Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Cardiovascular Intervention
QRS Score at Presentation Electrocardiogram Is Correlated With Infarct Size and Mortality in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention
Hiroki ShiomiMasami KosugeTakeshi MorimotoHiroki WatanabeTomohiko TaniguchiKenji NakatsumaToshiaki ToyotaErika YamamotoSatoshi ShizutaTomohisa TadaYutaka FurukawaYoshihisa NakagawaKenji AndoKazushige KadotaKazuo KimuraTakeshi Kimuraon behalf of the CREDO-Kyoto AMI Investigators
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Supplementary material

2017 Volume 81 Issue 8 Pages 1129-1136

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Abstract

Background: In ST-segment elevation myocardial infarction (STEMI), QRS score at presentation ECG may reflect the progression of infarction and facilitate prediction of the degree of myocardial salvage achieved by reperfusion therapy.

Methods and Results: Admission electrocardiogram (ECG) was studied in 2,607 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) within 24 h of symptom onset. Patients were classified into 3 groups according to QRS score: low (0–3, n=1,227), intermediate (4–7, n=810), and high (≥8, n=570). An increase of infarct size estimated by median peak creatine phosphokinase was observed as QRS score increased (low score, 1,836 IU/L; inter-quartile range (IQR), 979–3,190 IU/L; intermediate score, 2,488 IU/L; IQR, 1,126–4,640 IU/L; high score, 3,454 IU/L; IQR, 1,759–5,639 IU/L; P<0.001). Higher QRS score was associated with higher long-term mortality (low, intermediate, and high score, 15.6%, 19.7%, and 23.7% at 5 years, respectively; log-rank P<0.001). The positive relationship of QRS score with mortality was consistently seen when stratified by infarct location. The association of high QRS score with increased mortality was most remarkably seen in patients with early (≤2 h) presentation (low, intermediate, and high score: 16.7%, 16.6%, and 28.1% at 5 years, respectively; log-rank P<0.001).

Conclusions: Higher QRS score at presentation ECG was associated with larger infarct size, and higher long-term mortality in patients with STEMI undergoing primary PCI. QRS score appears to be important in the early risk stratification for STEMI.

The national campaign to shorten door-to-balloon (DTB) time in the USA achieved the great goal of DTB time <90 min in the majority of patients with ST-segment elevation myocardial infarction (STEMI).1,2 An improvement in mortality in STEMI patients, however, could not be observed over time,35 although the DTB times were consistently associated at the individual level with lower mortality rate using the same dataset.6 Importantly, the extent of myocardial damage that has occurred before reperfusion therapy, varies between patients even with similar total ischemic time, and limits myocardial salvage by reperfusion therapy.7 The presence of Q waves at presentation electrocardiogram (ECG) reflects a more advanced stage of infarct evolution. This ECG marker is superior to time from symptom onset in predicting mortality in STEMI patients treated with primary percutaneous coronary intervention (PCI) as well as with fibrinolysis.811 In these previous studies suggesting the prognostic significance of baseline Q wave in STEMI, however, 46–67% of patients had Q waves at presentation, thereby limiting its value in early risk stratification for STEMI.8,9,11 QRS score is a quantitative index of myocardial damage calculated not only using the number of Q waves but also increased Q wave width and decreased R wave amplitude and width.12 QRS score may be a more accurate indicator of the stages of infarct evolution than the mere presence or absence of Q waves.12,13 The aim of the current study, therefore, was to evaluate the relationship of QRS score at presentation ECG to infarct size and short- and long-term mortality in STEMI patients undergoing primary PCI.

Editorial p 1094

Methods

Subjects

The Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) Acute Myocardial Infarction (AMI) registry is a physician-initiated non-company-sponsored multicenter registry that enrolled consecutive patients with AMI who underwent coronary revascularization within 7 days of symptom onset between January 2005 and December 2007 at 26 tertiary hospitals in Japan (Appendix S1). The research protocol was approved by the relevant review board or the ethics committee at each participating center. Due to retrospective enrollment, written informed consent was waived, but patients who refused to participate in the study when contacted for follow-up were excluded. This strategy is concordant with the guidelines of the Japanese Ministry of Health, Labor and Welfare.

