Publish in this journal
Journal Information
Vol. 72. Issue 2.
Pages 120-129 (February 2019)
Share
Share
Download PDF
More article options
Visits
Not available
Vol. 72. Issue 2.
Pages 120-129 (February 2019)
Original article
DOI: 10.1016/j.rec.2018.01.005
Full text access
Clinical Significance of Reciprocal ST-segment Changes in Patients With STEMI: A Cardiac Magnetic Resonance Imaging Study
Significado clínico de los cambios recíprocos del segmento ST en pacientes con IAMCEST: estudio de imagen con resonancia magnética cardiaca
Visits
...
Ji-Won Hwanga,, Jeong Hoon Yangb,c,, Young Bin Songb,
Corresponding author
youngbin.song@gmail.com

Corresponding author: Division of Cardiology, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, Republic of Korea.
, Taek Kyu Parkb, Joo Myung Leeb, Ji-Hwan Kimd, Woo Jin Jange, Seung-Hyuk Choib, Joo-Yong Hahnb, Jin-Ho Choib, Joonghyun Ahnf, Keumhee Carriereg, Sang Hoon Leeb, Hyeon-Cheol Gwonb
a Division of Cardiology, Department of Medicine, Ilsan Paik Hospital, Inje University School of Medicine, Goyang, Republic of Korea
b Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
c Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
d Division of Cardiology, Department of Medicine, Namyangju Baek Hospital, Namtangju, Republic of Korea
e Division of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
f Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Republic of Korea
g Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, Alberta, Canada
This item has received
...
Visits
(Daily data update)
Article information
Abstract
Full Text
Bibliography
Download PDF
Statistics
Figures (2)
Tables (5)
Table 1. Baseline Clinical and Angiographic Characteristics
Table 2. Baseline Clinical and Angiographic Characteristics in Propensity Score-matched Patients
Table 3. Cardiac Magnetic Resonance Imaging Parameters
Table 4. Parameters of Cardiac Magnetic Resonance Imaging as Outcomes in Propensity Score-matched Subset Data
Table 5. Clinical Outcomes of the Group With Reciprocal Change Compared With the Group Without Reciprocal Change During the Follow-up Period
Show moreShow less
Additional material (1)
Abstract
Introduction and objectives

We sought to determine the association of reciprocal change in the ST-segment with myocardial injury assessed by cardiac magnetic resonance (CMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Methods

We performed CMR imaging in 244 patients who underwent primary PCI for their first STEMI; CMR was performed a median 3 days after primary PCI. The first electrocardiogram was analyzed, and patients were stratified according to the presence of reciprocal change. The primary outcome was infarct size measured by CMR. Secondary outcomes were area at risk and myocardial salvage index.

Results

Patients with reciprocal change (n=133, 54.5%) had a lower incidence of anterior infarction (27.8% vs 71.2%, P < .001) and shorter symptom onset to balloon time (221.5±169.8 vs 289.7±337.3min, P=.042). Using a multiple linear regression model, we found that patients with reciprocal change had a larger area at risk (P=.002) and a greater myocardial salvage index (P=.04) than patients without reciprocal change. Consequently, myocardial infarct size was not significantly different between the 2 groups (P=.14). The rate of major adverse cardiovascular events, including all-cause death, myocardial infarction, and repeat coronary revascularization, was similar between the 2 groups after 2 years of follow-up (P=.92).

Conclusions

Reciprocal ST-segment change was associated with larger extent of ischemic myocardium at risk and more myocardial salvage but not with final infarct size or adverse clinical outcomes in STEMI patients undergoing primary PCI.

Keywords:
ST-segment elevation myocardial infarction
Reciprocal change of electrocardiogram
Area at risk
Cardiac magnetic resonance imaging
Abbreviations:
AAR
CMR
ECG
LV
MSI
STEMI
Resumen
Introducción y objetivos

Se trató de determinar la asociación de los cambios recíprocos en el segmento ST con el daño miocardio evaluado mediante imagen con resonancia magnética cardiaca (RMC) en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) que recibieron intervención coronaria percutánea (ICP).

Métodos

Se realizó estudio de imagen con RMC a 244 pacientes tratados con ICP primaria durante el primer IAMCEST. El estudio con RMC se realizó de media 3 días después de la ICP primaria. Se analizó el primer electrocardiograma y los pacientes se estratificaron de acuerdo a la presencia de cambios recíprocos. El objetivo primario fue el tamaño del infarto medido por RMC y los secundarios el área en riesgo y el índice de miocardio rescatado.

Resultados

Los pacientes con cambios recíprocos (133 pacientes, 54,5%) tuvieron una menor incidencia de infarto de miocardio anterior (27,8 frente al 71,2%; p < 0,001) y un tiempo más corto desde el inicio de los síntomas hasta la restauración del flujo coronario (221,5±169,8 frente a 289,7±337,3min; p=0,042). Usando un modelo de regresión lineal múltiple, se encontró que los pacientes con cambios recíprocos tuvieron una mayor área en riesgo (p=0,002) y un mayor índice de miocardio rescatado (p=0,04) comparado con los pacientes sin cambios recíprocos. Consecuentemente, el tamaño del infarto de miocardio no fue significantemente diferente entre los 2 grupos (p=0,14). La tasa de eventos adversos cardiovasculares mayores, incluyendo muerte por todas las causas, infarto de miocardio, y nueva revascularización coronaria, fue similar entre los 2 grupos después de 2 años de seguimiento (p=0,92).

Conclusiones

Los cambios recíprocos del segmento ST se asociaron a una mayor extensión de miocardio isquémico en riesgo y a un mayor índice de miocardio rescatado, pero no a un mayor tamaño del infarto o eventos clínicos adversos en pacientes con IAMCEST tratados con ICP primaria.

