Women's Ischemia Syndrome Evaluation (WISE) Coronary Vascular Dysfunction

描述(由申请人提供)：NHLBI赞助的女性缺血综合征评估(WISE)记录了有缺血症状和证据且无梗阻性CAD的女性冠状动脉血管功能障碍的高患病率。这种情况与不利的预后和医疗费用类似于梗阻性CAD，估计有200-300万妇女患有现有疾病，预计每年新增10万例。这使得冠状动脉血管功能障碍的患病率、发病率和成本比所有女性生殖癌症的总和还要高。需要对诊断和预后的非侵入性方法进行前瞻性测试，作为将我们的发现转化为临床护理的关键下一步。采用前瞻性队列设计并进行随访，我们旨在调查：1)异常心脏磁共振成像(CMRI)预测冠状动脉反应性测试(CRT)异常；2)1年随访时持续心脏磁共振成像(CMRI)异常预测持续的缺血症状；3)CMRI预测不良结果，从而可作为未来治疗试验的结果。基线研究访问将包括体检和对病史、症状、生活方式和功能特征以及心理社会状况的启发。我们将招募375名怀疑无梗阻性冠心病的女性接受冠状动脉造影术。所有375人都将接受基线CMRI成像，200人的小组将接受重复的一年随访CMRI。另外200名心外膜冠状动脉无狭窄20%的女性将接受CRT治疗。每年将与妇女进行联系，以衡量症状、冠状动脉事件和相关成本的结果。将使用已建立的WISE核心实验室和临床站点。记录侵入性CRT和非侵入性CMRI成像之间的联系，以及这种测量对症状和不良结果的预后价值，将为临床试验提供一个平台，在适当的研究中测试治疗干预措施。正在计划的潜在治疗试验包括雷诺嗪和双嘧达莫等抗缺血疗法，以及针对冠状动脉血管功能的新干预措施，如促红细胞生成素和干细胞疗法。该应用的结果将为执业医生提供将这些发现转化为临床护理的能力，以使用非侵入性评估策略改善女性的IHD结果。

DESCRIPTION (provided by applicant): The NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) has documented a high prevalence of coronary vascular dysfunction in women with symptoms and evidence of ischemia with no obstructive CAD. The condition is associated with an adverse prognosis and healthcare costs similar to obstructive CAD, there are an estimated 2-3 million women with existent disease, and a projected 100,000 new cases annually. This places the prevalence, morbidity and costs of coronary vascular dysfunction higher than all female reproductive cancers combined. Prospective testing of a noninvasive approach for diagnosis and prognosis is needed as critical next steps toward translation of our findings into clinical care. Using a prospective cohort design with follow-up, we aim to investigate: 1) Abnormal cardiac magnetic resonance imaging (CMRI) predicts abnormalities in coronary reactivity testing (CRT); 2) Persistent cardiac magnetic resonance imaging (CMRI) abnormalities at 1-year follow-up predict persistent symptoms of ischemia; 3) CMRI predicts adverse outcomes, and thus can be used as an outcome in future therapeutic trials. The baseline study visit will include a physical exam and elicitation of medical history, symptoms, lifestyle and functional characteristics, and psychosocial status. We will recruit 375 women undergoing coronary angiography for suspected ischemia with no obstructive CAD. All 375 will undergo baseline CMRI imaging, and a subgroup of 200 will undergo repeat one-year follow-up CMRI. An additional subgroup of 200 women with no coronary stenosis >20% in any epicardial coronary artery will undergo CRT. Women will be contacted annually to measure outcome of symptoms, coronary events, and associated costs. Established WISE core laboratories and clinical sites will be used. Documentation of the link between invasive CRT and noninvasive CMRI imaging, and the prognostic value of this measure for symptoms and adverse outcomes, will provide a platform for clinical trials to test therapeutic interventions in appropriately powered studies. Potential therapeutic trials being planned include anti-ischemia therapies, such as ranolazine and dipyridamole, as well as novel interventions, such as erythropoietin and stem-cell therapy, targeting coronary vascular function. Results of the application will provide practicing physicians with the ability to translate these findings to clinical care to improve IHD outcomes in women using a noninvasive assessment strategy.