Impact of Sleep Disordered Breathing on Overnight Cardiac Injury in Patients with Acutely Decompensated Heart Failure

项目摘要和摘要：睡眠障碍呼吸(SDB)，包括阻塞性睡眠呼吸暂停(OSA) 中枢性睡眠呼吸暂停伴Hunter-Cheyne-Stokes呼吸在心力衰竭患者中很常见，1，2是 在急性失代偿期间被夸大，3，4，并可能在这一高风险环境中加重急性心脏损伤。 机制包括大的、负的胸膜压力波动(通过增加左心室后负荷 跨壁压)，6，7循环低通气量(低氧血症，高碳酸血症，酸中毒)，8和觉醒与 儿茶酚胺激增(心律失常)。9，10总体而言，SDB治疗阳性的数据 慢性稳定型心脏病患者的气道压力并未显示出改善的临床结果 衰竭，11-15越来越多的文献表明急性失代偿性心力衰竭(ADHF) 可能是进行干预的更好时机。持续的气道正压治疗已经被证明是 显著改善心力衰竭伴睡眠呼吸暂停患者的左心室射血分数。 在住院期间(或之后不久)因心力衰竭恶化而加快SDB的检查和治疗 降低再入院率。尽管有这些观察，ADHF的标准治疗通常不会 包括睡眠评估。原因是多方面的，但可能包括缺乏一夜之间的明确证据 心脏损伤，而不是SDB事件期间的一过性功能障碍。新一代肌钙蛋白检测已经 现已开发，现在允许对亚临床心脏损伤进行高度敏感的评估，20-22和 这些检测还没有在SDB和急性心力衰竭的背景下进行充分的研究。基于 这些概念这个项目的目的是确定睡眠呼吸障碍是否会导致 患者心脏损伤特异性血清生物标记物表达的夜间可测量增加 因ADHF入院治疗。SDB活动的类型和负担将使用便携 呼吸多导检查(即家庭睡眠呼吸暂停测试)，并将在睡前和睡后采集血样。 此方案将在入院时执行一次，并在出院前的第二阶段再次执行 确定一段时间的内科心力衰竭治疗是否能减少心肌肌钙蛋白的释放 睡眠呼吸暂停。这项研究的发现可能对SDB如何影响心脏以及对 治疗和预防急性心力衰竭的多学科方法。结果也可能是 对未来干预性研究的规划很重要。该奖学金项目将在苏尔皮奇奥举行。 加州大学心血管中心，提供全方位的心血管护理 圣地亚哥，呼吸生理学研究的领先者。该提案还包括对以下人员的正式培训 通过奥特曼临床和翻译研究所的临床研究和统计的PI。这个 这项建议的总体目标是为国际学生协会建立一个学术生涯学习的基础 临床相关的心-肺-睡眠相互作用，他坚定地致力于此。

Project Summary and Abstract: Sleep disordered breathing (SDB), including obstructive sleep apnea (OSA) and central sleep apnea with Hunter-Cheyne-Stokes respirations is common in patients with heart failure,1,2 is exaggerated during acute decompensation,3,4 and may potentiate acute cardiac injury in this high-risk setting.5 Mechanisms include large, negative pleural pressure swings (increased left ventricular afterload via increased transmural pressure),6,7 cyclic hypoventilation (hypoxemia, hypercapnia, acidosis),8 and arousal with catecholamine surges (arrhythmia).9,10 While in aggregate, the data regarding treatment of SDB with positive airway pressure have not shown improvement in clinical outcomes in patients with chronic stable heart failure,11-15 there is a growing body of literature suggesting that acutely decompensated heart failure (ADHF) may be the preferable time for intervention. Continuous positive airway pressure treatment has been shown to improve acutely left ventricular ejection fraction in heart failure patients with sleep apnea.16,17 Moreover, expedited SDB work-up and treatment during (or soon after) hospitalization for heart failure exacerbation reduces readmission rates. 18,19 Despite these observations, standard treatment of ADHF does not typically involve sleep assessment. Reasons are multiple but may include lack of clear demonstration of overnight cardiac injury, as opposed to transient dysfunction during SDB events. New generation troponin assays have now been developed which now allow a highly sensitive assessment of sub-clinical cardiac injury,20-22 and these assays have not yet been adequately studied in the context of SDB and acute heart failure. Based on these concepts the purpose of this project is to determine if sleep disordered breathing results in a measurable overnight increase in cardiac injury-specific serum biomarker expression in patients admitted to the hospital with ADHF. Type and burden of SDB events will be assessed using portable respiratory polygraphy (i.e. a home sleep apnea test), and blood samples will be collected pre and post-sleep. This protocol will be performed once upon admission, and again in a second phase prior to discharge to determine if a period of medical heart failure management attenuates cardiac troponin release associated with sleep apnea. Findings of this research may have important implications for how SDB affects the heart, and for a multidisciplinary approach to the treatment and prevention of acute heart failure. Results may also be important for the planning of future interventional studies. This fellowship project will take place at the Sulpizio Cardiovascular Center, which provides a full spectrum of cardiovascular care, at the University of California San Diego, a leader in the study of respiratory physiology. The proposal also incorporates formal training for the PI in clinical research and statistics through the Altman Clinical and Translational Research Institute. The overall objective of this proposal is for the PI to establish a foundation for an academic career studying clinically relevant heart-lung-sleep interactions, to which he is firmly committed.