Introdução: A apneia obstrutiva do sono (AOS) é caracterizada por episódios repetidos de colapso parcial ou completo das vias aéreas superiores durante o sono, resultando em eventos respiratórios caracterizados por hipopneias ou apneias, respectivamente. Os eventos respiratórios podem resultar em fragmentação do sono, hipoxemia recorrente e geração de pressão intratorácica negativa. Todos esses mecanismos são potencialmente deletérios ao sistema cardiovascular. A AOS é comum entre pacientes com doença cardiovascular, porém ainda é pouco reconhecida. O padrão ouro para o diagnóstico da AOS é a Polissonografia (PSG) completa. O acesso a PSG completa é limitado, contribuindo para o subdiagnóstico da AOS. A poligrafia noturna de variáveis respiratórias (PGR) é um método simplificado, sendo uma alternativa promissora para o diagnóstico da AOS. No entanto, estudos de validação de PGR incluíram somente populações pré-selecionadas ou referidas para laboratórios de sono e excluíram pacientes com comorbidades significativas. Atualmente a Academia Americana de Medicina do sono reconhece o uso da PGR para o diagnóstico da AOS em pacientes com alta probabilidade pré-teste de AOS moderada a grave e em pacientes sem comorbidades significativas. Objetivo: Validar a PGR para o diagnóstico de AOS entre pacientes consecutivos avaliados para cirurgia de revascularização miocárdica, portanto, com Doença Arterial Coronariana (DAC). Avaliar a prevalência da AOS e a utilidade dos sintomas clínicos para o diagnóstico da AOS entre os pacientes com DAC. Métodos: Pacientes com indicação de revascularização do miocárdio foram avaliados através de exames clínicos e laboratoriais de rotina, escala de sonolência diurna (Epworth) e risco clínico de apneia do sono (questionário de Berlin), ecocardiograma, PSG e PGR. A PGR utilizada é classificada como tipo 3, com os seguintes canais: fluxo de ar, esforço respiratório, oximetria de pulso, frequência de pulso, ronco e sensor de posição, (Stardust II ®). Resultados: Foram estudados 70 pacientes consecutivos (76% do sexo masculino); idade (média DP) = 58 ± 7 anos, índice de massa corpórea (IMC) [mediana (25-75%)] = 27,6 (25,8-31,1) kg/m2. Vinte pacientes (29%) apresentaram fração de ejeção do ventrículo esquerdo (FEVE) 45%. A PSG da população revelou índice de apneia e hipopneia (IAH)= 2320 eventos/h. A prevalência de AOS com um IAH 5, 15 e 30 eventos/h foi de 87%, 54% e 27%, respectivamente. A sonolência diurna medida pela escala de Epworth e o risco clínico de AOS verificado pelo questionário de Berlin foram pobres preditores de AOS. A sensibilidade / especificidade da PGR para detectar AOS (IAH 5 eventos/h) e AOS grave (IAH 30 eventos/h) foram 0,92/0,67% e 0,42/0,92%, respectivamente. A média da diferença do IAH entre os dois métodos diagnósticos apresentada no Bland-Altman foi de + 5,3, indicando que os valores do IAH da PGR foram em média inferiores aos da PSG. O desvio padrão da diferença foi de 14,6 eventos/hora, apresentando uma considerável concordância entre o IAH da PSG e da PGR. Conclusão: Este estudo valida o uso da PGR para o diagnóstico da AOS em uma população de pacientes consecutivos, avaliados para revascularização do miocárdio, em quem a doença cardíaca é significativa. A prevalência de AOS entre pacientes com DAC é alta atingindo mais de 50% dessa população. No entanto, os sintomas clínicos, nessa população, não são preditores adequados de AOS. Em função da alta prevalência de AOS e baixa especificidade de sintomas clínicos, nossos dados sugerem que a PGR é um instrumento promissor para a avaliação de pacientes com DAC avaliados para cirurgia de revascularização do micárdio / Introduction: Obstructive sleep apnea (OSA) is characterized by repeated episodes of partial or complete collapse of the upper airway during sleep, resulting in respiratory events characterized by hypopnea or apnea, respectively. Respiratory events may result in sleep fragmentation, hypoxemia and recurrent generation of negative intrathoracic pressure. All these mechanisms are potentially harmful to the cardiovascular system. OSA is common among patients with cardiovascular disease, but is still poorly recognized. The gold standard for diagnosis of OSA is polysomnography (PSG). Access to full PSG is limited, contributing to the under diagnosis of OSA. The polygraph nocturnal of respiratory variables (PGR) is a simplified method, being a promising alternative for the diagnosis of OSA. However, validation studies of PGR only included populations pre-selected or referred to sleep laboratories and excluded patients with significant comorbidities. Currently the American Academy of Sleep Medicine recognizes the use of PGR for the diagnosis of OSA in patients with high pretest probability of moderate to severe OSA and in patients without significant comorbidities. Objective: Validate the PGR for the diagnosis of OSA among consecutive patients evaluated for coronary artery bypass grafting (CABG), therefore with Coronary Artery Disease (CAD). To assess the prevalence of OSA and to evaluate the usefulness of clinical symptoms for diagnosis of OSA among patients with CAD. Methods: Patients with indication of CABG were evaluated by clinical examination and routine laboratory, the scale of daytime sleepiness (Epworth) and clinical risk of sleep apnea (Berlin questionnaire), echocardiogram, PSG and PGR. The PGR use is classified as type 3, with the following channels: airflow, respiratory effort, pulse oximetry, pulse rate, snoring and position sensor, (Stardust II ®). Results: We studied 70 consecutive patients (76% male); age (mean SD) = 58 ± 7 years; body mass index (BMI), [median (25-75%)] = 27,6 (25,8 to 31,1) kg/m2. Twenty patients (29%) had left ventricular ejection fraction (LVEF) 45%. The PSG of population showed apnea-hypopnea index (AHI) = 23 20 events / h. The prevalence of OSA with an AHI 5, 15 and 30 events / h was 87%, 54% and 27%, respectively. Daytime sleepiness measured by Epworth Sleepiness Scale and the clinical risk of OSA verified by the Berlin questionnaire were poor predictors of OSA. The sensitivity and specificity to detect OSA (AHI 5 events / h) and severe OSA (AHI 30 / events) of the PGR were 0,92/0,67% and 0,42/0,92%, respectively. The average difference in AHI between the two diagnostic methods presented in Bland-Altman was + 5,3, indicating that the values of the AHI of the PGR were on average lower than the PSG. The standard deviation of the difference was 14,6 events / hour, presenting a considerable agreement between the AHI of PSG and the PGR. Conclusion: This study validates the use of PGR for the diagnosis of OSA in a population of consecutive patients evaluated for CABG, in whom heart disease is significant. The prevalence of OSA among patients with CAD is high reaching over 50% of this population. However, the clinical symptoms are not adequate predictors of OSA in this population. Due to the high prevalence of OSA and low specificity of clinical symptoms, our data suggest that the PGR is a promising tool for the assessment of CAD patients evaluated for surgery for the CABG

No description available.

