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(Circulation. 1996;94:3369-3375.)
© 1996 American Heart Association, Inc.

Articles

The Myth of the Myocardial `Infarctlet' During Percutaneous Coronary Revascularization Procedures

Alaa E. Abdelmeguid, MD, PhD; Eric J. Topol, MD

the Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Dr Abdelmeguid is now with the Cardiology Division, Henry Ford Cardiovascular Institute, Detroit, Mich.

Correspondence to Eric J. Topol, MD, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail topole@cesmtp.ccf.org.

Key Words: myocardial infarction • angioplasty • atherosclerosis • embolism • creatine kinase • ischemia

	Introduction

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
One of the most controversial issues in interventional cardiology today is whether small MIs, diagnosed by enzymatic abnormalities coincident with percutaneous coronary interventional procedures, are clinically relevant.^{1 2 3 4 5} Among interventional cardiologists, the commonly used term "infarctlet" implies a small and insignificant event. However, the importance of these myocardial infarctlets after coronary revascularization procedures is both understudied and underappreciated, despite the well-established prognostic importance of even small enzymatic infarctions in the setting of unstable angina⁶ or after acute MI.⁷ The controversy is related in part to the difficulty associated with the diagnosis of nonfatal MI in trials involving myocardial revascularization. This problem was a major issue in the evaluation of coronary artery bypass surgery and was never satisfactorily resolved.⁸ In the setting of bypass surgery, elevation of CK and CK-MB is routine, and other noninvasive tests designed to detect myocardial injury are also commonly positive. Because a definition for an abnormal extent of necrosis with bypass surgery could not be established or adapted via consensus, the commonly used definition of postbypass infarction is the presence of new Q waves on the postoperative ECG. Unfortunately, this definition misclassifies patients with non–Q-wave infarction as not experiencing myocardial damage, and patients with new, major conduction disturbances (eg, left bundle branch block) may not be accurately diagnosed. A similar problem is evident in the evaluation of percutaneous procedures, and defining postangioplasty infarction exclusively by the presence of Q waves on ECG does not seem appropriate for these percutaneous procedures, in which the absence of any necrosis is a principal goal. This controversial issue was the topic of a recent expert conference that was convened to discuss this problem and attempt to develop a consensus; recommendations from this conference are forthcoming. The purpose of the current article is to provide perspective on the significance of even small MIs with percutaneous coronary revascularization.

	Early Studies

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
MI, as diagnosed by elevation of cardiac enzymes after percutaneous coronary interventions, is relatively common and reported in 8% to 15% of patients undergoing PTCA.^{1 2 3 4 5} In part because of this common occurrence after apparently successful coronary interventions, these infarctlets are assumed to be relatively benign and not to have any adverse impact on long-term outcome. This assumption has been strengthened by two small observational studies, with limited follow-up, which suggested that these enzyme elevations do not have negative prognostic importance.^{1 2} In one study, Oh et al² reported on 25 patients with elevated CK-MB (20% of a total of 128 patients). This group had a higher incidence of recent MI, postinfarction angina, and branch-vessel closure during the procedure. Limited follow-up for 10 months revealed no significant differences between the groups. However, the authors were careful to point out that because of its limited sample size and follow-up, a small but significant effect on long-term outcome could have been missed. In another small study, with no postdischarge follow-up, Klein et al¹ reported on 38 patients (15% of a total of 249 patients) with modest elevations of CK or CK-MB values after successful PTCA. The patients were divided into three very small groups: group I (15 patients) had elevated CK with positive MB fraction; group II (4 patients) had elevated CK with normal MB; and group III (19 patients) had normal CK with elevated MB. In these patients, there was a high incidence of prolonged chest pain and angiographic evidence of side-branch occlusion, saphenous vein graft embolism, intimal dissection, coronary spasm, and thrombosis. It is important to note that isolated CK-MB elevation with normal CK was associated with a clinical event in more than half of the patients. Although this rate was less than the 87% incidence of these clinical events in the group with combined elevation of both CK and CK-MB, the relatively high incidence pointed to an association between isolated elevation of CK-MB and adverse clinical events. This was unfortunately interpreted to mean that abnormal levels of both CK and CK-MB may more specifically identify true necrosis, neglecting the alternative explanation that it might simply mean a larger zone of necrosis. Since there were no apparent important clinical sequelae for several days until discharge, the conclusion was that "abnormal cardiac serum enzyme release results in no permanent clinical sequelae." Unfortunately, this conclusion has proven to be misleading, since there was no clinical follow-up and therefore any effect on permanent clinical sequelae could not be addressed. Importantly, since patients with in-hospital complications (death, Q-wave infarction, or emergency bypass surgery), resuscitation from cardiac arrest, prolonged hypotension, or prolonged ischemia were excluded from the study, a low-risk group of patients with an excellent in-hospital prognosis was selected.

