Some patients presenting with ST-segment elevation myocardial infarction (STEMI) have complete ST resolution in the electrocardiogram, which may be clinical useful in the triage of patients with STEMI. However, the importance of complete ST resolution in these patients remains uncertain. Thus, the purpose was to describe the prognosis of patients with complete ST resolution before primary percutaneous coronary intervention (PCI). Continuous ST monitoring from arrival until 90 minutes after PCI was performed in 933 patients with STEMI. Complete ST resolution was defined as no residual significant ST elevations before intervention. The patients were followed clinically for 5.5 years (range 0 to 6.8 years). Infarct size and myocardial salvage were assessed in a subgroup of patients (n = 221) by cardiovascular magnetic resonance. Complete ST resolution was observed in 24% of the patients, who had a higher incidence of Thrombolysis In Myocardial Infarction grade 2/3 flow before intervention (64% vs 24%), smaller infarct size (6% vs 11%), and higher myocardial salvage index (0.82 vs 0.69; all p <0.001) compared with patients with continuous ST elevations. Complete ST resolution was associated with a significantly lower rate of the composite end point of all-cause death and admission for heart failure (14% vs 22%; p = 0.006) although it only tended to be an independent predictor in a multivariate analysis (hazard ratio 0.69, 95% CI 0.49 to 1.06; p = 0.09). In conclusion, compared to patients without incomplete ST resolution, patients with STEMI and complete ST resolution before primary PCI have a higher incidence of normalized epicardial flow before PCI, a larger myocardial salvage and smaller infarct size after the procedure and presumably improved long-term outcome compared with incomplete ST resolution.
Patients with chest pain and significant ST elevations in the electrocardiogram (ECG) are considered to have ST-segment elevation myocardial infarction (STEMI), and the recommended treatment in these patients are immediately transferal for primary percutaneous coronary intervention (PCI). However, ST elevation is a dynamic process and after reperfusion the ST elevation is gradually diminished (ST resolution), which is a marker of the epicardial and microvascular perfusion and prognosis. In some patients, ST elevation transiently increases during primary PCI, which is also related to impaired myocardial perfusion and worse clinical outcome. In contrast, little is known about the ST change before intervention in patients with STEMI and some patients have normalized the ST elevations before intervention (complete ST resolution). Complete ST resolution before PCI is related to smaller release of cardiac biomarkers and smaller perfusion defect on single-photon emission computerized tomography (SPECT). It may thus be hypothesized that these patients represent a low-risk population, and that this ECG pattern may be used to risk stratify the patients on arrival at the coronary care unit before primary PCI. In patients treated with primary PCI, complete ST resolution before PCI has only been studied in a limited number of patients so the clinical importance of the pattern is uncertain. The purpose of this study was to compare the infarct size, myocardial salvage, and clinical outcome in patients with STEMI with complete ST resolution before primary PCI compared to those with incomplete ST resolution.
Methods
This study includes patients pooled from 2 randomized studies. One study evaluated the effect of distal protection and bare-metal versus drug-eluting stent in the setting of primary PCI (Drug Elution and Distal Protection in Acute Myocardial Infarction) and included 626 patients from May 2005 to December 2006. The other study evaluated the effect of adjuvant exenatide treatment during primary PCI (ischemic postconditioning II) and included 387 patients from January 2009 to December 2009. All patients were evaluated clinically, whereas analysis of infarct size, area at risk, and myocardial salvage was performed using cardiovascular magnetic resonance (CMR) scan in patients from the ischemic postconditioning II trial.
The inclusion and exclusion criteria were described previously. In brief, patients with STEMI were eligible if they were aged ≥18 years and presented to the catheterization laboratory within 12 hours after the onset of chest pain. The initial ECG was obtained either in the ambulance or at the referring hospital, and STEMI was defined as significant ST elevation measured at the J point in at least 2 contiguous leads (2 mm in V1 to V3 or 1 mm in all other leads). Patients were excluded in case the coronary angiogram or cardiac biomarkers did not confirm the diagnosis. All included patients were treated with aspirin 300 mg orally; clopidogrel 300 to 600 mg orally; and unfractionated heparin 10.000 units intravenously before PCI. Primary PCI was performed according to current guidelines, and bivalirudin/glycoprotein IIb/IIIa receptor antagonists were administered at the discretion of the operator. Unless a contraindication was present, the patients were treated with clopidogrel 75 mg daily for 12 months and aspirin 75 mg daily indefinitely. The studies were performed according to the Declaration of Helsinki, and all patients gave their written consent before inclusion. The Danish National Committee on Biomedical Research Ethics approved the protocol for all studies.
