Important determinants of incomplete ST-segment recovery in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have been incompletely characterized. Early risk stratification could identify patients with STEMI and incomplete ST-segment recovery who may benefit from adjunctive therapy. For the present study, we analyzed 12-lead electrocardiograms from 2,124 patients with STEMI who underwent primary PCI at our institution from 2000 to 2007. ST-segment recovery was defined as percent change in cumulative ST-segment deviation between preprocedural and immediately postprocedural electrocardiograms and categorized as incomplete when <50%. A total of 1,032 patients (49%) had incomplete ST-segment recovery. After multivariable adjustment, age >60 years (adjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06 to 1.54, p = 0.011), diabetes mellitus (OR 1.36, 95% CI 1.02 to 1.82, p = 0.034), left anterior descending coronary artery–related STEMI (OR 1.92, 95% CI 1.61 to 2.30, p<0.001), and multivessel disease (OR 1.34, 95% CI 1.10 to 1.63, p = 0.004) were independent predictors of incomplete ST-segment recovery. Current smoking (OR 0.79, 95% CI 0.65 to 0.95, p = 0.013) and a preprocedural Thrombolysis In Myocardial Infarction grade <3 flow (OR 0.70, 95% CI 0.53 to 0.93, p = 0.014) were inversely related to ST-segment recovery. Incomplete ST-segment recovery was a strong predictor of long-term mortality (hazard ratio 2.07, 95% CI 1.59 to 2.69, p <0.001) in addition to identified characteristics that independently predicted incomplete ST-segment recovery. In conclusion, incomplete ST-segment recovery at the end of PCI occurred significantly more often in the presence of an age >60 years, nonsmoking, diabetes mellitus, left anterior descending coronary artery–related STEMI, multivessel disease, and preprocedural Thrombolysis In Myocardial Infarction grade 3 flow. Patients with STEMI and these clinical features are at increased risk of impaired myocardial salvage and are appropriate candidates for adjunctive therapy.
In patients with ST-segment elevation myocardial infarction (STEMI), thrombolysis has been replaced by primary percutaneous coronary intervention (PCI) as the preferred treatment strategy. Nevertheless, primary PCI only facilitates myocardial reperfusion by restoring coronary epicardial flow. Microvascular dysfunction is a common complication after “successful” primary PCI and may be induced by distal embolization, reperfusion injury, or bioactive factors causing vasoconstriction downstream. Microvascular dysfunction is quantified by ST-segment recovery as measured on the 12-lead electrocardiogram (ECG). ST-segment recovery is a strong and independent predictor of adverse cardiac remodeling and increased mortality. As a result, incomplete ST-segment recovery often is a reason to administer adjunctive therapy to increase suboptimal microvascular reperfusion. Despite the value of ST-segment recovery as a predictor of outcome, little is known about which factors determine ST-segment recovery itself. Knowledge of powerful clinical predictors of incomplete ST-segment recovery could increase early risk stratification and thus improve therapy in patients with STEMI undergoing primary PCI. Therefore, we sought to identify independent predictors of incomplete ST-segment recovery in an unselected cohort of patients with STEMI undergoing primary PCI.
Methods
Data analyzed in our study were obtained from patients with STEMI who underwent primary PCI at the Academic Medical Center, University of Amsterdam (Amsterdam, The Netherlands), from November 1, 2000, to January 1, 2007. In general, primary PCIs were performed according to current guidelines. Patients with an indication for primary PCI received aspirin (500 mg) and unfractionated heparin (5,000 IU) during transportation to the catheterization laboratory. During 2005, clopidogrel 300 or 600 mg was added as pretreatment before primary PCI. Glycoprotein IIb/IIIa inhibitors were not routinely used but administered during the procedure at the discretion of the operator.
We obtained information on 1-year vital status from the institutional follow-up database of patients after PCI. Patients are surveyed 1 year after PCI by a mailed, self-administered questionnaire. Follow-up information was synchronized with computerized, long-term mortality records from the National Death Index and local authorities, which were updated until October 2008. We reviewed outpatients’ files and contacted general practitioners by telephone in case of conflicting or missing data. Follow-up could be obtained in 2,103 of 2,124 patients (99%).
