RESUMO
Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep apnea (CSA). The remede System Pivotal Trial population was examined for nocturnal hypoxemic burden. The minutes of sleep with oxygen saturation < 90% significantly improved in Treatment compared with control (p < .001), with the median improving from 33 min at baseline to 14 min at 6 months. Statistically significant improvements were also observed for average oxygen saturation and lowest oxygen saturation. Hypoxemic burden has been demonstrated to be more predictive for mortality than apnea-hypopnea index (AHI) and should be considered a key metric for therapies used to treat CSA. Transvenous phrenic nerve stimulation is capable of delivering meaningful improvements in nocturnal hypoxemic burden. There is increasing interest in endpoints other than apnea-hypopnea index in sleep-disordered breathing. Nocturnal hypoxemia burden may be more predictive for mortality than apnea-hypopnea index in patients with poor cardiac function. Transvenous phrenic nerve stimulation is capable of improving nocturnal hypoxemic burden. Graphical Abstract.
Assuntos
Ritmo Circadiano , Terapia por Estimulação Elétrica , Hipóxia/terapia , Saturação de Oxigênio , Oxigênio/sangue , Apneia do Sono Tipo Central/terapia , Idoso , Biomarcadores/sangue , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Hipóxia/sangue , Hipóxia/diagnóstico , Hipóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nervo Frênico , Estudos Prospectivos , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/fisiopatologia , Fatores de Tempo , Estimulação Elétrica Nervosa Transcutânea , Resultado do TratamentoRESUMO
BACKGROUNDS: As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions. METHODS: The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal. RESULTS: 177/214 patients were analysed (87.57% male) with a median (IQ25-75) age of 71 (65-77) years, an ASV-treatment duration of 2.88 (1.76-4.96) years, an ASV-usage of 6.52 (5.13-7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6-13.5) to 6 (3-9) (p < 0.001) with ASV-therapy, the apnea-hypopnea-index decreased from 50 (38-62)/h to a residual device index of 1.9 (0.7-3.8)/h (p < 0.001). The majority of patients were classified in a Central-Sleep-Apnea group (CSA; 59.3%), whereas the remaining are divided into an Obstructive-Sleep-Apnea group (OSA; 20.3%) and a Treatment-Emergent-Central-Sleep-Apnea group (TECSA; 20.3%). The Left Ventricular Ejection Fraction (LVEF) was > 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p < 0.05). CONCLUSIONS: In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management. TRIAL REGISTRATION: The OTRLASV study is registered on ClinicalTrials.gov (Identifier: NCT02429986 ) on 1 April 2015.
Assuntos
Respiração Artificial/métodos , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/terapia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Estudos Prospectivos , Apneia do Sono Tipo Central/sangue , Apneia Obstrutiva do Sono/sangueRESUMO
Background Congenital central hypoventilation syndrome (CCHS) is a rare disorder of autonomic control. A hypoglycaemic seizure in a 4-year-old girl with CCHS led to a more detailed examination of glycaemic control in a cohort of children with CCHS. Methods We conducted an observational cohort study of glucose homeostasis in seven children (3 months to 12 years) with genetically confirmed CCHS using a combination of continuous glucose monitoring (CGM), fasting studies and oral glucose tolerance test (OGTT). CGM was used to compare the effect of diazoxide and dietary intervention in the index patient. Results Hypoglycaemia was not elicited by fasting in any of the patients. Increased postprandial glycaemic variability was evident in all patients using CGM, with seven of seven patients demonstrating initial postprandial hyperglycaemia (plasma-glucose concentration >7.8 mmol/L), followed by asymptomatic hypoglycaemia (plasma-glucose concentration ≤2.8 mmol/L) in two of seven patients that was also demonstrated on OGTT. Both diazoxide and low Glycaemic Index (GI) dietary intervention reduced the proportion of CGM readings <4 mmol/L; however, diazoxide also increased the proportion of readings in the hyperglycaemic range. Conclusions Glucose variability associated with autonomic dysfunction may be unrecognised in CCHS, particularly in children with more severe phenotypes. This report highlights the occurrence of hyperglycaemia as well as hypoglycaemia in CCHS. Given the challenges of recognising hypoglycaemia based on clinical symptomatology, the use of CGM may facilitate its identification allowing appropriate management. The observed normoglycaemia during fasting combined with increased postprandial plasma blood glucose level (BGL) variability is more consistent with dumping syndrome than persistent hyperinsulinism. Dietary modifications therefore may be more effective than diazoxide in managing hypoglycaemia.
