Abstract
Background:
The association between the early repolarization pattern (ERP) and ventricular arrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) remains uncertain. We hypothesized that ERP predicts the risk of sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) during the acute phase of anterior STEMI.
Methods and Results:
We enrolled 1,460 consecutive patients with acute anterior STEMI. We identified an ERP-positive group and a 1:6 propensity-matched ERP-negative group of 183 and 471, respectively. Comparisons of sustained VT/VF, heart failure, major adverse cardiovascular events and all-cause death were based on Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression with adjustment for unmatched confounding factors. In our full matching propensity score cohorts, there were 8 out of 28 variables not matching between the 2 groups. The Kaplan-Meier curves showed ERP increased the risk of sustained VT/VF in 30 days (log-rank test P=0.00065). Adjusted for baseline unmatched confounding risk, the Cox hazards regression analysis showed sustained VT/VF was associated with the present of ERP (hazard ratio=2.915, 95% CI: 1.520–5.588, P=0.001).
Conclusions:
In a propensity score-adjusted cohort the presence of ERP had a multivariable-adjusted association with increased risk of sustained VT/VF in patients with anterior STEMI in the early 30 days.
Early repolarization pattern (ERP) has been recognized as a benign variant in young, healthy subjects, especially males, athletes, and African Americans.1–3
However, recent studies have shown that ERP is associated with an increased risk of cardiovascular death and sudden cardiac death (SCD).4–7
However, only a few studies have investigated the association between ERP and the risk of ventricular tachycardia (VT)/ventricular fibrillation (VF) and SCD in patients with acute myocardial infarction (AMI).7–14
The published studies suggest that ERP might increase the risk of VT/VF, but the study populations in these studies were heterogeneous. For example, 2 studies enrolled patients with non- ST-segment elevation myocardial infarction (STEMI),8,9
and some studies enrolled STEMI patients with different infarct sizes and locations.7–14
All these factors contribute to different propensity to the risk of VT/VF, so in our study, we enrolled patients who only had anterior STEMI caused by left anterior descending arterial (LAD) occlusion.
In our study, to avoid overlap of ERP and ST-T changes of AMI in precordial leads, we mainly focused on ERP in the inferior leads (II, III, aVF) and/or lateral limb leads (I, aVL), which were not affected by myocardial ischemia ST-T changes in the precordial leads. Furthermore, we used a preferable method of propensity score analysis, which is a superior and more refined statistical method of adjusting for potential baseline confounding variables, to investigate the association between the presence of ERP and sustained VT/VF in patients with anterior STEMI.
Methods
Study Population
From 1 January 2006 to 31 December 2015, we enrolled 1,460 consecutive patients with acute anterior STEMI from multiple centers. The data collection covered age, sex, cardiovascular risk factors, culprit artery, number of diseased coronary arteries, Killip class on admission, with or without percutaneous coronary intervention (PCI), and left ventricular ejection fraction (LVEF) on the initial echocardiography analysis. The presence of hypertension was both self-reported and measured 3 times with intervals of 5 min. Mean systolic blood pressure (SBP) ≥140 mmHg and/or mean diastolic blood pressure (DBP) ≥90 mmHg were deemed to indicate hypertension.15
Diabetes was also both self-reported and based on measurement of HbA1c
(HbA1c
>6.5) in line with the 2010 guidelines from the American Diabetes Association.16
Hyperlipidemia is measured up to Adult Treatment Panel III.17
Multivessel disease was defined as stenosis >75% in the LAD with >50% stenosis in more than 1 coronary artery. PCI, including balloon angioplasty and/or stent implantation, was performed only for the infarct-related artery.18,19
Diagnosis of STEMI and Indications for PCI and Coronary Artery Bypass Grafting (CABG)
STEMI is a clinical syndrome defined by characteristic symptoms of myocardial ischemia in association with persistent electrocardiographic (ECG) ST elevation and subsequent release of biomarkers of myocardial necrosis: (1) presentation within 12 h of the onset of symptoms (typical chest pain lasting for >30 min); (2) ST-segment elevation in V2–4
