doi: 10.1161/CIRCULATIONAHA.104.483297
(Circulation. 2005;112:906-922.)
© 2005 American Heart Association, Inc.
Controversies in Cardiovascular Medicine |
Does creatinine kinase-MB elevation after percutaneous coronary intervention predict outcomes in 2005?
Periprocedural Cardiac Enzyme Elevation Predicts Adverse Outcomes
From the Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio (D.L.B., E.J.T.); and the Harvard Clinical Research Institute, Division of Cardiology, Beth Israel Deaconess Medical Center, Division of Cardiology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Mass (D.E.C., R.E.K.).
Correspondence to Deepak L. Bhatt, MD, Dept of Cardiovascular Medicine, The Cleveland Clinic Foundation, 9500 Euclid Ave, Desk F25, Cleveland, OH 44195 (e-mail bhattd{at}ccf.org); or Donald E. Cutlip, MD, Interventional Cardiology Section, Beth Israel Deaconess Medical Center, 185 Pilgrim Rd, Baker 4, Boston, MA 02215 (e-mail dcutlip@bidmc.harvard.edu).
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Introduction |
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 Top Introduction Periprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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Extensive clinical investigation throughout the 1990s validated periprocedural myonecrosis as a powerful predictor of adverse outcomes, so it is surprising that this remains a contentious point. Originally derided as "enzyme leaks" or "myocardial infarctlets," periprocedural myocardial infarction (MI) has now been definitively linked in large data sets to long-term adverse outcomes, most notably mortality. It is not, however, always directly contributory or causative. For example, a large creatine kinase (CK) elevation caused by closure of a major side branch resulting in chest pain and development of new Q waves is obviously undesirable and causally related to the interventional procedure. Alternatively, even small, asymptomatic CK elevations have been clearly associated with worse long-term outcome, and although this may in part be causally related to the procedure, it is more likely that the relationship is caused by the underlying predisposing factors that led to the periprocedural MI, such as arterial inflammation predilecting to the occurrence of embolization or to a large degree of atheroma burden leading to more myonecrosis. Under these circumstances, it is likely that the heightened inflammatory state and the diffuse disease that is present are the real causative factors for worse long-term outcomes. Recently, aspirin resistance has been demonstrated to predict periprocedural myonecrosis. Thus, both through direct causation and also as an epiphenomenon, embolization and attendant periprocedural myonecrosis are associated with short, intermediate, and long-term adverse outcomes (Table 1). This review details this evolution in thought.
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Periprocedural Myonecrosis and Outcome |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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Periprocedural myonecrosis is a frequent occurrence in percutaneous coronary intervention (PCI). CK or CK myocardial band (CK-MB) elevation occurs in
25% of patients undergoing PCI. With the advent of sensitive troponin measurements, it is clear that at least 50% of patients undergoing PCI have postprocedural troponin elevation, reflecting the frequency with which embolization occurs. However, troponin offers relatively poor specificity for prognosis. In contradistinction, CK elevation has been validated as a marker of prognosis, perhaps due to a threshold phenomenon – that is, a certain degree of embolization may be necessary to be clinically relevant. The most common definition of periprocedural MI is a CK elevation 
3 times the upper limit of normal (ULN), although this is obviously an arbitrary cutoff.1,2 Numerous studies have corroborated the frequency with which periprocedural myonecrosis occurs, even in elective coronary intervention. With the advent of sophisticated imaging modalities, such as contrast enhanced MRI, even low levels of CK-MB elevation have been demonstrated to correspond to discrete areas of microinfarction.3 The Evaluation of Platelet IIb/IIIa Inhibition for Prevention of Ischemic Complication (EPIC) trial conclusively demonstrated the association between CK elevation and 3-year mortality (Figure 1).4 Examination of the event curves reveals that a large proportion of the deaths occur well after the index PCI. Although it is relatively intuitive that a CK elevation >10 times the ULN would be associated with negative outcomes, even relatively minor degrees of CK elevation were associated with adverse events.5 It appears that there is a graded response between degree of CK elevation and mortality risk; the absolute risks with periprocedural MI are lower than they are with spontaneous MI across the range of abnormal CK, but in both cases, as intuition would suggest, higher CK is worse.6
