ORIGINAL ARTICLES

Patients at Low Risk for Periprocedural Myocardial Infarction Can Be Identified by Assessment Immediately Following Percutaneous

Ehtisham Mahmud, MD, Kevin D. Shaw, BS, William F. Penny, MD
Ehtisham Mahmud, MD, Kevin D. Shaw, BS, William F. Penny, MD
Despite advances in the technical and pharmacologic aspects of percutaneous coronary intervention (PCI), periprocedural myocardial infarction (PPMI) remains a significant complication of the procedure. Previous studies identified clinical characteristics including age, unstable angina, renal insufficiency and low operator volume to be risk factors for unsuccessful PCI and subsequent PPMI.1–3 Similarly, angiographic characteristics considered to be features placing patients at high risk for PPMI during PCI include multivessel coronary artery disease, left ventricular dysfunction, lesion complexity and presence of intracoronary thrombus.4 However, these risk factors are relatively weak, and many patients who exhibit them have excellent PCI results and vice versa. The identification of patients at low risk for PPMI has implications for post-procedure therapy, level of in-hospital care and timing of hospital discharge. We hypothesized that evaluation of the clinical and angiographic characteristics present immediately after PCI more accurately predict the risk of PPMI than those prior to intervention. Furthermore, the accuracy of this immediate post-PCI evaluation could outweigh the presence of preprocedural high-risk characteristics. Methods The study protocol was approved by the University of California, San Diego Institutional Review Board. A consecutive series of PCI patients was risk-stratified based on intraprocedural features into 3 groups as outlined below: GROUP I (PPMI not expected): uneventful PCI. Acceptable angiographic result of culprit vessel (residual stenosis 5 minutes) of the culprit vessel or a major sidebranch (> 1.5 mm) with or without visualized intracoronary thrombus; • prolonged (> 5 minutes) chest pain or ECG changes, resolved by end of the procedure; • resolved slow flow or no reflow; • bailout glycoprotein (GP) IIb/IIIa inhibitor use • prolonged hypotension (systolic blood pressure [SBP] 50% of the culprit lesion and TIMI 3 flow (unsuccessful PCI). GROUP III (PPMI expected): PCI with major intraprocedural complication. Any/all of the following in a native coronary artery or SVG: • no reflow or angiographic result with 1.5 mm) or vessel A computerized database was queried for baseline demographics and criteria for risk stratification in a consecutive series of PCI patients. All PCI procedures were carried out with the standard technique via common femoral artery access. Patients received post-procedural thienopyridine loading followed by a 30-day regimen. Patients were excluded for incomplete data or if primary PCI was carried out for an acute myocardial infarction. Total creatine kinase (CK) and CK-MB measurements were obtained pre-PCI, 6 hours post-PCI and 18–24 hours post-PCI. PPMI was defined as CK-MB > 3 times the upper limit of normal (ULN) or total CK > ULN (if CK-MB was not measured or unavailable). Group stratification was then analyzed in relation to PPMI. Data were entered in a Microsoft Excel (Seattle, Washington) database and transferred to the statistical program StatView 4.1 (Cary, North Carolina) for analysis. Results are reported as the means ± standard deviations. Statistical analyses between the 3 groups were carried out using the analysis of variance (ANOVA). A p-value of 50%, closure of a major or minor sidebranch, presence of intracoronary thrombus, slow flow/no reflow, SVG PCI, or bailout GP IIb/IIIa inhibitor use. Of greater significance, we demonstrate that patients in whom these features are absent are at an extremely low risk for a PPMI (0.7%). This approach targets the identification of potential candidates for less intensive post-procedure monitoring, limited antithrombotic therapy and early hospital discharge. We deliberately utilized conservative criteria to define a group at low risk for PPMI and our group stratification did not result in a high sensitivity for subsequent PPMI in the moderate (Group II; 9.9%) and high-risk (Group III; 45.5%) groups. However, we were able to identify a low-risk cohort, comprising two-thirds of the study population, in whom a PPMI was subsequently diagnosed in only 1 of 141 patients. This patient had an uneventful course, and elevation of CK-MB to 3 times the ULN was the only manifestation of his myocardial infarction. In comparison, preprocedural assessment was much less successful in identifying the large number of patients who remained free of PPMI. Although no patient who presented with a type A/B1 lesion in the absence of unstable angina suffered a PPMI, this low-risk cohort comprised only 19% (43 patients) of the study population. Of the remaining 180 patients who presented with unstable angina or had a type B2/C lesion, the PPMI rate was 7.2% but we were able to stratify 105 of these patients into a low-risk group for PPMI (Group I; PPMI 0.7%). Our study confirms the logical construct that prediction of freedom from PPMI is more accurately made after the procedure than before, taking into consideration any untoward (and possibly unexpected) intraprocedural event. Multiple studies have reported on the prevalence of CK-MB