or extended to V1–6, in at least 2 contiguous leads with the following cutoff points: ≥0.2 mV in men or ≥0.15 mV in women in leads V2–3
and/or ≥0.1 mV in the other leads, and right (V3R–4R) and posterior (V7–9) derivations also obtained.18
The primary PCI was performed according to the ACC/AHA guideline as follows: in patients within 12 h of onset of STEMI; and in patients with STEMI presenting to a hospital with PCI capability within 90 min of first medical contact or within 120 min in a hospital without PCI capability; and in patients with STEMI who developed severe heart failure or cardiogenic shock and were suitable candidates for revascularization as soon as possible, irrespective of time delay; and in patients with STEMI and contraindications to fibrinolytic therapy with ischemic symptoms for <12 h.19
CABG is recommended in patients with acute MI according to the ACC/AHA guideline and was mainly performed in the following patients: (1) primary PCI had failed or could not be performed; (2) coronary anatomy was suitable for CABG; (3) persistent ischemia present in a significant area of myocardium at rest; and/or (4) hemodynamic instability refractory to nonsurgical therapy.20
ECG Analysis
ECG Collection
We analyzed the first recorded ECG (MAC 5000 ECG) at a paper speed of 25 mm/s when the patient arrived at hospital, calibration of 1 mV/10 mm, and filter of 150 Hz in 24 h when the patient arrived at the center. All ECGs were computer-analyzed and then manually read twice by 2 trained investigators blind to the clinical data and patient groupings. The QT interval was corrected for heart rate (HR) using the Bazett’s formula with a standard HR of 60 beats/min. Prolonged QTc interval was defined as QTc ≥440 ms (male), and ≥460 ms (female). Subjects were excluded for poor ECG quality, missing data, QRS duration ≥110 ms, paced rhythm, or atrial fibrillation/flutter on ECG.
Definition and Distribution of ERP
ERP was defined as QRS slurring or notching ≥0.1 mV or J-point elevation in ≥2 contiguous inferior (II, III, aVF) and/or lateral limb ECG leads (I, aVL).21,22
The leads V1–3
were excluded from the analysis. QRS “notching” was defined as a positive deflection inscribed on the terminal QRS complex, and “slurring” as a smooth transition from the terminal QRS complex to ST segment. The amplitude of ERP was measured from baseline to the peak of the QRS notch or the onset of the QRS slur.21,22
Because there was an overlap between ERP and ischemia ST-T changes in the precordial leads (V4–6), ERP were described mainly in the inferior leads (II, III, aVF) and/or lateral limb leads (I, aVL). Two forms of ST segment were coded: 1 was a concave/ascending ST-segment elevation >0.1 mV within 100 ms after the peak of QRS notching, or the onset of QRS slurring, or J point; the other one was a horizontal/descending ST elevation ≤0.1 mV within 100 ms, or lasting over than 100 ms. The isoelectric line was defined as the level between TP intervals.21–23
A typical ECG is shown in
Figure 1.
We observed VT and/or VF lasted at least 30 s, and terminated spontaneously or by external electric defibrillation. Nonsustained VT lasting <30 s was excluded. For inpatients, we evaluated sustained VT/VF by ECG monitoring. For outpatients, 24–72 h Holter monitoring was required when patients complained of symptoms that indicated potential arrhythmia events. Major adverse cardiovascular events (MACE) in our study included cardiovascular death, re-infarction, and re-PCI. For all patients, regular outpatient visits were required every 2 months, and a 12-lead surface ECG was performed at 6- and 12-month visits.
Statistical Analysis
To adjust for the nonrandomized assignment of patients to ERP, a propensity score analysis was performed. Variables that were considered in the calculation of the propensity score included body mass index (BMI), male, age, SBP, hypertension, diabetes, smoking, drink, LVEF, left ventricular end-diastolic dimension (LVEDD), cTnT, NT-proBNP, creatinine, potassium, low-density lipoprotein (LDL), statins, β-blocker, amiodarone, angiotensin-converting-enzyme inhibitor (ACEI), intra-aortic balloon pump (IABP), Killip class, acute PCI, coronary stenosis, left main stenosis, QTc and HR. We built a logistic regression model in which ERP at baseline was a dependent variable, and the variables eventually related to VT/VF, heart failure, MACE or overall death were independent variables. These models made it possible to calculate a propensity score, indicating the likelihood that any individual patient would have ERP characteristics, given all other known covariates.