Assuntos
Glicemia/metabolismo , Homeostase/fisiologia , Hipoglicemia/sangue , Hipoventilação/congênito , Apneia do Sono Tipo Central/sangue , Criança , Pré-Escolar , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Hipoventilação/sangue , Lactente , MasculinoRESUMO
BACKGROUND: The SERVE-HF study has raised questions concerning the higher mortality under adaptive servoventilation. The ventilatory mode was discussed as a possible aggravating factor. OBJECTIVES: We wondered if the data recorded by the adaptive servo-ventilation (ASV)-devices in heart failure patients with CSA-CSR ± OSA are different in terms of respiratory parameters and therapeutic pressures compared to patients with CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP. METHODS: Patients were included, if ASV had normalized respiratory disturbance index in the first night of application and after at least 6 weeks. ASV-device data were analyzed in terms of respiratory rate (RR), min ventilation (MV), endexpiratory (EEP), peak inspiratory pressure (Ppeak) and median pressure. RESULTS: Compared to CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP (n = 25), CSA-CSR- (n = 13) CSA-CSR+OSA-patients (n = 32) with elevated BNP/NT-pro-BNP had higher RR (p < 0.01) in the first night of ASV therapy and during follow-up (15.3 ± 1.3 vs. 17.3 ± 2.4/min) with similar MV (6.5 ± 1.3 vs. 6.6 ± 1.3 L), resulting in significantly lower tidal volumes. EEP (5.6 ± 1.1 vs. 5.5 ± 1.1 hPa), Pmedian and Ppeak (9.8 ± 1.5 vs. 9.7 ± 1.2 hPa) were comparable. Ventilatory parameters were not different between LVEF < 40, 40-49, and ≥50%, neither within the whole group nor the group of CSA-CSR ± OSA and heart failure. CONCLUSION: Patients with heart failure and CSA-CSR ± OSA have higher RRs but similar MV under ASV-therapy than patients with CSA and normal BNP. This indicates higher dead space ventilation. EF was not found to have an influence on the ventilatory parameters.
Assuntos
Respiração de Cheyne-Stokes/fisiopatologia , Insuficiência Cardíaca/complicações , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Respiração , Apneia do Sono Tipo Central/fisiopatologia , Respiração de Cheyne-Stokes/sangue , Respiração de Cheyne-Stokes/complicações , Respiração de Cheyne-Stokes/terapia , Humanos , Respiração Artificial , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/complicações , Apneia do Sono Tipo Central/terapia , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Volume SistólicoRESUMO
BACKGROUND: Analysis of subtle vital sign changes could facilitate earlier treatment of acute inflammatory illnesses. We previously showed that high cross-correlation of heart rate and oxygen saturation (XCorr-HR-SpO2) occurs in some very low birthweight (VLBW) infants with sepsis, and hypothesized that this corresponds to apnea. METHODS: In 629 VLBW infants, we analyzed XCorr-HR-SpO2 in relation to central apnea with bradycardia and desaturation (ABD), BD with or without central apnea (BD), and percent time in periodic breathing (PB) throughout the neonatal intensive care unit (NICU) stay (75 infant-years). We reviewed 100 days with extremely high XCorr-HR-SpO2 (>0.7) and control days for clinical associations. Next, we identified all cases of late-onset septicemia (LOS) and necrotizing enterocolitis (NEC) and analyzed change in XCorr-HR-SpO2 before diagnosis. RESULTS: Mean XCorr-HR-SpO2 was â¼0.10, and increasing XCorr-HR-SpO2 was associated with increasing ABD, BD, and PB (correlation coefficients >0.93). Days with maximum XCorr-HR-SpO2 >0.7 were more likely to have an adverse event than control days (49% versus 13%). In 93 cases of LOS or NEC, there was a 67% increase in XCorr-HR-SpO2 in the 24-hour period prior to diagnosis compared with the previous day (p < 0.01). CONCLUSION: High XCorr-HR-SpO2 is associated with apnea and adverse events including LOS and NEC.