	The CK Threshold

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
Another related controversial issue is the threshold at which postprocedure cardiac enzyme elevations should be considered abnormal. Presently, the "definition" of non–Q-wave MI after percutaneous coronary interventions requires an elevation of CK ranging in various studies from 2 to more than 5 times the laboratory's upper limit of normal.^{9 10 11 12} This wide range is due to the absence of any systematic evaluation of the prognostic implications of cardiac enzyme elevation in this setting. Owing to the belief that these enzyme "leaks" are benign, there has been a recent trend toward liberalizing the threshold above which enzyme elevations should be considered abnormal, with many recent studies using 5 times the control values as the new threshold of CK elevation after interventions instead of the traditional 2 times.¹² In an attempt to define the appropriate threshold of CK elevation after successful PTCA, our group undertook a comprehensive study to evaluate the clinical, morphological, procedural correlates and long-term follow-up of two commonly used threshold levels of CK elevation (2 to 5 times versus >5 times the laboratory's upper limit of normal) after successful percutaneous interventions in the largest series reported to date.^{13 14} We evaluated 4664 consecutive patients with successful PTCA or DCA (ie, no death, Q-wave MI, or bypass surgery). The patients were divided into three groups according to postprocedure peak CK. Group I (4480 patients) had peak CK levels after the procedure of <2 times the upper limit of laboratory normal (ie, CK<360 IU/L). Group II (123 patients) had peak CK levels 2 to 5 times the upper limit of laboratory normal (ie, 361 to 900 IU/L), with positive myocardial band isoenzymes (CK-MB>4%). Group III (61 patients) had peak levels >900 IU/L, with positive CK-MB.^{13 14} Patients with enzymatic evidence of myocardial necrosis (groups II and III compared with group I) had a higher incidence of recent MI (7% and 7% versus 1%; P<.0001) and a higher incidence of unstable angina (75% and 83% versus 69%; P=.02). Morphologically, this was reflected in a higher incidence of thrombus-associated lesions (13% and 10% versus 4%; P<.0001) and complex lesions (16% and 23% versus 7%; P<.0001). All clinical, morphological, and procedural variables that were different among the three groups were included in univariate and multivariate logistic regression analyses to identify the factors independently associated with increased CK. Directional coronary atherectomy and saphenous vein graft procedures commonly yielded small infarctions. Survival curves were calculated according to the Kaplan-Meier estimates of survival and compared using the Wald ² and the Cox proportional-hazards regression model. The stepwise Cox proportional-hazards procedure was used to identify the covariates that were independently associated with adverse events. Clinical follow-up, available in 99.6% of the patients and extending up to 8.5 years, revealed a striking difference in survival among the three groups (77.8%, 77.1%, and 88.5% for groups II, III, and I, respectively; P<.0001). This difference in survival was totally accounted for by a difference in cardiac survival (81.1%, 77.1%, and 92.3%; P<.0001), with no difference among the three groups in the incidence of noncardiac death (P=.67). There was also a higher incidence of CABG in group III (29.9% versus 12.0% in the other groups; P=.012). There was no significant difference among the three groups in the incidence of MI or repeat PTCA. Adding all major complications on follow-up together (death, MI, bypass surgery, and repeat angioplasty), the event-free survival rate was significantly higher in the group with no infarct (Fig 1).

View larger version (16K): [in this window] [in a new window]   Figure 1. Plot showing freedom from major cardiac events (death, MI, bypass surgery, repeat percutaneous coronary intervention) for the three groups.

The primary finding of this study from a large patient cohort is that elevations of CK more than twice the upper limit of laboratory normal are associated with decreased survival and event-free survival. This study confirms that a CK value of 2 to 5 times the control value, with abnormal MB levels after PTCA, imparts a worse prognosis than no CK elevation (CK<2 times control). Indeed, the prognosis of this group more closely resembles the group with CK elevation >5 times control than the group with no CK elevation, arguing against the recent trend to raise the threshold of CK elevation after coronary interventions for the diagnosis of MI.