Palabras clave:
Infarto de miocardio con elevación del segmento ST
Cambios recíprocos del electrocardiograma
Área en riesgo
Resonancia magnética cardiaca
Full Text
INTRODUCTION

Acute transmural myocardial infarction induces ST-segment elevation, enlargement of the R wave, and widening of the QRS complex in electrocardiogram (ECG) leads directly related to the ischemic region.1,2 Moreover, leads not related to the ischemic area can show concurrent reciprocal ST-segment depression.3,4 Numerous studies have aimed to determine the clinical implications of reciprocal change on ECG. However, the clinical significance of reciprocal change on ECG such as ST-segment depression remote from the infarct site remains controversial, as reflected in a more extensive infarct size or the benign mirror phenomenon.4–8 Cardiac magnetic resonance (CMR) imaging can accurately describe myocardial scar change and the area at risk (AAR) in acute myocardial infarction. This technique can also be used to estimate the myocardial salvage index (MSI), as a meaningful CMR outcome parameter of acute reperfused myocardial infarction.9,10 Therefore, our study aimed to investigate whether reciprocal change in ST-segments is related to markers of myocardial injury, as assessed by CMR imaging and clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).

METHODSStudy Population, Clinical Data, and Follow-up

ST-segment elevation myocardial infarction patients who visited our institution, a tertiary referral center from January 2008 to September 2013, were eligible if they had: a) ST-segment elevation in 2 or more contiguous leads on ECG as standard definition; and b) had undergone successful primary PCI and CMR imaging. Patients with the following were excluded: admission for more than 12hours after symptom onset, previous myocardial infarction, or previous coronary revascularization (coronary artery bypass graft or PCI). Baseline clinical data from the dedicated registry, including past medical history, presence of risk factors, medications, angiographic and procedural data, and clinical outcomes, were recorded prospectively by research coordinators. This study was approved by the local institutional review board and waived the requirement for informed consent.

Percutaneous coronary intervention was performed using standard intervention techniques.11 The decision to pursue invasive treatment, as well as determining the access site, stent type for intravascular ultrasound, and use of glycoprotein IIb/IIIa receptor inhibitors, was left to the physician's discretion. Myocardial blush grade was evaluated using a final angiogram, as described previously.12 All interventions and procedural anticoagulations were performed in accordance with current standard guidelines.13

The primary outcome was myocardial infarct size (% of the left ventricle [LV] mass) measured by CMR. Secondary outcomes were AAR (% of LV mass), MSI (%), microvascular obstruction, and hemorrhagic infarction. Major adverse cardiovascular events were defined as a composite of all-cause death, myocardial infarction, and repeat coronary revascularization.

Definition of Electrocardiogram Analysis

A STEMI diagnosis was made when ECG change fit the standard definition of new ST elevation at the J-point in at least 2 contiguous leads of at least ≥ 2mm (0.2mV) in men or ≥ 1.5mm (0.15mV) in women in leads V2-V3 and/or of ≥ 1mm (0.1mV) in other contiguous chest leads or the limb leads plus one of the following 2 criteria: duration of chest pain more than 30minutes or elevation of serum cardiac enzyme markers.14 A reciprocal change was defined as the presence of a 0.1-mV depression 80 msec after the J-point in 2 or more adjacent leads far from the leads exhibiting ST-segment elevation.15 Patients were stratified according to the presence or absence of reciprocal ECG changes.

Cardiac Magnetic Resonance Imaging Acquisition and Analysis

Cardiac magnetic resonance was performed using a 1.5-T scanner (Achieva; Philips Medical Systems, Best, The Netherlands) with a SENSE cardiac coil according to our laboratory protocol.16 Images were acquired using electrocardiographic gating and expiratory breath holds. The CMR protocol consisted of cine, T2-weighted images, first-pass perfusion, and late-gadolinium enhancement imaging. Cine imaging was carried out based on balanced steady-state free precession sequences along the long and short axes from the apex to the base of the LV. Next, T2Ws were acquired in the cardiac short-axis direction using a dark-blood T2W inversion-recovery fast-spin echo sequence. First-pass perfusion imaging was obtained with the T1-weighted dynamic sequence (turbo field echo with SENSE, repetition time/echo time=2.6/1.3ms) after intravenous infusion of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA, Magnevist; Bayer Schering Pharma, Berlin, Germany; 0.15 mmol/kg weight in total amount at 3mL/sec). Slice thickness was set to 6mm with a field of view of 40cm × 40cm and an image matrix of 128 × 128. Images of 4 locations for every 2 heartbeats were acquired for 40 phases.

The CMR images were analyzed using validated software (ARGUS; Siemens Medical System, Erlangen, Germany) at our MRI core laboratory by 2 experienced radiologists who were blinded to the clinical information. After acquisision of the short-axis images at the end of diastole and at the end of systole, endocardial borders were traced manually. Left ventricle, end-diastolic volume, end-systolic volume, and ejection fraction were calculated using the Simpson rule. The infarct volume was quantified as the sum of the area with late-gadolinium enhancement within each segment of the short-axis images multiplied by slice thickness to cover the entire LV.17 The infarct area was traced by the visual border detection via a manual drawing method using commercialized analysis software. Microvascular obstruction was defined and planimetered manually as a hypointense core within an infarcted myocardium on late-gadolinium enhancement images. The AAR mass was defined from T2W images as the myocardial mass with signal intensity ≥ 2 standard deviations above remote. The AAR mass was then normalized to the LV myocardial mass to estimate the AAR percentage. Intramyocardial hemorrhage was identified and planimetered manually as a hypointense core within the AAR on T2W images. Myocardial salvage was calculated as (AAR mass-infarct mass), and MSI was calculated as (myocardial salvage/AAR mass) and was expressed as a percentage.9,18Figure 1 shows a representative CMR image of reperfused nonanterior STEMI with or without reciprocal ST change.

Figure 1.

Representative cardiac magnetic resonance images from a study of nonanterior ST-segment elevation myocardial infarction with and without reciprocal change. A: a short-axis slice of a T2-weighted image with reciprocal change. B: a short-axis slice of a late-gadolinium enhancement image with reciprocal change. C: a short-axis slice of a T2-weighted image without reciprocal change. D: a short-axis slice of a late-gadolinium enhancement image without reciprocal change.