Assuntos
Enterocolite Necrosante/diagnóstico , Frequência Cardíaca , Oxigênio/sangue , Sepse/diagnóstico , Apneia do Sono Tipo Central/diagnóstico , Enterocolite Necrosante/sangue , Enterocolite Necrosante/fisiopatologia , Feminino , Humanos , Recém-Nascido , Doenças do Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Modelos Lineares , Masculino , Sepse/sangue , Sepse/fisiopatologia , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/fisiopatologiaRESUMO
Low leptin concentration has been shown to be associated with central sleep apnea in heart failure patients. We hypothesized that low leptin concentration predicts central sleep apnea. Consecutive ambulatory New York Heart Association (NYHA) classes I-IV heart failure patients were studied prospectively, including measurement of serum leptin, echocardiography and polysomnography. Sleep apnea was defined by type (central/mixed/obstructive) and by apnea-hypopnea index ≥5 by polysomnography. Subjects were divided into four groups by polysomnography: (1) central sleep apnea, (2) mixed apnea, (3) no apnea and (4) obstructive sleep apnea. Fifty-six subjects were included. Eighteen subjects were diagnosed with central sleep apnea, 15 with mixed apnea, 12 with obstructive apnea and 11 with no sleep apnea. Leptin concentration was significantly lower in central sleep apnea compared to obstructive apnea (8 ± 10.7 ng mL-1 versus 19.7 ± 14.7 ng mL-1 , P Ë 0.01) or no sleep apnea (8 ± 10.7 ng mL-1 versus 17.1 ± 8.4 ng mL-1 , P Ë 0.01). Logistic regression showed leptin to be associated independently with central sleep apnea [odds ratio (OR): 0.19; 95% confidence interval (CI): 0.06-0.62; area under the curve (AUC): 0.80, P < 0.01]. For the detection of central sleep apnea, a cut-off value for leptin concentration 5 ng mL-1 yielded a sensitivity of 50% and specificity of 89%. In conclusion, a low leptin concentration may have utility for the screening of heart failure patients for central sleep apnea.
Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Leptina/sangue , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/diagnóstico por imagem , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Estudos Prospectivos , Apneia do Sono Tipo Central/epidemiologiaRESUMO
CONTEXT: The aldosterone to renin ratio (ARR) is recommended to screen for primary aldosteronism (PA). OBJECTIVE: To evaluate whether dietary sodium restriction results in misinterpretation of PA screening. PARTICIPANTS: Untreated hypertensives with ARR more than 20 on a high dietary sodium intake (HS) were also evaluated on a low dietary sodium intake (LS) (n = 241). Positive screening for PA was defined as: plasma renin activity (PRA) less than or equal to 1.0 ng/mL · h with serum aldosterone more than or equal to 6 ng/dL. PA was confirmed by a 24-hour urinary aldosterone excretion more than or equal to 12 mcg with urinary sodium more than 200 mmol. RESULTS: Only 33% (79/241) of participants with an ARR more than 20 had a positive PA screen on HS. On LS, 56% (44/79) of these participants no longer met criteria for positive PA screening. When compared with participants with positive PA screening on both diets, participants with a positive screen on HS but negative on LS exhibited a significantly higher PRA on both diets. Remarkably, of the 48/79 participants who had PA confirmed, 52% had negative PA screening on LS. The distinguishing feature of these participants with "discordant" screening results was a larger rise in PRA on LS resulting in normalization of the ARR and higher Caucasian race prevalence. CONCLUSIONS: Sodium restriction is recommended in hypertension; however, it can significantly raise PRA, normalize the ARR, and result in false interpretation of PA screening. Milder phenotypes of PA, where PRA is not as suppressed, are most susceptible to dietary sodium influences on renin and ARR. Optimal screening for PA should occur under conditions of HS.