	Minor CK-MB Elevation

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
Since establishing the threshold at 2 times control defines an arbitrary cutoff value that entails an "all-or-none" effect occurring at the arbitrarily defined threshold level, we studied the correlates and effects of even smaller increases in CK to detect any effect that smaller increases in CK-MB might have in the largest series reported to date.¹⁵ To address this question properly, a large-scale study is particularly important, since any effect that minor changes in CK-MB might have would be expected to require a large number of patients observed for a long period of time. The study comprised all patients who underwent successful PTCA or DCA at the Cleveland Clinic between 1984 and 1991 and whose postprocedure peak CK levels did not exceed 2 times the upper limit of laboratory normal (ie, 2x180 IU/L). Patients with acute MI within 36 hours, those undergoing a salvage atherectomy for failed PTCA, and those with a procedure for chronic total occlusions were excluded from this analysis. There were 4484 patients who constituted the study population. The patients were divided into three groups, according to the peak CK and MB isoenzyme levels after the procedure. Group I (3776 patients) had no CK or MB elevation after the procedure (ie, CK 180 IU/L, with MB fraction 4%). Group II (450 patients) had a peak CK level between 100 and 180 IU/L, with MB fraction >4%. Group III (258 patients) had a peak CK level between 181 and 360 IU/L, with MB fraction >4%. Although there were no significant differences in demographic variables among the three groups, there was a higher incidence of some unfavorable morphological characteristics similar to those identified in the previous study in the groups with increased CK-MB. The groups with increased CK-MB had a higher incidence of thrombus-associated lesions (4% versus 7% and 5% for group I versus groups II and III; P=.02). Saphenous vein graft procedures and directional atherectomy procedures were performed more frequently in the same groups (19% versus 26% and 26%; and 6% versus 15% and 16%, respectively; P<.0001 for each). Long-term clinical follow-up, available in 99.5% of the patients, revealed results comparable to our previous analysis. Freedom from cardiac death was lower in the groups with elevated CK-MB (group I versus groups II and III: 92.9% versus 88.3% and 88.7%; P=.036). The incidence of noncardiac death was equally distributed among the three groups. Freedom from MI was also lower in the same groups (90.8% versus 89.7% and 86.8%; P=.025). There was also a trend toward more bypass surgery, repeat percutaneous revascularization, and cardiac hospitalization in the same groups. As a composite, the event-free survival rate was significantly higher in the group with no myocardial necrosis (group I): 62.7% versus 57.7% and 52.1%; P=.009. The results substantiate the finding that even minor elevations of CK are associated with adverse long-term outcome.

The interaction between the level of postprocedure CK-MB and the risk of cardiac death is shown in Fig 2 and illustrates that a modest increase of CK-MB to 40 IU/L is associated with more than doubling the risk of cardiac death. Further increases in myocardial isoenzymes are associated with further increase in risk, albeit not directly proportional. The plot shows a continuous relation between increased CK-MB and long-term outcome, pointing to the fact that any degree of necrosis is harmful and that attempting to conclude that a certain amount of necrosis is not significant by setting the threshold at an arbitrary level is simply not accurate. Indeed, there is no better reason to set the threshold at 2 times control level than at 1.5 or 2.5 times. It is more likely that an arbitrary threshold postprocedure is not as important as preprocedure and postprocedure determinations to detect a rise and fall. Fig 3 shows long-term survival for all groups in our studies according to postprocedure peak CK and verifies that there is an incremental death rate with increasing levels of CK, similar to a dose-response effect. Our results consequently raised a cautionary flag about the percutaneous coronary procedures associated with any release of CK-MB.

View larger version (7K): [in this window] [in a new window]   Figure 2. Plot showing the relation between risk for cardiac death on follow-up and the peak CK-MB after the procedure (logarithmic scale on the x axis). Reprinted with permission from Reference 14.

View larger version (15K): [in this window] [in a new window]   Figure 3. Plot showing long-term survival for all patients, grouped according to peak CK levels.

	Confirmation by Others

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
Our results have been recently confirmed by other centers. Tauke et al¹⁶ evaluated the prognostic value of CK elevation after elective coronary interventions and the long-term prognosis in 250 patients who developed CK elevation after elective coronary interventions and showed a relatively high death rate of 12% in this group at a median follow-up of 2.5 years. Peak total CK (P<.0004) and age (P<.01) were the only independent predictors of cardiac mortality. Similar to our findings, actuarial survival was related to the degree of CK elevation. Redwood et al¹⁷ determined the impact of "minor" (>1 and <4 times normal [5 to 16 ng/mL]) and "major" (>4 times normal) periprocedural CK-MB elevations on procedural success, in-hospital major complications (death, Q-wave infarction, or bypass surgery), and late clinical events in 1897 patients undergoing new-device coronary interventions (directional atherectomy, rotational atherectomy, or excimer laser–assisted angioplasty). For each of the ablative angioplasty modalities, after minor CK-MB rises 1-year mortality was similarly increased (directional atherectomy, 3.3%; rotational atherectomy, 3.6%; excimer laser angioplasty, 4.1%). Tardiff et al¹⁸ examined 2564 patients enrolled in GUSTO II to determine the frequency and magnitude of elevations in serum CK-MB after percutaneous or surgical interventions and investigated the relationship between postintervention CK-MB and clinical outcome at 30 days. Patients with no CK-MB elevation had a 30-day mortality of 2% and a combined death or repeat infarction rate of 4%. The respective values for patients with small infarctions (CK-MB of 1 to 3 times control) were 2% and 9% and for patients with larger infarcts (CK-MB>3 times control) were 4% and 14%. These studies lend support for the finding that elevations of CK-MB are relatively frequent after attempted revascularization and that patients with myocardial isoenzyme levels after interventions are at risk for cardiac events.