We used the full matching method (6→1 digit match) for the previously calculated propensity scores in order to make comparable patients in whom ERP was present vs. absent. Full matching made use of all individuals in the data set by forming a series of matched sets in which each set has either one treated individual and multiple comparison individuals or one comparison individual and multiple treated individuals. Full matching has been shown to be particularly effective at reducing bias related to observed confounding variables.24
After matching, we estimated the covariate balance between patients with or without ERP using absolute standardized differences,25
which directly quantifies the bias in the means and proportions of covariates across the groups, expressed as a percentage of the pooled standard deviations.
All continuous variables are expressed as mean±standard deviation and categorical variables as frequency (percentage) unless otherwise noted. We compared the baseline demographic, clinical, echocardiographic, and angiographic, electrocardiographic and medical variables, stratified by ERP. Continuous variables were analyzed using t test and categorical variables were compared using χ2
or Fisher’s exact test where appropriate. Because NT-proBNP values were not normally distributed, a logarithmic transformation was used. Survival curves were obtained by Kaplan-Meier analysis and compared with the log-rank test. Hazard risks of clinical variables for endpoints were determined with Cox proportional hazards regression analysis. To assess the independent association of ERP with endpoints, the Cox hazards regression analysis was performed including the 8 baseline clinical variables (ERP, ACEI, male, LVEF, cTnT, NT-proBNP, acute PCI, QTc, HR) that had the most significant difference between groups after propensity matching.
All statistical tests were two-sided, and P<0.05 was considered to indicate statistical significance. Propensity score matching was performed using the optmatch, RItools and MatchIt packages for R software (version 3.1.0).26
Stata (version 14, StataCorp LP, College Station, TX, USA) was used for analysis of the rest of the data. In the patients had ERP, we used χ2
analysis to evaluate the ECG characteristics of ERP in those with and without VT/VF.
Results
Baseline Characteristics of the Matching Population
The 1,460 consecutive patients with acute anterior STEMI were evaluated and divided into 2 groups based on ECG recorded within 24 h of their arrival at hospital. After using a full matching method (6→1 digit match) with 28 variables, there were 183 cases of ERP and 471 cases of no ERP. The comparison of their baseline characteristics is shown in
Table 1. As opposed to the entire population, these propensity-matched patients were well matched and there were only 8 baseline clinical variables (ACEI, Male LVEF, cTnT, NT-proBNP (log), acute PCI, QTc, HR) that had the most significant difference between groups after propensity matching (Table 1).
Table 1.
Baseline Characteristics of the Propensity Score Matching Population