Introdução: A doença arterial coronariana (DAC) constitui uma das principais causas de mortalidade mundial à despeito dos avanços no seu tratamento. Neste sentido, importantes comorbidades podem contribuir para este cenário desfavorável. Um dos fatores de pior prognóstico nos pacientes com DAC é a presença da doença renal crônica (DRC). Entre os potenciais novos candidatos para este prognóstico desfavorável, podemos citar os distúrbios do sono. Diversos estudos sugerem que a apneia obstrutiva do sono (AOS) e a curta duração do sono (CDS) isoladamente estão associados com piores desfechos cardiovasculares, incluindo uma maior incidência de DAC. No entanto, não está claro se a interação da AOS com a CDS está associada com pior função renal e com maior taxa de DRC em pacientes com DAC bem como maior taxa combinada de eventos cardiovasculares e não cardiovasculares. Métodos: Foram recrutados pacientes consecutivos com DAC estabelecida (pacientes com indicação clínica para a intervenção coronária percutânea, ICP) eletiva. Após a realização da ICP com implante de stent com sucesso (estenose residual < 20% e fluxo TIMI 2- 3), todos os pacientes foram submetidos à monitorização do sono com a poligrafia portátil (Embletta Gold®) por uma noite (ainda durante a internação hospitalar) e à actigrafia de pulso (Actiwatch 2, Respironics®) durante sete dias (após o retorno do paciente às atividades habituais). Definimos a AOS por um índice de apneia-hipopneia (IAH) >=15 eventos/hora e a CDS por <6 horas por noite de sono. Nós estratificamos a associação da AOS, da CDS e a interação de ambas baseada na taxa de filtração glomerular (TFG) e a presença de DRC com exame de creatinina coletado pré-ICP. Estimamos a TFG usando a equação do Chronic Kidney Disease: Epidemiology Consortium (CKD-EPI) de forma contínua e categorizada em dois níveis: TFG < 60mL/min/1.73 m2 (diminuição moderada a grave) e TFG > 60mL/min/1.73 m2 (normal ou levemente diminuído). Após o exame do sono, o seguimento clínico foi realizado por meio de ligações telefônicas e checagem dos prontuários com 1 mês, 6 meses e depois anualmente procurando avaliar a ocorrência de eventos cardiovasculares fatais e não fatais de forma sistematizada. Resultados: Foram estudados 262 pacientes (64,1% sexo masculino, idade média: 63±10 anos e índice de massa corpórea [IMC] 27,8±4,4 Kg/m2). A frequência da AOS e CDS foi de 58,4% e 25,6%, respectivamente. Pacientes com AOS apresentaram pior TFG em relação aos pacientes sem AOS (62±26 vs. 74±20 mL/min/1,73m2, p < 0,001) e consequentemente maior taxa de DRC (42,1 vs. 26,6%, p=0,009). Em contraste, a TFG foi similar nos pacientes com e sem CDS (65±29 vs. 68±23 mL/min/1,73m2, p=0,38) e uma frequência não significante de DRC (44.8 vs. 32.5%, p=0.07). Na análise multivariada, AOS, mas não a CDS, foi independentemente associada com a TFG: beta= -10,57 (-16,46 - - 4,68), p < 0,001) e com a DRC (OR=1,95; 95% IC=1,12-3.38, p=0,01). As interações da AOS e da CDS com a TFG e a presença da DRC não foram significantes. Os resultados permaneceram similares após avaliarmos a AOS (pelo IAH) e a duração do sono de forma continua ou ao classificarmos a CDS como < 5 horas. Em uma análise exploratória, após seguimento mediano foi de 25 meses, ocorreram 43 eventos cardiovasculares (15 infartos agudos do miocárdio; 1 revascularização do miocárdio; 6 acidentes vasculares cerebrais; 7 óbitos cardiovasculares e 14 reestenoses de stent). Considerando os eventos combinados, não encontramos até o momento diferenças significantes entre os grupos com AOS e CDS quando comparados aos respectivos grupos sem estes distúrbios. Conclusão: Em pacientes com DAC, a AOS, mas não a CDS, foi independentemente associada com pior TFG e DRC, marcadores de pior prognóstico nestes pacientes / Introduction: Coronary artery disease (CAD) is one of the main causes of worldwide mortality despite advances in the medical treatment. In this sense, important comorbidities can contribute to this unfavorable scenario. One of the factors associated with poor prognosis in patients with CAD is the presence of chronic kidney disease (CKD). Sleep disorders are potential new candidates contributing to poor prognosis in CAD as well. Although not consistent, several studies suggested that obstructive sleep apnea (OSA) or short sleep duration (SSD) are associated with a higher prevalence of CAD and poor cardiovascular outcomes, including higher CAD incidence. However, it is unclear whether the interaction of OSA with SSD is associated with lower renal function and higher frequency of CKD in patients with established CAD, as well as with increased rate of cardiovascular and non-cardiovascular events. Methods: Consecutive patients with established CAD (those with clinical indication for elective percutaneous coronary intervention, PCI) were recruited. After a successful PCI procedure (residual stenosis < 20% and TIMI 2-3 flow), all patients underwent sleep monitoring with portable polygraphy (Embletta Gold®) for one night (during hospital stay) and wrist actigraphy (Actiwatch 2, Respironics®) for seven days (after patient return to usual activities). We defined OSA by an apnea-hypopnea index (AHI) >= 15 events / hour and SSD for < 6 hours per night of sleep. We stratified the association of OSA, SSD and their interaction based on the eGFR