On arrival at the catheterization laboratory continuous 12-lead ST monitoring was initiated and continued for a minimum of 90 minutes after the primary PCI. The software generated a complete 12-lead ECG when the ST deviated with >0.1 mm for at least 2.5 minutes. The magnitude of ST elevation was measured by a computer software at the J point + 1/16 of the RR interval and used to detect ST deviations. Complete ST resolution was defined as no residual significant ST-segment elevations in all 12 ECG leads before the time of first wire. The lead with maximum ST elevation before intervention was used to determine baseline ST elevation. In the same lead, the maximum ST elevation during the primary PCI procedure (from first wire crossing to the last angiogram) was registered, and the ST change during reperfusion was evaluated as the maximum ST elevation during the procedure minus baseline ST elevation. An ST peak was defined as an increase in ST elevation ≥1 mm lasting ≥2.5 minutes. The ST changes were analyzed blinded to all other data using dedicated automatic computer software.
Our CMR protocol and image analyses in patients with STEMI have been described previously. Briefly, the first CMR scan was performed 1 to 7 days after the primary PCI, and the second CMR 3 months ± 3 weeks after discharge. The myocardial area at risk was assessed on the first CMR scan as myocardial edema using a T2-weighted short tau inversion recovery sequence. On the second CMR examination, delayed enhancement images were obtained to determine the final infarct size using an ECG-triggered inversion-recovery sequence. Left ventricular (LV) volumes were measured, and LV function assessed from both CMR examinations. The infarct size, defined as the hyperenhanced myocardium on the delayed enhancement images, was determined by an automatic approach as previously described. A myocardial area was regarded as hyperintense whenever the signal intensity was >2 SDs of the signal intensity in the normal myocardium. The salvage index was calculated as follows: (area at risk−infarct size)/area at risk.
The clinical outcome of our patients was assessed as all-cause mortality and admission for heart failure. Mortality events were registered according to previous definitions. Admission for heart failure was defined as hospital admission owing to peripheral edema or pulmonary congestion treated with antidiuretics, or admission for implantation of a prophylactic implantable cardioverter–defibrillator due to a postinfarction left ventricular ejection fraction (LVEF) <35%. A reviewer blinded to all data including ECG data, angiographic measurements, and randomization carefully evaluated all readmissions during the follow-up period by evaluating all hospital files. All patients were followed until the last patients included in the particular study were followed for minimum of 5 years, unless the patient died before.
All statistical analyses were performed with SPSS software version 20 (SPSS inc., Chicago, Illinois). A 2-sided p value <0.05 was considered statistically significant. Categorical variables were compared using the chi-square or Fisher’s exact test and continuous variables using Student t test or Mann–Whitney’s test as appropriate. To identify the independent predictors for complete ST resolution before PCI a logistic regression analysis was performed including any baseline variable with p ≤0.10. Multivariate linear regression models were performed with myocardial salvage index and final infarct size by CMR as dependent variables. In these models, any variable that was independently associated with the presence of complete ST resolution before PCI were included together with any known predictor of myocardial salvage index (pre-PCI Thrombolysis In Myocardial Infarction [TIMI] flow 0/1, preinfarction angina, treatment with glycoprotein IIb/IIa inhibitors, and treatment with exenatide) and final infarct size (pre-PCI TIMI flow 0/1 and anterior infarct location). Moreover, the infarct size was adjusted for area at risk in a regression analysis. To evaluate the prognostic importance of complete ST resolution before PCI, Kaplan–Meier and univariate Cox regression analyses were performed for all-cause mortality and all-cause mortality + admission for heart failure. Multivariate Cox regression analyses were also performed using any variable that was independently associated with the presence of complete ST resolution before PCI and any known predictors for outcome in patients with STEMI (age, diabetes mellitus, previous PCI, anterior infarct location, pre-PCI TIMI flow, and multivessel disease). The Cox regression assumptions were checked for each variable by interaction, linearity, and visually for proportionality.
Results
A total of 1,013 patients with STEMI were randomized in the 2 studies, and 80 patients were excluded from the present study because either they turned out not have an STEMI or their ECG data were insufficient for the analysis, leaving 933 patients to be included in the present study. Baseline characteristics are presented in Table 1 . Complete ST resolution before PCI had a higher incidence of TIMI 2/3 flow before and after the intervention. Patients with complete ST resolution before PCI developed significantly smaller infarct size ( Table 2 ), also when adjusted for area at risk (p = 0.002). Accordingly, myocardial salvage index and LVEF were higher in these patients ( Table 2 ). In multivariate models, complete ST resolution before PCI was an independent predictor for both final infarct size and myocardial salvage index ( Table 3 ).