From the local electronic database at the catheterization laboratory, we abstracted baseline demographic variables and procedural and angiographic information that had been prospectively collected and entered by specialized nurses and interventional cardiologists concurrently with routine patient care. This information included an operator’s online assessment of anterograde flow using the Thrombolysis In Myocardial Infarction (TIMI) scale, extent of coronary artery disease, and timing of re-establishment of anterograde flow through the infarct-related artery.
We retrospectively sought to collect 12-lead ECGs recorded immediately before arterial puncture at the catheterization laboratory for all patients with STEMI who underwent primary PCI at our institution. These preprocedural ECGs were compared with 12-lead ECGs recorded at the time of last contrast injection (i.e., immediate postprocedural ECGs), before patients were transferred to the coronary or intensive care unit.
ECGs of included patients were analyzed by 1 investigator (NV), unaware of the clinical, angiographic, and outcome data. ST-segment deviation was measured with a handheld caliper and magnifying glass at 80 ms after the J-point in all available leads. ST-segment deviation was measured to the nearest 0.05 mV with the TP segment as the preferred isoelectric baseline. We defined ST-segment recovery as the percent change of summed ST-segment deviations on the 12-lead ECG immediately after PCI compared to the ECG before PCI. The primary outcome of this analysis was the occurrence of incomplete ST-segment recovery. We defined ST-segment recovery as incomplete if <50%.
All consecutive patients with STEMI who underwent primary PCI at our institution according to our digital database were eligible for inclusion. We excluded patients who underwent primary PCI of the left main coronary artery or a bypass graft because of the distinctive electrocardiographic pattern observed in such cases. Patients from whom a preprocedural or postprocedural ECG could not be retrieved were excluded from this analysis. Furthermore, patients with electrocardiographic recordings containing a complete left bundle branch block, sustained ventricular arrhythmias (among others, an accelerated idioventricular rhythm), a paced rhythm, or severe artifacts that prohibit accurate ST-segment evaluation were excluded. For patients with STEMI who were referred for primary PCI but in whom we observed normalization of ST-segment elevation on arrival at the catheterization laboratory, ST-segment recovery analysis after PCI was not appropriate, and therefore these patients were also excluded.
We assessed the association between ST-segment recovery, clinical characteristics (age, gender, hypertension, hypercholesterolemia, diabetes mellitus, current smoking, previous MI, coronary artery bypass grafting, or PCI), and procedural characteristics (left anterior descending coronary artery [LAD]–related MI, preprocedural and postprocedural TIMI-graded flow, use of glycoprotein IIb/IIIa inhibitors, and intra-aortic balloon pump insertion) using binary logistic regression. This association was studied in crude and multivariable models. Backward selections were used to select the most parsimonious set of predictive variables and results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Total ischemic time and body mass index were not included in multivariable analyses because of a considerable amount of missing values.
To construct a ST-segment recovery prediction model, a simple risk score was calculated. We assigned points according to the adjusted OR of each predictive characteristic that would be available after emergency coronary angiography but before PCI. A score was calculated by adding up points corresponding to each patient’s risk factors. Hereafter, we defined low-, intermediate-, and high-risk groups according to this risk score.
Kaplan–Meier estimates according to category of ST-segment recovery were determined and compared with the use of the log-rank test. To determine whether the prognostic value of ST-segment recovery was independent of associated patient and procedural characteristics, these variables (age >60 years, smoking, diabetes mellitus, LAD-related MI, multivessel disease, TIMI-graded flow <3 before PCI, use of IIb/IIIa inhibitors, and TIMI-graded flow <3 after PCI) and ST-segment recovery were concurrently entered in a Cox regression model. Results were expressed as hazard ratios with 95% CIs.
Normally distributed, continuous variables are expressed as mean ± SD, and other continuous data are expressed as median with interquartile range. All categorical variables are depicted using relative frequency distributions. Characteristics of patients with complete and incomplete ST-segment recovery were compared using the chi-square test for categorical variables and the Student’s t test or Mann–Whitney U test for continuous variables. For all tests, differences were considered significant if the 2-sided p value was <0.05. All analyses were performed using SPSS 16.0 (SPSS, Inc., Chicago, Illinois).