and the presence of CKD with the creatinine collected pre PCI procedure. We estimated eGFR using the Chronic Kidney Disease: Epidemiology Consortium (CKD-EPI) equations and categorized into two levels: eGFR < 60mL / min / 1.73 m2 (moderate to severe decrease) and eGFR > 60mL / min / 1.73 m2 (normal or mildly decreased). After the sleep study, clinical follow-up was performed through phone calls and medical records revisions at 1 month, 6 months, and then annually, searching for the occurrence of fatal and non-fatal cardiovascular events in a systematized way. Results: A total of 262 patients (64.1% males, mean age: 63±10 years and body mass index [BMI] 27.8±4.4 kg/m2) were studied. The frequencies of OSA and SSD were 58.4% and 25.6%, respectively. Patients with OSA had lower eGFR compared to patients without OSA (62±26 vs. 74±20 mL/min/1.73m2, p < 0.001) and consequently a higher rate of CKD (42.1 vs. 26.6%, p=0.009). In contrast, eGFR was similar in patients with and without SSD (65±29 vs. 68±23 mL/min/1.73 m2, p=0.38) and a no significance frequency of CKD (44.8 vs. 32.5%, p=0.07). In the multivariate analysis, AOS, but not SSD, was independently associated with eGFR (-10.57 (-16.46 - -4.68), p < 0.001) and with CKD (OR = 1.95, 95% CI=1.12-3.38, p=0.01). The interactions of OSA and SSD with eGFR and the presence of CKD were not significant. These results remained unchanged after evaluating AHI and sleep duration as continuous variables or setting SSD as < 5 hours. In an exploratory analysis, after a median follow up of 25 months, forty-three cardiovascular events (15 episodes of acute myocardial infarction, 1 coronary artery bypass graft, 6 strokes, 7 deaths and 14 stent restenosis). Considering the combined events, we did not find significant differences between OSA and SSD groups and their counterparts so far. Conclusion: In patients with CAD, OSA, but not SSD was independently associated with lower GFR and CKD, markers of poor prognosis in these patients

Introdução: A acromegalia é uma doença crônica geralmente causada por adenoma hipofisário produtor de hormônio do crescimento (GH). Os pacientes com acromegalia são expostos a altos níveis de GH e do fator de crescimento semelhante à insulina 1 (IGF-1) e têm risco aumentado de doenças cardiovasculares. Os distúrbios respiratórios do sono, caracterizados por apneia obstrutiva do sono (AOS) e apneia central (AC), são comuns nos pacientes com acromegalia. Os distúrbios respiratórios do sono causam hipóxia intermitente e sono fragmentado e são fatores de risco para pior prognóstico cardiovascular. No entanto, não está claro se os distúrbios respiratórios do sono contribuem para pior desfecho cardiovascular entre pacientes com acromegalia. Objetivo: Elucidar a contribuição dos distúrbios respiratórios do sono na gênese de doenças cardiovasculares em pacientes com acromegalia. Neste contexto foram realizados dois estudos, um estudo transversal (Estudo I) e um estudo de intervenção (Estudo II) que serão descritos a seguir. Método: Estudo I: Foram avaliados pacientes consecutivos com diagnóstico confirmado de acromegalia e acompanhados no ambulatório da Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Os pacientes foram submetidos à avaliação clínica, questionário de sonolência de Epworth (ESE, escore variando entre 0 - 24), índice de qualidade de sono de Pittsburgh (PSQI, escore variando entre 0 - 21), questionário de qualidade de vida SF-36 (escore variando entre 0 - 100), polissonografia (PSG), monitorização ambulatorial da pressão arterial (MAPA), velocidade de onda de pulso (VOP), e ecocardiograma. Estudo II: Pacientes com acromegalia e AOS moderada a grave (índice de apneias hipopneias (IAH) 15 eventos/h) foram tratados por 3 meses em sequência aleatória com CPAP ou adesivo nasal. Os pacientes foram submetidos à avaliação clínica, questionários de ESE, PSQI, SF-36, questionário de satisfação do tratamento (0 - 10), MAPA, VOP, diâmetro e distensibilidade de carótida e PSG ao entrar no estudo, 3 meses e 6 meses. Resultados: Estudo I: Foram avaliados 48 pacientes (sexo masculino = 31%; idade = 52 ± 11 anos; índice de massa corpórea = 32,0 ± 5,5 Kg/m2). Vinte e nove pacientes (60,4%) apresentaram distúrbios respiratórios do sono moderado a grave (IAH 15 eventos/h) distribuídos em 23 (88%) com AOS e 6 (12%) com AC. Os pacientes com distúrbios respiratórios do sono eram mais velhos (56 ± 9 vs. 48 ± 12 anos, p= 0,018), mais obesos (33,3 ± 5,9 vs. 29,4 ± 4,0 Kg/m2, p = 0,014), apresentaram maior pressão arterial sistólica (131 ± 17 vs. 122 ± 11 mm Hg; p = 0,02) e diastólica (88 ± 14 vs. 81 ± 6 mm Hg, p = 0,02), maior diâmetro da carótida (7244 (6646 - 7685) vs. 6795 (6072 - 7341) m, p = 0,03), menor distensibilidade carotídea (5,01 ± 1,80 vs. 6,32 ± 2,16 m, p = 0,04) e pior qualidade de sono (9 (6 - 14) vs. 6 (5 - 8), p = 0,005) do que pacientes sem distúrbios respiratórios do sono. A presença de distúrbios respiratórios do sono se associou de forma independente com maior idade (p = 0,01), maior pressão arterial diastólica (p = 0,04) e menor distensibilidade carotídea (p = 0,04). Estudo II: Dezessete pacientes com acromegalia e AOS moderada a grave (masculino/feminino = 9/8, idade = 54 ± 10 anos, índice de massa corpórea = 34,0 ± 5,7 Kg/m2, IAH = 49,8 ± 23,7 eventos/h, ESE = 12 ± 6, PSQI = 12 (7- 