(0.3MB).
Statistical Analysis

Continuous variables were compared using Student t test or the Wilcoxon rank-sum test where applicable and are presented as mean±standard deviation or median with interquartile range [IQR]. Categorical data were tested using the Fisher exact test or the chi-square test, as appropriate. Covariates that appeared to be relevant by virtue of having P-values < .2 on univariate analysis or were otherwise clinically relevant were included in our risk factor adjustment model, using the multiple linear regression model. To balance the underlying demographic and clinical characteristics, we also considered the propensity score method. Propensity scores were estimated using a multiple logistic regression model that included all variables presented in Table 1. The covariate balance was assessed by comparing the absolute standardized differences in covariates between the 2 groups (Table of the supplementary material). In the propensity score-matched patients, continuous variables as primary outcome and secondary outcomes of CMR were compared with a paired t test or the Wilcoxon signed-rank test. Categorical variables were compared with the McNemar or Bowker test of symmetry, as appropriate. We checked the residual plots thoroughly, including Cook's distance and the normal probability plots, and confirmed them to be satisfactory before adopting any final model results.

Table 1.

Baseline Clinical and Angiographic Characteristics

Variables  With reciprocal change  Without reciprocal change  P 
  n=133  n=111   
Age  59.5±11.9  58.4±11.6  .5 
Male sex, %  101 (75.9)  92 (82.9)  .21 
Height, cm  165.4±8.1  166.1±7.9  .47 
Weight, kg  68.8±13.3  67.6±11.3  .49 
Body mass index, kg/m2  25.0±3.6  24.4±3.2  .19 
Body surface area, m2  1.77±0.20  1.76±0.18  .71 
Systolic blood pressure, mmHg  129.7±26.8  139.4±27.5  .09 
Diastolic blood pressure, mmHg  81.9±18.0  89.7±19.1  .006 
Initial heart rate, bpm  77.0±22.4  81.4±18.3  .001 
Electrocardiogram finding
Anterior infarction  37 (27.8)  79 (71.2)  < .001 
Resolution of ST change after 30 min  94 (70.7)  76 (68.5)  .78 
Resolution of ST change after 60 min  102 (76.7)  83 (74.8)  .77 
Total length of ST elevation  8.1±6.3  7.4±5.1  .31 
Past medical history
Smoking      .58 
Current smoker  64 (48.1)  55 (49.5)   
Ex-smoker  20 (15.0)  21 (18.9)   
Diabetes mellitus  37 (27.8)  18 (16.2)  .032 
Hypertension  68 (51.1)  43 (38.7)  .07 
Dyslipidemia  26 (19.55)  14 (12.60)  .17 
Previous stroke  5 (3.8)  2 (1.8)  .46 
Medication
Calcium channel blocker  19 (14.3)  11 (9.9)  .33 
Beta-blocker  7 (5.3)  8 (7.2)  .6 
Angiotensin converting enzyme inhibitor  0 (0.0)  2 (1.8)  .21 
Angiotensin II receptor blockers  13 (9.8)  11 (9.9) 
Diuretics  6 (4.5)  3 (2.7)  .52 
Symptom to balloon time, min  221.5±169.8  289.7±337.3  .042 
Symptom to door time, min  147.9±139.3  179.7±176.0  .12 
Troponin I  114.68±113.93  90.61±117.79  .11 
Killip class.34 
116 (87.2)  102 (91.9)   
2 (1.5)  3 (2.7)   
5 (3.8)  1 (0.9)   
10 (7.5)  5 (4.5)   
Infarct-related artery< .001 
Left main artery  2 (1.5)  0 (0.0)   
Left anterior descending artery  36 (27.1)  78 (70.3)   
Left circumflex artery  20 (15.0)  12 (14.6)   
Right coronary artery  75 (56.4)  21 (18.9)   
Proximal occlusion of infarct-related artery  84 (63.2)  66 (59.5)  .60 
Extent of coronary artery disease.51 
1-vessel disease  68 (51.1)  65 (58.6)   
2-vessel disease  45 (33.8)  33 (29.7)   
3-vessel disease  20 (15.0)  13 (11.7)   
TIMI flow (initial).06 
107 (80.5)  74 (66.7)   
9 (6.8)  8 (7.2)   
9 (6.8)  13(11.7)   
8 (6.0)  16 (14.4)   
TIMI flow (final)
6 (4.5)  5 (4.5)   
127 (95.5)  106 (95.5)   
Rentrop grade.99 
61 (45.9)  50 (45.0)   
51 (38.3)  44 (39.6)   
20 (15.0)  16 (14.4)   
1 (0.8)  1 (0.9)   
Final myocardial blush grade.38 
0 (0.0)  1 (0.9)   
11 (8.3)  6 (5.4)   
122 (91.7)  104 (93.7)   
Thrombus aspiration  95 (74.1)  60 (54.1)  .007 
Stent insertion  128 (96.2)  106 (95.5) 
Glycoprotein IIb/IIIa used  28 (21.15)  16 (14.45)  .19 
No reflow phenomenon  13 (9.8)  2 (1.8)  .014 
Side branch occlusion  2 (1.50)  4 (3.65)  .42 

TIMI, Thrombolysis In Myocardial Infarction.

Values are presented as mean±standard deviation or as No. (%).

All tests were 2-tailed, and P < .05 was considered statistically significant. All analyses were performed using the Statistical Analysis Software package (SAS version 9.2, SAS Institute, Cary, North Carolina, United States).

RESULTSPatient Baseline Characteristics

Of the 301 registered patients, 39 who had chest pain before the 12-hour evaluation period and 18 who underwent previous PCI and coronary artery bypass grafting were excluded from our analysis. A total of 244 patients met our inclusion criteria for undergoing successful primary PCI and CMR imaging. These patients were divided into 2 groups: those with reciprocal change (n=133) and those without reciprocal change (n=111; Figure 2).

Figure 2.

