Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death
Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death
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DOI：
10.1161/hc5001.100796
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发表时间：
2001-12-18
期刊：
影响因子：
37.8
通讯作者：
Costanzo, MR
中科院分区：
文献类型：
--
作者：
Hollenberg, SM;Klein, LW;Costanzo, MR
冠状动脉内皮功能障碍可能是原位心脏移植受者心脏移植物血管病变（CAV）的早期标志。通过血管内超声和多普勒血流导丝测量的系列研究，我们先前已经证明了冠状动脉内皮功能的年度递减与进行性内膜增厚相关。本研究测试是否内皮功能障碍预测随后的临床事件，包括心源性死亡和CAV development.Methods和Results-Seventy-three患者进行了研究，每年开始在移植，直到达到一个预先指定的终点。终点为CAV（> 50%狭窄）或心源性死亡（移植物衰竭或猝死）的血管造影证据。在每项研究中，冠状动脉内皮功能通过冠状动脉内输注腺苷（32 μ g推注）、乙酰胆碱（54 μ g，2分钟）和硝酸甘油（200 μ g）到冠状动脉左前降支来测量;同时记录血管内超声图像和多普勒速度。在研究的73例患者中，14例在研究期间达到终点（6例CAV和8例死亡，包括4例已知的CAV，1例移植失败和3例突发）。在进行的最后一项研究中，终点组的心外膜（收缩11.1 +/-2.9%对比扩张1.7 +/-2.2%，P=0.01）和微血管（流量增加75 +/- 20%对比149 +/-16%，P=0.03）与未达到终点的患者相比，对乙酰胆碱的内皮依赖性反应。腺苷和硝酸甘油的反应没有显着差异。结论内皮功能障碍，检测到的异常反应乙酰胆碱，之前的临床终点的发展。这些数据暗示内皮功能障碍在临床上显著的血管病变的发展，并表明内皮功能的系列研究具有临床实用性。
Background-Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development.Methods and Results-Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (> 50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-mug bolus), acetylcholine (54 mug over 2 minutes), and nitroglycerin (200 mug) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1 +/-2.9% versus dilation of 1.7 +/-2.2%, P=0.01) and microvascular (flow increase of 75 +/- 20% versus 149 +/- 16%, P=0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly.Conclusions-Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.