Circulation. 2005;112:906-922
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
Deepak L. Bhatt, MD;
Eric J. Topol, MD
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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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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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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Figure 1. Data from EPIC study demonstrated relationship between even moderate degrees of periprocedural myonecrosis and subsequent mortality. Reprinted with permission from Journal of the American Medical Association.4 Copyright 1997, American Medical Association. All rights reserved.
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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
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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Figure 2. Several different factors increase risk of periprocedural myonecrosis. Volume and composition of atheroma, arterial inflammation, resistance to antiplatelet therapy, and interventional device used contribute to occurrence of periprocedural MI. Ultimately, through both indirect and direct means, periprocedural myonecrosis may lead to cardiovascular morbidity (eg, LV dysfunction, arrhythmia) and mortality. EPD indicates embolic protection devices; GP, glycoprotein.
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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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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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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.
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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In an interesting analysis, Chen et al found that patients undergoing
elective PCI who were classified as aspirin resistant at baseline
using the VerifyNow
TM (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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Figure 3. Patients with evidence of aspirin resistance at baseline are much more likely than patients without evidence to have periprocedural myonecrosis during elective PCI. This tendency would likely be even greater in patients presenting for PCI with acute coronary syndromes. Reprinted with permission from Journal of the American College of Cardiology.24 Copyright 2004, American College of Cardiology Foundation.
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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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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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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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Figure 4. Treatment with statins before the procedure appears to reduce the rate of mortality (A) in patients undergoing PCI. Reprinted with permission from Circulation.36 Copyright 2002, Lippincott Williams & Wilkins. Rate of periprocedural MI (B) is also reduced. Apparent benefit in 1-year mortality (C) is most notable in patients with elevated baseline hsCRP. Reprinted with permission from Circulation.37 Copyright 2003, Lippincott Williams & Wilkins.
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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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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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Figure 5. Data from the SAFER trial demonstrated the value of embolic protection in saphenous vein graft intervention on periprocedural myonecrosis and a number of associated end points with the Medtronic GuardWire. Reprinted with permission from Circulation.43 Copyright 2002, Lippincott Williams & Wilkins.
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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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Figure 6. A, Angiogram of occluded right coronary artery with large thrombus burden in patient with acute inferior MI complicated by hypotension and complete heart block. B, Angiogram after placement of TAXUS drug-eluting stent with Boston Scientific FilterWire in off-label fashion. C, Large amount of atherothrombotic material captured by filter. D, Material largely thrombotic in nature, although there is also some atheroma.
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Periprocedural Myonecrosis in the Setting of Bypass Surgery
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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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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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Response to Bhatt and Topol
Donald E. Cutlip, MD; Richard E. Kuntz, MD, MSc
We congratulate Drs Bhatt and Topol on their excellent review of the available data regarding the significance of CK-MB elevation after PCI. Although their review and ours reach different conclusions, it may be helpful to the clinician faced with this dilemma to consider the points on which the 2 articles seemingly agree. There is agreement that large CK-MB elevations, especially if associated with major procedure-related complications, increase mortality. Both articles also agree that lesser CK-MB elevations probably do not have a causal
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Introduction
Periprocedural Myonecrosis and...