Oxygen versus PAP for treatment of sleep apnea in chronic heart failure

氧气与 PAP 治疗慢性心力衰竭睡眠呼吸暂停的比较

• 批准号: 8665860
• 负责人: Daniel J Gottlieb
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8665860
• 关键词: Adherence; Adverse effects; Alternative Therapies; Apnea; Biological Markers; Blood Pressure; Blood Vessels; Boston; Brain natriuretic peptide; C-reactive protein; Cardiac; Cardiopulmonary; Catecholamines; Cell Adhesion Molecules; Central Sleep Apnea; Cessation of life; Characteristics; Chronic; Collagen Type III; Continuous Positive Airway Pressure; Disease; EFRAC; Echocardiography; Environmental air flow; Event; Excretory function; Exercise stress test; Future; Generations; Healthcare Systems; Heart; Heart failure; Home environment; Hospitalization; Hour; Hyperactive behavior; Hypoxemia; Hypoxia; Inflammation; Inflammatory; Interleukin-6; Isoprostanes; Lead; Left Ventricular Ejection Fraction; Lipids; Measures; Medical; Monitor; Morbidity - disease rate; Muscle Cells; Myocardial; Myocardial dysfunction; Myocardium; NF-kappa B; Obstructive Sleep Apnea; Outcome; Outcome Measure; Outcome Study; Outpatients; Oxidative Stress; Oxygen; Oxygen Consumption; Pathway interactions; Patients; Plasma; Play; Polysomnography; Prevention; Randomized; Randomized Clinical Trials; Reactive Oxygen Species; Recruitment Activity; Recurrence; Research; Risk; Role; Severities; Sleep; Sleep Apnea Syndromes; Sleep Fragmentations; Strategic Planning; Sympathetic Nervous System; Symptoms; Testing; Transplantation; Tumor Necrosis Factor-alpha; Ventricular; Ventricular Remodeling; Veterans; active method; arm; base; cytokine; design; disability; experience; functional status; health care service utilization; hypoxia inducible factor 1; improved; indexing; inflammatory marker; isoprostaglandin F2alpha type-III; lifetime risk; mortality; nocturnal Hypoxemia; pressure; primary outcome; public health relevance; respiratory; secondary outcome; standard care; transcription factor; treatment duration; treatment trial; trend; trial comparing; urinary

DESCRIPTION (provided by applicant): Chronic heart failure (HF) is a highly prevalent disease associated with high rates of mortality, which have persisted despite recent advances in pharmacologic therapy. Within the VA, outpatient encounters for HF reached 900,000 in FY09 and VA hospitalizations were over 96,000. Central sleep apnea (CSA) is a common comorbid condition, with moderate to severe CSA present in approximately one-third of patients with chronic HF with reduced ejection fraction. Central sleep apnea is associated with a doubling of mortality in chronic HF. Several small treatment trials show improvement in left ventricular ejection fraction (LVEF) following treatment of CSA with continuous positive airway pressure (CPAP) or adaptive pressure-support servo-ventilation (ASV), although the single long-term outcome study of CPAP therapy for CSA in HF found no difference in transplant-free survival despite improved LVEF. Moreover, most HF patients with CSA do not experience typical sleep apnea symptoms and are therefore often unwilling to accept the discomfort of positive airway pressure therapy. Therefore, better tolerated and possibly more effective alternatives to positive airway pressure are needed for treating CSA in patients with chronic HF. Supplemental oxygen during sleep has been shown to reduce the severity of CSA in some patients with chronic HF. Moreover, although the adverse effects of CSA on HF are likely to be multifactorial, the intermittent hypoxia characteristic of sleep apnea appears to play a central role. Hypoxia is the major cause of sympathetic hyperactivity in sleep apnea, which may contribute to progression of myocardial dysfunction through both direct effects on the myocardium and through elevation of blood pressure; it stimulates the generation of reactive oxygen species, which may contribute to myocyte damage and death; and it induces transcription factors that promote systemic inflammation. This suggests that prevention of nocturnal hypoxemia might mitigate the adverse effects of sleep apnea on the heart, even if it does not eliminate CSA per se. This study is a randomized clinical trial to assess the effects of nocturnal supplemental oxygen (NSO), CPAP and ASV for the treatment of CSA in patients with chronic HF with reduced ejection fraction. Patients with chronic HF with LVEF <45% will be screened for CSA with overnight portable sleep monitoring in their own home. A total of 161 patients with moderate to severe CSA, defined as an apnea-hypopnea index >15 with >50% of events being central apneas or hypopneas, will then be randomized in a 1:2:2:2 ratio to 3 months of treatment with optimal medical management alone, optimal medical management plus CPAP, optimal medical management plus ASV, or optimal medical management plus nocturnal supplemental oxygen. The primary outcome measures, to be made at baseline and at the end of the treatment period, will be change in LVEF as measured by echocardiogram and change in peak VO2 as measured by cardiopulmonary exercise testing. Secondary outcome measures will include 24 hour ambulatory blood pressure profile, urinary catecholamine excretion, urinary excretion of isoprostanes (a marker of oxidative stress), aminoterminal propeptide of type III collagen (a marker of ventricular remodeling), B-type natriuretic peptide, and plasma levels of several markers of inflammation. Adherence to therapy with NSO, CPAP and ASV will also be compared. The primary analysis will compare each of the active treatment groups to control. A non-inferiority design will be used to assess whether NSO and CPAP are non-inferior to ASV.