The flowchart of the study population. CABG, coronary artery bypass graft; CMR, cardiac magnetic resonance imaging; ECG, electrocardiogram; STEMI, ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention.

(0.2MB).

The baseline clinical and angiographic characteristics by patient group are summarized in Table 1. Patients with reciprocal change had a higher frequency of diabetes mellitus (27.8% vs 16.2%; P=.032) and nonanterior infarction (72.2% vs 28.8%; P < .001) than those without. Pain onset to balloon time was shorter in patients with reciprocal change (221.5±169.8 vs 289.7±337.3 min; P=.042). Patients with reciprocal change had a higher incidence of baseline Thrombolysis In Myocardial Infarction flow of grade 0, thrombus aspiration, and no reflow during PCI compared with those without reciprocal change. Coronary angiography a found similar distribution of contralateral disease between the 2 groups (38.3% vs 35.1%; P=.69). The baseline clinical and angiographic characteristics in propensity score-matched patients are shown in Table 2.

Table 2.

Baseline Clinical and Angiographic Characteristics in Propensity Score-matched Patients

Variables  With reciprocal change  Without reciprocal change  P 
  n=65  n=65   
Age  59.6±11.4  59.4±12.7  .94 
Male sex, %  53 (81.5)  51 (78.5)  .83 
Height, cm  166.3±7.8  165.1±9.3  .43 
Weight, kg  69.8±11.9  67.9±12.8  .34 
Body mass index, kg/m2  25.1±3.1  24.8±3.6  .49 
Body surface area, m2  1.79±0.18  1.76±0.20  .32 
Systolic blood pressure, mmHg  135.3±24.3  137.4±27.9  .64 
Diastolic blood pressure, mmHg  85.8±16.8  88.0±19.9  .46 
Initial heart rate, bpm  82.8±22.0  82.1±19.5  .86 
Electrocardiogram finding
Anterior infarction  34 (52.3)  36 (55.4)  .86 
Resolution of ST change after 30 min  49 (75.4)  43 (66.2)  .21 
Resolution of ST change after 60 min  52 (80.0)  48 (73.8)  .045 
Total length of ST elevation  9.4±7.7  6.1±3.7  .004 
Past medical history
Smoking      .89 
Current smoker  31 (47.7)  29 (44.6)   
Ex-smoker  12 (18.5)  11 (16.9)   
Diabetes mellitus  17 (26.2)  12 (18.5)  .4 
Hypertension  29 (44.9)  30 (46.2) 
Dyslipidemia  11 (16.9)  9 (13.8)  .81 
Previous stroke  0 (0.0)  1 (1.5) 
Medication
Calcium channel blocker  6 (9.2)  9 (13.8)  .58 
Beta-blocker  3 (4.6)  6 (9.2)  .49 
Angiotensin converting enzyme inhibitor  0 (0.0)  2 (3.1)  .50 
Angiotensin II receptor blockers  6 (9.2)  9 (13.8)  .58 
Diuretics  3 (4.6)  3 (4.6) 
Symptom to balloon time, min  242.8±196.1  242.3±160.4  .99 
Door to balloon time, min  83.5±140.1  76.2±32.8  .68 
Symptom to door time, min  159.3±143.3  166.2±159.8  .79 
Killip class
58 (89.2)  59 (90.8)   
2 (3.1)  1 (1.5)   
1 (1.5)  1 (1.5)   
4 (6.2)  4 (6.2)   
Infarct-related artery.34 
Left main artery  2 (3.1)  0 (0.0)   
Left anterior descending artery  30 (46.2)  36 (55.4)   
Left circumflex artery  8 (12.3)  10 (15.4)   
Right coronary artery  23 (35.4)  19 (29.2)   
Extent of coronary artery disease.79 
1-vessel disease  34 (52.3)  33 (50.8)   
2-vessel disease  23 (35.4)  21 (32.3)   
3-vessel disease  8 (12.3)  11 (16.9)   
TIMI flow (initial)
50 (76.9)  49 (75.4)   
3 (4.6)  4 (6.2)   
7 (10.8)  6 (9.2)   
5 (7.7)  6 (9.2)   
TIMI flow (final) grade 3  63 (96.9)  62 (95.4) 
Rentrop grade.82 
33 (50.8)  29 (44.6)   
22 (33.8)  27 (41.5)   
9 (13.8)  8 (12.3)   
1 (1.5)  1 (1.5)   
Final myocardial blush grade.21 
0 (0.0)  1 (1.5)   
8 (12.3)  3 (4.6)   
57 (87.7)  61 (93.8)   
Thrombus aspiration  39 (60.0)  39 (60.0) 
Stent insertion  62 (95.4)  60 (92.3)  .72 
Glycoprotein IIb/IIIa used  12 (18.5)  10 (15.4)  .82 
No reflow phenomenon  1 (1.5)  2 (3.1) 
Side branch occlusion  1 (1.5)  2 (3.1) 

TIMI, Thrombolysis In Myocardial Infarction.

Values are presented as mean±standard deviation or as No. (%).

Cardiac Magnetic Resonance Imaging Findings

Patients underwent CMR at a median of 3 days [IQR 3-5] after primary PCI, and there was no a significant difference between 2 groups (4.9±5.7 vs 5.0±5.5 days; P=.93). Infarct size, the primary outcome, was not significantly different between patients without and with reciprocal change (median [IQR]: 18.33% [12.34–27.65] vs 17.95% [11.44–25.49]; P=.35). Although patients with reciprocal changes had significantly higher AAR than those without (37.24% [27.83–46.82] vs 33.28% [20.07–44.27]; P=.05), MSI was not significantly different between the groups (48.57% [34.65–58.69] vs 44.63% [33.15–56.88]; P=.27). The other CMR parameters, including LV ejection fraction (P=.46), LV end-diastolic volume (P=.89), LV end-systolic volume (P=.83), LV stroke volume (P=.46), LV cardiac output (P=.56), LV mass (P=.66), the presence of microvascular obstruction (P=.15), and hemorrhagic infarction (P=.12), were not significantly different between the groups (Table 3). In a propensity score-matched subset data, CMR outcome parameters were not significantly different (Table 4).