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Several other studies have corroborated the relationship between periprocedural MI and intermediate- and long-term outcome (Table 2). In a study of 15 637 patients undergoing elective PCI, mortality at 10 years was significantly higher in those with CK elevations >3 times the ULN.7 After excluding in-hospital and 30-day deaths, this degree of CK elevation remained an independent predictor of death. Even CK elevation 1.5 to 3.0 times the ULN is associated with higher mortality, with each 100 U/L increment of CK associated with a relative risk of cardiac mortality of 1.05.8 In fact, a meta-analysis of 7 studies with 23 230 patients undergoing PCI found that any CK elevation was associated with a small but statistically significant increase in mortality.9 Even troponin elevation in the setting of elective PCI has been linked to higher mortality, although this has been an inconsistent finding.10,11 Although 1 study did find that CK elevations <8 times the ULN were not associated with increased 2-year mortality, it is likely that with longer-term follow-up, there would have been an observed increase in mortality with even lower degrees of CK elevation, as seen in most other studies.12
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How, then, can one reconcile the fact that there are large studies that find an association between CK elevation and mortality and others that do not (Table 2)? Several analyses that did find a positive association did not exclude patients with procedural complications and did not stratify patients with varying degrees of postprocedural CK elevation. That is, an association between CK elevation >3 times the ULN may overestimate the strength of the relationship with mortality than if CK 3 to 5 times the ULN were compared with >5 times the ULN, if it is really just the large CK elevations that affect the mortality risk. A common thread among the negative analyses is a shorter duration of follow-up. In general, the longer the follow-up, the more likely the CK threshold associated with increased mortality drops. Perhaps, then, large CK elevations caused by complications from the procedure itself manifest as an increased mortality on a shorter time frame, whereas the associated mortality hazard from smaller CK elevations manifest only after longer-term follow-up through mechanisms described below (Figure 2).
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Thus, it is likely that with long enough follow-up, in a large enough cohort, any degree of CK elevation or troponin elevation would be associated with worse outcome. The incremental clinical utility and cost effectiveness of preventing small degrees of periprocedural embolization in patients with perceived low risk may not be attractive, however. Furthermore, it would likely be impractical to design a single long-term large-scale randomized study to determine the value of preventing common low-level troponin elevations after PCI. Fortunately, as a generalization, therapeutic modalities to reduce periprocedural infarction apply to both large and small degrees of CK elevation.
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Mechanisms Underlying the Risk of Periprocedural MI |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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Although it is obvious that large periprocedural myocardial infarctions, such as those caused by occlusion of a large side branch, flow-limiting dissection, or distal embolization of a large thrombus, would be undesirable and associated with worse subsequent cardiac outcomes, it is possible that even lower levels of periprocedural embolization may lead to microvascular obstruction and necrosis. Even this degree of necrosis may serve as a future nidus for arrhythmogenesis or may lower the arrhythmic threshold.13 Both the number of particles and their size affect the response of the microvasculature to embolization. Endogenous release of a vasodilator such as adenosine is able to compensate up to a point.14 A small number of large particles or a large number of small particles, if enough to exceed a certain threshold, may then lead ultimately to degradation of microvascular flow. Microembolization may also diminish ischemic tolerance and hence increase subsequent infarction size.15 Importantly, even careful angiographic assessment cannot fully predict which patients will ultimately develop myonecrosis from these "invisible showers."
Tissue level perfusion, as measured by the tissue myocardial perfusion grade (TMPG), also reflects the degree of myonecrosis detected by CK elevation. TMPG has been found to correlate with mortality in the setting of myocardial infarction, including in patients with Thrombolysis in Myocardial Infarction (TIMI) III flow. Even during elective stent implantation, CK elevation and impaired TMPG have been correlated with one another as well as with infarct mass on contrast-enhanced MRI.16 Thus, it appears that embolization may lead to impaired tissue perfusion and myonecrosis.
