The prognostic value of myocardial infarct size estimation by QRS scoring in patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI) is unclear. The standard 32-point Selvester QRS score on the discharge electrocardiogram (each point ∼3% left ventricular mass) was calculated in 4,113 patients with STEMI who underwent primary PCI and survived to hospital discharge in the APEX-AMI trial. QRS scores were divided into tertiles, i.e., ≤3 (<10% myocardium), 4 to 7 (10% to 21% myocardium), and ≥8 (>21% myocardium). Adjusted associations between QRS score and 90-day outcomes (death and composite of death/congestive heart failure (CHF)/shock) were examined. Higher QRS scores were associated with male gender, higher heart rate, worse Killip class, noninferior infarct location, greater ST-segment deviation, and longer times to reperfusion. Higher QRS scores were also associated with impaired culprit artery flow before and after PCI and more frequent multivessel disease. Adverse outcomes occurred more often in patients with higher QRS scores (90-day death: 1.9%, QRS score 0 to 3; 3.4%, 4 to 7; 4.9%, ≥8; 90-day death/shock/CHF: 4.5%, 0–3; 7.8%, 4 to 7; 12.1%, ≥8). After multivariable adjustment, patients with higher QRS scores remained more likely to develop an adverse outcome versus those with QRS scores ≤3 (score 4 to 7, hazard ratios [HR] for death 2.08, 95% confidence interval [CI] 1.26 to 3.41; HR for death/CHF/shock 2.00, 95% CI 1.26 to 3.17; score ≥8, HR for death 2.57, 95% CI 1.56 to 4.24, HR for death/CHF/shock 2.93, 95% CI 1.84 to 4.67). In conclusion, infarct size as estimated by QRS scoring at hospital discharge is an independent and prognostically relevant metric in patients with STEMI undergoing primary PCI.
The standard 12-lead electrocardiogram (ECG) can be used to estimate myocardial infarct size by applying the Selvester 54-criteria/32-point QRS scoring system. Previous studies of QRS scoring have shown good correlation with anatomic findings after death (each point represents infarction of ∼3% of left ventricle), left ventricular ejection fraction, and biochemical measurements of infarct size. More recently, QRS score has been shown to correlate well with infarct size as measured by thallium-201 perfusion imaging and contrast-enhanced magnetic resonance imaging in patients with ST-segment elevation myocardial infarction (STEMI) undergoing reperfusion therapy. Few studies have demonstrated an association between infarct size as assessed by QRS scoring and clinical outcomes. The first 2 studies were conducted in the prefibrinolytic era, whereas the method of reperfusion in the subsequent 2 studies was predominantly fibrinolysis. To our knowledge no studies have evaluated the prognostic value of the QRS score in a contemporary cohort of patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Accordingly, the purpose of this study was to examine the relation between QRS score at hospital discharge and 90-day clinical outcomes including death, congestive heart failure (CHF), and cardiogenic shock in 5,745 patients with PCI-treated STEMI enrolled in the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial.
Methods
The APEX-AMI trial was a multicenter, randomized, double-blind, placebo-controlled trial of intravenous pexelizumab (a novel humanized monoclonal antibody to C5 complement) in conjunction with primary PCI for patients presenting with acute STEMI. The specific entry criteria have been described previously. Briefly, patients were ≥18 years old, with symptom onset <6 hours, and had an ECG indicative of acute STEMI that fulfilled any of the following 3 criteria: (1) ≥2-mm ST-segment elevation in 2 anterior or lateral leads; or (2) ≥2-mm ST-segment elevation in 2 inferior leads coupled with ST-segment depression in 2 contiguous anterior leads for a total ST deviation of ≥8 mm; or (3) new left bundle branch block with ≥1-mm concordant ST-segment elevation.
Prospectively identified end points included 90-day mortality and the composite of death, centrally adjudicated CHF, or cardiogenic shock. Because no significant differences were observed in the primary end point between the treatment and placebo arms, the 2 arms were pooled for the present analysis. There were 5,745 patients enrolled in the APEX-AMI trial.
ECGs were obtained at baseline, 30 minutes after PCI, and at time of hospital discharge. Patients included in the present study were hospital survivors who had an interpretable 12-lead ECG at time of hospital discharge (n = 4,064) without confounders to QRS scoring, i.e., poor quality electrocardiographic tracing, left or right bundle branch block, left anterior or posterior fascicular block, left ventricular hypertrophy (Cornell or Sokolow-Lyon voltage criteria), right ventricular hypertrophy (Butler-Leggett criteria), Wolff-Parkinson-White syndrome, low voltage, or ventricular paced ECG. In patients who died in hospital but had electrocardiography performed at 30 minutes after PCI, we considered the 30-minute ECG after PCI as their “discharge” ECG (n = 49). A total of 1,632 patients were excluded because they had electrocardiographic confounding factors (n = 1,314), or missing or uninterpretable ECGs (n = 318).
All ECGs were evaluated centrally at electrocardiographic core laboratories (Canadian VIGOUR Centre, Edmonton, Alberta, Canada; Duke Clinical Research Institute, Durham, North Carolina) without knowledge of treatment assignment and outcomes. Each discharge ECG was manually scored according to the 54-criteria/32-point Selvester QRS scoring system as previously described. Each point in this system represents infarction of approximately 3% of the left ventricle. Examination of the inter-reader reliability between the 2 core laboratories revealed 96% agreement.
