Cardiac Autonomic Function in Women

女性心脏自主功能

• 批准号: 8820929
• 负责人: Puja Kiran Mehta
• 金额: $ 15.61万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8820929
• 关键词: Address; Attention; Autonomic nervous system; Benign; Blood Vessels; Blood flow; Breathing; Cardiac; Cardiomyopathies; Cardiovascular system; Clinical Trials Design; Communities; Control Groups; Coronary; Coronary Arteriosclerosis; Data Collection; Devices; Equilibrium; Evaluation; Event; Functional disorder; Funding; Future; Goals; Guanethidine; Heart; Heart Rate; Image; Investigation; Ischemia; Knowledge; Label; Left; Link; Measures; Medicine; Mentors; Microvascular Angina; Myocardial Infarction; Myocardial Ischemia; Myocardial dysfunction; National Heart, Lung, and Blood Institute; Nerve; Neurons; Norepinephrine; Outcome; Outcome Measure; Pathology; Pathway interactions; Peripheral; Population; Populations at Risk; Psyche structure; Questionnaires; Randomized; Recruitment Activity; Research; Risk; Role; Severities; Signs and Symptoms; Stress; Stress Tests; Symptoms; Syndrome; Testing; Therapeutic; Therapeutic Trials; United States National Institutes of Health; Vascular Diseases; Woman; Women' s Group; Work; analog; animal data; arterial tonometry; base; biobehavior; cardiovascular risk factor; cardiovascular stress test; cardiovascular visualization; design; heart rate variability; human data; improved; malignant breast neoplasm; mental function; neuroimaging; novel; outcome forecast; patient oriented research; primary outcome; prognostic; receptor; response; secondary outcome; single photon emission computed tomography; stressor; sudden cardiac death; uptake

DESCRIPTION (provided by applicant): Microvascular coronary dysfunction (MCD) is prevalent in approximately 50% of women with signs and symptoms of myocardial ischemia but no obstructive coronary artery disease (CAD) and carries an adverse cardiovascular (CV) prognosis, comparable to obstructive CAD. Previously thought to be benign and labeled "Cardiac Syndrome X" (CSX), there is a 3-fold increase in major adverse cardiac events (MACE) in women with no obstructive CAD compared to asymptomatic women. Traditional CV risk factors poorly predict MCD; therapeutics are poorly developed. While animal and human data demonstrate the importance of the cardiac autonomic nervous system (ANS) in the mechanistic pathways for myocardial ischemia and sudden cardiac death, this has not been studied in MCD with well-defined measures of coronary blood flow and myocardial ischemia. Women with MCD have low heart rate/mental stress-related angina, myocardial infarctions, and links to "broken heart syndrome" (Takotsubo cardiomyopathy). We hypothesize that cardiac ANS sympathovagal balance characterized by sympathetic predominance is positively associated with the presence and severity of MCD. To further test ANS as a mechanistic pathway of MCD, we hypothesize that MCD subjects randomized to paced breathing will have beneficially altered ANS sympathovagal balance and improved ischemic symptoms as a marker of MCD. Three groups will be compared: (1) Women with MCD; (2) Women with CSX (symptomatic controls without MCD); (3) Reference Control women (asymptomatic normal controls). Subjects will be recruited from the on-going NIH-NHLBI funded Women's Ischemia Syndrome Evaluation (WISE) - Coronary Vascular Dysfunction study (R01 HL090957, PI: Bairey Merz) to test the following Aims: 1) To characterize the association between cardiac ANS sympathovagal balance in MCD compared to CSX and reference control subjects by (1a) measuring cardiac sympathetic activity by 123iodine-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) imaging, and (1b) testing the effect of low heart rate stress on ANS sympathovagal balance in the three groups via mental stress testing and peripheral vascular testing; 2) To test ANS sympathovagal balance as a mechanistic pathway in MCD using device- based paced breathing. We propose to study three groups of women including CSX subjects without evidence of MCD because prior work in CSX has suggested a role for ANS balance but has not linked this to measures of MCD (coronary flow and ischemia), leaving an important knowledge gap regarding whether ANS balance is a mechanistic pathway in MCD or simply a benign consequence of symptoms. Addressing this knowledge gap will provide guidance regarding whether the ANS should be targeted as a mechanistic pathway in clinical trials designed to reduce MACE in this at-risk MCD population.

描述（由申请人提供）：在大约50％的具有心肌缺血体征和症状的女性中，微血管冠状动脉功能障碍（MCD）普遍存在，但没有阻塞性殖民动脉疾病（CAD），并且具有不良心血管（CV）预后，与阻塞性CAD相当。以前认为与无症状女性相比，没有阻塞性CAD的妇女的主要不良心脏事件（MACE）增加了良性和标记为“心脏综合征X”（CSX）。传统的简历风险因素很难预测MCD；治疗剂的发育不良。尽管动物和人类数据证明了心脏自主神经系统（ANS）在心肌缺血和猝死的机理途径中的重要性，但在MCD中尚未对冠状动脉血流和心肌缺血的措施进行明确的措施。患有MCD的女性心率/心理压力相关的心绞痛，心肌梗塞以及与“破碎心脏综合症”（Takotsubo心肌病）的联系。我们假设以同情占主导地位为特征的心脏ANS交感神经平衡与MCD的存在和严重程度呈正相关。为了进一步测试ANS作为MCD的机械途径，我们假设MCD受试者随机进行节奏的呼吸将有益地改变ANS交感神经平衡，并改善了作为MCD标记的缺血性症状。将比较三个小组：（1）患有MCD的女性； （2）患有CSX的女性（无MCD的症状对照）； （3）参考对照妇女（无症状正常对照）。受试者将从正在进行的NIH-NHLBI资助的妇女缺血综合征评估（明智） - 冠状动脉血管功能障碍研究（R01 HL090957，PI：Bairey Merz）中招募，以测试以下目的：1：1通过MCD（MCD）的相关性，以测试以下目标：1） 123iodine-Metaiododobenzylguanidine（MIBG）单光子发射计算机断层扫描（SPECT）成像，以及（1B）测试低心率应激对三组ANS交感神经平衡的影响通过精神应激测试和外周血管测试对三组的影响； 2）使用基于设备的节奏呼吸测试ANS交感神经平衡作为MCD中的机械途径。我们建议研究三组女性，包括CSX受试者，没有MCD证据，因为CSX中的先前工作提出了ANS平衡的作用，但没有将其与MCD的度量（冠状动脉流和缺血）的措施联系起来，留下了关于ANS平衡是否是MCD的机械途径还是仅仅是症状的良性后果的重要知识差距。解决此知识差距将提供有关是否应将ANS作为机械途径作为机械途径的指导，旨在减少这种高危MCD人群的MACE。