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Devices and Periprocedural MI |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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Through what has been termed the "cheese grater effect," stents always lead to some degree of embolization, more so than does balloon angioplasty (Table 3).17 High-pressure stent implantation or purposeful stent overexpansion are also associated with increased rates of CK elevation.18 This effect is amplified in lesions containing thrombus, such as in acute MI. Initial trials of stenting in acute MI showed worrisome trends toward increased ischemic events; however, incorporation of appropriate periprocedural antithrombotic therapy appears to ameliorate any hazard caused by stenting. In fact, the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial supports the synergy of stenting with potent antiplatelet blockade across a wide variety of patient and lesion subtypes.19 Specifically, the EPISTENT trial demonstrated a reduction in periprocedural MI and 1-year mortality with the use of glycoprotein (GP) IIb/IIIa inhibitors. Of note, the majority of late mortality was caused by sudden cardiac death. Whether these deaths were the result of arrhythmia or de novo plaque rupture is unknown.
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Directional coronary atherectomy (DCA) is associated with increased rates of periprocedural MI compared with angioplasty/stenting. Randomized clinical trials such as Coronary Angioplasty versus Excisional Atherectomy Trial (CAVEAT) have demonstrated this and meta-analyses have confirmed it.20 Furthermore, the 1-year data from CAVEAT demonstrated a significant increased out-of-hospital death rate in patients who had been randomized to DCA versus percutaneous transluminal coronary angioplasty (2.2% versus 0.2%, P=0.01).21 This analysis provides direct supportive evidence that devices that increase periprocedural MI may also increase mortality.
It is important to note that intravenous antiplatelet therapy appears to be able to diminish the impact of embolization in all of these settings, perhaps most prominently with the techniques that lead to the most embolization, such as rotational and directional atherectomy. Indeed, rotational atherectomy may serve as the best in vivo model of embolization. Koch et al demonstrated that rotational atherectomy may produce a transient myocardial perfusion defect but that pretreatment with abxicimab abolished this response.22,23 Indeed, the benefit of abciximab in PCI is evident across all of the devices used, including directional atherectomy. Thus, the sequelae of embolization—myocardial ischemia and necrosis—can be attenuated by potent antithrombotic therapy.
In the setting of ST elevation MI, where periprocedural embolization is most likely, the benefits of GP IIb/IIIa inhibition during PCI are most pronounced. On the opposite end of the risk spectrum, GP IIb/IIIa inhibition seems to be unnecessary in low-risk elective PCI, at least if patients are adequately pretreated with aspirin and a large enough loading dose of clopidogrel.
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Aspirin Resistance and Periprocedural Myonecrosis |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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In an interesting analysis, Chen et al found that patients undergoing elective PCI who were classified as aspirin resistant at baseline using the VerifyNowTM (Accumetrics) point-of-care platelet function assay were likely to develop periprocedural myonecrosis (Figure 3).24 Indeed, 66% of the patients categorized as aspirin resistant had a postprocedural troponin elevation as compared with 39% of the aspirin-sensitive patients.24 This study did not use GP IIb/IIIa inhibitors and used only a 300-mg loading dose of clopidogrel. Perhaps a significant degree of periprocedural myonecrosis that is linked to aspirin resistance can be decreased by more potent oral and intravenous antiplatelet and anticoagulant therapy.25 Other studies have demonstrated an association between aspirin resistance and long-term cardiac events. Thus, if aspirin resistance is linked to periprocedural MI and aspirin resistance is linked to long-term adverse cardiovascular outcome, then some of the association between periprocedural MI and long-term outcome may be mediated by aspirin resistance. Of note, in the study by Chen et al, even the aspirin-sensitive patients had a significant rate of periprocedural myonecrosis; therefore, aspirin resistance is only part of the story.