Table 3.

Cardiac Magnetic Resonance Imaging Parameters

Variables  With reciprocal change  Without reciprocal change  P 
  n=133  n=111   
LVEDV, mL  142.70 [121.71-164.48]  143.04 [123.02-163.04]  .89 
LVESV, mL  66.55 [50.04-82.18]  67.96 [49.43-82.62]  .83 
LV ejection fraction, %  53.80 [45.05-60.61]  53.81 [46.93-60.92]  .46 
LV stroke volume, mL  72.67 [63.28-85.49]  75.62 [64.2-85.79]  .87 
LV cardiac output, L/min  4.93 [4.26-5.61]  5.13 [4.55-5.88]  .56 
LV mass, g  100.70 [84.33-118.61]  100.45 [78.81-116.45]  .66 
Infarct size/LV, % of LV mass  18.33 [12.34-27.65]  17.95 [11.44-25.49]  .35 
Area at risk/LV, % of LV mass  37.24 [27.83-46.82]  33.28 [20.07-44.27]  .05 
Myocardial salvage index, %  48.57 [34.65-58.69]  44.63 [33.15-56.88]  .27 
Presence of microvascular obstruction  84 (63.2)  60 (54.1)  .15 
Presence of hemorrhagic infarction  65 (48.9)  43 (38.7)  .12 
Variables  Slope estimate*  Standard error*  P* 
Infarct size/LV, % of LV mass  2.11  1.43  .14 
Area at risk/LV, % of LV mass  6.97  2.20  .002 
Myocardial salvage index, %  5.47  2.66  .041 

LV, left ventricle; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume.

Unless otherwise indicated, values are presented as median [interquartile range] or No. (%).

*

Results were from the multiple linear regression model, including propensity score and the covariates such as reciprocal change, sex, body mass index, systolic blood pressure, diastolic blood pressure, symptom to balloon time (min), previous stroke, Killip class, infarct-related artery, Rentrop grade, and thrombus aspiration for confounding adjustment.

Table 4.

Parameters of Cardiac Magnetic Resonance Imaging as Outcomes in Propensity Score-matched Subset Data

Variables  With reciprocal change  Without reciprocal change  P* 
  n=65  n=65   
Infarct size/LV, % of LV mass)  18.34 [10.61-26.92]  17.99 [12.31-25.97]  .65 
Area at risk/LV, % of LV mass  37.62 [25.85-50.71]  33.60 [20.56-42.52]  .06 
Myocardial salvage index, %  46.86 [38.18-56.47]  40.18 [32.51-54.00]  .12 

LV, left ventricle.

Values are presented as median with interquartile range [Q1-Q3].

*

P-values were estimated with the Wilcoxon signed-rank test.

After the performance of multiple linear regressions that included propensity scores and other adjustments for confounding variables, patients with reciprocal change had a larger extent of AAR (slope estimate=6.97, standard error [SE]=2.20, P=.002), and a greater MSI (slope estimate=5.47, SE=2.64, P=.04) compared with those without. Consequently, myocardial infarct size was not significantly different between the 2 groups (slope estimate=2.11, SE=1.43, P=.14).

The overall reciprocal change in ST depression was associated with infarct size (slope estimate=0.57, SE=0.25, P=.021) and AAR (slope estimate=1.02, SE=0.35, P=.004), according to our analysis.

Clinical Outcomes

The cumulative clinical outcomes of the study patients are summarized in Table 5. The median length of follow-up was 26.7 [IQR: 12.8–40.9] months and was not significantly different between patients without reciprocal change (28.2 [IQR: 11.1–42.8] months) and those with reciprocal change (25.9 [IQR: 13.3–38.9] months, P=.54).

Table 5.

Clinical Outcomes of the Group With Reciprocal Change Compared With the Group Without Reciprocal Change During the Follow-up Period

Total population  With reciprocal change  Without reciprocal change  Unadjusted HR  Pa 
n=244  n=133  n=111  (95%CI)   
All-cause death  3 (2.3)  4 (3.6)  0.74 (0.16-3.43)  .70 
Myocardial infarction  2 (1.5)  2 (1.8)  0.84 (0.12-6.00)  .87 
Any repeat revascularization  9 (6.8)  6 (5.4)  1.22 (0.44-3.44)  .70 
MACEb  12 (9.0)  10 (9.0)  1.05 (0.45-2.44)  .92 

95%CI, 95% confidence interval; HR, hazard ratio; MACE, major adverse cardiovascular events.

Unless otherwise indicated, data are expressed as No. (%)

a

P-values from the log-rank test, along with hazard ratio from a simple Cox regression.

b

MACE included all-cause death, recurrent myocardial infarction, and any revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

The log-rank test indicated no significant differences in event times to clinical outcomes between the 2 groups (Table 5). The major adverse cardiovascular events occurred in 9% of patients with or without reciprocal change and were not significantly different (HR, 1.05; 95%CI, 0.45–2.44; P=.92; Table 5).

DISCUSSION

We compared CMR imaging findings and clinical outcomes between patients with and without reciprocal ECG change in the context of STEMI. The major findings of this study were as follows: a) patients with reciprocal change had a higher frequency of nonanterior infarction and shorter total ischemic time than those without; b) reciprocal ST-segment change was associated with a larger extent of at-risk ischemic myocardium, but also more salvaged myocardium. Final infarct size, as assessed by CMR imaging, was not associated with reciprocal ST-segment change, and c) there was no significant difference in major adverse cardiovascular event-free survival according to the presence or absence of reciprocal ECG change.

