Impact of electrocardiographic morphology on clinical outcomes in patients with non-ST elevation myocardial infarction receiving coronary angiography and intervention: a retrospective study

Setting and patient population

This study retrospectively analyzed all patients who had received PCI after being diagnosed with NSTEMI at Kaohsiung Chang Gung Memorial Hospital from January 2008 to December 2010. Data were collected as previously described in Wang, Chen & Wu (2016). Specifically, the definition of NSTEMI was typical chest pain, troponin-I elevation ≥ 0.5 ng/ml and no ST-segment elevation by clinical ECG finding. The inclusion criterion in our study was patients with NSTEMI who received angiography within 72 h after presentation. The exclusion criteria included the availability of only one set of troponin-I data, the absence of a rising pattern of the troponin-I level during follow-up, or delayed PCI (more than 72 h) due to other etiologies (mostly to poor renal function, active bleeding and sepsis). Stent implantations for stenotic vessels were performed according to clinical guidelines  (Amsterdam et al., 2014). Data collection included baseline characteristics, ECG findings, left ventricular ejection fraction (LVEF) obtained by echocardiography or left ventricular angiography, coronary angiography and PCI data. Blood samples were evaluated when patients arrived at the ER (emergency room), and ECG was performed after the patients arrived, or if they had acute typical chest pain during hospitalization. We analyzed the in-hospital outcomes, including total mortality, cardiac death, ventricular arrhythmia and pulmonary edema. Patients received continued clinical follow-up after being discharged. The primary endpoint of this study was long-term mortality. The secondary endpoint was long-term cardiac death and non-fatal major adverse cardiac events (MACE), which were defined as target vessel revascularization, myocardial infarction (MI), stroke, and hospitalization for heart failure. An advanced Killip score was defined as a score ≥ 3 and advanced chronic kidney disease (CKD) was defined as an estimated glomerular filtrating rate <60 ml/min/1.73 m2. The study protocol was approved by the Institutional Review Committee for Human Research of Kaohsiung Chang Gung Memorial Hospital (201900344B0). The need for consent was waived by the Institutional Review Board of Kaohsiung Chang Gung Memorial Hospital.

Electrocardiography (ECG) definition

The ECG findings were classified as no significant ST-T change, ST depression or T wave inversion. ST depression was defined as horizontal or down-sloping ST segment depression ≥1 mV at 80 ms after a J point over at least 2 consecutive leads. T wave inversion was defined as the amplitude of an inverted T wave of at least 1 mm over at least 2 consecutive leads. Patients with 1 mm ST-segment depression and T-wave inversion were classified as having ST depression. ECG results that did not meet these criteria without significant ST segment elevation were defined as showing no significant ST-T change. Those patients who had some ST elevation, but not enough to meet STEMI criteria, were also classified as “no significant ST-T change”.

Coronary angiography and stenting

Coronary stent implantation was performed using procedures and protocols described in our previous publications (Wang, Chen & Wu, 2016; Chen et al., 2007; Chen et al., 2011). Briefly, diagnostic catheterization and intervention were performed as soon as possible within 72 h after the diagnosis of NSTEMI was confirmed. Before the procedure, dual antiplatelets (aspirin and clopidogrel) were given, and unfractionated heparin or low molecular weight heparin was given for heparinization, based on renal function. We did total revascularization for culprit lesions and all other radiographically significant stenoses at the index procedure for those patients presenting with NSTEMI, or treated non-culprit lesions at the staged procedure during the index admission. Left main (LM) lesions with ≥50% stenosis and lesions of the main trunk of triple vessels with more than 70% stenosis were usually treated (stenting if the vascular reference was ≥ 2.5 mm or balloon angioplasty for vascular references of 2.0–2.5 mm). Chronic total occlusive lesions usually did not undergo revascularization during the index procedure. We usually evaluated myocardial perfusion using a thallium-201 scan thereafter, during the OPD follow-up, and decided if revascularization was indicated for those patients. Most lesions were predilated with a 1:1 ratio of balloons prior to stent implantation. Most patients underwent post-stenting dilatation with a high-pressure balloon. Multiple-vessel disease (MVD) was defined as stenosis ≥50% in ≥2 major epicardial coronary arteries.

Post-percutaneous coronary intervention management

Patients were treated according to current clinical guidelines for post-PCI management (Wang, Chen & Wu, 2016). Our patients were covered under Taiwan’s National Health Insurance (NHI) program, which is a compulsory single-payer healthcare system featuring care coverage for more than 99.8% of the population in Taiwan. In accordance with NHI reimbursement criteria, dual antiplatelet therapies were given for at least 9 months and statin therapy was given for those patients with low-density lipoprotein ≥ 100 mg/dl, in the absence of contraindications. Patients were referred for cardiac rehabilitation routinely and the compliance rate was about 90%. Major risk factors such as smoking, hypertension, dyslipidemia, physical inactivity, obesity, and diabetes mellitus (DM) were also treated.

Statistical analysis

Unless otherwise stated, data were expressed as means ± standard deviation or as a number (percentage). Differences in continuous variables were analyzed using one-way analysis of variance for continuous variables, and categorical variables were analyzed using the chi-square test. Pairwise post hoc multiple comparisons between any 2 study groups were made using the Bonferroni adjustment. For long-term outcome analysis, those patients with T wave inversion and no significant ST change pattern were defined as the no-ST depression group. The independent predictors of long-term mortality were analyzed using the multiple stepwise Cox regression method. Event-free survival in patients with and without ST depression and also with different ECG patterns was evaluated and compared by the Kaplan–Meier method and log rank test. Statistical analysis was performed with statistical software (SPSS Statistics for Windows, version 17.0; SPSS Inc., Chicago, IL, USA). A 2-tailed p value <0.05 was considered statistically significant.