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Clopidogrel pretreatment (ie, before PCI as opposed to afterward) was initially understood to decrease periprocedural ischemic events in observational registries.26 Subsequently, the concept of pretreatment was validated in the Percutaneous Coronary Intervention-Clopidogrel in Unstable angina to prevent Recurrent Events (PCI-CURE) study and the Clopidogrel for the Reduction of Events During Observation (CREDO) study. Although antiplatelet effects of pretreatment are the obvious explanations for the benefit from clopidogrel, anti-inflammatory effects have also been postulated. Recent data suggest that clopidogrel lowers CD40 expression and high-sensitivity C-reactive protein (hsCRP) levels.27–29 These potential anti-inflammatory effects are more expeditiously achieved by higher loading doses.
Advanced anticoagulants such as the low-molecular-weight heparin enoxaparin or the direct thrombin inhibitor bivalirudin decrease platelet reactivity and may have some enhanced role in aspirin-resistant patients. These observations may explain the benefits of enoxaparin over unfractionated heparin in acute coronary syndromes and of bivalirudin over unfractionated heparin in PCI.
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Atheroma Burden and Embolization |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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An interesting analysis of preinterventional intravascular ultrasound (IVUS) found several important determinants of subsequent periprocedural myonecrosis.30 The amount of plaque burden, lesion site calcification, cross-sectional narrowing at the lesion and reference sites, and positive remodeling all were associated with higher CK elevation. In addition, atheroablative techniques were also associated with an increased incidence of myonecrosis.
It also appears that purposeful IVUS-guided stent overexpansion, in an effort to reduce restenosis, is associated with higher degrees of CK elevation.18 In a study of 989 consecutive patients, progressively greater degrees of CK elevation were seen with more aggressive stent-to-artery ratios. One-year mortality did not increase in parallel with the degrees of CK elevation observed in this study, however, again suggesting that at least some part of the association between CK elevation and longer-term mortality may be caused by the underlying plaque burden. Similarly, in an analysis of 1226 consecutive patients, longer stent implantation as compared with shorter stent implantation was associated with more periprocedural myonecrosis but no observed effect on 1-year mortality.31
Plaque vulnerability may also be linked to periprocedural MI; that is, plaque that contains rich lipid pools may be most friable. This, too, may explain part of the association of periprocedural embolization and late outcome, inasmuch as the patient with lipid-rich plaque is the one who is most likely to have future ischemic events. Although PCI-induced embolization is the focus of this review, spontaneous embolization is also caused by plaque that is vulnerable. Indeed, this is the basis of the majority of acute coronary syndromes. Interestingly, this phenomenon of spontaneous embolization has also been demonstrated in saphenous vein grafts.32 It is likely that this explains in part the greater proclivity of unstable thrombotic coronary plaque and vein graft atheroma to embolize during PCI.
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Inflammation and Periprocedural MI |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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It appears that baseline inflammatory marker status can predict the occurrence of periprocedural myonecrosis.33 Several studies have established the prognostic value of baseline hsCRP in patients undergoing PCI.34 In a study of elective PCI patients, Saadeddin et al found that patients with elevated baseline levels of CRP were more likely to sustain periprocedural troponin elevation.35 Thus, it is the patient with arterial inflammation at baseline who is most likely to be the embolizer; this is a key point. Perhaps this is why statin treatment before PCI has been demonstrated to improve outcomes, including periprocedural MI and mortality, so dramatically. Initially, observational studies linked pretreatment with statins (ie, statins before the procedure as opposed to only afterward) with a decreased rate of ischemic events, including mortality (Figure 4A).36,37 A lipid-lowering effect is unlikely in the time frame examined, but an anti-inflammatory mode of action may influence PCI-related events and reduce periprocedural MI (Figure 4B). In fact, it appeared that the bulk of the benefit of statin pretreatment was confined to those patients in the highest quartile of baseline hsCRP (Figure 4C). A randomized trial, Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA), prospectively validated the observations regarding the benefit of statin pretreatment, demonstrating a significant reduction in periprocedural MI.38 Studies such as Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin Or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) lend additional credence to the powerful relationships among plaque burden, inflammation, CRP reduction, and statin therapy.