The underlying mechanism of concomitant ST-segment depression in patients with STEMI is highly controversial. Previous studies have found that reciprocal change in ST-segment depression was a main electrocardiographic finding across a broad spectrum of patients with regard to myocardial infarction size, severity of coronary artery disease, and the amount of jeopardized myocardium.19–21 Therefore, there is a need for better evaluations that allow for a more accurate gradation of risk. Other researchers have speculated that reciprocal ST-segment depression may reflect a more extensive infarction,5,22,23 additional ischemia beyond the infarct zone,6,23,24 more diffuse coronary artery disease,25,26 or simply a benign mirror projection of the ST-segment elevation without significant clinical relevance.8,27 Most of the previous studies cited above investigated the association of reciprocal change with myocardial injury through cardiac enzyme assessment, positron emission tomography, or ventriculography.7,28–30 However, the pathologic mechanisms underlying this association are still unclear. Cardiac magnetic resonance imaging can accurately estimate the extent of myocardial injury and salvaged myocardium and thus offer a better understanding of reciprocal ST-segment depression in STEMI patients. Therefore, we assessed the relationship between reciprocal ECG change and myocardial injury as determined by CMR in STEMI patients undergoing primary PCI.

In this study, reciprocal ST-segment change was associated with a larger risk extent of ischemic myocardium and more salvaged myocardium, as assessed by CMR imaging. The results of this study are consistent with those of a previous study, which reported that 35 STEMI patients with reciprocal changes on admission ECG had a larger AAR mass and higher extent of salvaged myocardium according to CMR than those without.31 In both studies, no relationship was found between reciprocal change and myocardial infarct size. However, previous studies failed to explain why patients with reciprocal change had larger AAR with similar infarct size compared with those without.

We evaluated the impact of reciprocal ECG change on clinical outcomes between the study groups and found no significant differences in terms of major adverse cardiovascular events. Considering that myocardial infarct size is the most important prognostic factor for STEMI patients and that reciprocal change could not predict left ventricular dysfunction or adverse clinical outcomes, it seems that reciprocal change is not a reliable ischemia marker.15,32 In previous studies,30,33,34 the reciprocal ECG change was associated with larger infarction size. Increased AAR, not infarct size, in those with reciprocal ECG changes suggested a larger exposed ischemic mass at the time of the ECG in the era of primary PCI. The extent of AAR on T2-weighted imaging, as the myocardium to be infarcted prior to opening of the infarct-related artery, could be viable in the absence of complete necrosis. Our study found that compared with patients without reciprocal ECG changes, those with reciprocal ECG changes had a greater ischemic myocardium at risk, and a shorter total ischemic time. In addition, reciprocal ECG change was associated with a larger salvaged myocardium, but similar infarct size following primary PCI. Therefore, reciprocal ECG changes could be a marker of a larger ischemic myocardium at risk with viability in the early stage of STEMI, and suggest that there is a possibility of improving myocardial salvage following prompt and timely reperfusion therapy.

Comparing outcomes across patients with reciprocal change, however, the degree of total summation of ST depression with reciprocal change was significantly associated with a larger AAR (slope estimate=1.02, SE=0.35, P=.004). Initial total summation of ST depression was also associated with a larger infarct size (slope estimate=0.57, SE=0.25, P=.021). Consequently, this did not have a decisive effect on interventions for myocardial salvage. Whether these subsets of patients with reciprocal change allow us to predict outcomes from additional therapeutic interventions needs to be determined in future prospective studies.

Limitations

This study has several limitations. This was a nonrandomized observational study, and our results may have been significantly affected by confounding factors. Our study included data from a single center and had a limited number of patients, despite being the largest CMR study to date that assessed AAR values, infarct size, myocardial salvage, and MSI. Based on the inclusion and exclusion criteria of this single-center study and the treatment protocols used in specialized high-volume hospitals, our results may not be not generalizable to other STEMI populations, such as late STEMI presenters (> 12hours). Additionally, the predominantly male study populations limited the generalizability of the results. The patients were included over a relatively long time period during which therapeutic and guidelines changes could have occurred that could have influenced the results.

Additionally, the 2 groups were qualitatively quite different, and as a result, our participant loss was fairly significant when we attempted to match the groups. The number of pairs matched was extremely limited. Therefore, matched analysis was used to compare the results with those of the original unmatched cases. Had the number of unmatched cases been small, we would have attempted to identify the clinical reasons why they became unmatched.

Whether the real AAR is accurately delineated by T2-weighted CMR has been a matter of intense debate.35,36 Indeed, recent experimental data suggest that T2 may represent the actual infarct size rather than the real AAR,37 or may be influenced by the time between the acute event and image acquisition.38 It might be that hyperintense areas in T2-weighted sequences may not reflect the real AAR, and therefore provide biased estimates of myocardial salvage and inaccurate adjustments in statistical models. It has been recently suggested that edema might a dynamic phenomenon, and therefore unstable, during the first week after myocardial infarction. As opposed to early assessment alone, it might be crucial to perform CMR in a systematic narrow time window. For myocardial salvage measurement, we considered that early assessment of the AAR was crucial because myocardial edema was maximal and constant during the first week after infarction and decreased thereafter.39,40 Despite the lack of difference in the time interval from primary PCI to CMR between the groups (4.9±5.7 vs 5.0±5.5 days; P=.93), AAR size may vary significantly if measured 1 to 40 days after primary PCI, and the patients were not scanned at such a consistent narrow time window.

We could not completely rule out possible overestimation of the infarct size caused by the presence of edema on CMR within first 5 days. However, it would not have affected the results of our study because there was no significant difference in the time interval from primary PCI to CMR between the 2 groups.

The low event rate in our study population and the wide confidence intervals do not provide convincing evidence of poorer outcomes. In addition, the low incidence of events could be caused by a recruitment bias, with the inclusion of patients with nonsevere myocardial infarction in this CMR registry, as it showed a higher than expected incidence of Killip class I (87.2% and 91.9% in patients with and without reciprocal change). While adverse clinical events were not centrally adjudicated in our registries, all events were identified by the patients’ physicians and confirmed by the hospital's principal investigator.

CONCLUSIONS

Reciprocal ECG change was not associated with larger myocardial infarct size, but was associated with greater extent of ischemic myocardium and more myocardial salvage as assessed by CMR imaging in STEMI patients undergoing primary PCI. The presence of reciprocal ECG change might facilitate early diagnosis and reperfusion of STEMI, which in turn, would improve myocardial salvage.

