ACE Inhibition and Cardiac Allograft Vasculopathy

ACE 抑制和心脏同种异体移植血管病

• 批准号: 8458621
• 负责人: WILLIAM F FEARON
• 金额: $ 37.7万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8458621
• 关键词: Acetylcholine; Anatomy; Angiotensin II; Angiotensin II Receptor; Angiotensin-Converting Enzyme Inhibitors; Anterior Descending Coronary Artery; Anti-Inflammatory Agents; Anti-inflammatory; Arterial Fatty Streak; Arteries; Atherosclerosis; Bradykinin; Caliber; Cardiac; Cell Count; Clinical; Clinical Research; Complication; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary artery; Data; Development; Double-Blind Method; Endothelium-Dependent Relaxing Factors; Enzyme Gene; Evaluation; Event; Experimental Models; Fibrosis; Functional disorder; Genetic Polymorphism; Goals; Graft Survival; Heart Transplantation; Heart failure; Immune response; Infection; Left; Left Ventricular Function; Measurement; Measures; Mediator of activation protein; Morbidity - disease rate; Nitric Oxide Synthase; Outcome; Oxidative Stress; Pathway interactions; Patients; Peptidyl-Dipeptidase A; Pharmaceutical Preparations; Physiological; Physiology; Placebos; Property; Prophylactic treatment; Ramipril; Randomized; Renin-Angiotensin System; Research Project Grants; Risk Factors; Role; Staging; Stem cells; Thrombosis; Transplant Recipients; Transplantation; Ultrasonography; Up-Regulation; Vascular Diseases; Vascular Proliferation; Vascular blood supply; Vascular remodeling; base; heart allograft; high risk; improved; improved functioning; interstitial; mortality; pilot trial; placebo controlled study; pressure; prevent; prospective; randomized trial; vascular inflammation

Cardiac transplantation is the ultimate treatment option for patients with end stage heart failure. Cardiac allograft vasculopathy remains a leading cause of morbidity and mortality after transplantation. Angiotensin converting enzyme inhibitors are used in less than one half of transplant recipients. Preliminary data suggest that angiotensin converting enzyme inhibitors retard the atherosclerotic plaque development that is the hallmark of cardiac allograft vasculopathy. Moreover, this class of drug appears to increase circulating endothelial progenitor cell number and has anti-inflammatory properties, both of which improve endothelial dysfunction, the key precursor to the development of cardiac allograft vasculopathy. The objective of this project is to investigate the role of an angiotensin converting enzyme inhibitor, ramipril, in preventing the development of cardiac allograft vasculopathy. During the first month after cardiac transplantation subjects will undergo coronary angiography with intravascular ultrasound measurements of plaque volume in the left anterior descending coronary artery. Using a coronary pressure wire, epicardial artery and microvascular physiology will be assessed. Finally, endothelial function and mediators of endothelial function, including circulating endothelial progenitor cells, will be measured. Subjects will then be randomized in a double blind fashion to either ramipril or placebo. After 1 year, the above assessment will be repeated. The primary endpoint will be the development of cardiac allograft vasculopathy based on intravascular ultrasound-derived parameters. The second aim will be to assess the effect of ramipril on endothelial dysfunction early after transplantation. The final aim is to determine the impact of ramipril on coronary physiology early after transplantation.

心脏移植是终末期心力衰竭患者的最终治疗选择。 心脏同种异体移植血管病变仍然是移植后发病和死亡的主要原因。 不到一半的移植受者使用血管紧张素转换酶抑制剂。初步的 数据表明，血管紧张素转换酶抑制剂可延缓动脉粥样硬化斑块的发展， 是心脏同种异体移植血管病的标志。此外，此类药物似乎会增加循环 内皮祖细胞数量并具有抗炎特性，两者均能改善内皮细胞 功能障碍，是心脏同种异体移植血管病发生的关键先兆。 该项目的目的是研究血管紧张素转换酶抑制剂的作用， 雷米普利，预防心脏同种异体移植血管病的发展。心脏病发作后第一个月 移植受试者将接受冠状动脉造影和血管内超声测量 左冠状动脉前降支的斑块体积。使用冠状动脉压力丝、心外膜 将评估动脉和微血管生理学。最后，内皮功能和介质 将测量内皮功能，包括循环内皮祖细胞。然后主题将是 以双盲方式随机分配雷米普利或安慰剂。 1年后，上述评估将 重复。主要终点是心脏同种异体移植血管病变的发展 血管内超声衍生参数。第二个目标是评估雷米普利对 移植后早期内皮功能障碍。最终目的是确定雷米普利对 移植后早期的冠状动脉生理学。

项目成果

Association of Endothelin-1 With Accelerated Cardiac Allograft Vasculopathy and Late Mortality Following Heart Transplantation.

Endothelin-1 与加速心脏同种异体移植血管病变和心脏移植后晚期死亡率的关系。

• DOI: 10.1016/j.cardfail.2018.12.001
• 发表时间: 2019
• 期刊: Journal of cardiac failure
• 影响因子: 6
• 作者: Parikh,RushiV;Khush,Kiran;Pargaonkar,VedantS;Luikart,Helen;Grimm,David;Yu,Michelle;Okada,Kozo;Honda,Yasuhiro;Yeung,AlanC;Valantine,Hannah;Fearon,WilliamF
• 通讯作者: Fearon,WilliamF

Percutaneous coronary intervention should be guided by fractional flow reserve measurement.

• DOI: 10.1161/circulationaha.113.004300
• 发表时间: 2014-05-06
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Fearon WF

Change in lymphocyte to neutrophil ratio predicts acute rejection after heart transplantation.

• DOI: 10.1016/j.ijcard.2017.10.060
• 发表时间: 2018-01-15
• 期刊: International journal of cardiology
• 影响因子: 3.5
• 作者: Choi DH;Kobayashi Y;Nishi T;Luikart H;Dimbil S;Kobashigawa J;Khush K;Fearon WF
• 通讯作者: Fearon WF

Coronary Endothelial Dysfunction and the Index of Microcirculatory Resistance as a Marker of Subsequent Development of Cardiac Allograft Vasculopathy.

• DOI: 10.1161/circulationaha.116.025268
• 发表时间: 2017-03-14
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Lee JH;Okada K;Khush K;Kobayashi Y;Sinha S;Luikart H;Valantine H;Yeung AC;Honda Y;Fearon WF
• 通讯作者: Fearon WF

Usefulness of Asymmetric Dimethylarginine to Predict Outcomes After Heart Transplantation.

不对称二甲基精氨酸用于预测心脏移植后的结果。

• DOI: 10.1016/j.amjcard.2018.07.048
• 发表时间: 2018
• 期刊: The American journal of cardiology
• 作者: Parikh,RushiV;Khush,Kiran;Luikart,Helen;Sakarovitch,Charlotte;Lee,Justin;Desai,Manisha;Valantine,Hannah;Yeung,AlanC;Fearon,WilliamF
• 通讯作者: Fearon,WilliamF