Baseline characteristics and in-hospital outcomes of the study patients

During the study period, 409 patients who had a clinical diagnosis of NSTEMI received coronary angiography and PCI. Forty-seven patients who met our exclusion criteria were excluded from analysis. Of the 362 patients enrolled in this study, 264 (72.9%) were males and the average age was 65.6 ± 12.2 years. Sixty-seven (18.5%) patients were classified as having ST depression, 91 (25.1%) as having T wave inversion, and the remaining 204 (56.4%) as having no significant ST-T change pattern. Patients with ST depression had a significantly higher percentage of DM and CKD than patients with T wave inversion and no significant ST-T changes (both P < .05). More of the patients with ST depression and T wave inversion had a past history of old MI and coronary artery bypass surgery (CABG) than the patients with no significant ST-T changes (both P <0.05). More patients with ST depression had an advanced Killip score, and patients with T wave inversion had a lower body mass index than patients with no significant ST-T change (both P <0.05). There was no significant difference in age, male gender, current smoker, hypertension, dyslipidemia, old stroke, peripheral vascular disease, percutaneous transluminal coronary angioplasty, or time to angiography among patients with different ECG patterns. Patients with ST depression had a higher creatinine level than other patients and a higher troponin-I level than patients with T wave inversion (both P <0.05). There was no significant difference in LVEF among patients with different ECG patterns (Table 1).

Total revascularization for culprit lesions and all other radiographically significant stenoses were achieved in 95.6% of patients during hospitalization (93.8% at the index procedure simultaneously for those patients presenting with NSTEMI and 1.8% at the staged procedure for non-culprit lesions during the index admission.) In terms of coronary angiography and PCI findings, more patients presenting with ST depression had left main disease than patients presenting with other ECG findings (P <0.05). There was no difference in the percentage of significant coronary artery disease (CAD), MVD, total stents number and types and post-PCI final thrombolysis in MI (TIMI)-3 flow among patients with different ECG patterns. Patients presenting with an ST depression pattern had more total in-hospital mortality, cardiac death and pulmonary edema events (P <0.05). The number of events of in-hospital ventricular tachycardia and fibrillation did not differ.

Primary outcome analysis: long-term mortality

The mean follow-up period was 66.3 ± 44.1 months: 60 (16.6%) patients died during that period. Total mortality was significantly higher among patients with ST depression than among those with T wave inversion and no significant ST-T change (P = 0.001) (Table 1).

Compared to the patients who survived, those who had died were significantly older (71.4 ± 9.4 vs. 64.4 ± 12.4 years, p < 0.001), and more likely to have DM, prior percutaneous transluminal coronary angioplasty (PTCA), advanced CKD, advanced Killip score and lower LVEF (all p < .05). Those patients who died were also more likely to have an ECG pattern of ST depression than the patients who survived (35.0 vs. 15.2%, p < 0.001) (Table 2). All variables with a P value ≤ 0.1 by univariate analysis were put into multiple stepwise Cox regression analysis, which showed that advanced Killip score (hazard ratio [HR] = 3.417, 95% confidence interval (CI): 1.966–5.939, P <0.001), age (HR = 1.043, 95% CI [1.015–1.072], P = 0.002), prior PTCA (HR = 1.987, 95% CI [1.110–3.558], P = 0.021), advanced CKD (HR = 1.871, 95% CI [1.044–3.354], P = 0.035) and ECG pattern of ST depression (HR = 1.809, 95% CI [1.015–3.223], P = 0.044) were the only independent predictors of long-term mortality (Table 3).

Figure 1A compares the Kaplan–Meier curves for primary endpoint among patients with and patients without an ECG pattern of ST depression. Long-term mortality was significantly higher in patients with ST depression than in those without ST depression (Log-rank p value <0.001). Figure 1B compares the Kaplan–Meier curves for primary endpoint among patients with different ECG patterns. Patients with ST depression were found to have a higher rate of long-term mortality than patients with T wave inversion and no significant ST-T changes (Log-rank p value <0.001).

Secondary endpoint analysis: long-term cardiac death and non-fatal MACE

Long-term cardiac death was significantly higher in patients with an ST depression ECG pattern than in patients with T wave inversion and no significant ST change pattern (P = 0.001) (Table 1). There was no difference in long-term non-fatal MACE among patients with different ECG patterns. The cardiac death rate was significantly higher in patients with an ST depression ECG pattern than in those without ST depression (Fig. 2A; Log-rank p value = 0.001). In Fig. 2B, a comparison of Kaplan–Meier curves for cardiac death among patients with different ECG patterns revealed that patients with ST depression had a higher rate of long-term cardiac death than patients with T wave inversion and no significant ST-T changes (Log-rank p value <0.001). Kaplan–Meier curves for non-fatal MACE among patients with and without an ST depression ECG patterns revealed that there was no difference in both groups (Log-rank P value = 0.228) (Fig. 3A). There was no difference in non-fatal MACE among patients with ST depression, no significant ST-T changes and T wave inversion (Log-rank P value = 0.482) (Fig. 3B).

Study limitations

Some limitations in this study should be noted. First, this was a retrospective cohort study. Second, this study did not include in the analysis NSTEMI patients who received conservative therapy. Therefore, this study might have selection bias. However, the clinical outcome was better in those patients who received in-hospital PCI compared with those patients who received conservative therapy, as reported in previous studies (Fox et al., 2006; Wong et al., 2009; Singh, 2005). All of our patients with significant CAD received PCI during hospitalization, and ST depression was still a strong predictor of long-term mortality and cardiac death.