The study design and patient enrollment of the registry have been previously described in detail.5,14 Among 3,885 STEMI patients undergoing primary PCI within 24 h of symptom onset in the 25 centers that agreed to participate in the current ECG study of the CREDO-Kyoto AMI registry, 12-lead ECG at presentation was available for this retrospective analysis in 2,938 patients and was analyzed by the independent ECG core laboratory (Appendix S2). The inclusion criteria of the current analysis were STEMI, suitable ECG for analyzing QRS score, excluding left or right bundle branch block (n=171), ventricular paced ECG (n=10), and poor quality ECG (n=150). Therefore, the current subjects consisted of 2,607 STEMI patients with primary PCI within 24 h of symptom onset in whom QRS score was analyzed with ECG at presentation (Figure 1).

Figure 1.

Subject selection. CABG, coronary artery bypass graft; CREDO-Kyoto AMI, Coronary REvascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction; ECG, electrocardiogram; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

Data Collection

Experienced clinical research coordinators from the independent clinical research organization (Research Institute for Production Development, Kyoto, Japan; Appendix S3) collected baseline clinical, angiographic and procedural characteristics from hospital charts or hospital databases according to the pre-specified definitions. Collection of follow-up information was mainly conducted via review of inpatient and outpatient hospital charts by the clinical research coordinators, and additional follow-up information was collected via contact with patients, relatives and/or referring physicians by sending mail with questions regarding vital status, subsequent hospitalization, and status of antiplatelet therapy. Death, myocardial infarction (MI), and stroke were adjudicated by the clinical event committee (Appendix S4).

ECG

Twelve-lead ECG was recorded on admission at a paper speed of 25 mm/s and an amplification of 10 mm/mV. ECG at presentation and immediately after primary PCI were collected and evaluated at the ECG core laboratory. All ECG analysis was conducted blinded to the clinical data.

QRS score was calculated manually by the members of the independent ECG core laboratory using the 54-criteria/32-point Selvester QRS scoring system, which takes only a few minutes (per case) for calculation.12 The present interobserver variability for the calculation of QRS score indicated substantial agreement (kappa=0.76).15 The cut-offs for QRS score tertiles (low [0–3], intermediate [4–7], high [≥8]) were defined according to the previous studies.16 Representative ECG are shown in Figure 2.

Figure 2.

Representative electrocardiogram (ECG) and QRS scoring system in patients with (A) low, (B) intermediate, and (C) high QRS scores at presentation. Scores are assigned for each lead (excluding leads III and aVR) in accordance with the QRS scoring system, and QRS score is defined as the total score. When more than 1 criterion is met, the criterion with the highest score is selected. The criteria met are shown in red. (A) QRS score, 0. Time from symptom onset to presentation, 1.5 h; culprit lesion, seg. 6; peak creatine phosphokinase (CPK), 1145 IU/L; survival at 1,569 days after acute myocardial infarction (AMI). (B) QRS score, 6. Time from symptom onset to presentation, 2.4 h; culprit lesion, seg. 6; peak CPK, 2,956 IU/L; death from stroke at 1,250 days after AMI. (C) QRS score, 8. Time from symptom onset to presentation, 2.8 h; culprit lesion, seg. 6; peak CPK, 5,573 IU/L; death from cardiac rupture at 9 days after AMI.

ST-segment elevation was measured at the J point. The sum of ST-segment elevation (ΣST-segment elevation) was defined as follows: sum of ST elevation in leads I, aVL, and V1–V6, for anterior AMI, and the sum of ST-segment elevation in leads II, III, aVF, and V5–V6 for non-anterior AMI. ST-segment elevation resolution was defined as >50% resolution in the sum of ST-elevation on ECG immediately after primary PCI compared with that in ECG at presentation.