14) completaram o estudo. A média da pressão do CPAP foi de 11 ± 2 cm H2O. O CPAP foi usado em média 6 ± 2 h/noite. O uso do adesivo nasal foi utilizado em 80% das noites. O IAH diminuiu significativamente com CPAP, mas não mudou com dilatador nasal (8,1 ± 5,2 vs. 47,4 ± 25,4 eventos/h, respectivamente, p = 0,0001). Todos os sintomas subjetivos melhoraram com ambos os tratamentos, no entanto significativamente mais com CPAP do que com dilatador nasal (ESE = 5 ± 4 vs. 9 ± 7, p = 0,002; PSQI = 3 (1- 5) vs. 5 (4-10), p <0,0001; satisfação do tratamento = 9 ± 1 vs. 6 ± 3, p = 0,001, respectivamente). O tratamento da AOS com CPAP comparado com adesivo nasal não resultou em melhora significativa nos níveis de pressão arterial no período da vigília (pressão arterial sistólica = 127 ±11 vs. 129 ± 10, p = 0,23; pressão arterial diastólica = 79 ± 11 vs. 80 ± 10, p = 0,46, respectivamente) e no período do sono (pressão arterial sistólica = 120 ± 14 vs. 124 ± 15, p = 0,66; pressão arterial diastólica = 71 (66 - 82) vs. 54 (52 - 63), p = 0,54, respectivamente) avaliado pela MAPA e rigidez da arterial (VOP = 9,0 ± 1,2 vs. 9,6 ± 1,5 m/s, p = 0,69 respectivamente). Conclusão: Os distúrbios respiratórios do sono são comuns entre os pacientes com acromegalia e estão associados de forma independente com maior pressão arterial diastólica, menor distensibilidade da carótida e pior qualidade do sono. O tratamento da AOS com CPAP em pacientes com acromegalia melhora a qualidade do sono. No entanto, não existe evidência até o momento de melhora em parâmetros cardiovasculares / Introduction: Acromegaly is a chronic disease usually caused by pituitary adenoma producing growth hormone (GH). Patients with acromegaly are exposed to high levels of GH and insulin-like growth factor 1 (IGF-1) and have increased risk of cardiovascular disease. Sleep-disordered breathing, characterized by obstructive sleep apnea (OSA) and central sleep apnea (AC), are common in patients with acromegaly. Sleep-disordered breathing cause intermittent hypoxia and fragmented sleep and are risk factors for poor cardiovascular outcome among patients with acromegaly. However, it is unclear whether sleep-disordered breathing are simply a result of acromegaly contribute to worse cardiovascular outcomes in patients with acromegaly. Objective: To elucidate the contribution of sleep-disordered breathing in the genesis of cardiovascular disease in patients with acromegaly. Two studies were conducted a cross sectional study (Study I) and a interventional study (Study II). Method: Study I: We evaluated consecutive patients with a confirmed diagnosis of acromegaly of a dedicated outpatient clinic of tertiary University Hospital (Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo). Patients underwent clinical assessment questionnaire for evaluation of daytime somnolence (Epworth sleepiness - ESS score, ranging from 0 - 24), index of Pittsburgh sleep quality (PSQI score, ranging from 0 - 21), quality of life questionnaire SF-36 (score ranging from 0 - 100), polysomnography (PSG), ambulatory blood pressure (ABMP), pulse wave velocity (PWV), diameter and distensibility carotid and echocardiography. Study II: Patients with acromegaly and moderate to severe OSA (apnea index - hypopnea index (AHI) 15 events / h) were treated for 3 months in random sequence with nasal CPAP or nasal dilator strips. The patients underwent clinical evaluation, questionnaires ESS, PSQI, SF-36, treatment satisfaction questionnaire (0-10), ABMP and PWV, diameter and distensibility carotid and PSG at study entry, 3 months and 6 months. Results: Study I: We evaluated 48 patients (male = 31%, age = 52 ± 11 years, body mass index = 32.0 ± 5.5 kg/m2). Twenty-nine patients (60.4%) had moderate to severe sleep-disordered breathing (AHI 15 events / h) distributed n = 23 (88%) OSA and n = 6 (12%) CA. Patients with sleep-disordered breathing were older (56 ± 9 vs. 48 ± 12 years, p = 0.018), more obese (33.3 ± 5.9 vs. 29.4 ± 4.0 kg/m2, p = 0.014), had higher systolic blood pressure (131 ± 17 vs. 122 ± 11 mm Hg, p = 0.02) and diastolic (88 ± 14 vs. 81 ± 6 mm Hg, p = 0.02), larger Carotid diameter (7244 (6646 - 7685) vs. 6795 (6072 - 7341) m, p = 0.03), lower carotid distensibility (5.01 ± 1.80 vs. 6.32 ± 2.16 mm, p = 0.04) and worse sleep quality (9 (6 -14) vs. 6 (5 - 8) score, p = 0.005) than patients without sleep-disordered breathing. The presence of sleep-disordered breathing was independently associated with older age (p = 0.01), higher diastolic blood pressure (p = 0.04) and lower carotid distensibility (p = 0.04). Study II: Seventeen patients with acromegaly and moderate to severe OSA (male / female = 9/8, age = 54 ± 10 years, body mass index = 34.0 ± 5.7 kg/m2, AHI = 49.8 ± 23.7 events / h, SE = 12 ± 6 score, PSQI = 12 (7 - 14) score) completed the study. The average CPAP pressure was 11 ± 2 cm H2O. CPAP was used on average 6 ± 2 h / night. The use of the nasal dilator strips was used in 80% of nights. The AHI decreased significantly with CPAP, but did not change with nasal dilator (8.1 ± 5.2 vs. 47.4 ± 25.4 events / h, respectively, p = 0.0001). All subjective symptoms improved with both treatments, but significantly more than with CPAP than nasal dilator strips (ESE = 5 ± 4 vs. 9 ± 7, p = 0.002; PSQI = 3 (1 - 5) vs. 5 (4 - 10), p <0.0001; treatment