Cardiac Autonomic Function in Women

女性心脏自主功能

• 批准号: 8648403
• 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 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8648403
• 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; 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; Therapy Clinical 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; design; heart rate variability; human data; improved; malignant breast neoplasm; 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）：微血管冠状动脉功能障碍（MCD）在约50%的有心肌缺血体征和症状但无阻塞性冠状动脉疾病（CAD）的女性中普遍存在，并伴有不良心血管（CV）预后，与阻塞性CAD相当。以前被认为是良性的，并标记为“心脏X综合征”（CSX），与无症状的女性相比，无阻塞性CAD的女性的主要不良心脏事件（MACE）增加了3倍。传统的CV风险因素对MCD的预测效果不佳;治疗方法也不完善。虽然动物和人体数据证明了心脏自主神经系统（ANS）在心肌缺血和心脏性猝死的机制途径中的重要性，但尚未在MCD中使用明确的冠状动脉血流量和心肌缺血指标进行研究。患有MCD的女性有低心率/精神压力相关的心绞痛、心肌梗死，并与“心碎综合征”（Takotsubo心肌病）有关。我们假设心脏ANS交感迷走神经平衡的特点是交感神经优势与MCD的存在和严重程度呈正相关。为了进一步测试ANS作为MCD的机制途径，我们假设随机接受起搏呼吸的MCD受试者将有益地改变ANS交感迷走神经平衡并改善缺血症状作为MCD的标志物。将比较三组：（1）患有MCD的妇女;（2）CSX女性（无MCD的症状对照）;（3）参考对照女性（无症状正常对照）。受试者将从正在进行的NIH-NHLBI资助的女性缺血综合征评价（WISE）-冠状动脉血管功能障碍研究中招募（R 01 HL 090957，PI：Bairey Merz）以测试以下目标：1）通过（1a）用123碘-间碘苄基胍（123 iodin-metiodobenzylguanidine，123 iodine）测量心脏交感神经活性（MIBG）单光子发射计算机断层扫描（SPECT）成像;（1b）通过精神应激测试和外周血管测试测试低心率应激对三组中ANS交感迷走神经平衡的影响; 2）使用基于设备的起搏呼吸测试ANS交感迷走神经平衡作为MCD中的机制通路。我们建议研究三组女性，包括CSX受试者，没有MCD的证据，因为之前在CSX的工作表明了ANS平衡的作用，但没有将其与MCD（冠状动脉流量和缺血）的测量联系起来，留下了一个重要的知识空白，关于ANS平衡是否是MCD的机械途径或仅仅是症状的良性后果。解决这一知识差距将为ANS是否应作为临床试验中的机制途径提供指导，旨在减少该高危MCD人群的MACE。