Definitions and Endpoints

The primary outcome measure in the current analysis was all-cause death. The secondary outcome measures included ST-segment elevation resolution; infarct size estimated by peak enzyme elevation (peak creatine phosphokinase [CPK] and creatine kinase-MB [CK-MB]); left ventricular ejection fraction (LVEF); cardiac death; sudden cardiac death (SCD); and congestive heart failure. Death was regarded as cardiac in origin unless obvious non-cardiac causes could be identified. Any death during hospitalization for the index AMI was regarded as cardiac death. Congestive heart failure was defined as admission to hospital for worsening heart failure requiring intravenous drug treatment.

Statistical Analysis

Continuous variables are expressed as mean±SD or median (IQR). Categorical variables are expressed as numbers and percentages. We compared continuous variables using Student’s t-test or the Wilcoxon rank-sum test on the basis of distribution. Categorical variables were compared using chi-squared test when appropriate; otherwise, Fisher’s exact test was used. Cumulative incidence of clinical event rates was estimated with the Kaplan-Meier method, and differences were assessed using log-rank test. All statistical analysis was conducted using JMP 10.0 (SAS Institute, Cary, NC, USA). All the statistical analysis was 2-tailed, and P<0.05 was considered to be statistically significant.

Results

Baseline Characteristics

Baseline subject characteristics are listed in Table 1. Patients with higher QRS score more often had hemodynamic compromise such as heart failure and cardiogenic shock, resulting in a higher rate of intra-aortic balloon pump use. Regarding the clinical presentation of STEMI, onset-to-presentation time and onset-to-balloon time were significantly longer in patients with higher QRS score, whereas door-to-balloon time did not differ with QRS score tertile. Patients with higher QRS score had significantly higher prevalence of left anterior descending coronary artery culprit lesion. The use of cilostazol and calcium channel blockers was significantly more prevalent in the lower QRS score group, while warfarin was more often prescribed in the higher QRS score group.

Table 1. Baseline Characteristics vs. QRS Score Tertile
Clinical characteristics QRS score at presentation
Low (0–3)
(n=1,227)
Intermediate (4–7)
(n=810)
High (≥8)
(n=570)
P value
Age (years) 67.0±12.4 67.9±12.0 67.0±12.5 0.23
Male 875 (71) 596 (74) 430 (75) 0.16
BMI (kg/m2) 23.8±3.5 23.4±3.4 23.8±3.6 0.04
Hypertension 970 (79) 654 (81) 448 (79) 0.55
Diabetes mellitus 410 (33) 239 (30) 175 (31) 0.16
 Treated with insulin 55 (4.5) 32 (4.0) 21 (3.7) 0.69
Current smoker 499 (41) 331 (41) 243 (42) 0.72
Heart failure 275 (22) 253 (31) 220 (39) <0.001
Prior MI 95 (7.7) 81 (10) 59 (10) 0.10
Prior stroke 83 (6.8) 68 (8.4) 51 (9.0) 0.19
PVD 33 (2.7) 29 (3.6) 20 (3.5) 0.45
eGFR (mL/min/1.73 m2) 68.9 (54.3–84.1) 69.9 (53.3–85.7) 70.4 (53.2–88.4) 0.49
Atrial fibrillation 122 (9.9) 89 (11) 54 (9.5) 0.62
Anemia (Hemoglobin<11.0 g/dL) 97 (7.9) 88 (11) 47 (8.3) 0.06
COPD 31 (2.5) 36 (4.4) 19 (3.3) 0.06
Presentation
 Onset-to-presentation time (h) 2.0 (1.0–4.0) 2.7 (1.2–5.5) 3.4 (1.5–8.3) <0.001
 Onset-to-balloon time (h) 3.8 (2.6–5.8) 4.5 (2.9–7.5) 5.2 (3.2–9.8) <0.001
 Door-to-balloon time (min) 90 (60–126) 84 (60–126) 84 (60–126) 0.43
  ≤90 min 567 (53) 390 (56) 275 (58) 0.12
 Hemodynamics
  Killip class 1 1,000 (82) 605 (75) 391 (69) <0.001
  Killip class 2 66 (5.4) 68 (8.4) 65 (11)
  Killip class 3 23 (1.9) 22 (2.7) 27 (4.7)
  Killip class 4 (cardiogenic shock) 138 (11) 115 (14) 87 (15)
 IABP use 135 (11) 119 (15) 119 (21) <0.001
Angiographic characteristics
 Infarct-related artery location
  LAD 383 (31) 437 (54) 402 (71) <0.001
  LCX 172 (14) 55 (6.8) 31 (5.4)
  RCA 655 (53) 300 (37) 117 (21)
  LMC 12 (1.0) 15 (1.9) 16 (2.8)
  CABG 5 (0.4) 3 (0.4) 4 (0.7)
 Multivessel disease 642 (52) 409 (50) 270 (47) 0.15
Medications at discharge
 Antiplatelet therapy
  Thienopyridine 1,168 (95) 777 (96) 545 (96) 0.73
  Aspirin 1,213 (99) 802 (99) 560 (98) 0.44
  Cilostazol 498 (41) 281 (35) 185 (32) 0.001
 Other medications
  Statins 706 (58) 445 (55) 296 (52) 0.08
  β-blockers 514 (42) 345 (43) 264 (46) 0.20
  ACEI/ARB 900 (73) 584 (72) 422 (74) 0.70
  Nitrates 347 (28) 228 (28) 156 (27) 0.92
  CCB 309 (25) 154 (19) 88 (15) <0.001
  Nicorandil 302 (25) 217 (27) 132 (23) 0.29
  Warfarin 92 (7.5) 100 (12) 92 (16) <0.001

