (%Sync), the number of synchronized epochs (NumSync), and the frequency ratio between the cardiac and respiratory oscillators (FreqRat). These measures were studied using two different thresholds (0.1 and 0.05) for the amplitude of the synchronization and a minimum duration threshold of 10s. According to the results, the AvgDurSync and %Sync had a decreasing trend in patients with breathing periodicity. In addition, CSR patients presented the lowest values A vgDurSync and %Sync. Therefore, the CRPS method could be a useful tool for characterizing periodic respiratory patterns in elderly patients, which might be related to chronic heart failure. Clinical Relevance- This study analyzes the synchronization between cardiac and respiratory systems in elderly patients with a possible progressive decompensation in the cardiac function.

Central sleep apnea.

Central apnea syndrome is a disorder with protean manifestations and concomitant conditions. It can occur as a distinct clinical entity or as part of another clinical syndrome. The pathogenesis of central sleep apnea (CSA) varies depending on the clinical condition. Sleep-related withdrawal of the ventilatory drive to breathe is the common denominator among all cases of central apnea, whereas hypocapnia is the final common pathway leading to apnea in the majority of central apnea. Medical conditions most closely associated with CSA include heart failure, stroke, spinal cord injury, and opioid use, among others. Nocturnal polysomnography is the standard diagnostic method, including measurement of sleep and respiration. The latter includes detection of flow, measurement of oxyhemoglobin saturation and detection of respiratory effort. Management strategy incorporates clinical presentation, associated conditions, and the polysomnographic findings in an individualized manner. The pathophysiologic heterogeneity may explain the protean clinical manifestations and the lack of a single effective therapy for all patients. While research has enhanced our understanding of the pathogenesis of central apnea, treatment options are extrapolated from treatment of obstructive sleep apnea. Co-morbid conditions and concomitant obstructive sleep apnea influence therapeutic approach significantly. Therapeutic options include positive pressure therapy, pharmacologic therapy, and supplemental Oxygen. Continuous positive airway pressure (CPAP) is the initial standard of care, although the utility of other modes of positive pressure therapy, as well as pharmacotherapy and device-based therapies, are currently being investigated.

Sleep Breathing Disorders in Heart Failure.

Sleep-disordered breathing (SDB), including obstructive sleep apnea, central sleep apnea (CSA), and Cheyne-Stokes respiration, is common in patients with heart failure (HF) and associated with lower left ventricular ejection fraction (EF), increased arrhythmia burden, and increased mortality. Continuous positive airway pressure therapy improves short-term and long-term outcomes in HF patients. Adaptive servoventilation (ASV) therapy in patients with low-EF HF with predominant CSA is not recommended. Ongoing trials are evaluating whether ASV will have a role in SDB treatment. Phrenic nerve stimulation is an emerging treatment option that has shown promising outcomes. All HF patients should be screened for SDB.

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.

Disordered breathing in severe cerebral illness - Towards a conceptual framework.

Despite potentially life-threatening symptoms of disordered breathing in severe cerebral illness, there are no clear recommendations on diagnostic and therapeutic strategies for these patients. To identify types of breathing disorders observed in severely neurological comprised patients, to direct further research on classification, pathophysiology, diagnosis and treatment for disordered breathing in cerebral disease. Data including polygraphy, transcutaneous capnometry, blood gas analysis and radiological examinations of patients with severe cerebral illness and disordered breathing admitted to the neurological intensive care were analyzed. Patients (15) presented with acquired central hypoventilation syndrome (ACHS), central bradypnea, central tachypnea, obstructive, mixed and central apneas and hypopneas, Cheyne Stokes respiration, ataxic (Biot's) breathing, cluster breathing and respiration alternans. Severe cerebral illness may result in an ACHS and in a variety of disorders of the respiratory rhythm. Two of these, abrupt switches between breathing patterns and respiration alternans, suggest the existence of a rhythmogenic respiratory network. Polygraphy, transcutaneous capnometry, blood gas analysis and MRI are promising tools for diagnosis and research alike.

Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration.

STUDY OBJECTIVES: Cheyne-Stokes respiration (CSR), a kind of central sleep apnea, is referred to as a poor prognostic factor in heart failure patients with reduced ejection fraction (HFrEF). Matrix metalloproteinase (MMP) and B-type natriuretic peptide (BNP) play important roles in HFrEF patients and are markers of poor prognosis. However, there is no literature mentioning the changes in MMP and BNP in HFrEF patients with CSR. METHODS: From June 2018 to June 2019, 41 adult patients with stable heart failure and left ventricular ejection fraction < 50% were enrolled from the cardiology clinic. After history-taking and medication review to exclude possible central nervous system- or medication-related central sleep apnea, an overnight polysomnography study was performed, and CSR was identified. The morning serum MMP-2, MMP-9, and BNP levels were determined using enzyme-linked immunosorbent assay and fluorescence immunoassay techniques. A positive airway pressure device was applied to 7 patients for 3 months. RESULTS: The serum MMP-2 and BNP levels were significantly higher in HFrEF patients with CSR than in patients without CSR. In addition, elevated serum MMP-2 levels correlated well with the severity of sleep apnea and intermittent hypoxia, which were represented as the apnea-hypopnea index and the oxygen desaturation index. No positive correlation was found between those markers and left ventricular ejection fraction. Finally, the treatment of sleep apnea with continuous positive airway pressure for 3 months tended to reduce the elevated serum MMP-2 levels. CONCLUSIONS: Higher serum MMP-2 and BNP levels were found in HFrEF patients with CSR. Elevated MMP-2 levels were correlated with the severity of sleep apnea and intermittent hypoxia. CITATION: Chuang L-P, Pang J-HS, Lin S-W, et al. Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration. J Clin Sleep Med. 2022;18(5):1365-1373.