satisfaction = 9 ± 1 vs. 6 ± 3, p = 0.001, respectively). Treatment of OSA with CPAP compared with nasal dilator strips did result in significant improvements in ABMP during wakefulness (systolic blood pressure = 127 ± 11 vs. 129 ± 10, p = 0.23, diastolic blood pressure = 79 ± 11 vs. 80 ± 10, p = 0.46, respectively) and during sleep (systolic blood pressure = 120 ± 14 vs. 124 ± 15, p = 0.66; diastolic blood pressure = 71 (66 - 82) vs. 54 (52 - 63), p = 0.54, respectively) measured by ABMP and arterial stiffness (PWV = 9.0 ± 1.2 vs. 9.6 ± 1.5 m / s, p = 0,69 respectively). Conclusion: Sleep-disordered breathing is independently associated with higher diastolic blood pressure and lower carotid distensibility. However, there is no evidence that treatment of OSA with CPAP in patients with acromegaly results in significant improvement in blood pressure and carotid artery distensibility.

Introdução: A apneia obstrutiva do sono (AOS) é caracterizada por episódios repetidos de colapso parcial ou completo das vias aéreas superiores durante o sono, resultando em eventos respiratórios caracterizados por hipopneias ou apneias, respectivamente. Os eventos respiratórios podem resultar em fragmentação do sono, hipoxemia recorrente e geração de pressão intratorácica negativa. Todos esses mecanismos são potencialmente deletérios ao sistema cardiovascular. A AOS é comum entre pacientes com doença cardiovascular, porém ainda é pouco reconhecida. O padrão ouro para o diagnóstico da AOS é a Polissonografia (PSG) completa. O acesso a PSG completa é limitado, contribuindo para o subdiagnóstico da AOS. A poligrafia noturna de variáveis respiratórias (PGR) é um método simplificado, sendo uma alternativa promissora para o diagnóstico da AOS. No entanto, estudos de validação de PGR incluíram somente populações pré-selecionadas ou referidas para laboratórios de sono e excluíram pacientes com comorbidades significativas. Atualmente a Academia Americana de Medicina do sono reconhece o uso da PGR para o diagnóstico da AOS em pacientes com alta probabilidade pré-teste de AOS moderada a grave e em pacientes sem comorbidades significativas. Objetivo: Validar a PGR para o diagnóstico de AOS entre pacientes consecutivos avaliados para cirurgia de revascularização miocárdica, portanto, com Doença Arterial Coronariana (DAC). Avaliar a prevalência da AOS e a utilidade dos sintomas clínicos para o diagnóstico da AOS entre os pacientes com DAC. Métodos: Pacientes com indicação de revascularização do miocárdio foram avaliados através de exames clínicos e laboratoriais de rotina, escala de sonolência diurna (Epworth) e risco clínico de apneia do sono (questionário de Berlin), ecocardiograma, PSG e PGR. A PGR utilizada é classificada como tipo 3, com os seguintes canais: fluxo de ar, esforço respiratório, oximetria de pulso, frequência de pulso, ronco e sensor de posição, (Stardust II ®). Resultados: Foram estudados 70 pacientes consecutivos (76% do sexo masculino); idade (média DP) = 58 ± 7 anos, índice de massa corpórea (IMC) [mediana (25-75%)] = 27,6 (25,8-31,1) kg/m2. Vinte pacientes (29%) apresentaram fração de ejeção do ventrículo esquerdo (FEVE) 45%. A PSG da população revelou índice de apneia e hipopneia (IAH)= 2320 eventos/h. A prevalência de AOS com um IAH 5, 15 e 30 eventos/h foi de 87%, 54% e 27%, respectivamente. A sonolência diurna medida pela escala de Epworth e o risco clínico de AOS verificado pelo questionário de Berlin foram pobres preditores de AOS. A sensibilidade / especificidade da PGR para detectar AOS (IAH 5 eventos/h) e AOS grave (IAH 30 eventos/h) foram 0,92/0,67% e 0,42/0,92%, respectivamente. A média da diferença do IAH entre os dois métodos diagnósticos apresentada no Bland-Altman foi de + 5,3, indicando que os valores do IAH da PGR foram em média inferiores aos da PSG. O desvio padrão da diferença foi de 14,6 eventos/hora, apresentando uma considerável concordância entre o IAH da PSG e da PGR. Conclusão: Este estudo valida o uso da PGR para o diagnóstico da AOS em uma população de pacientes consecutivos, avaliados para revascularização do miocárdio, em quem a doença cardíaca é significativa. A prevalência de AOS entre pacientes com DAC é alta atingindo mais de 50% dessa população. No entanto, os sintomas clínicos, nessa população, não são preditores adequados de AOS. Em função da alta prevalência de AOS e baixa especificidade de sintomas clínicos, nossos dados sugerem que a PGR é um instrumento promissor para a avaliação de pacientes com DAC avaliados para cirurgia de revascularização do micárdio / Introduction: Obstructive sleep apnea (OSA) is characterized by repeated episodes of partial or complete collapse of the upper airway during sleep, resulting in respiratory events characterized by hypopnea or apnea, respectively. Respiratory events may result in sleep fragmentation, hypoxemia and recurrent generation of negative intrathoracic pressure. All these mechanisms are potentially harmful to the cardiovascular system. OSA is common among patients with cardiovascular disease, but is still poorly recognized. The gold standard for diagnosis of OSA is polysomnography (PSG). Access to full PSG is limited, contributing to the under diagnosis of OSA. The polygraph nocturnal of respiratory variables (PGR) is a simplified method, being a promising alternative for the