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Beyond statins, other targeted anti-inflammatory agents may be useful to diminish periprocedural myonecrosis. The use of such drugs before, during, and/or after PCI may diminish myonecrosis and improve clinical outcomes.39 In addition to anti-inflammatory medications, drugs that affect vascular tone such as adenosine may be proven to be useful in decreasing periprocedural myonecrosis.40 β-blockers have been shown in some analyses to reduce periprocedural MI, whereas other analyses have disputed this finding.41,42
Although markers of inflammation such as hsCRP appear capable of predicting embolization and myonecrosis, other inflammatory markers such as soluble CD40L or myeloperoxidase may prove to be of greater utility. More likely, panels of inflammatory markers measured before PCI would provide greater incremental prognostic ability. Ultimately, the characterization of single-nucleotide polymorphisms (SNPs) and haplotypes may allow more precise prediction of an individual patient’s likelihood of periprocedural myonecrosis and may facilitate the development of strategies to minimize its occurrence.33 Polymorphisms have already been identified that affect levels of inflammatory markers and mediators.
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Devices to Reduce Periprocedural MI |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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Pharmacotherapy, such as the use of antiplatelet drugs, can reduce the impact of embolization. Preventing embolization in the first place would be even better. Embolic protection devices (EPD) capitalize on this approach.17 Interestingly, periprocedural MI was the end point principally affected in the embolic protection trials, similar to the initial data with GP IIb/IIIa inhibitors. Indeed, there is no direct evidence from a single trial that the EPD significantly reduce mortality. Nevertheless, controversy over the validity of periprocedural MI as an end point in the setting of EPD did not erupt. Unlike the debate over platelet GP IIb/IIIa blockade in the 1990s, concerns about cost are not voiced as often in this setting.
The Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) trial put mechanical embolic protection on the map.43 This trial demonstrated a significant reduction in periprocedural MI in patients undergoing PCI of bypass grafts, although it was not powered to look at reductions in mortality (Figure 5). Although SAFER investigators used a distal occlusion balloon, distal filters have also been validated as effective in reducing myonecrosis. Interestingly, the use of GP IIb/IIIa inhibitors have not convincingly been shown to be beneficial in patients undergoing bypass PCI, perhaps because the volume of emboli generated overwhelms the ability of antiplatelet therapy to "soften the blow" to the myocardium.44 Although EPD have not directly been proved to decrease mortality, other studies have shown that periprocedural MI is common in saphenous vein graft PCI, with CK elevation occurring in roughly 15% of cases.45 Even in patients without angiographic or in-hospital complications, elevated CK was associated with increased mortality, including CK elevations 1 to 5 times the ULN. Therefore, it is logical to believe that because EPD have been demonstrated to decrease periprocedural MI that occurs with vein graft PCI, and because periprocedural MI appears to be associated with increased mortality, EPD should reduce mortality, assuming a large enough study with long-term follow-up were ever to be performed.
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Embolic protection has also been used in acute MI.46 The Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberalized Debris (EMERALD) trial examined the use of the Medtronic GuardWire in patients presenting with acute ST-segment elevation MI.47 This is the area where embolic protection should seemingly shine. It is surprising that this trial did not demonstrate any clear advantage in patients who were randomized to this device. There are several possible explanations. It is conceivable that the optimal end points were not examined; however, ST-segment resolution is generally believed to be a sensitive marker of the degree of successful tissue level reperfusion. Also, nuclear perfusion scans may not be the best marker in the PCI setting. In fact, the studies of nuclear perfusion in primary PCI versus fibrinolytic trials did not show clear benefit, although it is generally agreed that PCI yields superior clinical benefit as compared with fibrinolytics. Also, the benefit of embolic protection may not manifest without longer-term follow-up, for example, to detect an improvement in LV function. Continued recovery of myocardial function after primary PCI has been documented to occur up through 3 months, so it is possible that it would take at least this long to detect any additional incremental benefit from a reduction in embolization; however, this recovery of LV function is at least somewhat dependent on the time to treatment. Another possibility has to do with the specific device. Unlike in a saphenous vein graft, a native coronary artery has branches, so a distal occlusion device may prevent embolization down the parent vessel but still permit some degree of embolic shunting down other branches; filter-based devices would help address that limitation. Of course, the embolic protection device itself may generate some degree of embolization as it initially passes through the lesion.
