Location, size, thickness of the myocardial scar determined by CMR-LGE
Myocardial scars were diagnosed in 41 of 42 STEMI patients (96.7%) by using CMR-LGE. A patient-by-patient visual analysis of scar tissue location in the STEMI group, with bull’s eye segmental comparison of CMR-LGE findings is shown in Supplemental Figure 1. In all patients, the anatomic locations of scars defined by CMR-LGE corresponded to the distributions of the culprit vessels treated with primary angioplasty. For example, in a patient with angiographically proven left anterior descending coronary artery occlusion, CMR-LGE indicated scarification of the basal and middle segments of the left anterior ventricular wall. In another patient with right coronary artery occlusion, CMR-LGE disclosed a scar that involved the entire inferior wall of the left ventricle and the middle and apical segments of the posterior interventricular septum (Supplement Figure 2). However, scar size and thickness were unrelated to the degree of coronary artery occlusion. Stenoses in all culprit arteries exceeded 90%; nonetheless, there were significant inter-patient differences in scar size and thickness (P<0.001).
Determination of STR cut-off value
A transmural scar was defined as a myocardial lesion extending >75% of the wall thickness. All myocardial scars were classified as either non-transmural (0-75%) or transmural (76-100%) according to CMR-LGE results. The relationship of the ST-segment resolution percentage to transmural scarification was identified by the ROC curve. The ROC curve analysis demonstrated a sensitivity of 96% and a specificity of 88% to predict transmural myocardial scarification following STEMI at an STR cut-off value of 40.15%. The area under the curve was 0.92 (Figure 1).
Receiver operating characteristic (ROC) curve analysis demonstrated a sensitivity of 96% with a specificity of 88% to predict transmural myocardial scar following STEMI at a cut-off of ST-segment resolution of 40.15%. Area under curve (AUC)=0.92.
Patient characteristics of STR groups
Patients were divided into two groups: STR<40.15% (n=16) and STR≥40.15% (n=26). Compared with patients with STR≥40.15%, patients with STR<40.15% had significantly longer pain-to-balloon time; higher aspartate aminotransferase (AST), peak troponin-I, and brain natriuretic peptide (BNP) levels; lower left ventricular ejection fraction (LVEF); and a higher prevalence of diuretic therapy. Other characteristics such as age; gender; body mass index; histories of smoking, hypertension, and diabetes; hyperlipidemia; culprit artery; leukocyte, erythrocyte, and platelet counts; hemoglobin, hemoglobin A1(c), alanine aminotransferase (ALT), and creatinine levels; left ventricular diastolic diameter; the use of therapeutic drugs other than diuretics; and coronary care unit residence time were similar between the two groups (Table 1).
Table 1. Baseline patient characteristics of different degrees of ST-segment resolution.
Variables
|
All(n=42)
|
ST-segment resolution≥40.15%
|
ST-segment resolution<40.15%
|
P
|
|
(n=26)
|
(n=16)
|
Male/female (n)
|
30/12
|
20/6
|
10/6
|
0.483
|
Age (years)
|
62.0(54.5-70.0)
|
60.5(52.8-70.3)
|
63.5(59.5-69.5)
|
0.534
|
BMI (Kg/m2)
|
24.2(23.0-25.6)
|
24.3(23.4-25.8)