| No. |
Variable |
ERP (+)
(n=183) |
ERP (−)
(n=1,277) |
P value |
Standardized
difference |
ERP (+)
(n=183) |
ERP (−)
(n=471) |
P value |
Standardized
difference |
| 1 |
Male (n) |
167
(91.2%) |
994
(77.8%) |
<0.001 |
37.8 |
167
(91.26%) |
393
(83.44%) |
0.009 |
23.7 |
| 2 |
Age (years) |
57.3±14.1 |
59.8±13.5 |
0.019 |
−18.1 |
57.3±14.1 |
58.8±13.3 |
0.2176 |
−10.6 |
| 3 |
BMI (kg/m2) |
25.1±3.4 |
24.8±3.4 |
0.297 |
8.8 |
25.1±3.4 |
24.9±3.4 |
0.5653 |
5.8 |
| 4 |
SBP (mmHg) |
125.0±20.4 |
122.0±20.0 |
0.133 |
14.8 |
125.0±20 |
124.0±20 |
0.6607 |
5.0 |
| 5 |
Hypertension (n) |
107
(58.5%) |
708
(55.4%) |
0.546 |
6.1 |
107
(58.47%) |
266
(56.48%) |
0.661 |
4.0 |
| 6 |
Diabetes (n) |
44
(24.0%) |
346
(27.1%) |
0.340 |
−7.0 |
44
(24.04%) |
114
(24.2%) |
1 |
−0.4 |
| 7 |
Smoking (n) |
105
(57.4%) |
686
(53.7%) |
0.392 |
7.4 |
106
(57.92%) |
258
(54.78%) |
0.484 |
6.3 |
| 8 |
Drink (n) |
57
(31.1%) |
398
(31.2%) |
0.926 |
0.0 |
57
(31.15%) |
152
(32.27%) |
0.852 |
−2.4 |
| 9 |
LVEF (%) |
51.6±7.9 |
46.6±9.6 |
0.000 |
56.9 |
51.6±7.9 |
49.4±9.5 |
0.008 |
25.1 |
| 10 |
LVEDD (mm) |
45.8±4.5 |
47.6±7.0 |
<0.001 |
−30.6 |
45.8±4.5 |
46.4±7.2 |
0.307 |
−10.0 |
| 11 |
cTnT (ng/ml) |
3.6±5.7 |
5.6±7.7 |
<0.001 |
−29.5 |
3.6±5.6 |
4.8±6.3 |
0.021 |
−20.1 |
| 12 |
NT-proBNP (ng/ml) |
6.67±1.45 |
7.56±1.50 |
<0.001 |
−60.3 |
6.7±1.5 |
7.2±1.5 |
0.0001 |
−33.3 |
| 13 |
Ccr (μmol/L) |
82.9±43.8 |
85.9±46.6 |
0.427 |
−6.6 |
83.0±43.0 |
83.2±40.4 |
0.947 |
−0.5 |
| 14 |
K+ (mmol/L) |
3.9±0.5 |
4.0±0.5 |
0.394 |
−20.0 |
3.93±0.42 |
3.95±0.40 |
0.495 |
4.9 |
| 15 |
LDL (mmol/L) |
2.7±1.0 |
2.6±0.9 |
0.161 |
10.5 |
2.6±1.0 |
2.6±0.8 |
0.610 |
0 |
| 16 |
Statins (n) |
176
(96.2%) |
1,189
(93.1%) |
0.155 |
13.7 |
179
(97.81%) |
454
(96.39%) |
0.463 |
8.5 |
| 17 |
β-blocker (n) |
156
(85.2%) |
970
(476.0%) |
0.01 |
|
158
(86.34%) |
403
(85.56%) |
0.901 |
2.2 |
| 18 |
Amiodarone (n) |
9
(4.9%) |
82
(6.4%) |
0.408 |
−6.5 |
9
(4.92%) |
20
(4.25%) |
0.677 |
3.2 |
| 19 |
ACEI (n) |
121
(66.1%) |
544
(42.6%) |
0.000 |
48.6 |
121
(66.12%) |
248
(60.3%) |
0.002 |
27.7 |
| 20 |
IABP (n) |
10
(5.5%) |
134
(10.5%) |
0.033 |
−18.6 |
10
(5.65%) |
36
(7.64%) |
0.396 |
−8.8 |
| 21 |
Killip class (n) |
|
|
<0.001 |
|
|
|
0.137 |
|
| 1–2 |
171
(93.4%) |
1,041
(81.5%) |
|
36.6 |
171
(93.44%) |
421
(89.38%) |
|
14.5 |
| 3–4 |
12
(6.6%) |
233
(18.2%) |
|
−36.0 |
12
(6.56%) |
50
(10.62%) |
|
−14.5 |
| 22 |
Acute PCI (n) |
99
(54.1%) |
488
(38.2%) |
0.016 |
32.3 |
99
(54.1%) |
205
(43.52%) |
0.015 |
21.2 |
| 23 |
Intervention (n) |
|
|
<0.001 |
|
|
|
0.513 |
|
| 0–1 |
18
(9.8%) |
305
(23.9%) |
|
−38.1 |
18
(9.84%) |
55
(11.68%) |
|
−5.9 |
| 2–4 |
163
(89.1%) |
958
(75.0%) |
|
37.2 |
163
(89.07%) |
413
(87.69%) |
|
4.3 |
| 24 |
Coronary arteries
affected Stenosis |
|
|
0.007 |
|
|
|
0.446 |
|
| 0 |
2
(1.1%) |
3
(0.2%) |
|
10.6 |
2
(109%) |
1
(0.212%) |
|
10.9 |
| 1 |
95
(52.0%) |
485
(38.0%) |
|
28.3 |
95
(51.91%) |
239
(50.74%) |
|
2.3 |
| 2 |
53
(29.0%) |
329
(25.8%) |
|
7.18 |
63
(34.43%) |
162
(34.39%) |
|
0.1 |
| 3 |
23
(12.5%) |
246
(19.3%) |
|
−18.4 |
23
(12.57%) |