Data given as mean±SD, median (IQR) or n (%). ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; CABG, coronary artery bypass graft; CCB, calcium channel blockers; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; IABP, intra-aortic balloon pump; LAD, left anterior descending artery; LCX, left circumflex artery; LMC, left main coronary artery; MI, myocardial infarction; PVD, peripheral vascular disease; RCA, right coronary artery.

QRS Score and ST-Segment Analysis, Infarct Size, and Cardiac Function

Compared with low QRS score, the higher QRS score group had significantly greater summed ST-segment elevation, and a lower rate of ST-segment elevation resolution (Table 2).

Table 2. ST-Segment Analysis vs. QRS Score Tertile
Variables QRS score at presentation
Low (0–3)
(n=1,227)
Intermediate (4–7)
(n=810)
High (≥8)
(n=570)
P value
ECG findings
 QRS score at presentation 1 (0–2) 5 (4–6) 10 (9–12) <0.001
 ΣST-segment elevation at presentation 5.0 (2.5–9.5) 7.0 (3.0–14.0) 10.0 (5.5–17.0) <0.001
 ST-segment elevation resolution ≥50% 659 (59)
(n=1,122)
351 (48)
(n=739)
196 (38)
(n=519)
<0.001
Peak cardiac enzyme
 Peak CPK (IU/L) 1,836 (979–3,190)
(n=1,223)
2,488 (1,126–4,640)
(n=806)
3,454 (1,759–5,639)
(n=566)
<0.001
 Peak CK-MB (IU/L) 159 (76–284)
(n=998)
197 (89–389)
(n=674)
286 (132–517)
(n=460)
<0.001
Cardiac function
 LVEF 55.8±10.8
(n=962)
52.0±13.3
(n=636)
48.1±13.8
(n=455)
<0.001
Clinical outcomes
 No. patients with event (cumulative 5-year incidence)
 All-cause death 180 (15.6) 152 (19.7) 130 (23.7) <0.001
 Cardiac death 94 (8.1) 75 (9.7) 92 (16.9) <0.001
 Sudden cardiac death 15 (1.5) 11 (1.6) 17 (3.6) 0.002
 Congestive heart failure 71 (6.5) 66 (9.2) 58 (12.3) <0.001

Data given as mean±SD, median (IQR) or n (%). ΣST-segment elevation in leads I, aVL, and V1–V6, for anterior AMI, and ΣST-segment elevation in leads II, III, aVF, and V5–V6 for non-anterior AMI. AMI, acute myocardial infarction; CK-MB, creatine kinase-MB; CPK, creatine phosphokinase; ECG, electrocardiogram; LVEF, left ventricular ejection fraction.