|
24.2(21.9-24.7)
|
0.378
|
Smoking history (No, %)
|
27(64.3%)
|
17(65.4%)
|
10(62.5%)
|
0.850
|
HP history (No, %)
|
27(64.3%)
|
14(53.8%)
|
13(81.2%)
|
0.072
|
DM history (No, %)
|
16(38.1%)
|
12(46.2%)
|
4(25.0%)
|
0.170
|
Hyperlipidemia (No, %)
|
21(50.0%)
|
13(50.0%)
|
8(8.0%)
|
1.000
|
Pain to balloon time (h)
|
5.79(3.67-7.60)
|
4.33(3.50-6.23)
|
7.04(5.81-8.40) *
|
0.001
|
Killip classification (No, %)
|
|
|
|
0.757
|
Killip I
|
29(74.4%)
|
19(79.2%)
|
10(66.67%)
|
|
Killip II
|
10(25.6%)
|
5(20.8%)
|
5(33.33%)
|
|
Number of DES (No, %)
|
|
|
|
0.142
|
One
|
34(87.2%)
|
22(95.7%)
|
12(75.0%)
|
|
Two
|
3(7.7%)
|
1(4.3%)
|
2(12.5%)
|
|
Three
|
2(5.1%)
|
0(0.0%)
|
2(12.5%)
|
|
Culprit artery, (No, %)
|
|
|
|
0.171
|
LAD
|
18(42.9%)
|
8(30.8%)
|
10(62.5%)
|
|
LCC
|
11(26.2%)
|
8(30.8%)
|
3(18.8%)
|
|
RCA
|
13(31.0%)
|
10(38.5%)
|
3(18.8%)
|
|
WBC count (109/L)
|
9.85(8.28-12.06)
|
10.09(8.28-12.06)
|
9.72(8.03-14.12)
|
0.875
|
RBC count (1012/L)
|
4.44(3.91-4.82)
|
4.44(4.14-4.86)
|
4.45(3.71-4.72)
|
0.449
|
Hb (g/L)
|
139.0(125.0-151.0)
|
139.0(128.0-151.0)
|
135.5(113.3-150.8)
|
0.449
|
PLT (109/L)
|
198.0(163.0-238.0)
|
195.0(160.0-213.0)
|
212.5(175.0-282.3)
|
0.204
|
HbA1c (%)
|
6.0(5.7-7.2)
|
6.1(5.7-8.2)
|
5.9(5.7-6.4)
|
0.188
|
ALT (U/L)
|
42.0(35.0-56.0)
|
41.0(35.0-56.0)
|
46.0(36.0-53.5)
|
0.689
|
AST (U/L)
|
126.0(52.0-209.0)
|
75.0(35.0-153.0)
|
185.5(101.1-237.3)
|
0.015
|
Cr (umol/L)
|
73.0(60.0-81.0)
|
73.0(59.0-81.0)
|
71.5(60.3-83.3)
|
0.954
|
BNP (pg/ml)
|
57.9(7.9-245.0)
|
11.7(5.0-62.7)
|
227.5(80.0-381.2) *
|
<0.001
|
Peak troponin-T (ng/ml)
|
11.6(6.2-19.3)
|
7.0(3.8-14.0)
|
18.6(12.2-24.9) *
|
<0.001
|
LVIDd (mm)
|
49.0±3.3
|
49.0±3.3
|
49.5±3.2
|
0.298
|
LVEF (%)
|
53.5(48.0-58.25)
|
57.0(53.5-61.0)
|
47.5(44.3-50.0) *
|
<0.001
|
Scar thickness
|
70.0(55.0-80.0)
|
59.0(50.0-70.0)
|
81.0(80.0-85.0) *
|
<0.001
|
Transmural myocardial scar (No, %)
|
17(40.5%)
|
2(7.7%)
|
15(93.8%)*
|
<0.001
|
Scar size
|
17.35(12.23-20.30)
|
12.90(11.13-19.40)
|
20.00(18.13-23.63) *
|
0.001
|
IIa/IIIb inhibitor (No, %)
|
17(43.6%)
|
11(47.8%)
|
6(37.5%)
|
0.522
|
Aspirin (No, %)
|
39(100.0%)
|
23(100.0%)
|
16(100.0%)
|
1.000
|
Ticagrelor/Clopidogrel (No, %)
|
39(100.0%)
|
23(100.0%)
|
16(100.0%)
|
1.000
|
Statins (No, %)
|
39(100.0%)
|
23(100.0%)
|
16(100.0%)
|
1.000
|
β-blocker (No, %)
|
31(79.5%)
|
17(73.9%)
|
14(87.5%)
|
0.432
|
ACEI/ARB
|
24(61.5%)
|
14(60.9%)
|
10(62.5%)
|
0.918
|
Nitrates (No, %)
|
38(97.4%)
|
22(95.7%)
|
16(100.0%)
|
1.000
|
Diuretics (No, %)
|
16(41.0%)
|
6(26.1%)
|
10(62.5%)
|
0.023
|
CCU (hours)
|
48.0(39.0-62.0)
|
47.0(38.0-58.0)
|
52.5(44.0-82.8)
|
0.123
|
Data are Data are presented as mean ± SD, median (interquartile ranges), or number (%). Abbreviations: STEMI, ST-segment elevation myocardial infarction; BMI, body mass index; HP, hypertension; DM, diabetes mellitus; DES, Drug eluting stents; LAD, left anterior descending coronary artery; LCC, left circumflex coronary artery; RCA, right coronary artery; LVIDD, left ventricular diastolic diameter; LVEF, left ventricular ejection fraction. ACEI, angiotensin converting enzyme inhibitors; ARB, Angiotensin Receptor Blocker; CCU: Coronary heart disease Care Unit. *P<0.05 comparing with ST-segment resolution≥40% group.