diagnosis of OSA. However, validation studies of PGR only included populations pre-selected or referred to sleep laboratories and excluded patients with significant comorbidities. Currently the American Academy of Sleep Medicine recognizes the use of PGR for the diagnosis of OSA in patients with high pretest probability of moderate to severe OSA and in patients without significant comorbidities. Objective: Validate the PGR for the diagnosis of OSA among consecutive patients evaluated for coronary artery bypass grafting (CABG), therefore with Coronary Artery Disease (CAD). To assess the prevalence of OSA and to evaluate the usefulness of clinical symptoms for diagnosis of OSA among patients with CAD. Methods: Patients with indication of CABG were evaluated by clinical examination and routine laboratory, the scale of daytime sleepiness (Epworth) and clinical risk of sleep apnea (Berlin questionnaire), echocardiogram, PSG and PGR. The PGR use is classified as type 3, with the following channels: airflow, respiratory effort, pulse oximetry, pulse rate, snoring and position sensor, (Stardust II ®). Results: We studied 70 consecutive patients (76% male); age (mean SD) = 58 ± 7 years; body mass index (BMI), [median (25-75%)] = 27,6 (25,8 to 31,1) kg/m2. Twenty patients (29%) had left ventricular ejection fraction (LVEF) 45%. The PSG of population showed apnea-hypopnea index (AHI) = 23 20 events / h. The prevalence of OSA with an AHI 5, 15 and 30 events / h was 87%, 54% and 27%, respectively. Daytime sleepiness measured by Epworth Sleepiness Scale and the clinical risk of OSA verified by the Berlin questionnaire were poor predictors of OSA. The sensitivity and specificity to detect OSA (AHI 5 events / h) and severe OSA (AHI 30 / events) of the PGR were 0,92/0,67% and 0,42/0,92%, respectively. The average difference in AHI between the two diagnostic methods presented in Bland-Altman was + 5,3, indicating that the values of the AHI of the PGR were on average lower than the PSG. The standard deviation of the difference was 14,6 events / hour, presenting a considerable agreement between the AHI of PSG and the PGR. Conclusion: This study validates the use of PGR for the diagnosis of OSA in a population of consecutive patients evaluated for CABG, in whom heart disease is significant. The prevalence of OSA among patients with CAD is high reaching over 50% of this population. However, the clinical symptoms are not adequate predictors of OSA in this population. Due to the high prevalence of OSA and low specificity of clinical symptoms, our data suggest that the PGR is a promising tool for the assessment of CAD patients evaluated for surgery for the CABG

Les maladies chroniques impliquant le système respiratoire nécessitent un suivi sur la durée. L’activité physique et les paramètres cardiovasculaires sont essentiels pour ces pathologies. Nous nous sommes intéressés en particulier à la BPCO et à l’apnée obstructive du sommeil. La BPCO est caractérisée par un cercle vicieux d’inactivité : une gêne respiratoire entraîne une diminution de l’activité, qui elle-même augmente la gêne respiratoire par désentraînement. Le monitoring de l’activité, en lien avec la SpO2 est donc essentiel pour cette pathologie. Les désaturations nocturnes sont un paramètre cardinal de l’apnée du sommeil. Un actimètre permet d’évaluer la qualité du sommeil, complétant ainsi le suivi de cette pathologie. De plus, l’activité diurne est un indicateur de l’asthénie provoquée par le syndrome. Le but de ce travail a donc été la mise au point d’un actimètre communicant, capable de mesurer l’activité diurne, d’évaluer le temps de sommeil et de s’interfacer avec un oxymètre de pouls pour synchroniser la collecte de données. À partir des données récoltées durant 26 jours d’enRégistrements, nous avons mis au point et évalué un algorithme permettant de mesurer le temps passé assis, debout et allongé. Cet algorithme a été conçu pour être embarqué dans un microcontrôleur, ayant des ressources de calcul limitées. Nous avons également proposé un algorithme de détection des pas, dont le fonctionnement a été validé sur plus de 5 heures de marche, sur 22 patients différents, contre un comptage manuel. Nous avons enfin proposé une méthode de détection des transitions assis-debout pour l’instrumentation du test de levers de chaise de 3 minutes. Lors de l’analyse nocturne, nous avons mis au point un algorithme de détection du temps de sommeil, testé sur 25 nuits. Nous avons également proposé une méthode d’analyse de l’onde de pouls permettant d’extraire le rapport LF/HF de la variabilité cardiaque, permettant de détecter le sommeil paradoxal. Nous avons montré le résultat de l’agrégation des différentes données acquises par le système formé de l’actimètre et de l’oxymètre lors d’une nuit d’examen, comme outils à disposition du praticien. L’actimètre mis au point dans le cadre de ces travaux et les méthodes d’analyse du signal associées sont adaptés au suivi non invasif de pathologies respiratoires. Ils peuvent également être intégrés à un système de télémédecine via une passerelle informatique pour un suivi de long terme. / Chronic diseases affecting the respiratory system require a long-term monitoring. Physical activity and cardiovascular parameters are essential in those pathologies. We focused on two of those