Troponisms, Necrosettes, Enzyme Leaks, Creatinine Phosphokinase Bumps, and Infarctlets
2001; Lippincott Williams & Wilkins; Volume: 104; Issue: 6 Linguagem: Inglês
10.1161/01.cir.104.6.627
ISSN1524-4539
AutoresDavid R. Holmes, Peter B. Berger,
Tópico(s)Acute Myocardial Infarction Research
ResumoHomeCirculationVol. 104, No. 6Troponisms, Necrosettes, Enzyme Leaks, Creatinine Phosphokinase Bumps, and Infarctlets Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBTroponisms, Necrosettes, Enzyme Leaks, Creatinine Phosphokinase Bumps, and InfarctletsWhat's Behind This New Lexicon and What Does It Add? David R. Holmes Jr, MD and Peter B. Berger, MD David R. Holmes JrDavid R. Holmes Jr and Peter B. BergerPeter B. Berger Originally published7 Aug 2001https://doi.org/10.1161/01.CIR.104.6.627Circulation. 2001;104:627–629Dramatic improvements in angioplasty technology have allowed initial patient and lesion selection criteria to expand and to include the treatment of complex lesions in critically ill patients. Most recent estimates indicate that 900 000 patients were treated with a percutaneous approach in the United States in 2000 and 1.7 million patients were treated with one worldwide. As the technology has become more complex with the introduction of a variety of stents, atherectomy devices, capture devices, and filters, among others, interventionists have learned more about the procedures and the patients undergoing them.See p 642In the early years of balloon angioplasty, success rates were low. In the initial National Heart, Lung and Blood Percutaneous Transluminal Coronary Angioplasty Registry from 1977 and 1981, clinical success, which was defined as a reduction in luminal diameter stenosis by ≥20% and no death, infarction, or coronary bypass surgery, was achieved in 61% of patients.1,2 Failures were often the result of dissection or refractory acute closure, emergency coronary bypass graft surgery (often required), and Q-wave myocardial infarction (often resulted). Nonfatal Q-wave myocardial infarction occurred in 4.9% of patients and death, nonfatal Q-wave myocardial infarction, or emergency surgery occurred in 8.8%.1–3 There was often nothing subtle about an angioplasty complication at that time. As operator experience has improved and improvements in technology have become available, these morbid complications have decreased markedly. The need for emergency surgery has declined from 5.8% (initial registry) to ≈0.5% (today).Satisfaction from these advances has been tempered by the recognition of just how frequently enzyme elevations result from even successful percutaneous revascularization procedures. The issue of cardiac enzyme elevation (or "biomarker" elevation, in the case of the troponins, which are not enzymes) has become increasingly important for 2 reasons.4–10 (1) The definition of acute infarction has changed, and now the definition includes even asymptomatic enzyme and biomarker elevations as myocardial infarctions. These elevations were not thought to represent myocardial infarctions under the former World Health Organization definition. That definition8 required the presence of at least 2 of the following 3 factors: a clinical history of ischemic chest pain, serial changes on the ECG, and a rise and fall in serum cardiac markers. Subsequent refinements to the definition have expanded it to include the use of more sensitive and specific cardiac markers of myocardial necrosis, including troponin.4,5 (2) Monitoring of enzymes after all percutaneous revascularization procedures is now widespread and sometimes mandatory.Although it seems obvious that no cardiac enzyme or biomarker elevation can possibly be good for patients, it is not at all clear that all such elevations are measurably bad for patients either. The prognostic implications of even procedural myocardial infarctions likely depend on the absolute size of the infarction, its effect on left ventricular function, and its cause. For example, whether the revascularization procedure was successful or not is likely a critical determinant of outcome. Whether there was transient or sustained occlusion of a minor or major side branch also likely affects clinical outcome. Finally, which revascularization device is used seems to affect both the frequency and the severity of procedural infarction.The issue of procedural infarctions and the physician's interest in minimizing their significance has spawned a new lexicon, including troponisms, enzyme leaks, creatinine phosphokinase (CPK) bumps, necrosettes, and infarctlets, among others. It has also resulted in considerable controversy and has been the subject of entertaining and sometimes enlightening debates at national and international scientific meetings. The article by Stone et al11 in the present issue of Circulation contributes to our understanding of the issues involved for a number of reasons. The study includes (1) a systematic post-procedural enzyme analysis in a large number of consecutive patients treated with a large number of different devices and (2) a correlation between the degree of enzyme elevation and the presence of electrocardiographic data with early and longer term clinical outcome.As has become apparent from multiple studies, CPK elevation is much more common than initially thought. In this current study, an elevation of CPK above the upper limits of normal was present in 37.3% of patients. In most cases, the elevation was quite mild, peaking at between 1 to 3 times the upper limit of normal. Using a definition of myocardial infarction as a peak CPK-MB >3 times normal, myocardial infarction occurred in 17.9% of patients. The frequency of enzyme elevation was related to the device used and