| No complete ST-resolution (n=708) | Complete ST-resolution (n=225) | P | |
|---|---|---|---|
| Baseline | |||
| Age, years | 62 ±12 | 62 ±12 | 0.34 |
| Men | 75 % | 74 % | 0.79 |
| Diabetes Mellitus | 10 % | 10 % | 0.80 |
| Hypertension | 34 % | 35 % | 0.69 |
| Hypercholesterolemia | 31 % | 24 % | 0.05 |
| Previous PCI | 6 % | 5 % | 0.82 |
| Preinfarction angina pectoris | 16 % | 20 % | 0.16 |
| Symptoms to balloon, minutes | 172 (126-260) | 209 (140-310) | <0.001 |
| Anterior wall infarct | 43 % | 46 % | 0.42 |
| Angiography | |||
| Culprit vessel (Right/LAD/Cx) | 47/41/12 % | 42/43/15 % | 0.28 |
| Pre-PCI TIMI 0/1 flow | 64 % | 23 % | <0.001 |
| Rentrop grade 2/3 ∗ | 19 % | 14 % | 0.14 |
| Multivessel coronary disease | 29 % | 35 % | 0.14 |
| Visual coronary thrombus | 80 % | 65 % | <0.001 |
| Treatment | |||
| Treatment with glycoprotein IIb/IIIa inhibitor | 95 % | 87 % | <0.001 |
| Stent implantation | 95 % | 96 % | 0.85 |
| Length of stented segment (mm) | 20 | 19 | 0.46 |
| Stent diameter (mm) | 3.5 | 3.6 | 0.66 |
| Outcomes | |||
| Post-PCI TIMI 3 flow | 90 % | 97 % | 0.001 |
| Peak CKMB (μg/l) | 208 (107-370) | 104 (38-190) | <0.001 |
| Peak troponin T (μg/l) | 5.5 (2.8-9.6) | 2.5 (0.8-4.7) | <0.001 |
| ST peak † | 29 % | 19 % | 0.008 |
∗ Data only available from 630 patients.
† ST peak, an increase in the ST-segment elevation ≥0.1 mm lasting ≥2.5 minutes during the PCI procedure.
| N | No complete ST- resolution | N | Complete ST- resolution | P | |
|---|---|---|---|---|---|
| Area at risk (%LV) | 183 | 33 ±11 | 38 | 27 ±11 | 0.002 |
| Final infarct size (g) | 181 | 14 ±11 | 40 | 8 ±9 | <0.001 |
| Final infarct size (%LV) | 181 | 11 ±6 | 40 | 6 ±6 | <0.001 |
| Salvage index ∗ | 160 | 0.69 ±0.14 | 34 | 0.82 ±0.12 | <0.001 |
| LVEF acute (%) | 183 | 52 ±10 | 38 | 57 ±11 | 0.003 |
| LVEF 3 mo (%) | 181 | 55 ±10 | 40 | 61 ±7 | <0.001 |
∗ Salvage index: (area at risk (g)−infarct size (g))/area at risk (g).
| Myocardial salvage index | Final infarct size | |||
|---|---|---|---|---|
| β | P | β | P | |
| Pre-PCI TIMI flow 0/1 | -0.32 | <0.001 | 0.30 | 0.001 |
| Complete ST-resolution before PCI | 0.22 | 0.001 | -0.19 | 0.004 |
| Pre-infarction angina pectoris | 0.14 | 0.028 | – | – |
| Anterior infarct location | – | – | 0.23 | <0.001 |
Pre-PCI TIMI flow (0/1 vs 2/3) was not related to either infarct size (p = 0.07) or myocardial salvage index (p = 0.18) in the patients with complete ST resolution before PCI but was associated with both infarct size (p <0.001) and myocardial salvage index (p <0.001) in patients with continuous ST elevation before PCI. However, there was no interaction between complete ST resolution before PCI and pre-PCI TIMI flow in terms of infarct size (p = 0.31) or myocardial salvage index (p = 0.19).
During the follow-up period of median 5.5 years (range 0 to 6.8 years), a total of 123 patients (13.1%) died from any cause, 65 (7.1%) were admitted for heart failure and 49 (5.3%) developed a new myocardial infarction. Complete ST resolution before PCI was associated with a significantly lower rate of all-cause mortality + admission for heart failure (13.7% vs 22.2%; Figure 1 ) with hazard ratio 0.59 (95% CI 0.40 to 0.87; p = 0.007). Complete ST resolution before PCI was not significantly associated with death alone (hazard ratio 0.83, 95% CI 0.54 to 1.27, p = 0.39; Figure 1 ). In the multivariate analysis, complete ST resolution had a strong trend toward being an independent predictor of all-cause mortality and admission for heart failure ( Table 4 ).