elevation after PCI with balloon angioplasty alone and with the use of interventional devices. Initially, Abdelmeguid et al.10 reported on the adverse long-term prognosis of low-level CK-MB elevation post-PCI, and this has subsequently been confirmed by multiple investigators.11–13 Califf et al.14 have suggested that peri-PCI CK-MB > 3 times the ULN should be treated as a non-Q wave myocardial infarction and has the same clinical significance. Therefore, current efforts have been focused on reducing periprocedural myocardial infarctions (CK-MB > 3 times the ULN) with the routine use of GP IIb/IIIa inhibitors in some cardiac catheterization laboratories (up to 80% of cases). While distal microembolization of thrombus or plaque contents is probably ubiquitous in PCI and results in elevated markers of myocardial necrosis, it is usually undetectable by clinical and angiographic assessment. In our study, PPMI was diagnosed only once in the absence of an identifiable intraprocedural event. Kini et al.15 attempted to identify clinical and angiographic predictors of CK-MB elevation post-PCI. They noted that Canadian Cardiovascular Society angina class III-IV, multivessel disease, diffuse atherosclerosis, systemic atherosclerosis, stent use and SVG interventions remained significant independent predictors of CK-MB release post-PCI. However, they noted procedural complications in only 49% of patients and felt that in the remaining patients any CK-MB elevation was unpredictable and unsuspected. This may be true, but in their analysis they were identifying patients with any CK-MB elevation above the ULN and this finding has never been shown to be of any clinical significance post-PCI. In fact, Stone et al.16 suggest that increase in mortality with peri-PCI myocardial infarction only occurs at CK-MB > 8 times the ULN. In our study, we specifically focused on the identification of patients who had a PPMI defined as the CK-MB > 3 times the ULN or total CK > ULN if CK-MB was unavailable. Blankenship et al.17 recently noted that a large number of enzymatically defined myocardial infarctions (CK-MB > 3 times the ULN) occurred in the ESPRIT trial in the absence of conventionally reported in-lab angiographic complications. In their ESPRIT subanalysis, eighty-nine percent of the patients were identified as free of angiographic complications, but the PPMI rate was 6.5% in this group. In comparing this conclusion to our findings, it should be noted that our assessment is not solely angiographic but also clinical, including episodes of sustained angina and ECG changes which were not included as higher risk indicators for PPMI in the ESPRIT subanalysis by Blankenship et al. Second, the approach we have taken is to identify patients with an uneventful PCI, not just one free of defined angiographic “complications” e.g., a procedure with transient coronary flow diminution but normal coronary flow at the completion of the procedure would be judged as being at a higher risk for PPMI and stratified to the moderate risk Group II. This is the first study to utilize pre- and immediate post-procedural clinical and angiographic characteristics to identify a group of patients at very low risk for PPMI. Utilizing a conservative design, we were able to stratify approximately two-thirds of our study population, and over half the patients with high-risk features on pre-procedural evaluation, into this very low-risk group. In the present study, this group of patients included a high percentage of patients with unstable angina (41.9%) and type B2/C lesions (55%). Furthermore, these results were obtained with infrequent use of GP IIb/IIIa inhibitors (10.1%) in this group. However, it is important to note that 13 patients (18.3%) in Group II were stratified in that group due to bailout GP IIb/IIIa inhibitor use (predominantly for visible thrombus or distal embolization). Prospective utilization of GP IIb/IIIa inhibitors in all patients may have enabled more patients to be stratified to Group I. This suggests that while GP IIb/IIIa inhibition may improve procedural results (and make more procedures uneventful), the absence of a PPMI following an uneventful procedure is unlikely to be dependent upon sustained use of parenteral GP IIb/IIIa inhibitors. Study limitations. Post-PCI CK/CK-MB measurements were obtained at 6 hours and 18–24 hours after the procedure, capturing early and later rises of CK and CK-MB, while a peak CK or CK-MB could have been missed for some patients. Systematic measurements of CK/CK-MB every 6–8 hours post-PCI could have helped address this issue. Thienopyridine preloading was not routinely done and this has the potential to overestimate the rate of PPMI in the study population. Conclusions. We demonstrate that immediate post-PCI evaluation of the combination of clinical and angiographic characteristics can help in accurately predicting the likelihood of PPMI. A group of patients at low risk for PPMI can be identified based on immediate post-PCI assessment regardless of the preprocedural clinical or angiographic presentation. This group of patients is unlikely to benefit from prolonged GP IIb/IIIa inhibitor use or post-PCI hospitalization. In this era of cost containment, a prospective randomized trial could help in clarifying this issue.
References
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