An increase in infarct size, as estimated by peak CPK and CK-MB, was observed as QRS score increased (Table 2).

Compared with the low QRS score group, the higher QRS score group had significantly lower LVEF (Table 2).

Clinical Outcome According to QRS Score

Median follow-up duration for the surviving patients was 5.4 years (IQR, 4.6–6.1 years). Higher QRS score was associated with higher short- and long-term mortalities (low, intermediate, and high QRS score: 2.5%, 5.2% and 7.7% at 30 days; and 15.6%, 19.7%, and 23.7% at 5 years, log-rank P<0.001, respectively; Figure 3A). The cumulative incidences of cardiac death, SCD, and congestive heart failure were also higher with higher QRS score (Table 2).

Figure 3.

Kaplan-Meier event curves for all-cause death according to QRS score tertile for (A) the entire cohort; (B) anterior infarction; and (C) non-anterior infarction.

The positive relationship of QRS score with mortality was consistently seen when stratified by infarct location (Figure 3B,C), and history of prior MI (Figure S1).

When patients were further stratified according to time from symptom onset to presentation (≤2 h, >2 h), the association of high QRS score with increased mortality was most remarkably seen in patients with early (≤2 h) presentation: low, intermediate, and high QRS score, 2.5%, 7.4% and 11.5% at 30 days; and 16.7%, 16.6%, and 28.1% at 5 years, respectively (log-rank P<0.001; Figure 4). In delayed presentation, mortality in the intermediate and high QRS score groups was higher than in the low QRS score group: low, intermediate, and high QRS score, 2.2%, 3.5% and 5.8% at 30 days; and 14.4%, 22.2%, and 21.3% at 5 years, respectively (log-rank P=0.002; Figure 4). There was no significant interaction, however, between QRS score and time from symptom onset to presentation (≤2 h or >2 h; interaction, P=0.59).

Figure 4.

All-cause death at 5 years according to QRS score tertile for (A) early presentation (≤2 h) and (B) delayed presentation (>2 h).

Discussion

This ECG sub-study of the CREDO-Kyoto AMI registry evaluating 2,607 patients with STEMI who underwent primary PCI has shown that higher QRS score at presentation ECG is associated with a larger infarct size, and higher short- and long-term mortality. The strong positive relationship of QRS score with mortality was consistently seen when stratified by infarct location. Moreover, among patients with early (≤2 h) presentation, highest QRS score was associated with very high mortality, suggesting the presence of high-risk patients whose infarct evolution is very rapid. Because ECG is simple, inexpensive, non-invasive, readily available, and rapidly interpretable at the time of presentation, risk stratification based on QRS score is considered very useful clinically.

QRS score could be regarded as a weighed quantitative index of myocardial damage. Several previous studies have reported a positive relationship of QRS score evaluated at discharge (when the acute infarct process had completely finished) with mortality.17,18 The present study evaluated whether QRS score at presentation, when the infarct process is ongoing, could predict infarct size and mortality, leading to early risk stratification of STEMI patients. High QRS score at presentation ECG was found to be associated with delayed presentation, more advanced Killip class, more frequent anterior STEMI, and greater baseline ST-segment elevation, indicating that more extensive and severe myocardial damage has occurred before reperfusion therapy. Many factors including time from symptom onset, medication before infarction, ischemic preconditioning, extent of area at risk, level of oxygen demand and collateral flow affect the progression of infarction. QRS score at presentation might reflect the stage of infarct evolution. Patients with a high QRS score would be expected to have less salvageable myocardium, as indicated by less ST-segment elevation resolution and larger infarct size estimated via peak cardiac enzymes, resulting in higher mortality. QRS score thus provides important information in estimating the effectiveness of primary PCI in improving clinical outcome. We have previously demonstrated that higher QRS score at presentation ECG was associated with larger infarct size and impaired myocardial reperfusion according to myocardial blush grade in a single-center study of 416 patients with anterior STEMI who received reperfusion therapy within 6 h after symptom onset, but did not examine the prognostic implication of QRS score.13 Uyarel et al reported that high QRS score at presentation ECG was associated with incomplete ST recovery as well as with 30-day adverse clinical events in 112 patients with STEMI within 12 h after symptom onset who underwent primary PCI.19 To the best of our knowledge, this is the first study to demonstrate the long-term prognostic significance of QRS score at presentation ECG in a large-scale cohort of PCI-treated STEMI patients.