Assuntos
Erros de Diagnóstico , Dieta Hipossódica/efeitos adversos , Regulação para Baixo , Hipertensão/dietoterapia , Hipoventilação/congênito , Apneia do Sono Tipo Central/diagnóstico , Adulto , Aldosterona/sangue , Aldosterona/urina , Algoritmos , Estudos de Coortes , Erros de Diagnóstico/prevenção & controle , Reações Falso-Negativas , Feminino , Humanos , Hipertensão/etiologia , Hipoventilação/sangue , Hipoventilação/diagnóstico , Hipoventilação/fisiopatologia , Hipoventilação/urina , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Renina/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/fisiopatologia , Apneia do Sono Tipo Central/urina , Sódio na Dieta/administração & dosagemAssuntos
Pressão Positiva Contínua nas Vias Aéreas , Oxigênio/sangue , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/terapia , Idoso de 80 Anos ou mais , Humanos , Masculino , Oximetria , Apneia do Sono Tipo Central/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapiaRESUMO
OBJECTIVE: To evaluate whether jaundice, indexed by unbound bilirubin (UB), is associated with central apnea in premature infants. STUDY DESIGN: A prospective observational study was performed with 27-33 weeks' gestational age infants who were not requiring either mechanical ventilation or noninvasive ventilation with continuous positive airway pressure beyond 24 hours after birth. Infants with congenital infections, chromosomal disorders, craniofacial anomalies, and/or family history of hearing loss were excluded. Total serum bilirubin and UB were measured twice daily during the first postnatal week and then when clinically indicated. Central apnea was evaluated by visual inspection of continuous, electronic cardiorespiratory recordings until 2 weeks of age. RESULTS: One hundred infants were subdivided into 2 groups via median peak UB level: the high UB group (greater than median) and low UB group (less than median). The high UB group had an increased frequency of apnea events during the first 2 weeks compared with infants in the low UB group. After we controlled for confounders, the high UB group had more events of apnea during the first 2 postnatal weeks compared with the low UB group (incidence rate ratio: 1.9, 95% CI 1.2-3.2). CONCLUSIONS: Our findings suggest that jaundice, as indexed by UB, is associated with central apnea in premature infants.
Assuntos
Bilirrubina/sangue , Hiperbilirrubinemia/etiologia , Doenças do Prematuro/sangue , Recém-Nascido Prematuro , Apneia do Sono Tipo Central/complicações , Feminino , Seguimentos , Idade Gestacional , Humanos , Hiperbilirrubinemia/sangue , Recém-Nascido , Masculino , Estudos Prospectivos , Apneia do Sono Tipo Central/sangueRESUMO
Congenital Central Hypoventilation Syndrome is a genetic disease characterized by alveolar hypoventilation and autonomic dysregulation. Patients have hypoventilations, especially during sleep, conditioning hypercapnia which can lead to neurological damage and death. They therefore need mechanical ventilators, that provide sufficient gas exchange, and pulse-oximeters that monitor oxy-hemoglobin blood concentration. Due to the restrictions regarding domiciliary assistive devices, the presence of a caregiver is required all night long. Currently, the only alarm systems available are the ones integrated in the ventilators and monitoring systems. During the night, multiple false alarms may occur, interrupting the sleep and causing anxiety. In this work we describe an assistive device that acquires real-time data from a pulse-oximeter, provides a multisensory stimulation if oxygen saturation falls under a certain threshold, and wakes up the patient if the hypoxia is severe. Tests on healthy subjects have shown that the device guarantees rapid awakenings, with a stimulator-dependent efficacy, and that it does not affect sleep efficiency. The purpose of the device is to determine a gentle awakening if mild hypoxia conditions persist, and to assure rapid awakening when a severe hypoxia occurs, reducing false alarms, improving the quality of sleep and increasing the self-sufficiency of the patients.