69
(14.65%) |
|
−6.1 |
| 25 |
Left main Stenosis |
6
(3.3%) |
71
(5.6%) |
|
−11.1 |
6
(3.28%) |
16
(3.4%) |
1.000 |
−0.7 |
| 26 |
QTc (ms) |
435.3±34.7 |
459.9±40.4 |
0.000 |
−65.3 |
435±35 |
449±35 |
0.001 |
−40.0 |
| 27 |
HR (beats/min) |
69.5±12.5 |
79.5±16.9 |
0.000 |
−67.3 |
69±13 |
74±13 |
0.0003 |
−38.4 |
NT-proBNP values were not normally distributed, a logarithmic transformation was used. Intervention: 0=no intervention; 1=coronary angiography; 2=percutaneous transcoronary angioplasty; 3=percutaneous intervention with stent; 4=coronary bypass grafting. Coronary Stenosis: 0=no stenosis; 1=stenosis in LAD; 2=stenosis in LAD and the 1 other coronary vessel; 3=LAD and 2 other coronary vessels. ACEI, angiotensin-converting enzyme inhibitor; BMI, body mass index; HR, heart rate; IABP, intra-aortic balloon pumping; LAD, left anterior descending; LDL, low-density lipoprotein; LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; SBP, systolic blood pressure.
Kaplan-Meier survival curves are shown in
Figure 2. The log-rank test indicated that ERP was significantly associated with an increased the 30-day risk of VT/VF in patients with acute anterior STEMI (P=0.0065, log-rank test;
Figure 2A). Survival curves showed no difference in the incidence of heart failure (P=0.07), MACE (P=0.198), and all-cause death (P=0.7767) between patients with and without ERP (Figure 2B–D). The total number of endpoints (sustained VT/VF, all-cause death, heart failure, and MACE) are shown in
Table 2.
Table 2.
Endpoints of Acute Anterior STEMI Patients With or Without ERP
| |
ERP (+)
(n=183) |
ERP (−)
(n=471) |
P value |
| Sustained VT/VF |
19 |
22 |
0.007 |
| All-cause death |
10 |
23 |
0.760 |
| Heart failure |
41 |
30 |
0.064 |
| MACE |
26 |
50 |
0.198 |
P value refers to comparison using χ2. ERP, early repolarization pattern; MACE, major adverse cardiovascular events; STEMI, ST-segment elevation myocardial infarction; VF, ventricular fibrillation; VT, ventricular tachycardia.
We used Cox hazards regression analysis to evaluate the risk factors for VT/VF among propensity-matched patients (Table 3). ERP was associated with VT/VF (hazard ratio=2.915, 95% CI: 1.520–5.588, P=0.001); NT-proBNP was independently associated with VT/VF events in females (hazard ratio per unit increase on log-scale=1.332, 95% CI: 1.025–1.732, P=0.032); HR was associated with VT/VF (hazard ratio=1.031, 95% CI: 1.009–1.053, P=0.005).
Table 3.
Adjusted Cox Proportional Hazard Risk of VT/VF With Unmatched Variables Among Propensity Score Matched Cohort
| Variable |
HR |
95% CI |
P value |
| ERP |
2.915 |
1.520–5.588 |
0.001 |
| ACEI |
0.862 |
0.459–1.620 |
0.645 |
| Male |
1.343 |
0.605–2.982 |
0.468 |
| LVEF |
0.993 |
0.958–1.030 |
0.716 |
| cTnT |
0.950 |
0.886–1.019 |
0.150 |
| NT-proBNP |
1.332 |
1.025–1.732 |
0.032 |
| Acute PCI |
1.225 |
0.605–2.375 |
0.547 |
| QTc |
0.999 |
0.991–1.008 |
0.901 |
| HR |
1.031 |
1.009–1.053 |
0.005 |
BNP, B-type natriuretic peptide; cTnT, cardiac troponin TERP, early repolarization pattern; HR, heart rate. Other abbreviations as in Table 1.