Results
A total of 3,185 consecutive patients with STEMI underwent primary PCI at our institution from November 1, 2000, to January 1, 2007. We excluded 67 patients who underwent primary PCI of the left main coronary artery or of a bypass graft. ECGs of 508 patients could not be retrieved. Electrocardiographic exclusion criteria were applicable in 132 of 2,610 patients with a complete set of ECGs. Preprocedural ST-segment normalization had occurred in 354 patients. Thus, 2,124 patients could be included in this analysis. Baseline and procedural characteristics of these patients are presented in Table 1 . Incomplete ST-segment recovery occurred in 1,032 of 2,124 patients (49%).
| Variable | Included Patients |
|---|---|
| (n = 2,124) | |
| Age (years), mean ± SD | 61 ± 13 |
| Men | 72% |
| Current smoker ⁎ | 46% |
| Diabetes mellitus † | 11% |
| Hypertension ‡ | 31% |
| Hypercholesterolemia § | 22% |
| Previous myocardial infarction | 11% |
| Previous coronary bypass grafting | 1% |
| Previous percutaneous coronary intervention | 7% |
| Left anterior descending coronary artery–related myocardial infarction | 46% |
| Multivessel disease | 31% |
| Preprocedural Thrombolysis In Myocardial Infarction grade 3 flow | 11% |
| Stent inserted | 87% |
| Glycoprotein IIb/IIIa inhibitor used | 31% |
| Postprocedural Thrombolysis In Myocardial Infarction grade 3 flow | 89% |
| Intra-aortic balloon counterpulsation used | 7% |
| Total ischemic time (minutes) (25th, 75th percentile) ∥ | 172 (130, 250) |
| Peak creatine kinase-MB fraction (μg/L) (25th, 75th percentile) ¶ | 248 (131, 435) |
⁎ Defined as patients who smoke ≥1 tobacco product per day or smoked in the 30 days before admission.
† Defined as a documented history of diabetes mellitus diagnosed and/or treated by a physician.
‡ Defined as a documented history of hypertension diagnosed and/or treated by a physician.
§ Defined as a documented history of hypercholesterolemia diagnosed and/or treated by a physician.
∥ Data available in 1,897 patients.
The left side of Table 2 displays the univariable relation between occurrence of incomplete ST-segment recovery and various patient characteristics. Incomplete ST-segment recovery was significantly more frequent in older patients and in patients with diabetes mellitus or hypertension, with unadjusted ORs of 1.52 (95% CI 1.28 to 1.80, p <0.001), 1.58 (95% CI 1.20 to 2.08, p = 0.001), and 1.23 (95% CI 1.02 to 1.48, p = 0.03), respectively. Patients who were smokers at the time of primary PCI significantly less often had incomplete ST-segment recovery compared to nonsmoking counterparts (unadjusted OR 0.65, 95% CI 0.55 to 0.77, p <0.001). In multivariable logistic regression, age >60 years, nonsmoking status, and presence of diabetes mellitus were independently predictive of incomplete ST-segment recovery ( Table 2 , right side).