Diagnostic value of STR<40.15% for transmural myocardial scar
In the logistic regression analysis, male gender (odds ratio [OR]=0.500, 95% confidence interval [CI] 0.234–1.068), history of diabetes (OR=0.333, 95% CI 0.108–1.034), LVEF (OR=0.520, 95% CI 0.341–0.792), and STR <40.15% (OR=15.0, 95% CI 1.981–113.556) were significant risk factors for transmural scars (Table 2).
Table 2. Effects of various variables on transmural myocardial scar in logistic regression analysis.
Characteristics
|
OR (95%CI)
|
P
|
Male, yes vs. no
|
0.500(0.234-1.068)
|
0.074
|
Age, per 1 years
|
0.994(0.984-1.004)
|
0.238
|
BMI, per 1 Kg/m2
|
0.984(0.959-1.009)
|
0.206
|
Smoking history, yes vs. no
|
0.588(0.269-1.285)
|
0.183
|
HP history, yes vs. no
|
1.077(0.506-2.291)
|
0.847
|
DM history, yes vs. no
|
0.333(0.108-1.034)
|
0.057
|
Hyperlipidemia, yes vs. no
|
0.615(0.255-1.485)
|
0.280
|
Pain to balloon time, per 1 min
|
1.018(0.928-1.118)
|
0.702
|
Killip classification, II vs. I
|
1.500(0.423-5.315)
|
0.530
|
Number of DES, two& three vs. one
|
4.000(0.447-35.788)
|
0.215
|
Culprit artery: RCD
|
1.00
|
|
Culprit artery: LAD
|
0.571(0.167-1.952)
|
0.372
|
Culprit artery: LCC
|
0.444(0.137-1.443)
|
0.177
|
WBC count, per 1×109/L
|
0.971(0.917-1.028)
|
0.317
|
RBC count, per 1×1012/L
|
0.915(0.792-1.058)
|
0.229
|
Hb, per 1×g/L
|
0.997(0.993-1.002)
|
0.241
|
PLT, per 1×109/L
|
0.999(0.996-1.002)
|
0.567
|
HbA1c, per 1%
|
0.936(0.852-1.029)
|
0.172
|
ALT, per 1U/L
|
0.995(0.984-1.007)
|
0.442
|
AST, per 1U/L
|
1.001(0.998-1.004)
|
0.561
|
Cr, per 1umol/L
|
0.995(0.987-1.004)
|
0.283
|
BNP, per 1pg/ml
|
1.003(0.999-1.008)
|
0.120
|
Peak troponin-T, per 1 ng/ml
|
1.014(0.975-1.054)
|
0.500
|
LVIDd, per 1mm
|
0.993(0.980-1.005)
|
0.255
|
LVEF, per 1%
|
0.520(0.341-0.792)
|
0.002
|
ST-segment <40.15%, yes vs. no
|
15.0(1.981-113.556)
|
0.009
|
Scar thickness
|
1.000(0.991-1.009)
|
0.975
|
Scar size
|
0.993(0.960-1.027)
|
0.685
|
IIa/IIIb inhibitor, yes vs. no
|
0.545(0.202-1.475)
|
0.232
|
β-blocker, yes vs. no
|
0.824(0.406-1.671)
|
0.591
|
ACEI/ARB, yes vs. no
|
0.846(0.379-1.889)
|
0.683
|
Nitrates, yes vs. no
|
0.727(0.382-1.385)
|
0.332
|
Diuretics, yes vs. no
|
2.200(0.764-6.332)
|
0.144
|
CCU, per 1 hours
|
1.000(0.989-1.011)
|
0.987
|
Abbreviations: STEMI, ST-segment elevation myocardial infarction; BMI, body mass index; HP, hypertension; DM, diabetes mellitus; DES, Drug eluting stents; LAD, left anterior descending coronary artery; LCC, left circumflex coronary artery; RCA, right coronary artery; WBC, white blood cell; RBC, red blood cell; Hb, Hemoglobin; PLT, platelet count; HbA1c, Hemoglobin A1c; ALT, alanine aminotransferase; AST, aspartate transaminase; Cr, creatinine; BNP, brain natriuretic peptide; LVIDD, left ventricular diastolic diameter; LVEF, left ventricular ejection fraction; ACEI, angiotensin converting enzyme inhibitors; ARB, Angiotensin Receptor Blocker; CCU: Coronary heart disease Care Unit.