Assuntos
Hipoventilação/congênito , Hipóxia/diagnóstico , Monitorização Fisiológica/instrumentação , Apneia do Sono Tipo Central/fisiopatologia , Sono/fisiologia , Adolescente , Adulto , Feminino , Humanos , Hipoventilação/sangue , Hipoventilação/fisiopatologia , Hipóxia/fisiopatologia , Lactente , Masculino , Oximetria , Oxigênio/sangue , Qualidade de Vida , Apneia do Sono Tipo Central/sangue , Adulto JovemRESUMO
OBJECTIVE: To investigate clinical features and therapeutic methods of late-onset central hypoventilation syndrome. METHOD: A nine-year old boy was trachea-intubated and mechanically ventilated because of pneumonia, respiratory and heart failure and pulmonary hypertension. It was found that hard to extubate the patient as he was breathing normally while awake but had shallow breathing, oxygen desaturation and CO2 retention when falling asleep. Nocturnal polysomnography together with transcutaneous CO2 supported the diagnosis of central hypoventilation. The final diagnosis was late-onset congenital central hypoventilation syndrome as the patient gained weight rapidly since 3 years of age and the brain magnetic resonance imaging (MRI) and genetic screening were unremarkable. RESULT: The patient was treated with bi-level positive air pressure ventilation via nasal mask which showed good oxygen saturation and CO2 dropped down. The follow up study done one year later showed normal brain MRI, relief of pulmonary hypertension and better CO2 level in both awaken and sleeping status. CONCLUSION: The late-onset congenital central hypoventilation syndrome in this case had onset of symptoms at 2 years of age, he had normal breathing while he was awake but had oxygen desaturation and CO2 retention during sleep, therefore, respiratory support is required in severe cases. Mechanical ventilation via tracheotomy and non-invasive ventilation via mask are the major choice.
Assuntos
Hipoventilação/terapia , Ventilação não Invasiva , Apneia do Sono Tipo Central/terapia , Gasometria , Dióxido de Carbono/sangue , Criança , Diagnóstico Diferencial , Dispneia/diagnóstico , Dispneia/fisiopatologia , Dispneia/terapia , Seguimentos , Humanos , Hipoventilação/sangue , Hipoventilação/diagnóstico , Masculino , Oxigênio/sangue , Polissonografia , Respiração com Pressão Positiva/métodos , Insuficiência Respiratória/sangue , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/diagnóstico , Fases do SonoRESUMO
We report a case of clonidine poisoning in a breastfed newborn. At 2 days of life, this boy presented a consciousness deficit with drowsiness, hypotonia, and suspected generalized seizures. There were no cardiorespiratory problems outside of progressive central apneas beginning the 5th day. Further initial investigations were normal (extensive biological exams, cranial ultrasonography and transfontanellar Doppler, electroencephalography, and brain MRI study), excluding the main causes of neonatal hypotonia (encephalitis, infection, metabolic disorder). However, new medical questioning revealed maternal daily intake of 0.15 mg clonidine for hypertension during and after pregnancy. Since it was impossible to quantify clonidine quantification in newborn serum and breast milk, a weaning test was performed the 9th day. Twenty-four hours after cessation of breastfeeding, complete regression of symptoms was obtained. Poisoning by clonidine after fetal and neonatal exposure through breast milk is rare but severe enough to simulate a neurological disease. Diagnosis is based on the search for drug use and the cessation of breastfeeding if doubt persists. Recovery of normal examination results is then rapid and complete.
