第三版心肌梗死通用定义发布

慕尼黑——在敏感性心脏生物标志物测定和影像学技术飞速发展的形势下，新的心肌梗死通用定义在欧洲心脏病学会(ESC)2012年会上发布了。

专家共识工作组共同主席、丹麦奥胡斯大学的Kristian Thygeysen 博士指出，新的高敏感性心脏肌钙蛋白(cTn)测定已在欧洲进入临床，同时正在美国等待审批，它已给心肌梗死的诊断带来了困惑，因为它可以检测出cTn小幅升高，而心力衰竭、心律失常和肺栓塞等疾病也可出现这一现象。“过去我们诊断了太多的心肌梗死，而这是有问题的……”


Kristian Thygesen博士
 
由ESC、美国心脏病学会(ACC)、美国心脏协会(AHA)和世界心脏联盟(WHF)共同制订的这份专家共识，维持了急性心肌梗死的病理学定义——由持续较长时间的心肌缺血导致的心肌细胞死亡，但重新界定了5种情况下的心肌梗死定义，包括存在争议的血管重建治疗相关性心肌梗死。

PCI相关性心肌梗死

经皮冠状动脉介入(PCI)相关性心肌梗死被定义为：基线肌钙蛋白水平正常的患者，在接受PCI治疗后48 h内cTn水平升高至超过参考值上限(URL)第99百分位的5倍；或者基线水平升高的患者，cTn水平上升超过20%，且保持稳定或逐渐下降。

这一定义还要求出现下列事件中的1种：症状提示心肌缺血，新出现缺血性心电图改变，血管造影结果与PCI并发症相吻合，或者有存活心肌新损失或新出现局部心壁运动异常的影像学证据。

在2007年发表的前一版定义中，肌钙蛋白阈值被设定为超过URL第99百分位的3倍，本次提高阈值的依据是对接受PCI治疗者的长期随访新数据显示PCI伴随着难以避免的损伤。

CABG相关性心肌梗死

与之相似的是，2012版定义提高了冠状动脉旁路移植术(CABG)相关性心肌梗死的肌钙蛋白阈值，对于cTn基线水平正常的患者，阈值从2007版定义中的URL第99百分位的5倍增至10倍。

这一定义也要求有下列事件中的1项：新出现病理性Q波或新出现左束支传导阻滞(LBBB)，血管造影显示移植物或原有冠状动脉新出现闭塞，或者有存活心肌新损失或新出现局部心壁运动异常的影像学证据。

工作组共同主席、亚利桑那大学的Joseph Alpert博士介绍，与PCI相关心肌梗死的定义一样，本次决定提高阈值是因为在CABG术中针刺、触碰心脏和采取心肌保护措施难免会对心脏造成损伤。

多种原因可导致心脏损伤

“每位医生——不仅是心脏科医生，也包括内科和外科医生——都会遇到的有关肌钙蛋白检测的问题是(尤其是其中的高敏感性检测)，有太多人存在心脏损伤了。我们几十年前就知道了，肝脏损伤在重症患者中并不罕见，而现在我要说的是，‘天哪，他们还有心脏损伤，而且这些损伤不是心肌梗死，或者我们没有证据说存在缺血’。”

新版共识指出，诸如经导管主动脉瓣置换或二尖瓣钳夹等新术式可能也会导致心肌损伤伴坏死，而且“有可能与CABG相似的是，生物标志物水平升高越明显，预后就越差，不过目前还缺乏相关证据”。


Joseph Alpert博士
 
Alpert博士指出，尽管高敏感性肌钙蛋白检测尚未被美国批准，但其进入临床只是个时间问题，而且经济利益可能会使心肌损伤和心肌梗死之间的差别被忽视——目前的医保并未覆盖心肌损伤，因而处理心肌损伤的花费无法被医保报销。“我们正在争取将心肌损伤纳入医保，因为肌钙蛋白水平升高无论如何都意味着存在某些异常。”

尽管肌酸激酶-MB(CKMB)等敏感性稍逊一筹的生物标志物也有一定价值，但心脏肌钙蛋白(I或T)确实是备受亲睐的急性心肌梗死生物标志物。

急性心肌梗死的诊断标准包括检测到心脏生物标志物水平上升和/或下降超过URL第99百分位，且符合下列条件中的至少1项：

•有缺血症状。

•新出现或很可能新出现ST段显著抬高/T波改变或新出现LBBB。

•心电图出现病理性Q波。

•有存活心肌新损失或新出现局部心壁运动异常的影像学证据。

•血管造影或尸检发现冠状动脉内血栓。

新版心肌梗死定义有望成为诊断金标准，并被美国食品药品管理局(FDA)采纳用于临床试验。其意义在于这将有助于使临床试验中界定心肌梗死的方式标准化，我们就能更有效地对不同研究的结果进行比较。

这份专家共识及其袖珍版已刊登在ESC、ACC、AHA和WHF的网站上，同时还在5份期刊上发表：《美国心脏病学会杂志》、《欧洲心脏杂志》、《循环》、《全球心脏》和《自然评论：心脏病学》。

Thygesen博士报告称无利益冲突。Alpert博士披露称担任多家制药公司和北美继续医学教育中心的顾问。

爱思唯尔版权所有  未经授权请勿转载

By: PATRICE WENDLING, Cardiology News Digital Network

MUNICH – A new universal definition of myocardial infarction has been unveiled, sparked by the development of ever more sensitive cardiac biomarker assays and imaging techniques.