Multivariate logistic proportional hazards regression analyses were used to evaluate the independent predictive value of STR<40.15%. After adjusting for age, gender, and pain-to-balloon time (Mode 1), the OR of STR<40.15% for transmural scar was 211.40 (95% CI 9.64-4636.69, P=0.001). After adjusting for histories of smoking, hypertension, and DM (Mode 2), the OR was 280.14 (95% CI 12.42–6320.36, P<0.001). After adjusting for BNP, peak troponin-I, and diuretic use (Mode 3), the OR was 6394.05 (95% CI 8.51–4807147.53, P=0.010). After adjusting for LVEF and AST (Mode 4), the OR was 187.94 (95% CI 11.33-3116.99, P<0.001). After adjusting for LVEF, smoking history, and peak troponin-I (Mode 5), the OR was 112.95 (95% CI 6.20–2059.35, P=0.001). In aggregate, smoking history, peak troponin-I, and LVEF showed significance for predicting transmural scar (Table 3).
Table 3. Results of multivariate logistic proportional-hazards regression analyzing the effect of baseline variables on transmural myocardial scar.
Mode
|
OR (95%CI)
|
P
|
Not Adjusted ST-segment resolution<40.15%, yes vs. no
|
15.0(1.98-113.56)
|
0.009
|
Mode 1
|
ST-segment resolution<40.15%, yes vs. no
|
211.40(9.64-4636.69)
|
0.001
|
Male, yes vs. no
|
0.19(0.02-2.31)
|
0.192
|
Age, per 1 years
|
0.94(0.87-1.01)
|
0.092
|
Pain to balloon time, per 1 hour
|
1.51(0.85-2.70)
|
0.160
|
Mode 2
|
|
|
ST-segment resolution<40.15%, yes vs. no
|
280.14(12.42-6320.36)
|
<0.001
|
Smoking history, yes vs. no
|
0.10(0.01-0.82)
|
0.032
|
HP history (No, %)
|
0.49(0.09-2.61)
|
0.399
|
DM history (No, %)
|
0.15(0.01-2.09)
|
0.158
|
Mode 3
|
|
|
ST-segment resolution<40.15%, yes vs. no
|
6394.05(8.51-4807147.53)
|
0.010
|
BNP, per 1pg/ml
|
1.00(0.99-1.02)
|
0.636
|
Peak Troponin-I, per 1 ng/ml
|
0.74(0.58-0.95)
|
0.020
|
Diuretics, yes vs. no
|
2.15(0.13-35.54)
|
0.592
|
Mode 4
|
|
|
ST-segment resolution<40.15%, yes vs. no
|
187.94(11.33-3116.99)
|
<0.001
|
LVEF, per 1%
|
0.94(0.89-0.99)
|
0.016
|
AST, per 1U/L
|
1.00(0.99-1.02)
|
0.616
|
Mode 5
|
ST-segment resolution<40.15%, yes vs. no
|
112.95(6.20-2059.35)
|
0.001
|
LVEF, per 1%
|
0.95(0.90-1.01)
|
0.079
|
Smoking history, yes vs. no
|
0.50(0.04-6.97)
|
0.605
|
Peak Troponin-I, per 1 ng/ml
|
1.04(0.88-1.23)
|
0.629
|
Abbreviations: STEMI, ST-segment elevation myocardial infarction; BNP, brain natriuretic peptide; LVEF, left ventricular ejection fraction; AST, aspartate transaminase.
Relationship between STR percentage and myocardial scar thickness and size
Linear regression analyses demonstrated negative correlations between STR percentage and both scar thickness (β= -0.838, 95% CI -1.182~-0.774, P<0.001) and size (β= -0.714, 95% CI -3.126~-1.635, P<0.001) (Figure 2). In addition, compared with patients with STR>40.15%, patients with STR<40.15% had significantly thicker and larger scars (Figure 3).