The ECG characteristics of ERP were studied, including QRS slurring, QRS notching, ERP located in inferior leads, ERP amplitude >2 mm, ERP accompanied by horizontal ST segment, and the combinations of these characteristics (Table 3). Of the 183 patients with ERP, 91 (49.73%) showed notching, and 79 (43.17%) showed slurring. In 150 ERP (81.97%) was detected in the inferior leads and in the lateral limb leads in 33 (18.03%). Our χ2
analysis to evaluate whether the characteristics of ERP in patients with and without VT/VF differed revealed that neither the characteristics nor the lead distribution of ERP was significantly different between patients with and without VT/VF (Table 4).
Table 4.
ECG Characteristics of ERP in Patients With or Without VT/VF
| |
No-VT/VF
(n=164) (%) |
VT/VF
(n=19) (%) |
P value |
| Slurring |
75/164 (45.73) |
4/19 (21.05) |
0.070 |
| Notching |
78/164 (47.56) |
13/19 (68.42) |
0.139 |
| Inferior lead |
135/164 (82.31) |
15/19 (78.94) |
0.963 |
| J >2 mm |
26/164 (15.85) |
4/19 (21.05) |
0.801 |
| Horizontal ST |
146/164 (89.02) |
17/19 (89.47) |
0.742 |
| Slurring+inferior+horizontal ST |
55/164 (33.54) |
3/19 (15.79) |
0.189 |
| Notching+inferior+horizontal ST |
53/164 (32.32) |
8/19 (42.11) |
0.549 |
| Notching+inferior+J >2 mm+horizontal ST |
21/164 (12.80) |
4/19 (21.05) |
0.523 |
| Slurring+inferior+J >2 mm+horizontal ST |
3/164 (1.83) |
0 |
0.719 |
Abbreviations as in Table 2.
Discussion
The main finding in our study was that the presence of ERP had a multivariable-adjusted and propensity score-adjusted association with increased 30-day risk of sustained VT/VF in patients with anterior STEMI. There was no significant association between ERP and heart failure, MACE or overall death during the 15-month follow-up. Furthermore, in patients with ERP, the characteristics and lead distribution of ERP were comparable between patients with and without VT/VF. This is the first report of an association between the presence of ERP and VT/VF in patients with anterior STEMI using a propensity score analysis.
Association Between ERP and VT/VF in Patients With STEMI
It has been reported that, in community-based general subjects, ERP is associated with other ECG characteristics, such as lower resting HR, longer QRS duration, and shorter QTc interval, which was also reflected in our data.27,28
Because a lower resting HR and normal QTc interval are generally associated with reduced cardiovascular risk,29–31
the effects of ERP on VT/VF might be independent of these ECG characteristics. Furthermore, there are only a few reports about ERP associated with an increased risk of VT/VF in patients with STEMI or non-STEMI. In Patel et al’s retrospective case-control study, ERP was reported to be associated with VT (nonsustained VT was included) and VF in patients with STEMI after adjustment for creatine kinase-MB or LVEF.7
In Rudic et al’s prospective case-control study, ERP was reported to be associated with VF in 60 patients with STEMI or non-STEMI.8
And, in Ali Diab et al’s case-control study with 102 male STEMI patients, ERP was reported to be associated with sustained VT and VF.9
In Park et al’s study of STEMI patients who accepted PCI were enrolled consecutively, ERP was reported to be associated with atrial arrhythmia and VT (nonsustained VT was included) and VF,10
while in Ozcan et al’s study of prospectively enrolled STEMI patients who accepted PCI, ERP was associated with in-hospital and long-term death.11
In Naruse et al’s studies, AMI patients with J waves were more likely to develop VF within 48 h after the AMI onset.12,13
And Kim et al reported that ERP was associated with VF in their retrospective study.14
Even though these studies indicated that ERP is associated with VT/VF, they had inconsistent patient cohorts and outcome measurements, so studies without these inconsistencies are required to explore the association. In the present study, we enrolled more patients than the published studies7–14
and our patients only had anterior STEMI with the anterior left ventricular wall as the site of infarction, and we observed that sustained VT and VF were as common causes of SCD.