CONFLICTS OF INTEREST

None declared.

WHAT IS KNOWN ABOUT THE TOPIC?

  • Numerous studies have aimed to determine the clinical implications of reciprocal change on ECG. However, the clinical significance of reciprocal change on ECG as ST-segment depression remote from the infarct site remains controversial, as reflected in a more extensive infarct size or the benign mirror phenomenon. Cardiac magnetic resonance imaging can accurately describe myocardial scar change and AAR in acute myocardial infarction. It can also be used to estimate the MSI, as a meaningful CMR outcome parameter of acute reperfused myocardial infarction.

WHAT DOES THIS STUDY ADD?

  • Patients with reciprocal change had a higher frequency of nonanterior infarction and shorter total ischemic time than those without.

  • Reciprocal ST-segment change was associated with a larger extent of at-risk ischemic myocardium, but also more salvaged myocardium. Final infarct size, as assessed by CMR imaging, was not associated with reciprocal ST-segment change.

  • There was no significant difference in major adverse cardiovascular event-free survival according to the presence or absence of reciprocal ECG change.

  • The presence of reciprocal ECG change might facilitate early diagnosis and reperfusion of STEMI would improve myocardial salvage.

References
[1]
F.J. Noriega, E. Jorge, D. Arzamendi, J. Cinca.
Mechanism and diagnostic potential of reciprocal ECG changes induced by acute coronary artery occlusion in pigs.
Heart Rhythm., 10 (2013), pp. 883-890
[2]
J. Cinca, M.J. Janse, H. Morena, J. Candell, V. Valle, D. Durrer.
Mechanism and time course of the early electrical changes during acute coronary artery occlusion. An attempt to correlate the early ECG changes in man to the cellular electrophysiology in the pig.
Chest., 77 (1980), pp. 499-505
[3]
E.J. Camara, N. Chandra, P. Ouyang, S.H. Gottlieb, E.P. Shapiro.
Reciprocal ST change in acute myocardial infarction: assessment by electrocardiography and echocardiography.
J Am Coll Cardiol., 2 (1983), pp. 251-257
[4]
M. Pichler, P.K. Shah, T. Peter, et al.
Wall motion abnormalities and electrocardiographic changes in acute transmural myocardial infarction: implications of reciprocal ST segment depression.
Am Heart J., 106 (1983), pp. 1003-1009
[5]
J.L. Willems, R.J. Willems, G.M. Willems, A.E. Arnold, F. Van de Werf, M. Verstraete, European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator..
Significance of initial ST segment elevation and depression for the management of thrombolytic therapy in acute myocardial infarction.
Circulation, 82 (1990), pp. 1147-1158
[6]
P.K. Shah, M. Pichler, D.S. Berman, et al.
Noninvasive identification of a high risk subset of patients with acute inferior myocardial infarction.
Am J Cardiol., 46 (1980), pp. 915-921
[7]
R. Katz, R.M. Conroy, K. Robinson, R. Mulcahy.
The aetiology and prognostic implications of reciprocal electrocardiographic changes in acute myocardial infarction.
Br Heart J., 55 (1986), pp. 423-427
[8]
R.N. Stevenson, K. Ranjadayalan, V. Umachandran, A.D. Timmis.
Significance of reciprocal ST depression in acute myocardial infarction: a study of 258 patients treated by thrombolysis.
Br Heart J., 69 (1993), pp. 211-214
[9]
I. Eitel, S. Desch, G. Fuernau, et al.
Prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction.
J Am Coll Cardiol., 55 (2010), pp. 2470-2479
[10]
M.G. Friedrich, H. Abdel-Aty, A. Taylor, J. Schulz-Menger, D. Messroghli, R. Dietz.
The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance.
J Am Coll Cardiol., 51 (2008), pp. 1581-1587
[11]
H.S. Jo, J.S. Park, J.W. Sohn, et al.
Culprit-Lesion-Only Versus Multivessel Revascularization Using Drug-Eluting Stents in Patients With ST-Segment Elevation Myocardial Infarction: A Korean Acute Myocardial Infarction Registry-Based Analysis.
Korean Circ J., 41 (2011), pp. 718-725
[12]
A.W. Van‘t Hof, A. Liem, H. Suryapranata, J.C. Hoorntje, M.J. De Boer, F. Zijlstra.
Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group.
Circulation, 97 (1998), pp. 2302-2306
[13]
P. Kolh, W. Wijns, N. Danchin, et al.
Guidelines on myocardial revascularization.
Eur J Cardiothorac Surg., 38 (2010), pp. S1-S52
[14]
G.N. Levine, E.R. Bates, J.C. Blankenship, et al.
2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions.
Circulation., 133 (2016), pp. 1135-1147
[15]
C.H. Croft, W. Woodward, P. Nicod, et al.
Clinical implications of anterior S-T segment depression in patients with acute inferior myocardial infarction.
Am J Cardiol., 50 (1982), pp. 428-436
[16]
Y.B. Song, J.Y. Hahn, H.C. Gwon, et al.
A high loading dose of clopidogrel reduces myocardial infarct size in patients undergoing primary percutaneous coronary intervention: a magnetic resonance imaging study.
Am Heart J., 163 (2012), pp. 500-507
[17]
O. Bondarenko, A.M. Beek, M.B. Hofman, et al.
Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR.
J Cardiovasc Magn Reson., 7 (2005), pp. 481-485
[18]
J. Ganame, G. Messalli, S. Dymarkowski, et al.
Impact of myocardial haemorrhage on left ventricular function and remodelling in patients with reperfused acute myocardial infarction.
Eur Heart J., 30 (2009), pp. 1440-1449
[19]
H.S. Lee, S.J. Cross, J.M. Rawles, K.P. Jennings.
Patients with suspected myocardial infarction who present with ST depression.