	Predictors of Cardiac Enzyme Elevation

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
There are several risk factors for increased CK after coronary interventions. The performance of directional atherectomy and the occurrence of coronary thromboembolism, such as is encountered more often in revascularization of saphenous vein grafts, were the strongest predictors of CK-MB elevation after a successful procedure.^{14 15} Other predictive variables included a history of recent infarction, the occurrence of minor procedural complications (transient in-laboratory closure, side-branch compromise, large dissections, hypotension requiring intravenous pressors or intra-aortic balloon counterpulsation), a multivessel procedure, higher residual stenosis, complex lesions, and a severe initial stenosis. The relationship between DCA and increased CK-MB is consistent with our recently published atherectomy series¹⁹ and with those of the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) study, which reported a twofold higher incidence of CK release after DCA than PTCA.⁹ The precise reason for the increased incidence of myocardial necrosis with atherectomy is not known. It is possible that DCA is associated with an increased rate of distal embolization resulting from active excision of the atherosclerotic plaque or simply related to the bulkier, high-profile device. It is also possible that the deeper injury associated with DCA might act as a nidus for platelet deposition and microembolization.

	Sources of CK-MB

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
Enzyme elevations may occur for a variety of reasons in the setting of percutaneous interventions and may or may not reflect irreversible ischemia. Few studies have demonstrated that prolonged balloon inflations in the absence of other clinical or pathological evidence of MI can result in relatively minor increases in CK-MB and myoglobin levels. Piper et al²⁰ showed a gradual release of cytosolic enzymes from reversibly injured myocardial cells subjected to anoxia in a cell culture of adult heart cells. These findings were supported by those of Heyndrickx et al,²¹ who showed that in baboons, short periods (15 minutes) of coronary artery occlusion, which do not result in demonstrable myocardial necrosis or permanent derangement in regional myocardial function, are associated with a significant increase in plasma CK as well as in CK-MB. They speculated that in patients with coronary artery disease, some episodes of ischemia associated with modestly elevated plasma levels of CK in blood do not reflect myocardial necrosis. There is also indirect evidence that transient ischemic episodes not associated with necrosis may be associated with enzyme leakage. Chiong et al²² reported increases in CK release in the coronary sinus during pacing-induced ischemia in patients with coronary artery disease. In humans, Mager et al²³ have shown that CK release can be detected after ischemic episodes as short as 7.8 minutes, a period that may be insufficient to engender myocardial necrosis. On the other hand, several studies suggest that minor increases in CK-MB are indeed associated with myocardial necrosis. Dillon et al²⁴ examined 724 consecutive patients admitted to an intensive care unit for chest pain and evaluated the electrocardiographic and enzymatic markers of myocardial necrosis to determine the importance of CK-MB regarding myocardial necrosis. They found that an increase in CK-MB in the absence of an elevation of total CK activity does indicate myocardial necrosis, although the extent of the damage may be small and therefore not result in electrocardiographic changes. Histological data available from that study also confirmed that elevated CK-MB without an abnormal elevation of total CK activity is associated with several small areas (<1 cm) of myocardial necrosis that correlated chronologically with the appearance of MB band. Recent studies using very specific measures of myocardial necrosis (Tn-T) also show that minor increases in CK-MB after PTCA might indeed reflect myocardial damage and uncover clinically and electrocardiographically inapparent severe myocardial ischemia/minor myocardial damage (microembolization) in 26% of patients after visually successful PTCA.³ Since the release kinetics of Tn-T indicates an ongoing release from necrotizing myocytes, it seems probable that the patients having increased Tn-T are likely to have minor myocardial damage.

