We studied patients who developed after undergoing PCI for AMI between March 2010 and December 2019 at Jeju National University Hospital in Korea. AMI included ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI). The inclusion criteria for the present analysis were as follows: patients aged ≥18 years, patients demonstrating STEMI or NSTEMI, and patients undergoing PCI. The investigators defined AMI as per the universal definition of MI [13].

This study was approved by the Institutional Review Board (IRB) of Jeju National University Hospital (IRB No. 2022-02-001). The requirement for informed consent was waived by the IRB.

STEMI was defined as the experience of chest pain with ST-segment elevation ≥2 mm in ≥2 contiguous precordial leads, ≥1 mm in ≥2 limb leads, or new-onset left bundle branch block on electrocardiogram at admission, along with elevation of cardiac enzymes to at least more than three times the upper limit of the normal range [14]. If the patients showed an absence of persistent ST-segment elevation, with increased cardiac biomarkers, and the clinical context was appropriate, the patients were considered to have NSTEMI [15,16]. Diagnostic coronary angiography and PCI were performed through either the femoral or the radial artery after administration of unfractionated hepar in (50 to 100 I U/ kg), according to the general standard PCI guidelines [17]. Before PCI, all the patients were administered loading doses of 200-300 mg of aspirin and other antiplatelet agents. Coronary revascularization was defined as ≥70% diameter restenosis in a coronary artery by visual estimation, or the occurrence of typical angina and/or presentation of signs of ischemia and ≥50% diameter restenosis. During the in-hospital period, the patients received antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, and lipid-lowering agents. After discharge, patients were encouraged to stay on the same medications that they received during hospitalization. The total duration of the dual antiplatelet therapy was recommended to be more than 12 months in patients who had undergone PCI. The left ventricular (LV) wall motion score index (WMSI) was assessed using a 16-segment model [18]. Segmental wall motion was assessed by an experienced cardiologist as normal=1, hypokinetic=2, akinetic=3, and dyskinetic=4. Clinical follow-ups were routinely performed by visiting the outpatient department of cardiology at 6, 12, and 24 months, and whenever any clinical events occurred. If patients did not visit the hospital, outcome data were assessed via telephone interviews. The clinical events were not centrally adjudicated. The physician identified all the events, and the principal investigator of each hospital confirmed the events.

The exclusion criteria were as follows: fever before admission, active inf lammatory or infectious diseases, recent antibiotic consumption, use of thrombolytic agents, development of infarct-related mechanical complications, current treatment with corticosteroids, coronary artery bypass grafting, and therapeutic hypothermia. The duration of PCI was defined as the time from arrival to departure from the angiography room.

BT was measured every 4 or 8 hours during hospitalization using an infrared ear thermometer. Fever was defined as peak ear BT of more than 37.7℃. The patients were divided into two groups according to the presence or absence of fever after PCI. The fever group had BT ≥37.7℃, and the no-fever group had BT <37.7℃.

If the BT of patients undergoing PCI was above 37.7℃, they underwent physical examination as well as imaging and culture study to exclude infections. Culture studies included two pairs of blood, urine, sputum, and wound cultures, if the patients had a wound. If a culture was obtained, the site of the culture, type of organism detected by the culture, and the outcome were recorded. We detected organisms on culture studies by reviewing the list of positive cultures processed by the clinical microbiology laboratory at Jeju National University Hospital.

For continuous variables, differences between the two groups were evaluated using Student’s t -test. Data were expressed as mean±standard deviation. For discrete variables, differences were expressed as counts and percentages and analyzed using the chi-square test. Various clinical outcomes up to 2 years were estimated using the Kaplan-Meier analysis, and differences between the groups were compared using the log-rank test. Univariate and multivariate Cox proportional hazard models were used to analyze prognostic factors for mortality at 2 years. Statistical analyses were performed using SPSS version 20.0 for Windows (IBM, Markham, Canada), and a P-value of less than 0.05 was considered statistically significant.

Baseline characteristics of this study population are summarized in Table 1. The patients in the fever group were more likely to be female, had a higher prevalence of chronic kidney disease (CKD), and a longer duration of PCI. Systolic blood pressure, diastolic blood pressure, BT at admission, and LV ejection fraction (LVEF) after PCI in the fever group were lower than those in the non-fever group. In laboratory findings, white blood cell (WBC) count, hsCRP level, and peak creatine kinase-myocardial band (CKMB) were higher in the fever group, and other laborator y findings were not different between the groups. The rates of AMI and multivessel disease did not differ between the two groups.

Various clinical outcomes of the 2 years follow-up were analyzed using Cox proportional hazards ratio model analysis and Kaplan-Meier curve analysis, as shown in Fig. 2 and Table 2. Fever after PCI was associated with higher incidence of major adverse cardiac events (MACE) (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.07-2.28; P=0.021) (Fig. 2A), all-cause death (HR, 2.32; 95% CI, 1.18-4.45; P=0.014) (Fig. 2B), cardiac death (CD) (HR, 2.57; 95% CI, 1.02-6.76; P=0.049) (Fig. 2C) and any revascularization (HR, 1.69; 95% CI, 1.02-2.81; P=0.044) (Fig. 2D) than without fever. However, there was no significant difference in the incidence of recurrent MI, CVA, re-hospitalization due to heart failure, or stent thrombosis between the two groups.

Subgroup analyses were performed to compare the clinical outcomes according to LVEF (Table 3, Fig. 3). In patients with decreased LVEF (<50%), the incidence of MACE, re-hospitalization due to HF, and stent thrombosis was higher than that in patients with preserved LVEF (≥50%). The incidence of other clinical outcomes did not differ significantly between the groups. In patients with decreased LVEF, fever after PCI was associated with a higher incidence of any revascularization (HR, 2.11; 95% CI, 1.02-4.35; P =0.043); however, there was no significant difference in the incidence of other clinical outcomes. In patients with preserved LVEF, fever after PCI was not associated with the 2 years clinical outcomes.

Regression analysis was performed to evaluate predictors of fever after PCI (Table 4). In women, prior CKD, lower LVEF, higher LV WMSI, WBC count, peak CKMB level, and longer PCI duration were associated with fever after PCI. Procedures such as intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT), central line insertion, arterial line insertion, and cardiopulmonary resuscitation (CPR) were associated with fever after PCI. However, hsCRP or the procedural approach were not associated with the development the development of fever after PCI.

Culture studies were performed on the patients in the fever group. Culture results were positive in 30 patients (23.1% of the ten groups). Positive culture was found in 11 cases in blood culture, 13 cases in sputum, and 11 cases in urine. The main organisms of infection were coagulase-negative Staphylococcus, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus (Table 5).