Mechanism of ERP and VT/VF in Patients With STEMI
It has been postulated that ERP is a sign of transmural electrical heterogeneity between the endocardium and epicardium during ventricular repolarization or depolarization. The electrophysiological changes of ERP result from a decrease in inward sodium or calcium currents or an increase in outward potassium currents of Ito, IK-ATP, and IK-Ach. This heterogeneity enlarges the repolarization dispersion and causes phase 2 re-entry-related ventricular arrhythmias.32–34
Acute myocardial ischemia is one of the most important factors for initiation of VT/VF, while ERP may suggest an existing repolarization heterogeneity that may have the same ionic basis for VT/VF during early acute myocardial ischemia. Therefore, patients with ERP on ECG may be more prone to develop VT/VF during the early phase of STEMI than those without ERP.7–14
However, there are many risk factors for VT/VF in STEMI patients, including infarct size and location, Killip class, door-to-balloon time, and LVEF, etc. Thus, we used propensity score analysis to reduce the bias from these factors and Cox hazard regression analysis to evaluate the association of ERP and the 8 mismatched variables after propensity matching. We found that ERP was associated with VT/VF.
Association Between ERP Characteristics and VT/VF
In our study, ERP was defined as a terminal QRS notch or slur (latter 50% of the R wave), or J-point elevation ≥0.1 mV (measured from isoelectric baseline to the peak of the notch or onset of a slur) in ≥2 contiguous leads. This definition is consistent with the terminology standardization proposed recently.21,22,35
It also suggested that ERP in an inferior lead, larger amplitude of ERP or J wave (>2 mm), and ERP manifesting as J wave or QRS notching may be associated with an increase in the risk of VT/VF, but the added risk value of these characteristics is limited to clinical decision making.1,6,14,23,36,37
In Naruse et al’s reports, ERP in the inferior leads, high-amplitude ERP, notched morphology of the ERP, and ERP with a horizontal/descending ST segment, were significantly associated with VF occurrence.12,13
In Rudic et al’s study, notching of the terminal portion of the QRS complex was the predominant morphology associated with the risk of VF, even after adjustment for LVEF and QTc.8
In Ali Diab et al’s study, inferior/inferolateral and global ERP, notched J wave, increasing J wave amplitude, and ST-segment elevation were associated with a higher risk of ventricular arrhythmias.9
However, Ozca et al reported that the presence of notching or a slurring pattern did not correlate with long-term mortality rates.11
In a retrospective study, Kim et al found that patients with VF were likely to have a notched J wave in the inferior leads and J-point elevation ≥0.2 mV, and the presence of notched QRS was associated with the occurrence of VF during acute MI.14
In our study, most of the ERP was located in the inferior leads with horizontal ST segment consistent with other reports.7,9,12,13
However, we did not find any difference in the ERP characteristics of patients with and without VT/VF, and there was no evidence to support that patients with anterior STEMI and ERP amplitude >2 mm in the inferior leads with horizontal ST segment had increased risk for VT/VF.
Study Limitations
First, this was a non-randomized, retrospective observational study. Second, propensity score matching was used to reduce selection bias, but the matching was limited and arbitrariness was not fully denied, and there were still 8 unmatched variables out of 28. However, the Cox proportional hazard model also identified that ERP was an independent predictor of VT/VF in propensity-matched anterior STEMI patients. Third, PCI reduced the malignant arrhythmia events in patients with acute STEMI, so the number of patients with sustained VT/VF was small and subject to reporting bias. Fourth, ECG data before acute MI were not available and we could not exclude that ERP was caused by ongoing myocardial ischemia. Fifth, ERP in precordial leads might be obscured by ischemic ST-T changes.
Conclusions
We used a full matching method and found that the presence of ERP had a multivariable-adjusted association with increased risk of sustained VT/VF in patients with anterior STEMI in the early 30 days in a propensity score-adjusted cohort.
Funding Source
This study was supported by Grants from Hebei Province Scientific and Technological Project (No. 16277707D) and Hebei Natural Science Foundation (H2015206386).
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