	Potential Mechanisms of Adverse Outcome

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
The studies reviewed demonstrate a prognostic significance for minor elevations of CK-MB after percutaneous interventions but do not establish the mechanism(s) by which increased CK-MB affects long-term prognosis. The possibility that increased CK-MB reflects small zones of necrosis has been raised.²⁵ Animal studies of coronary microembolization reveal numerous small infarcts with angiographically normal epicardial coronary arteries.²⁶ Microscopic zones of necrosis can create zones of slow conduction that increase the susceptibility to ventricular arrhythmias via microreentrant circuits.^{27 28 29} Additionally, ventricular arrhythmias after microembolization may also be triggered by a focal mechanism.³⁰ Thus, it is conceivable that microinfarcts associated with minor increases in CK-MB provide a nidus for ventricular arrhythmias via a microreentry or a focal mechanism.^{27 28 30} It is important to note that cardiac deaths, when they occurred, were typically manifested late in the follow-up period, well after 12 to 18 months from the index procedure (Fig 3). The fact that most of the event excesses appear long after the index procedure and also that most of the deaths are sudden further bespeaks the potential importance of cardiac arrhythmic etiology. Another mechanism by which microembolization could increase the likelihood of MI and cardiac death is through the compromise of coronary collaterals. The interruption of collateral blood flow by embolization has been shown to potentiate the ischemic effects of subsequent coronary occlusion.²⁸ This course of events can lead to a higher incidence of ventricular arrhythmias and a larger infarct. In other words, the initial microembolization event may negatively predispose the heart to the effect of a subsequent ischemic insult. It is thus possible that a particularly "vulnerable" subset of patients is identified who experienced enzymatic leaks during their periprocedural phase and had subsequent events in the same distribution. In a sense, these myocardial segments could be viewed as "watershed" zones that are vulnerable to subsequent ischemic insults. Whether the subsequent adverse events may be related to endothelial dysfunction, cyclic flow oscillations, platelets, or the activation of the coagulation system, each of which has been suggested,^{31 32} remains unresolved. Alternatively, the occurrence of cardiac enzyme elevation might represent a marker of a high-risk population of patients who are prone to develop myocardial necrosis with any minor perturbation: "the leaker syndrome." For example, some patients will tolerate protracted balloon inflations or manipulations in the coronary arteries without CK elevation or MB leakage.^{5 23} However, the reasons certain patients and not others go on to develop micronecrosis, with its associated poor long-term prognosis, remains unknown. Accordingly, it is important to emphasize that the studies have so far shown an association between elevations of CK and adverse clinical outcome and that a cause-and-effect relationship has not yet been demonstrated.

	Integration Into Clinical Practice

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
The real question now for the interventional cardiology community is how to integrate these findings into clinical practice. This is a very important question, since it is becoming clearer that overall percutaneous revascularization procedures carry 15% risk of some (any) CK-MB elevation. Using the critical threshold of a threefold increase over the CK upper limit of normal, 8% of patients suffer a periprocedural MI. The risk increases significantly with the use of new devices such as directional and rotational atherectomy and is uncertain for stenting, and the question becomes whether we should reduce the use of new-device procedures, which is a substantial change from our current approach to coronary disease treatment. Regarding this issue, it is worthwhile to present the alternative views. One perspective is to be skeptical of the significance of these data and emphasize the lack of proof regarding cause and effect, ie, the relationship between elevated CK-MB and death during follow-up. The proponents of this view argue that enzyme elevations are an intrinsic part of the procedure, that they have been observed for years, and that patients who experience these elevations appear to do quite well during extended follow-up.³³ Accordingly, the solution adopted by some interventional cardiologists is to view the problem as a laboratory anomaly or spurious finding and to stop routine measurement of CK after angioplasty.

A parallel can be drawn to not obtaining ECGs after open heart surgery (a practice which, surprisingly, was followed at some institutions) to minimize the detection of Q-wave infarction after cardiac surgery. Clearly, this approach may be considered untenable; at the very least, ascertainment of the data is vital. We therefore suggest the alternative view, that cardiac enzymes be monitored routinely in all laboratories performing percutaneous coronary revascularization procedures, in a way similar to the monitoring of other major procedure-related complications (death, Q-wave MI, and CABG). We also propose that measurements of cardiac enzymes be an essential part of coronary interventional prospective randomized trials, since only the results of these trials can ultimately and confidently answer the very important question of whether CK-MB elevations seen after successful coronary procedures actually cause an increased risk of late cardiac death. Such a definitive conclusion can be made only after analyzing combined prospective data. We also suggest that the results of new devices be scrutinized, with particular attention being paid to detailed and accurate measurements of cardiac enzymes. Until recently, many important trials in the field of interventional cardiology have not systematically assayed CK after the procedures.^{34 35}