Assuntos
Clonidina/farmacocinética , Clonidina/intoxicação , Transtornos da Consciência/induzido quimicamente , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Troca Materno-Fetal/fisiologia , Leite Humano/metabolismo , Hipotonia Muscular/induzido quimicamente , Fases do Sono/efeitos dos fármacos , Clonidina/uso terapêutico , Transtornos da Consciência/sangue , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Convulsões/sangue , Convulsões/induzido quimicamente , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/induzido quimicamenteRESUMO
RATIONALE: Acetazolamide has been used to attenuate Hunter-Cheyne-Stokes breathing with central sleep apnea (CSA) associated with heart failure. However, the mechanisms underlying this improvement remain to be fully elucidated. OBJECTIVES: We hypothesized that acetazolamide stabilizes CSA by attenuating the ventilatory sensitivity to CO2, which is increased in patients with heart failure and is thought to be the major mechanism mediating CSA. METHODS: Six consecutive male patients with stable systolic heart failure and CSA (apnea-hypopnea index [AHI] ≥ 15 episodes/h) were randomized to a double-blind crossover protocol with acetazolamide or placebo received 1 hour before bedtime for six nights with 2 weeks of wash-out. Under both conditions, we measured the hypercapnic ventilatory response (HCVR), arterial blood Pco2, steady-state metabolic CO2 production, overnight attended polysomnography, and also assessed cardiac and pulmonary function. MEASUREMENTS AND MAIN RESULTS: Compared with placebo, acetazolamide significantly decreased the AHI (65 ± 32 vs. 31 ± 19 events/h, mean ± SD). Acetazolamide increased the HCVR slope by 55% (3.3 ± 1.7 vs. 5.1 ± 2.4 L/min/mm Hg; P = 0.03), an increase that far exceeded the 12% fall in arterial Pco2 (P = 0.02). The acetazolamide-induced change in the balance of these effects (ΔHCVR × Pco2) was inversely associated with the reduction in AHI (r = 0.8; P = 0.045). CONCLUSIONS: This placebo-controlled study indicates that acetazolamide improves CSA in patients with heart failure despite an increase in the slope of the HCVR. However, because the degree of HCVR elevation inhibits the improvement in unstable breathing, an increased CO2 chemosensitivity may be a key mechanism underlying an incomplete resolution of CSA with acetazolamide.
Assuntos
Acetazolamida/uso terapêutico , Inibidores da Anidrase Carbônica/uso terapêutico , Respiração de Cheyne-Stokes/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Apneia do Sono Tipo Central/tratamento farmacológico , Idoso , Gasometria , Dióxido de Carbono , Células Quimiorreceptoras/fisiologia , Respiração de Cheyne-Stokes/sangue , Respiração de Cheyne-Stokes/etiologia , Estudos Cross-Over , Método Duplo-Cego , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Humanos , Hipercapnia/sangue , Masculino , Pessoa de Meia-Idade , Polissonografia , Fenômenos Fisiológicos Respiratórios , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/etiologiaRESUMO
BACKGROUND: Manifestation of central sleep apnea (CSA) with Cheyne-Stokes respiration is of major prognostic impact in chronic heart failure (CHF). Inflammatory processes have been linked to a progression of cardiovascular diseases, including heart failure. While an association of C-reactive protein (CRP) levels to obstructive sleep apnea has been documented before, there is a lack of information regarding variation of CRP levels in patients with CSA. OBJECTIVES: The objective of this study was to investigate a potential association of CRP levels to CSA severity in CHF patients. METHODS: High sensitivity CRP levels were analyzed in 966 patients with CHF (BMI 26.3 ± 4.6, New York Heart Association class 2.6 ± 0.5, left ventricular ejection fraction 29.4 ± 7.9%, N-terminal pro-brain natriuretic peptide, NT-proBNP, level 2,209 ± 3,315 pg/ml) without sleep-disordered breathing (SDB; Apnea-Hypopnea Index, AHI, <5/h) or various degrees of CSA, documented by in-hospital cardiorespiratory polygraphy or polysomnography. RESULTS: The CRP concentration in CHF patients was 0.550 ± 0.794 mg/dl in patients without SDB (AHI 0-4/h, n = 403) versus 0.488 ± 0.708 mg/dl in patients with mild CSA (AHI 5-14/h, n = 123, p = n.s.) and 0.660 ± 0.963 mg/dl in patients with moderate CSA (AHI 15-29/h, n = 160, p = n.s.). In patients with severe CSA (AHI ≥ 30/h, n = 280), significantly higher CRP concentrations were documented (0.893 ± 1.384 mg/dl, p < 0.05). Stepwise regression analysis revealed AHI, NT-proBNP and heart rate to be independently associated with elevated CRP levels. CONCLUSION: Severe CSA in CHF patients is associated with elevated levels of CRP, a systemic marker of inflammation and cardiovascular risk. This might explain in part the negative prognostic impact of CSA in these patients.