Newer-generation, lower-profile filters such as the Rubicon filter are much less likely to cause embolization when compared with the available, bulkier devices. This device, planned for evaluation in acute MI, may yet find clinical benefit. Proximal emboli protection devices such as the Kerberos Proximal Solutions Rinspirator or Velocimed Proxis systems may also further decrease the potential for embolization with passage of the device through the lesion and allow more complete aspiration of embolic debris. Mechanical protection may be of greatest utility in large vessels such as a vein graft or a carotid artery, where plaque volume and embolic burden are greatest, and perhaps in smaller vessels, such as coronary arteries. Here, the actual volume of debris is not as large in relationship to the distal circulation, and in this setting, pharmacotherapy is relatively more important. A final, more disturbing possibility for the lack of a positive finding in EMERALD is that in acute MI the window of time in which embolic protection may be useful may be more narrow than originally imagined. By the time most patients have reached the interventional suite, the "horse is out of the barn" and prevention of additional embolization is of minimal clinical consequence. If this were true, then it would mean that time to treatment is even more crucial and that initial pharmacological pretreatment will be necessary and, indeed, complementary to PCI with embolic protection (a strategy of facilitated primary PCI). Therefore, there may yet be a role for EPD in acute MI (Figure 6) and for EPD in high-risk non–ST-segment elevation acute coronary syndromes. Additional trials of embolic protection devices should sort out these important issues.
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Periprocedural Myonecrosis in the Setting of Bypass Surgery |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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CABG–related CK elevation is also associated with worse outcomes. This has not been an easy area to study because many cardiac surgeons are resistant to the idea of measuring myocardial necrosis after surgery. Nevertheless, a number of studies have found that elevations in CK after cardiac surgery are associated with worse outcome. The Guard During Ischemia Against Necrosis (GUARDIAN) study found a strong relationship between CK elevation >10 times the ULN and 6-month mortality.48 Although lower degrees of CK elevation were not associated with mortality in that study, with a longer follow-up, a relationship may have emerged. Other studies have found a graded increase in mortality across the full spectrum of CK elevation, including CK-MB >3 times the ULN.49 In a mechanistic study of 23 patients without previous MI who underwent CABG, infarctions were found in 18 patients.50 Contrast-enhanced MRI corroborated the occurrence of infarction in patients with elevated biochemical markers, especially those with CK-MB >5 times the ULN.
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Conclusions |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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Periprocedural myonecrosis is associated with an increased risk of adverse outcomes, including mortality. Therapies that decrease periprocedural myonecrosis such as antithrombotic and anti-inflammatory medications also appear to yield clinical benefit. In part, this may be caused by the fact that antiplatelet resistance and heightened states of arterial inflammation each predispose to periprocedural embolization and necrosis but have also themselves been independently linked to worse long-term outcomes. In addition to pharmacological methods to mitigate the effects of embolization, to decrease periprocedural myonecrosis, and to improve clinical outcomes, mechanical approaches such as embolic protection appear to also diminish myonecrosis. Although these lessons have been demonstrated most elaborately about the coronary circulation, data are being amassed in the cerebral and peripheral circulations as well, although the optimal combination of specific drugs and devices may not be constant for different applications. Refinements in pharmacotherapy and ongoing developments in embolic protection will lead to additional decrements in macro- and microembolization, less periprocedural tissue necrosis, and associated improvements in short- and long-term clinical outcomes.
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References |
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TopIntroductionPeriprocedural Myonecrosis and...Mechanisms Underlying the Risk...Devices and Periprocedural MIAspirin Resistance and...Atheroma Burden and EmbolizationInflammation and Periprocedural...Devices to Reduce Periprocedural...Periprocedural Myonecrosis in...ConclusionsReferences |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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