What should we do while awaiting the results of prospective randomized trials? We believe that in addition to maintaining complete, routine records of cardiac enzymes after all interventions, we should attempt to study, understand, and if possible avoid the factors associated with increased cardiac enzymes that we described in our studies. Standard practice to avoid the sacrifice of side branches, quick reversal of in-laboratory closure, and prevention of coronary embolism and slow flow remain important objectives.^{25 26 36 37} Furthermore, the new antiplatelet and antithrombin agents might play a role in decreasing the incidence of MI.^{38 39 40 41} The predominant salutary effect of the platelet glycoprotein IIb/IIIa inhibitors has been to reduce the incidence of periprocedural MIs, be they small, enzymatic events or large, overtly clinically manifest events.^{40 41} The suppression of MI events with IIb/IIIa blockade strongly implicates platelet aggregation in the pathogenesis; this is especially the case with directional atherectomy, for which the excess in MI events is nearly abolished by full inhibition of platelet aggregation.⁴² Similarly, in patients undergoing coronary intervention with unstable angina or recent MI, hirudin and hirulog (compared with heparin) have reduced periprocedural myocardial necrosis.^{38 39}

In another study, Rupprecht et al³¹ measured Tn-T levels in 61 patients with unstable angina after PTCA who were randomly assigned to peri-interventional intravenous treatment with either hirudin or heparin. An elevated serum Tn-T concentration was found in 24% of the patients in the hirudin group compared with 58% of patients in the heparin group (P=.01). Major cardiac events were observed in 5% of patients of the hirudin group compared with 14.3% of patients in the heparin group, suggesting that platelet/thrombus plays an important role in CK release after coronary interventional procedures and that the use of new antiplatelet or antithrombin agents, or both, might become an essential part of the coronary interventional procedures in selected patients. Whether or not agents such as ß-blockers will reduce arrhythmic outcomes in patients who develop micronecrosis certainly deserves further study.

In summary, a growing body of evidence is accumulating linking the myocardial infarctlets after apparently successful coronary interventions to an adverse long-term prognosis, and particularly to an increase in late mortality. The findings have important implications for daily interventional cardiology practice and future research in coronary revascularization and highlight the risks associated with the common practice of not detecting or ignoring small non–Q-wave infarctions as a complication of percutaneous coronary interventions.⁴³ Considerable investigation is required to more fully understand and prevent these significant events and on a secondary basis, to prevent their adverse long-term sequelae.

	Selected Abbreviations and Acronyms

 

CABG = coronary artery bypass graft CK = creatine kinase CK-MB = CK–myocardial band isoenzymes DCA = directional coronary atherectomy MI = myocardial infarction PTCA = percutaneous transluminal coronary angioplasty Tn-T = troponin T

	References

Top Introduction Early Studies The CK Threshold Minor CK-MB Elevation Confirmation by Others Predictors of Cardiac Enzyme... Sources of CK-MB Potential Mechanisms of Adverse... Integration Into Clinical... References

 
1. Klein LW, Kramer BL, Howard E, Lesch M. Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non–Q-wave myocardial infarction associated with coronary angioplasty. J Am Coll Cardiol. 1991;17:621-626.[Abstract]

2. Oh JK, Shub C, Ilstrup DM, Reeder GS. Creatine kinase release after successful percutaneous transluminal coronary angioplasty. Am Heart J. 1985;109:1225-1231.[Medline] [Order article via Infotrieve]

3. Ravkilde J, Nissen H, Mickley H, Anderson PE, Thayssen P, Horder M. Cardiac troponin T and CK-MB mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris. Am Heart J. 1994;127:13-20.[Medline] [Order article via Infotrieve]

4. Spadaro JJ, Ludbrook PA, Tiefenbrunn AJ, Kurnik PB, Jaffe AS. Paucity of subtle myocardial injury after angioplasty delineated with MB CK. Cathet Cardiovasc Diagn. 1986;12:230-234.[Medline] [Order article via Infotrieve]

5. Pauletto P, Piccolo D, Scannapieco G, Vescovo G, Zaninotto M, Corbara F, Cuman G, Chioin R, Casiglia E, Maddalena F, Pessina AC, Del Palu C. Changes in myoglobin, creatine kinase and creatine kinase-MB after percutaneous transluminal coronary angioplasty for stable angina pectoris. Am J Cardiol. 1987;59:999-1000.[Medline] [Order article via Infotrieve]

6. Hamm CW, Ravkilde J, Gerhardt W, Jorgensen PJ, Peheim E, Ljungdahl L, Goldmann B, Katus HA. The prognostic value of serum troponin T in unstable angina. N Engl J Med. 1992;327:146-150.[Abstract]

7. Roberts R. Enzymatic estimation of infarct size: thrombolysis induced its demise: will it now rekindle its renaissance? Circulation. 1990;81:707-710.[Free Full Text]

8. Balderman SC, Bhayana JN, Steinbach JJ, Musud ARZ, Michalek S. Perioperative myocardial infarction: a diagnostic dilemma. Ann Thorac Surg. 1980;30:370-377.[Abstract]