| Variable | Incomplete ST-Segment Recovery | Univariable Analysis | Multivariable Analysis ⁎ | ||||
|---|---|---|---|---|---|---|---|
| OR | CI | p Value | OR | CI | p Value | ||
| Age (years) | |||||||
| >60 | 53% (603/1,128) | 1.52 | 1.28–1.80 | <0.001 | 1.28 | 1.06–1.54 | 0.011 |
| Men | 49% (744/1,531) | 1.00 | 0.83–1.21 | 0.99 | — | — | — |
| Current smoker | 43% (421/984) | 0.65 | 0.55–0.77 | <0.001 | 0.79 | 0.65–0.95 | 0.013 |
| Diabetes mellitus | 59% (138/235) | 1.58 | 1.20–2.08 | 0.001 | 1.36 | 1.02–1.82 | 0.034 |
| Hypertension | 52% (343/658) | 1.23 | 1.02–1.48 | 0.03 | — | — | — |
| Hypercholesterolemia | 47% (219/465) | 0.93 | 0.75–1.14 | 0.47 | — | — | — |
| Previous myocardial infarction | 51% (122/237) | 1.14 | 0.87–1.49 | 0.35 | — | — | — |
| Previous coronary bypass grafting | 53% (8/15) | 1.21 | 0.44–3.35 | 0.71 | — | — | — |
| Previous percutaneous coronary intervention | 47% (69/146) | 0.94 | 0.68–1.32 | 0.74 | — | — | — |
⁎ Backward selection model including patient characteristics and available procedural characteristics: left anterior descending coronary artery–related myocardial infarction, multivessel disease, preprocedural Thrombolysis In Myocardial Infarction grade <3 flow, stent insertion, glycoprotein IIb/IIIa inhibitor use, postprocedural Thrombolysis In Myocardial Infarction grade <3 flow, and intra-aortic balloon counterpulsation used.
Table 3 presents univariable and multivariable associations between available procedural characteristics and occurrence of incomplete ST-segment recovery. As shown on the left side, incomplete ST-segment recovery was significantly more frequent in patients with LAD-related MI (unadjusted OR 1.86, 95% CI 1.57 to 2.21, p <0.001), in patients with multivessel disease (unadjusted OR 1.36, 95% CI 1.13 to 1.64, p = 0.001), in patients with postprocedural TIMI-graded flow <3 (unadjusted OR 2.43, 95% CI 1.81 to 3.26, p <0.001), and in patients with a need for intra-aortic balloon pump insertion (unadjusted OR 1.78, 95% CI 1.26 to 2.52, p = 0.001). Also, incomplete ST-segment recovery was more common in patients who received glycoprotein IIb/IIIa inhibitors during PCI, with an unadjusted OR of 1.51 (95% CI 1.25 to 1.82, p <0.001). Patients with TIMI-graded flow <3 before PCI showed a trend toward less frequent incomplete ST-segment recovery (unadjusted OR 0.78, 95% CI 0.60 to 1.03, p = 0.08). After multivariable modeling, ORs of LAD-related MI, multivessel disease, glycoprotein IIb/IIIa inhibitor use, and TIMI-graded flow <3 after PCI were sustained, whereas the association between intra-aortic balloon pump insertion and incomplete ST-segment recovery lost significance ( Table 3 , right side). The association between preprocedural TIMI-graded flow <3 and incomplete ST-segment recovery was more outspoken in multivariable analysis, with an adjusted OR of 0.70 (95% CI 0.53 to 0.93, p = 0.014).
| Variable | Incomplete ST-Segment Recovery | Univariable Analysis | Multivariable Analysis ⁎ | ||||
|---|---|---|---|---|---|---|---|
| OR | 95% CI | p Value | OR | 95% CI | p Value | ||
| Left anterior descending coronary artery–related myocardial infarction | 57% (553/971) | 1.86 | 1.57–2.21 | <0.001 | 1.92 | 1.61–2.30 | <0.001 |
| Multivessel disease | 54% (351/651) | 1.36 | 1.13–1.64 | 0.001 | 1.34 | 1.10–1.63 | 0.004 |
| Stent inserted | 48% (894/1,858) | 0.86 | 0.67–1.11 | 0.25 | — | — | — |
| Glycoprotein IIb/IIIa inhibitor used | 56% (361/648) | 1.51 | 1.25–1.82 | <0.001 | 1.33 | 1.09–1.62 | 0.004 |
| Intra-aortic balloon counterpulsation used | 62% (89/144) | 1.78 | 1.26–2.52 | 0.001 | — | — | — |
| Preprocedural Thrombolysis In Myocardial Infarction grade flow | |||||||
| <3 | 48% (905/1,889) | 0.78 | 0.60–1.03 | 0.08 | 0.70 | 0.53–0.93 | 0.014 |
| Postprocedural Thrombolysis In Myocardial Infarction grade flow | |||||||
| <3 | 68% (153/226) | 2.43 | 1.81–3.26 | <0.001 | 2.27 | 1.66–3.09 | <0.001 |
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