描述（由申请人提供）： 慢性心力衰竭（HF）是一种高度流行的疾病，死亡率高，尽管药物治疗最近取得了进展，但这种情况仍然持续存在。 2009 财年，退伍军人管理局内因心力衰竭门诊就诊的人数达到 900,000 人次，退伍军人管理局住院治疗的人数超过 96,000 人次。中枢性睡眠呼吸暂停 (CSA) 是一种常见的合并症，大约三分之一的射血分数降低的慢性心力衰竭患者存在中度至重度 CSA。中枢性睡眠呼吸暂停与慢性心力衰竭死亡率加倍相关。几项小型治疗试验显示，采用持续气道正压通气 (CPAP) 或适应性压力支持伺服通气 (ASV) 治疗 CSA 后，左心室射血分数 (LVEF) 有所改善，尽管 CPAP 治疗心力衰竭 CSA 的单一长期结果研究发现，尽管 LVEF 有所改善，但无移植生存率没有差异。此外，大多数患有CSA的心力衰竭患者不会出现典型的睡眠呼吸暂停症状，因此往往不愿意接受气道正压通气治疗带来的不适。因此，需要更好的耐受性和可能更有效的气道正压替代方案来治疗慢性心力衰竭患者的 CSA。睡眠期间补充氧气已被证明可以减轻某些慢性心力衰竭患者 CSA 的严重程度。此外，虽然 CSA 对心力衰竭的不利影响可能是多因素的，但睡眠呼吸暂停的间歇性缺氧特征似乎起着核心作用。缺氧是睡眠呼吸暂停中交感神经过度活跃的主要原因，这可能通过对心肌的直接影响和血压升高而导致心肌功能障碍的进展；它刺激活性氧的产生，这可能导致心肌细胞损伤和死亡；它会诱导促进全身炎症的转录因子。这表明，预防夜间低氧血症可能会减轻睡眠呼吸暂停对心脏的不利影响，即使它本身并不能消除 CSA。 本研究是一项随机临床试验，旨在评估夜间补充供氧 (NSO)、CPAP 和 ASV 对射血分数降低的慢性心力衰竭患者 CSA 的治疗效果。 LVEF <45% 的慢性心力衰竭患者将在自己家中通过夜间便携式睡眠监测仪进行 CSA 筛查。总共 161 名中度至重度 CSA 患者（定义为呼吸暂停低通气指数 >15，其中 >50% 的事件为中枢性呼吸暂停或呼吸不足）将以 1:2:2:2 的比例随机分组，接受 3 个月的单独最佳医疗管理、最佳医疗管理加 CPAP、最佳医疗管理加 ASV 或最佳医疗管理加夜间补充氧气的治疗。在基线和治疗期结束时进行的主要结果测量将是通过超声心动图测量的 LVEF 的变化以及通过心肺运动测试测量的峰值摄氧量的变化。次要结果指标包括 24 小时动态血压曲线、尿儿茶酚胺排泄量、尿异前列腺素排泄量（氧化应激标志物）、III 型胶原氨基末端前肽（心室重构标志物）、B 型利尿钠肽和几种炎症标志物的血浆水平。还将比较 NSO、CPAP 和 ASV 治疗的依从性。主要分析将比较每个活性治疗组与对照组。将使用非劣效性设计来评估 NSO 和 CPAP 是否不劣于 ASV。