9. Topol EJ, Leya F, Pinkerton CA, Whitlow PL, Hoffling B, Simonton CA, Masden RR, Serruys PW, Leon MB, Williams DO, King SB, Mark DB, Isner JM, Holmes DR, Ellis SG, Lee KL, Keeler GP, Berdan LG, Hinohara T, Califf RM. A comparison of directional atherectomy with coronary angioplasty in patients with coronary disease. N Engl J Med. 1993;329:221-227.[Abstract/Free Full Text]

10. Meester BJ, Samson M, Suryapranata H, Bonsel G, Van Den Brand M, De Feyter PJ, Serruys PW. Long-term follow up after attempted angioplasty of saphenous vein grafts: the Thoraxcenter experience 1981-1988. Eur Heart J. 1991;12:648-653.[Abstract/Free Full Text]

11. Platko WP, Hollman J, Whitlow PL, Franco I. Percutaneous transluminal angioplasty of saphenous vein graft stenosis: long-term follow-up. J Am Coll Cardiol. 1989;14:1645-1650.[Abstract]

12. Wong SC, Popma JJ, Pichard AD, Kent KM, Salter LF, Mintz GS, Chuang YC, Hong MK, Ditrano CJ, Leon MB. Comparison of clinical and angiographic outcomes after saphenous vein graft angioplasty using coronary versus biliary tubular slotted stents. Circulation. 1995;91:339-350.[Abstract/Free Full Text]

13. Abdelmeguid AE, Whitlow PL, Sapp SK, Ellis SG. Elevation of creatine kinase after percutaneous coronary interventions: should we set the threshold at 2 or 5 times control? Circulation. 1994;90(suppl I):I-279. Abstract.

14. Abdelmeguid AE, Ellis SG, Sapp SK, Whitlow PL, Topol EJ. Defining the appropriate threshold of creatine kinase elevation after percutaneous interventions. Am Heart J. 1996;131:1097-1105.[Medline] [Order article via Infotrieve]

15. Abdelmeguid AE, Sapp SK, Ellis SG. Significance of mild transient elevations of creatine kinase after successful PTCA. Circulation. 1993;88(suppl I):I-299. Abstract.

16. Tauke JT, Kong TQ, Meyers SN, Srinivasan G, Niemyski PR, Parker MA, Davidson CJ. Prognostic value of creatine kinase elevation following elective coronary interventions. J Am Coll Cardiol. 1995;special issue:269A. Abstract.

17. Redwood SR, Popma JJ, Kent KM, Pichard AD, Satler LF, Hong MH, Chuang YC, Clark CE, Bucher TA, Mackenzie J, Leon MB. `Minor' CPK-MB elevations are associated with increased late mortality following ablative new-device angioplasty in native coronary arteries. Circulation. 1995;92(suppl I):I-544. Abstract.

18. Tardiff BE, Granger CB, Woodlief L, Mahaffey KW, Harrington RA, Califf RM. Prognostic significance of postintervention isozyme elevations. Circulation. 1995;92 (suppl I):I-544. Abstract.

19. Abdelmeguid AE, Ellis SE, Sapp SK, Simpfendorfer C, Franco I, Whitlow PL. Directional coronary atherectomy in unstable angina. J Am Coll Cardiol. 1994;24:46-54.[Abstract]

20. Piper HM, Schwartz P, Spahr R, Hutter JF, Spieckermann PG. Early enzyme release from myocardial cells is not due to irreversible cell damage. J Mol Cell Cardiol. 1984;16:385-388.[Medline] [Order article via Infotrieve]

21. Heyndrickx GR, Amano J, Kenna T, Fallon JT, Patrick TA, Manders WT, Rogers GG, Rosendorff C, Vatner SF. Creatine kinase release not associated with myocardial necrosis after short periods of coronary artery occlusion in conscious baboons. J Am Coll Cardiol. 1985;6:1299-1303.[Abstract]

22. Chiong MA, West R, Parker JO. Myocardial balance of inorganic phosphate and enzymes in man: effects of tachycardia and ischemia. Circulation. 1974;49:283-290.[Abstract/Free Full Text]

23. Mager A, Sclarovsky S, Wurtzel M, Menkes H, Strasberg B, Rechavia E. Ischemia and reperfusion during intermittent coronary occlusion in man: studies of electrocardiographic changes and CPK release. Chest. 1991;99:386-392.[Abstract/Free Full Text]

24. Dillon MC, Calbreath DF, Dixon AM, Rivin BE, Roark SF, Ideker RE, Wagner GS. Diagnostic problems in acute myocardial infarction: CK-MB in the absence of abnormally elevated total creatine kinase levels. Arch Intern Med. 1982;142:33-38.[Abstract/Free Full Text]

