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

项目摘要和摘要：睡眠呼吸障碍（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， 在急性失代偿期间被夸大，3，4并可能在这种高风险环境中加强急性心脏损伤。 机制包括大的、负的胸膜压力波动（通过增加的左心室后负荷增加）。 透壁压）、6、7循环性通气不足（低氧血症、高碳酸血症、酸中毒）、8和觉醒， 儿茶酚胺激增（心律失常）。9，10总体而言，关于SDB治疗的数据， 在慢性稳定性心脏病患者中，气道压力没有显示出临床结果的改善 衰竭，11-15有越来越多的文献表明，急性失代偿性心力衰竭（ADHF） 可能是最好的干预时机。持续气道正压通气治疗已被证明， 改善伴有睡眠呼吸暂停心力衰竭患者的急性左心室射血分数。16，17此外， 在因心力衰竭加重住院期间（或住院后不久）加速SDB检查和治疗 降低再入院率。18，19尽管有这些观察结果，ADHF的标准治疗通常 包括睡眠评估。原因是多方面的，但可能包括缺乏明确的证明过夜 心脏损伤，而不是SDB事件期间的短暂功能障碍。新一代肌钙蛋白检测具有 现在已经开发出了一种高灵敏度的亚临床心脏损伤评估方法，20-22， 在SDB和急性心力衰竭的情况下，这些测定尚未得到充分的研究。基于 这个项目的目的是确定睡眠呼吸障碍是否会导致 患者中心脏损伤特异性血清生物标志物表达的可测量过夜增加 因多动症入院SDB事件的类型和负担将使用便携式 呼吸多导描记术（即家庭睡眠呼吸暂停试验），并在睡前和睡前采集血样。 该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， 确定一段时间的医疗心力衰竭管理是否减弱了与以下相关的心肌肌钙蛋白释放： 睡眠呼吸暂停这项研究的发现可能对SDB如何影响心脏以及如何影响心脏有重要意义。 多学科方法治疗和预防急性心力衰竭。结果也可以 这对未来的介入性研究规划很重要。这个奖学金项目将在苏尔皮齐奥举行 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导者。该提案还纳入了正式培训， 通过Altman临床和转化研究所进行临床研究和统计的PI。的 本提案的总体目标是为PI建立一个学习学术生涯的基础 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.