Patients were categorized into approximate tertiles according to their estimated infarct size: QRS score ≤3 (small infarct, <10% myocardium), QRS score 4 to 7 (medium infarct, 10% to 21% myocardium), and QRS score ≥8 (large infarct, >21% myocardium). These particular QRS score cutpoints have also been used in a previous study from the Framingham cohort.
Percentages were reported for discrete variables and medians (25th, 75th percentiles) for continuous variables. For comparisons between groups, chi-square and Kruskal-Wallis tests were applied, respectively. At least 1 peak biomarker of myocardial necrosis (i.e., creatine kinase [CK], CK-MB, troponin I, or troponin T) was available in the entire study population. Biomarker values were locally measured and are presented as multiples of the upper limit of normal.
According to tertiles of QRS score, time to first occurrence of death or composite of death, CHF, or cardiogenic shock was examined by Kaplan-Meier survival methods. Pairwise comparisons were made using log-rank test. These associations were then adjusted for baseline characteristics using Cox proportional hazards regression. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are reported for tertiles of QRS score, with QRS score 0 to 3 as the reference group. Because QRS score includes the contribution of previous infarction(s) in addition to the acute index event, we also performed a sensitivity analysis by excluding patients with a history of or with electrocardiographic evidence for previous infarction at baseline (i.e., Q waves outside acute infarct territory). All tests were 2-sided with a 5% level of significance. All analyses were performed with SAS 9.1.3 (SAS Institute, Cary, North Carolina).
Results
Of the 5,745 patients enrolled in the APEX-AMI trial, 4,113 patients were included in the present analysis. Median discharge QRS score of the study cohort was 6 (3, 8). Table 1 presents selected baseline characteristics according to tertiles of discharge QRS score. Patients with higher QRS scores were more often men and presented with faster heart rates and higher Killip class. These patients were more likely to have noninferior infarcts and a greater extent of ST-segment deviation on baseline ECG. Time from symptom onset to PCI was approximately 17 minutes longer in patients with QRS scores ≥8 versus those with QRS scores ≤3.
| Variable | Discharge QRS Score | |||
|---|---|---|---|---|
| 0–3 (n = 1,277) | 4–7 (n = 1,599) | ≥8 (n = 1,237) | p Value | |
| Age (years) | 60 (51.70) | 60 (51.70) | 60 (52.68) | 0.928 |
| Women | 27% | 22% | 20% | <0.001 |
| Heart rate (beats/min) | 72 (61.84) | 75 (65.87) | 76 (66.87) | <0.001 |
| Systolic blood pressure (mm Hg) | 131 (116, 150) | 134 (119, 150) | 133 (118, 150) | 0.270 |
| Killip class >I | 6.7% | 9.9% | 12% | <0.001 |
| Inferior myocardial infarction | 52% | 38% | 40% | <0.001 |
| Baseline sum of ST-segment deviation (mm) | 12 (8.5, 16.0) | 14 (9.5, 19) | 16 (11.22) | <0.001 |
| Diabetes mellitus | 13% | 15% | 16% | 0.214 |
| Hypertension | 45% | 49% | 48% | 0.102 |
| Previous percutaneous coronary intervention/coronary artery bypass grafting | 9.4% | 9.7% | 9.9% | 0.898 |
| Previous congestive heart failure | 2.6% | 3.0% | 2.7% | 0.790 |
| Time from symptom onset to percutaneous coronary intervention (hours) | 3.2 (2.4, 4.3) | 3.3 (2.5, 4.4) | 3.5 (2.6, 4.6) | <0.001 |
| Time from symptom onset to discharge electrocardiogram (days) | 4 (2.6) | 4 (2.5, 6) | 5 (3.7) | <0.001 |
Table 2 presents selected angiographic characteristics before and after PCI and peak biomarkers according to tertiles of discharge QRS score. Compared to patients with QRS scores ≤3, those with QRS scores ≥8 were 3 times less likely to have culprit Thrombolysis In Myocardial Infarction grade 3 flow before PCI, more often had multivessel disease, and less often achieved complete angiographic reperfusion, i.e., Thrombolysis In Myocardial Infarction grade 3 flow after PCI. A striking gradient in peak biomarker levels with increasing QRS score was observed: patients with QRS scores ≥8 had approximately threefold higher peak serum CK or CK-MB versus those with QRS scores ≤3.
| Variable | Discharge QRS Score | |||
|---|---|---|---|---|
| 0–3 (n = 1,277) | 4–7 (n = 1,599) | ≥8 (n = 1,237) | p Value | |
| Thrombolysis In Myocardial Infarction grade 3 flow before percutaneous coronary intervention | 19% | 10% | 6.2% | <0.001 |
| Thrombolysis In Myocardial Infarction grade 3 flow after percutaneous coronary intervention | 93% | 92% | 88% | <0.001 |
| Multivessel disease | 36% | 40% | 40% | 0.037 |
| Peak creatine kinase, ratio of upper limit of normal | 4.8 (2.1–9.3) | 10 (5.4–17) | 15 (8.4–24) | <0.001 |
| Valid number | 948 | 1,228 | 981 | |
| Peak creatine kinase-MB, ratio of upper limit of normal | 14 (5.6–31) | 32 (16.4–54) | 43 (23–69) | <0.001 |
| Valid number | 553 | 623 | 474 | |
| Peak troponin T, ratio of upper limit of normal | 39 (12–99) | 92 (37–202) | 130 (63–250) | <0.001 |
| Valid number | 357 | 424 | 292 | |
| Peak troponin I, ratio of upper limit of normal | 98 (30–276) | 256 (94–695) | 413 (135–1,230) | <0.001 |
| Valid number | 629 | 862 | 697 | |
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