Lancet., 342 (1993), pp. 1204-1207
[20]
L. Holmvang, P. Clemmensen, G. Wagner, P. Grande.
Admission standard electrocardiogram for early risk stratification in patients with unstable coronary artery disease not eligible for acute revascularization therapy: a TRIM substudy. ThRombin Inhibition in Myocardial Infarction.
Am Heart J., 137 (1999), pp. 24-33
[21]
H. Raunio, V. Rissanen, M. Helin, S. Rehnberg, T. Romppanen, E. Janatuinen.
Early pronounced ST segment depression with marked J point decline heralding acute lethal clinical myocardial infarction: Necropsy-electrocardiographic correlative study.
Am Heart J., 103 (1982), pp. 32-37
[22]
G. De Luca, A.C. Maas, A.W. Van ‘t Hof, et al.
Impact of ST-segment depression resolution on mortality after successful mechanical reperfusion in patients with ST-segment elevation acute myocardial infarction.
Am J Cardiol., 95 (2005), pp. 234-236
[23]
F.J. Noriega, M. Vives-Borrás, E. Solé-González, J. García-Picart, D. Arzamendi, J. Cinca.
Influence of the extent of coronary atherosclerotic disease on ST-segment changes induced by ST elevation myocardial infarction.
Am J Cardiol., 113 (2014), pp. 757-764
[24]
M. Zoghi, C. Gurgun, O. Yavuzgil, et al.
The angiographic correlation between ST segment depression in noninfarcted leads and the extent of coronary artery disease in patients with acute inferior myocardial infarction: a clue for multivessel disease.
Can J Cardiol., 19 (2003), pp. 67-71
[25]
M. Kyriakidis, A. Antonopoulos, J. Barbetseas, et al.
Correlation of reciprocal ST-segment depression after acute myocardial infarction with coronary angiographic findings.
Int J Cardiol., 36 (1992), pp. 163-168
[26]
M.C. Tjandrawidjaja, Y. Fu, C.M. Westerhout, et al.
Resolution of ST-segment depression: A new prognostic marker in ST-segment elevation myocardial infarction.
Eur Heart J., 31 (2010), pp. 573-581
[27]
R.A. Tabbalat, J.I. Haft.
Are reciprocal changes a consequence of “ischemia at a distance” or merely a benign electric phenomenon? A PTCA study.
Am Heart J., 126 (1993), pp. 95-103
[28]
A. Nakano, J.D. Lee, H. Shimizu, et al.
Reciprocal ST-segment depression associated with exercise-induced ST-segment elevation indicates residual viability after myocardial infarction.
J Am Coll Cardiol., 33 (1999), pp. 620-626
[29]
T.E. Chen, P.H. Lo, T.C. Li, et al.
Prognostic significance of reciprocal ST-segment depression in patients with acute STEMI undergoing immediate invasive intervention.
Am J Emerg Med., 30 (2012), pp. 1865-1871
[30]
N.G. Dewhurst, A.L. Muir.
Clinical significance of “reciprocal” S-T segment depression in acute myocardial infarction. Relative contributions of infarct size and ischemia at a distance.
Am J Med., 78 (1985), pp. 765-770
[31]
A. Kidambi, A.N. Mather, A. Uddin, et al.
Reciprocal ECG change in reperfused ST-elevation myocardial infarction is associated with myocardial salvage and area at risk assessed by cardiovascular magnetic resonance.
Heart., 99 (2013), pp. 1658-1662
[32]
A.G. Wasserman, A.M. Ross, D. Bogaty, D.W. Richardson, R.G. Hutchinson, J.C. Rios.
Anterior ST segment depression during acute inferior myocardial infarction: evidence for the reciprocal change theory.
Am Heart J., 106 (1983), pp. 516-520
[33]
R.S. Gibson, R.S. Crampton, D.D. Watson, et al.
Precordial ST-segment depression during acute inferior myocardial infarction: clinical, scintigraphic and angiographic correlations.
Circulation., 66 (1982), pp. 732-741
[34]
H.L. Goldberg, J.S. Borer, J.G. Jacobstein, J. Kluger, S.S. Scheidt, D.R. Alonso.
Anterior ST-segment depression in acute inferior myocardial infarction: indicator of posterolateral infarction.
Am J Cardiol., 48 (1981), pp. 1009-1015
[35]
P. Croisille, H.W. Kim, R.J. Kim.
Controversies in cardiovascular MR imaging: T2-weighted imaging should not be used to delineate the area at risk in ischemic myocardial injury.
Radiology., 265 (2012), pp. 12-22
[36]
M.G. Friedrich, H.W. Kim, R.J. Kim.
T2-weighted imaging to assess post-infarct myocardium at risk.
JACC Cardiovasc Imaging., 4 (2011), pp. 1014-1021
[37]
H.W. Kim, L. Van Assche, R.B. Jennings, et al.
Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area-At-Risk.
Circ Res., 117 (2015), pp. 254-265
[38]
R. Fernandez-Jimenez, J. Sanchez-Gonzalez, J. Aguero, et al.
Myocardial edema after ischemia/reperfusion is not stable and follows a bimodal pattern: imaging and histological tissue characterization.
J Am Coll Cardiol., 65 (2015), pp. 315-323
[39]
E. Dall’Armellina, N. Karia, A.C. Lindsay, et al.
Dynamic changes of edema and late gadolinium enhancement after acute myocardial infarction and their relationship to functional recovery and salvage index.
Circ Cardiovasc Imaging., 4 (2011), pp. 228-236
[40]
T. Ibrahim, T. Hackl, S.G. Nekolla, et al.
Acute myocardial infarction: serial cardiac MR imaging shows a decrease in delayed enhancement of the myocardium during the 1st week after reperfusion.
Radiology., 254 (2010), pp. 88-97

Both authors contributed equally to this work as first authors.

Copyright © 2018. Sociedad Española de Cardiología
Idiomas
Revista Española de Cardiología (English Edition)

Subscribe to our newsletter

Article options
Tools
Supplemental materials
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.