diseases : COPD and obstructive sleep apnea. COPD is characterized by a downward cycle of inactivity : a respiratory impairment leads to a reduction of activity, whose in turn worsen the respiratory impairment by a conditioning loss. As a consequence, activity monitoring and SpO2 are essential for the monitoring of this pathology. Nocturnal oxygen desaturation are a main feature of sleep apnea. An actimeter allows for sleep quality evaluation, and is a logical choice for a complementary measure of this disease. Moreover, diurnal activity is an indicator of the degree of physical weakness that can occur as a consequence of sleep apnea. The main goal of the work has been the developement of a connected actimeter, able to monitor diurnal activity, estimate the duration of sleep and collect data from a pulse oximeter to synchronise the data. From 26 days of accelerometric measures, we designed and validated an algorithm that compute the time spend sitting, standing and lying. This algorithm has been designed to be embedded in a microcontroler with limited computing power. We also proposed a step detection algorithm validated on 5 hours of walking, on 22 different patients, against a visual count. Finally, we designed a method to detect the sitting-standing change of posture to monitor the 3-minutes chair stand test. On the nocturnal aspect, we designed an algorithm used to estimate the sleep duration during a night. It as been tested on 25 nights. We also proposed a pulse wave analysis method to extract the LF/HF ratio of cardiac variability, to detect REM sleep. We showed the result of the aggregation of the different parameters collected by the system composed of the actimeter and the oximeter during a monitored night, as a tool to the healthcare professional. The actimeter design in the context of this work and the associated signal processing methods are appropriate to the monitoring of respiratory pathologies with a light equipment. They also can be integrated into a telemedecine system through a gateway computer, allowing for a long-term monitoring.

Existant en tant que pratique sportive, l’apnée est également de plus en plus utilisée dans d’autres activités sportives dont la natation, à l’entraînement et/ou en compétition. Toutefois, les réponses à l‘apnée dynamique ont été peu explorées lors d’efforts physiques intenses, en particulier en natation. L’objectif de ce travail de thèse est donc d’étudier sur le terrain en situation de nage (étude 1 et 2) et en laboratoire (étude 3) lors d’un exercice intermittent de pédalage, les réponses physiologiques, psychologiques et ergogéniques à l’apnée aiguë apparaissant lors d’efforts intenses. Le métabolisme a été notamment évalué à partir de la mesure de l’oxygénation tissulaire, de paramètres sanguins et de marqueurs hormonaux. Les principaux résultats de ces études montrent qu’en apnée la performance dépendrait de la capacité des sujets à maintenir leur fréquence cardiaque et que l’effort est globalement perçu comme plus dur. L’apnée n’induisait pas d’augmentation de la lactatémie, sans doute en lien avec l’absence de modification de l’extraction musculaire de l’oxygène. Au niveau cérébral, le maintien de l’oxygénation expliquerait la non modification du temps de réaction en apnée. Enfin toutes nos études ont révélé une désaturation artérielle significative en apnée, dès la première apnée de 10 secondes (étude 3) mais sans effet de la capacité d’apnée (étude 1) ou de l’intensité de nage (étude 2) suggérant que la durée compenserait l’intensité. Il serait donc intéressant d’étudier ultérieurement les effets respectifs du couple intensité/durée et les effets chroniques d’un entraînement comportant un exercice intermittent intense lors d’apnées dynamiques. / Existing as a sport practice, apnea is also increasingly used in other sports activities including swimming, training and/or competition. However, responses to dynamic apnea have been little explored during intense physical exercise, especially in swimming. The objective of this thesis is to study, in the field in swimming situations (study 1 and 2) and in the laboratory (study 3) during an intermittent cycling exercise, the physiological, psychological and ergogenic responses to acute apnea appearing during intense exercises. Metabolism was especially assessed by measurement of tissue oxygenation, blood parameters and hormonal markers. The main results of these studies show that in apnea the performance would depend on the ability of the subjects to maintain their heart rate and that the exercise is globally perceived as harder. Apnea did not induce an increase in lactatemia, probably related to the lack of modification of the muscle extraction of oxygen. At the cerebral level, the maintenance of the oxygenation would explain that the reaction time is not altered with apnea. Finally, all our studies revealed a significant arterial desaturation in apnea at the first repetition of the 10-second apnea (study 3) but without the effect of apnea capacity (study 1) or swimming intensity (study 2) suggesting that the duration would compensate for the intensity. It would therefore be interesting to study later the respective effects of the intensity/duration pair and the chronic effects of training involving intense intermittent exercise during dynamic apneas.