These assays, including the new high-sensitivity cardiac troponin (cTn) assays available throughout Europe and awaiting approval in the United States, have created confusion in the diagnosis of myocardial infarction because they detect small cTn elevations associated with many other clinical conditions such as heart failure, arrhythmias, and pulmonary embolism that are not MIs, but rather myocardial injury with necrosis.

"I think there has been a little bit of a problem in the past where we’ve had too many infarctions [diagnosed] ... where there is some damage or injury to the myocardial cells," said document task force cochair Dr. Kristian Thygeysen, who presented the third universal MI definition at the annual meeting of the European Society of Cardiology (ESC).

The expert consensus document, developed by the ESC, American College of Cardiology (ACC), American Heart Association (AHA), and World Heart Federation (WHF), maintains the pathological definition of acute MI as myocardial cell death due to prolonged myocardial ischemia, but goes on to refine the definition of MI in five settings, including the controversial area of MIs associated with revascularization procedures.

MI in the PCI Setting

An MI related to percutaneous coronary intervention (PCI) is defined as an elevation of cTn values more than five times the 99th percentile upper reference limit (URL) in the first 48 hours after a procedure in patients with normal baseline troponin values, or a rise of cTn values of more than 20% in patients with elevated baseline levels that are stable or falling.

It also requires one of the following events: symptoms suggestive of myocardial ischemia, new ischemic ECG changes, angiographic findings consistent with a procedural complication, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.

In the previous 2007 document, the troponin threshold had been more than three times the 99th percentile, and was raised based on new prognostic information from long-term follow-up of patients undergoing PCI showing that there is unavoidable injury associated with the procedure, document task force codirector Dr. Joseph Alpert said during the presentation.

CABG-Related MI

Similarly, the 2012 version raises the troponin threshold for MI related to coronary artery bypass graft surgery from five times the 99th percentile URL in the 2007 document to 10 times the 99th percentile in patients with normal cTn baseline values.

It also requires one of the following: new pathological Q waves or new left bundle branch block (LBBB), angiographically documented new graft or new native coronary artery occlusion, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.

Once again, the decision to raise the troponin threshold was made because there is unavoidable injury to the heart during CABG from needle sticks, handling of the heart, and the myocardial preservation procedure, said Dr. Alpert, a professor of medicine at the University of Arizona, Tucson.

Many Sources of Heart Injury

"The problem that every clinician – not just cardiologists, but internists and surgeons – is having with these troponin tests, and particularly with the high-sensitivity test, is that it turns out we’re finding that there are lots and lots of people having heart injuries," he said in an interview. "We’ve known for decades that it’s not uncommon for a very sick patient to have liver injuries, but now we’re saying, ‘My goodness, they’re having heart injuries, and these injuries are not MIs, or at least we have no evidence there is ischemia.’ "

The updated guideline points out that novel procedures such as transcatheter aortic valve implantation or mitral clip may also cause myocardial injury with necrosis, and that "it is likely that, similarly to CABG, the more marked the elevation of the biomarker values, the worse the prognosis – but data on that are not available.&qu

Although high-sensitivity troponin assays are not yet approved in the United States, it is only a matter of time before they are and the financial battle heats up over the distinction between myocardial injury and MI, according to Dr. Alpert. The reason is that there is currently no reimbursement code for patients with myocardial injury, who require substantial time and resources that currently are not being reimbursed.

"We’re pushing to get that code, because when you have an elevated troponin it means something, and it always means something not good," he said in the interview.

Cardiac troponin (I or T) is the preferred biomarker for the definition of acute MI, although less sensitive biomarkers such as the creatine kinase-MB (CKMB) mass can still be used when cardiac troponin is not available, said Dr. Thygesen, with the department of cardiological medicine, Aarhus (Denmark) University.

The criteria for an acute MI include detection of a rise and/or fall of cardiac biomarker values exceeding the 99th percentile URL, plus at least one of the following:

•Symptoms of ischemia.

•New or presumably new significant ST-segment/T wave changes or new LBBB.

•Development of pathological Q waves in the ECG.

•Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.

•Identification of an intracoronary thrombus by angiography or autopsy.

The new MI definition is expected to become the gold standard for diagnosis and to be adopted by the U.S. Food and Drug Administration for use in clinical trial protocols accepted by the agency. This is significant because it will help standardize the way MI is defined in clinical trials, making comparisons between studies more meaningful, Dr. Thygesen observed.

The expert consensus document, as well as pocket versions, are available on the websites of the ESC, ACC, AHA, and World Heart Federation.

The document is also being copublished in five journals: the Journal of the American College of Cardiology, European Heart Journal, Circulation, Global Heart, and Nature Reviews of Cardiology.

Dr. Thygesen reported no conflicts of interest. Dr. Alpert reported consulting for several pharmaceutical firms as well as the North American Center for Continuing Medical Education.