In terms of the utility of QRS score for discriminating risk for SCD in patients with reduced cardiac function, previous results are inconsistent.20,21 In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) enrolling ischemic and non-ischemic patients with LVEF ≤35%, high QRS score was significantly associated with the higher rate of ventricular tachycardia/fibrillation and SCD.20 In contrast, QRS score failed to discriminate the risk for SCD in Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) enrolling ischemic patients with LVEF ≤30%.21 In the present study involving STEMI patients in real-world clinical practice, QRS score appears to be useful in the risk stratification for SCD.

Moreover, the combination of QRS score and time from symptom onset identified patients with high QRS score (≥8) and early presentation as the highest risk subgroup. The very high mortality in this subgroup despite early presentation suggests very rapid infarct evolution. Improving the mortality in this subgroup might be the next focus for further improving the outcome of STEMI.

During the past decades, mortality in STEMI dramatically improved as the use of primary PCI increased worldwide.2225 Many recent clinical trials aimed at limiting infarct size, however, not been successful in demonstrating significant efficacy of new treatments.26,27 In addition to the current low in-hospital mortality in STEMI patients, one of the possible reasons for this difficulty might be related to the fact that heterogeneous patients with a variety of infarct evolution process were enrolled in these trials. It might be useful to incorporate baseline QRS score into the design and evaluation of future clinical trials aimed at limiting infarct size for STEMI.

Study Limitations

There are several limitations in the current study. First, the biggest limitation was that QRS score was not analyzed in all patients with STEMI enrolled in the registry. The reason for unavailability of ECG in some patients, however, was purely due to logistics, without any selection bias. The present sample size is one of the largest on ECG at presentation in STEMI patients who underwent primary PCI. Second, data on the precise time of blood sampling for CPK, time to peak CPK, or cumulative CPK release were lacking because of the retrospective nature of the current study. Third, the presence of prior MI might influence the results, including QRS score and relationship of QRS score to mortality. The prevalence of prior MI, however, was 9% in the group as a whole, and was slightly, but not significantly, greater in patients with higher QRS score. Fourth, left or right bundle branch block, and ventricular paced ECG were excluded from analysis as confounders of QRS score calculation, as in previous studies.16,18 Fifth, the practice patterns including the use of antiplatelet therapy in the present enrollment period might be different from those in current clinical practice. Finally, the prescription rates of evidence-based medicine such as statins and β-blockers were low compared with the current standard.

Conclusions

In patients with STEMI undergoing primary PCI, QRS score at presentation provides important short- and long-term prognostic information. The poorer outcomes in patients with high QRS score are likely to be related to less myocardial salvage due to rapid infarct evolution before reperfusion. QRS score at presentation can potentially be used as a simple, but reliable tool for the early identification of high-risk patients.

Acknowledgments

We appreciate the support and collaboration of the co-investigators participating in the CREDO-Kyoto AMI Registry. We are indebted to the outstanding effort of the clinical research coordinators for data collection.

Disclosures

The authors declare no conflict of interest.

Funding sources

The current study was supported by the Health, Labour and Welfare Ministry in Japan and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan.

Supplementary Files

Supplementary File 1

Appendix S1. Participating Centers and Investigators for the CREDO-Kyoto Registry Cohort-2

Appendix S2. ECG Core Laboratory Members

Appendix S3. Clinical Research Coordinators

Appendix S4. Clinical Event Committee Members

Figure S1. Kaplan-Meier event curves for all-cause death according to QRS tertiles for (A) presence and (B) absence of prior myocardial infarction.

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-16-1255

References
 
© 2017 THE JAPANESE CIRCULATION SOCIETY
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