Assuntos
Proteína C-Reativa/metabolismo , Respiração de Cheyne-Stokes/sangue , Insuficiência Cardíaca/sangue , Apneia do Sono Tipo Central/sangue , Idoso , Respiração de Cheyne-Stokes/complicações , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Apneia do Sono Tipo Central/complicaçõesRESUMO
BACKGROUND: Leptin-deficient animals hyperventilate. Leptin expression by adipocytes is attenuated by atrial natriuretic peptide (ANP). Increased circulating natriuretic peptides (NPs) are associated with an increased risk of central sleep apnea (CSA). This study tested whether serum leptin concentration is inversely correlated to NP concentration and decreased in patients with heart failure (HF) and CSA. METHODS: Subjects with HF (N = 29) were studied by measuring leptin, NPs, CO2 chemosensitivity (Δminute ventilation [V.e]/Δpartial pressure of end-tidal CO2 [Petco2]), and ventilatory efficiency (V.e/CO2 output [V.co2]) and were classified as CSA or no sleep-disordered breathing by polysomnography. CSA was defined as a central apnea-hypopnea index ≥ 15. The Student t test, Mann-Whitney U test, and logistic regression were used for analysis, and data were summarized as mean ± SD; P < .05 was considered significant. RESULTS: Subjects with CSA had higher ANP and brain natriuretic peptide (BNP) concentrations (P < .05), ΔV.e/ΔPetco2 (2.39 ± 1.03 L/min/mm Hg vs 1.54 ± 0.35 L/min/mm Hg, P = .01), and V.e/V.co2 (43 ± 9 vs 34 ± 7, P < .01) and lower leptin concentrations (8 ± 10.7 ng/mL vs 17.1 ± 8.8 ng/mL, P < .01). Logistic regression analysis (adjusted for age, sex, and BMI) demonstrated leptin (OR = 0.07; 95% CI, 0.01-0.71; P = .04) and BNP (OR = 4.45; 95% CI, 1.1-17.9; P = .05) to be independently associated with CSA. CONCLUSIONS: In patients with HF and CSA, leptin concentration is low and is inversely related to NP concentration. Counterregulatory interactions of leptin and NP may be important in ventilatory control in HF.
Assuntos
Fator Natriurético Atrial/sangue , Insuficiência Cardíaca/sangue , Leptina/deficiência , Peptídeo Natriurético Encefálico/sangue , Apneia do Sono Tipo Central/sangue , Idoso , Instituições de Assistência Ambulatorial , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/complicações , Humanos , Leptina/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia do Sono Tipo Central/complicaçõesRESUMO
Congenital Central Hypoventilation Syndrome (CCHS) is a genetic disease that causes an autonomous nervous system dysregulation. Patients are unable to have a correct ventilation, especially during sleep, facing risk of death. Therefore, most of them are mechanically ventilated during night and their blood oxygenation is monitored, while a supervisor keeps watch over them. If low oxygen levels are detected by the pulse-oximeter, an alarm fires; the supervisor deals with the situation and, if there is neither a technical problem nor a false alarm, wakes the subject, as CCHS patients usually recover from hypoxia when roused from sleep. During a single night multiple alarms may occur, causing fractioned sleep for the subject and a lasting state of anxiety for supervisors.