Le traitement de première ligne de l’apnée obstructive du sommeil est l’appareil à pression positive, soit le CPAP, qui est le plus souvent utilisé avec un masque nasal. Certains patients, incapables de tolérer le masque nasal, doivent se tourner vers le masque facial, qui peut parfois requérir une pression supérieure à celle utilisée avec le masque nasal pour éliminer tous les événements respiratoires. Nous supposons que l’ajustement serré du masque facial, dans le but de réduire les fuites, entraîne une pression de recul sur la mandibule; ceci diminuerait le calibre des voies aériennes supérieures, nécessitant donc une pression effective thérapeutique supérieure pour rétablir un passage de l’air. Nos objectifs étaient : 1) de démontrer s’il y avait une différence de pression effective entre le masque nasal et le masque facial, 2) de quantifier la fuite entre les deux masques, 3) d’évaluer l’effet d’une orthèse de rétention mandibulaire neutre (OMN), qui empêche le recul mandibulaire, sur la pression effective des deux masques et 4) d’évaluer s’il existait un lien entre la céphalométrie et les réponses variables des individus. Méthodologie : Lors de cette étude expérimentale croisée, huit sujets (2 femmes, 6 hommes) avec une moyenne d’âge de 56,3ans [33ans-65ans] ont reçu un examen orthodontique complet incluant une radiographie céphalométrique latérale. Ils ont ensuite passé deux nuits de polysomnographie au laboratoire du sommeil en protocole « split-night » où les deux masques ont été portés, seuls, la première nuit, et avec l’OMN, la deuxième nuit. Résultats : Nous avons trouvé que la pression effective thérapeutique était supérieure avec le masque facial comparativement au masque nasal de manière statistiquement significative. Nous avons observé une fuite supérieure avec le masque nasal, ce qui permet de dire que la fuite n’explique probablement pas cette différence de pression entre les deux masques. L’OMN n’a pas donné d’effet statistiquement significatif lorsque combinée au masque nasal, mais il aurait probablement été possible de trouver un effet positif avec le masque facial si le Bi-PAP avait été inclus dans le protocole de recherche. Conclusion : Nos résultats ne permettent pas de confirmer le rôle du recul mandibulaire, causé par la force exercée avec le masque facial, dans l’obtention de pressions supérieures avec ce masque, mais nous ne pouvons toutefois pas éliminer l’hypothèse. Les résultats suggèrent également que ce phénomène est peut-être plus fréquent qu’on ne le croit et qu’il pourrait y avoir un lien avec certains facteurs anatomiques individuels. / The first line of treatment for obstructive sleep apnea is continuous positive airway pressure or CPAP used via a nasal mask. Some patients, unable to tolerate the nasal mask, have to turn to the facial mask, which sometimes requires a superior level of pressure to eliminate all the respiratory events. We believe that the force applied on the chin from a tight adjustment of the facial mask may retrude the mandible and diminish the upper airway caliber. Our objectives for this study were to: 1) demonstrate that a difference of effective therapeutic pressure between the nasal and facial masks does exist, 2) quantify the leaks associated with each mask, 3) evaluate the effect of a neutral mandibular appliance (NMA), that prevents the retrusion of the mandible, on the effective pressure of both masks and 4) evaluate if a link between the cephalometric values and varied individual responses to both masks exists. Methods: Eight subjects (2 females, 6 males) mean age 56.3 years (33-65y) participated in the cross-over design pilot study. All subjects underwent a complete orthodontic examination including lateral cephalometric radiograph before spending two nights in a sleep laboratory for a polysomnography in split-night protocol, where both mask were worn alone on the first night and with the NMA on the second night. Results: We found that the therapeutic effective pressure was higher with the facial mask compared to the nasal mask, and this difference was statistically significant. The leak was more elevated with the nasal mask, thus eliminating this factor as a probable cause of the higher pressure with the facial mask. The NMA did not have any statistically significant effect on both masks; however a possible positive effect might be seen if the Bi-level PAP was included in the protocol. Conclusion: Our results cannot confirm the role of the retrusion of the mandible, caused by the force applied by the facial mask, in the necessity of a superior level of pressure with that mask, but we cannot eliminate that possibility either. Our results suggest that this phenomenon is more frequent that we may think and that a link with some anatomical factors may exist.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Background: Although the negative impact of sleep apnea on the clinical course of acute ischemic stroke (AIS) is well known, data regarding non-invasive ventilation in acute patients are scarce. Several studies have shown its tolerability and safety, yet no controlled randomized sequential phase studies exist that aim to establish the efficacy of early non-invasive ventilation in AIS patients. Methods/design: We decided to examine our hypothesis that early non-invasive ventilation with auto-titrating bilevel positive airway pressure (auto-BPAP) positively affects short-term clinical outcomes in AIS patients. We perform a multicenter, prospective, randomized, controlled, third rater- blinded, parallel-group trial. Patients with AIS with proximal arterial obstruction and clinically suspected sleep apnea will be randomized to standard stroke care alone or standard stroke care plus auto-BPAP. Auto-BPAP will be initiated within 24 hours of stroke onset and performed for a maximum of 48 hours during diurnal and nocturnal sleep. Patients will undergo unattended cardiorespiratory polygraphy between days three and five to assess sleep apnea. Our primary endpoint will be any early neurological improvement on the NIHSS at 72 hours from randomization. Safety, tolerability, short-term and three-months functional outcomes will be assessed as secondary endpoints by un-blinded and blinded observers respectively. Discussion: We expect that this study will advance our understanding of how early treatment with non-invasive ventilation can counterbalance, or possibly reverse, the deleterious effects of sleep apnea in the acute phase of ischemic stroke. The study will provide preliminary data to power a subsequent phase III study.