procedure performed. It was most common with athero-ablation in combination with stent implantation and least common with balloon angioplasty alone. Despite the frequent occurrence of myocardial infarction, the development of new Q-waves was uncommon, ranging from 0.4% after stent implantation to 0.8% after athero-ablation. In-hospital mortality was rare, occurring in only 1.0% of patients. On multivariate analysis, the most important correlate of in-hospital mortality was the development of a Q-wave myocardial infarction (odds ratio, 67.1; 95% confidence interval [CI], 30.2 to 166.7; P 8 times normal in patients without Q-wave infarction was also a strong correlate of in-hospital mortality, but much less so, with an odds ratio of 8.0 (95% CI, 4.4 to 14.7; P=0.0001). Lesser elevations of CPK-MB were not significantly related to in-hospital mortality.Although the frequency of enzyme elevation and the development of Q-waves varied with the device used, long-term survival seemed to be independent of the specific device. During a mean follow-up period of 1.4±1.2 years, the most important determinate of mortality was Q-wave myocardial infarction (odds ratio, 9.9; 95% CI, 6.0 to 16.4; P 8 times the upper limit of normal was also a correlate of late mortality, but the odds ratio was substantially smaller at 2.2 (95% CI, 1.6 to 3.0; P=0.0001). Again, lesser degrees of periprocedural CPK-MB elevation were not significantly related to mortality during follow-up.There are a number of limitations to this study. First, the investigators seem to include unsuccessful procedures in their analysis, although the number of these is presumably quite small. This tends to obfuscate rather than clarify the debate, which in the past has generally focused on what significance, if any, small procedural infarctions have after an otherwise successful procedure. The inclusion of unsuccessful procedures that result in the need for emergency bypass surgery and in-hospital death further confuses the debate.There are other important issues that the article does not directly address. (1) During the course of this study, the investigators were, in their words, "skeptics" about the value of platelet glycoprotein IIb/IIIa inhibitors and administered them to only 4.0% of the patients. Given the very well-documented ability of these agents to decrease post-procedural cardiac enzyme elevation by ≈50%, one cannot know what effect on mortality, if any, these agents might have had if they been used in a larger percentage of patients. (2) There are no data provided on the mechanism of CPK-MB elevation or Q-wave myocardial infarction. Some studies have found that CPK elevations after a procedure reflect the severity and extent of atherosclerotic disease12; others have found it is related to specific identifiable complications, such as distal embolization or branch occlusion. Some investigators suggest that isolated asymptomatic CPK elevations without an angiographically apparent cause have no prognostic impact. This study does not advance our understanding of these issues. (3) The short duration of follow-up is another limitation of the study. It seems obvious and there are data to suggest that longer periods of follow-up are required to identify differences in mortality among patients with no infarction versus small infarctions. However, data from large studies of "spontaneous" infarction indicate that by far the greatest risk of death is within 6 months of infarction, and the duration of follow-up in this study exceeded that. (4) Finally, this study cannot address what impact using a more sensitive indicator of myocardial necrosis such as troponins might have, because troponins were not measured in this population.Despite these limitations, this study is very important and should have a significant impact on practice. It supports the following conclusions. (1) Even after successful percutaneous revascularization procedures, myocardial infarctions, when defined as an enzyme elevation in even asymptomatic patients, occur frequently. They are likely to be diagnosed even more frequently when procedural myocardial infarctions are defined as a rise in troponins, and it is likely troponins will soon be routinely measured after all revascularization procedures. (2) Small degrees of cardiac enzyme and biomarker elevations undoubtedly reflect myocardial necrosis, but whether this has any impact on survival after otherwise uncomplicated procedures requires huge numbers of patients and long-term follow-up. (3) The procedural device used influences the frequency and degree of enzyme elevation. (4) The larger the procedural infarction, the greater the impact on prognosis. Infarctions large enough to cause a rise in CPK-MB >8 times the upper limit of normal are often clinically important, even in the short-term. Such patients should probably be considered to have had a myocardial infarction in the traditional sense and be treated accordingly. (5) Finally, old-fashioned tests such as the ECG provide important information above and beyond enzyme analyses and have the most discriminant value. Although only a small number of patients develop a Q-wave myocardial infarction, this factor was more closely associated with increased in-hospital mortality in Stone et al's study11 (25%), and it continues to identify patients at risk for follow-up mortality. 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August 7, 2001Vol 104, Issue 6 Advertisement Article InformationMetrics https://doi.org/10.1161/01.CIR.104.6.627 Originally publishedAugust 7, 2001 KeywordsangioplastystentscathetersEditorialsmyocardial infarctionPDF download Advertisement
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