Assuntos
Hipoventilação/congênito , Oximetria/instrumentação , Apneia do Sono Tipo Central/terapia , Humanos , Hipoventilação/sangue , Hipoventilação/fisiopatologia , Hipoventilação/terapia , Monitorização Fisiológica , Oxigênio/sangue , Sono , Apneia do Sono Tipo Central/sangue , Apneia do Sono Tipo Central/fisiopatologiaRESUMO
AIMS: We examined whether the severity of central sleep apnoea (CSA) and the level of C-reactive protein are associated with the prevalence and complexity of arrhythmias, and whether these factors contribute to increased risk of nocturnal sudden death. METHODS AND RESULTS: We prospectively examined 178 patients (age 70 ± 1 years) who were admitted to our hospital due to worsening heart failure. We recorded a simultaneous overnight cardiorespiratory polygraph and Holter ECG. Obstructive sleep apnoea was excluded and patients were dichotomized based on the median value of the central apnoea index (CAI) of 7.5/h. The prevalence and complexity of arrhythmias were compared between daytime (06:00 h to 15:00 h) and night-time (21:00 h to 06:00 h). A multivariate logistic regression analysis revealed that the CAI was associated with prevalence of atrial fibrillation (AF) [odds ratio 1.03, 95% confidence interval (CI) 1.02-2.51)] and sinus pause during the night-time period (1.12, 95% CI 1.08-1.35). The CAI and C-reactive protein were independently associated with non-sustained ventricular tachycardia during both daytime (1.22, 95% CI 1.00-6.92; and 5.82, 2.58-56.1, respectively) and night-time periods (3.57, 95% CI 1.06-13.1; and 10.7, 3.30-44.4, respectively). During a mean follow-up period of 22 months, 30 (17%) patients had cardiovascular deaths and the CSA was an independent predictor (hazard ratio 1.29, 95% CI 1.16-2.32); only 5 (2.8%) of them died due to ventricular tachyarrhythmia, occurring during wakefulness. CONCLUSIONS: We demonstrated that the severity of CSA and C-reactive protein levels are independently associated with the prevalence and complexity of arrhythmias. CSA was associated with increased mortality risk, but it was not related directly to nocturnal death due to ventricular tachyarrhythmia.
Assuntos
Arritmias Cardíacas/etiologia , Proteína C-Reativa/metabolismo , Morte Súbita Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , Inflamação/complicações , Apneia do Sono Tipo Central/complicações , Idoso , Morte Súbita Cardíaca/etiologia , Ecocardiografia , Eletrocardiografia Ambulatorial , Feminino , Seguimentos , Humanos , Inflamação/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polissonografia , Prevalência , Estudos Prospectivos , Fatores de Risco , Apneia do Sono Tipo Central/sangueRESUMO
Although periodic breathing during sleep at high altitude occurs almost universally, the likely mechanisms and independent effects of altitude and acclimatization have not been clearly reported. Data from 2005 demonstrated a significant relationship between decline in cerebral blood flow (CBF) at sleep onset and subsequent severity of central sleep apnea that night. We suspected that CBF would decline during partial acclimatization. We hypothesized therefore that reductions in CBF and its reactivity would worsen periodic breathing during sleep following partial acclimatization. Repeated measures of awake ventilatory and CBF responsiveness, arterial blood gases during wakefulness. and overnight polysomnography at sea level, upon arrival (days 2-4), and following partial acclimatization (days 12-15) to 5,050 m were made on 12 subjects. The apnea-hypopnea index (AHI) increased from to 77 ± 49 on days 2-4 to 116 ± 21 on days 12-15 (P = 0.01). The AHI upon initial arrival was associated with marked elevations in CBF (+28%, 68 ± 11 to 87 ± 17 cm/s; P < 0.05) and its reactivity to changes in PaCO2 [>90%, 2.0 ± 0.6 to 3.8 ± 1.5 cm·s(-1)·mmHg(-1) hypercapnia and 1.9 ± 0.4 to 4.1 ± 0.9 cm·s(-1)·mmHg(-1) for hypocapnia (P < 0.05)]. Over 10 days, the increases resolved and AHI worsened. During sleep at high altitude large oscillations in mean CBF velocity (CBFv) occurred, which were 35% higher initially (peak CBFv = 96 cm/s vs. peak CBFv = 71 cm/s) than at days 12-15. Our novel findings suggest that elevations in CBF and its reactivity to CO(2) upon initial ascent to high altitude may provide a protective effect on the development of periodic breathing during sleep (likely via moderating changes in central Pco2).