25. Abdelmeguid AE, Whitlow PL, Sapp SK, Ellis SG, Topol EJ. Long-term outcome of transient, uncomplicated in-laboratory coronary artery closure. Circulation. 1995;91:2733-2741.[Abstract/Free Full Text]

26. Jacobey JA, Taylor WJ, Smith GT, Gorlin R, Harken DE. A new therapeutic approach to coronary artery occlusion. Am J Cardiol. 1962;9:60-73.[Medline] [Order article via Infotrieve]

27. Euler DE, Prood CE, Spear JF, Moore EN. The interruption of collateral blood flow to the ischemic myocardium by embolization of a coronary artery with latex: effects on conduction delay and ventricular arrhythmias. Circ Res. 1981;49:97-108.[Free Full Text]

28. Marcus E, Katz LN, Pick R, Stamler J. The production of myocardial infarction, chronic coronary insufficiency and chronic heart disease in the dog. Acta Cardiol. 1958;13:190-198.[Medline] [Order article via Infotrieve]

29. Kaplinsky E, Ogawa S, Balke W, Dreifus L. Two periods of early ventricular arrhythmias in the canine acute myocardial infarction model. Circulation. 1979;60:397-403.[Abstract/Free Full Text]

30. Pogwizd SM. Focal mechanisms underlying ventricular tachycardia during prolonged ischemic cardiomyopathy. Circulation. 1994;90:1441-1458.[Abstract/Free Full Text]

31. Rupprecht HJ, Terres W, Ozbek C, Luz M, Jessel A, Hafner G, vom Dahl JV, Kromer EP, Prellwitz W, Meyer J. Recombinant hirudin (HBW 023) prevents troponin-T release after coronary angioplasty in patients with unstable angina. J Am Coll Cardiol. 1995;26:1637-1642.[Abstract]

32. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Circulation. 1985;71:699-708.[Abstract/Free Full Text]

33. Kugelmass AD, Cohen CJ, Moscucci M, Piana RN, Senerchia C, Kuntz RE, Baim DS. Elevation of creatine kinase myocardial isoform following otherwise successful directional coronary atherectomy and stenting. Am J Cardiol. 1994;74:748-754.[Medline] [Order article via Infotrieve]

34. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, Belardi J, Sigwart U, Colombo A, Goy JJ, van den Heuvel P, Delcan J, Morel MA, for the BENESTENT Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med. 1994;331:489-495.[Abstract/Free Full Text]

35. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, Cleman M, Heuser R, Almond D, Teirstein PS, Fish D, Colombo A, Brinker J, Moses J, Shaknovich A, Hirshfeld J, Bailey S, Ellis S, Rake R, Goldberg S, for the Stent Restenosis Study Investigators. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med. 1994;331:496-501.[Abstract/Free Full Text]

36. Laskey MAL, Deutsch E, Hirshfield JW, Kussmaul WG, Barnathan E, Laskey WK. Influence of heparin therapy on percutaneous coronary angioplasty outcome in patients with coronary arterial thrombus. Am J Cardiol. 1990;65:179-182.[Medline] [Order article via Infotrieve]

37. Talasz H, Genser N, Mair J, Dworzak EA, Friedrich G, Moes N, Muhlberger V, Puschendorf B. Side-branch occlusion during percutaneous transluminal coronary angioplasty. Lancet. 1992;339:1380-1382.[Medline] [Order article via Infotrieve]

38. Serruys PW, Herrman JP, Simon R, Rutsch W, Bode C, Laarman GJ, van Dijk R, van den Bos A, Umans V, Fox KAA, Close P, Deckers JW, for the HELVETICA Investigators. A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. N Engl J Med. 1995;333:757-763.[Abstract/Free Full Text]

39. Bittl JA, Strony J, Brinker JA, Ahmed WH, Meckel CR, Chaitman BR, Maraganore J, Deutsch E, Adelman B, for the Hirulog Angioplasty Study Investigators. Treatment with bivalirudin (hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. N Engl J Med. 1995;333:764-769.[Abstract/Free Full Text]

40. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med. 1994;330:956-961.[Abstract/Free Full Text]

41. Tcheng JE, Lincoff AM, Sigmon KN, Califf RM, Topol EJ, for the IMPACT II Investigators. Platelet glycoprotein IIb/IIIa inhibition with Integrelin during percutaneous coronary intervention: the IMPACT II trial. Circulation. 1995;(suppl I):I-543. Abstract.

42. Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med. 1995;332:1553-1559.[Free Full Text]

43. Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG. Significance of mild transient release of creatine kinase MB fraction after percutaneous interventions. Circulation.. 1996;94:1528-1536.[Abstract/Free Full Text]

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