Association of C₂HEST Score and New-Onset Atrial Fibrillation in Patients with Non-ST-Segment Elevation Myocardial Infarction

Introduction

Despite the significant improvement in the survival rate of patients with non-ST-segment elevation myocardial infarction (NSTEMI), due to the standardized application of percutaneous coronary intervention (PCI), a variety of complications still exists in this patient population [1,2]. New-onset atrial fibrillation (NOAF) is a frequent complication in patients with NSTEMI, with its reported incidence ranging from roughly 5% to 11% throughout the inpatient stay [3,4]. Research shows the development of NOAF in patients with NSTEMI who have undergone PCI is significantly related to their clinical outcomes [4,5]. Particularly important is that the treatment of patients with NSTEMI complicated by AF is still a challenge in clinical practice [6]. Therefore, it is important to implement effective risk stratification and identify patients who are at high risk as early as possible.

In recent years, the C2HEST score, a risk stratification tool for cardiovascular diseases, has been widely used in clinical practice [7,8]. Previous studies have confirmed that the C2HEST score not only effectively identifies the risk of AF occurrence in the general population but also has good predictive efficacy in some high-risk groups for AF [9–11]. Recently, Wang et al demonstrated that the combination of the C2HEST score and inflammatory markers can effectively predict the occurrence of NOAF during hospitalization in elderly patients with STEMI [12]. However, in the population of patients with NSTEMI, the relationship between the C2HEST score and NOAF remains unclear. In this study, we aimed to evaluate the value of the C2HEST score in predicting the occurrence of NOAF during hospitalization in patients with NSTEMI.

Material and Methods

STUDY POPULATION:

In this study, patients who received a diagnosis of NSTEMI at Suining County People’s Hospital from September 2022 to March 2025 were consecutively enrolled. NSTEMI was defined as a troponin I (TnI) level exceeding the 99th percentile, accompanied by clinical evidence as described in the Fourth Universal Definition of Myocardial Infarction, and no ST-segment elevation on electrocardiogram (ECG) [13]. The inclusion criteria were as follows: (1) successful PCI within 24 h after admission (thrombolysis in myocardial infarction [TIMI] grade 3); (2) ECG monitoring for at least 36 h during hospitalization; and (3) complete clinical data. The exclusion criteria were as follows: (1) history of previous MI; (2) history of previous AF, or patient taking antiarrhythmic drugs other than β-blockers; (3) severe renal insufficiency (estimated glomerular filtration rate <30 mL/min·1.73 m2); (4) severe valvular heart disease; (5) inflammatory diseases or autoimmune diseases; and (6) hematological diseases or malignant tumors. AF was diagnosed according to ECG findings. Specifically, it was characterized by the absence of P waves on a single-lead ECG recording for at least 30 s or on a 12-lead ECG. Instead, irregular f waves with variable morphology, amplitude, and cycle length were observed, accompanied by irregularly irregular R-R intervals [14]. NOAF was defined as the initial episode of AF that developed during hospitalization in patients who presented with sinus rhythm at admission and had no prior history of AF. The patients were divided into 2 groups according to whether NOAF occurred during hospitalization. This study protocol was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Suining County People’s Hospital (approval number: LL-2023–044). As per the IRB’s guidelines, given that this was a retrospective investigation without any potential risks to participants, the need for obtaining written informed consent was waived. Finally, a total of 665 patients with NSTEMI were enrolled (Figure 1).

DATA COLLECTION:

In this study, data regarding demographic characteristics, medical history, personal past history, and medication usage of the patients were collected through the electronic medical record system. Personal information included age, sex, height, and weight. The past medical history included heart failure, cerebral infarction, chronic obstructive pulmonary disease (COPD), diabetes mellitus, and hypertension. The medications recorded included antiplatelet agents, β-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins. Laboratory hematological indices included serum lipid, TnI, C-reactive protein (CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP). The calculation method of the C2HEST score was as follows: coronary artery disease was scored 1 point, COPD was scored 1 point, hypertension was scored 1 point, age ≥75 years was scored 2 points, heart failure was scored 2 points, and hyperthyroidism was scored 1 point [9–12]. Meanwhile, the infarct-related artery was carefully recorded according to the results of coronary angiography.

STATISTICAL ANALYSIS:

In this study, the collected data were analyzed using SPSS statistical software (IBM, SPSS, Version 16) and R statistical software (R Version 4.0.5, R Foundation for Statistical Computing). The Kolmogorov-Smirnov test was used to examine whether continuous variables followed a normal distribution. Continuous variables conforming to a normal distribution were expressed by mean±standard deviation, and independent sample t test was used for comparisons between the 2 groups. Continuous variables not conforming to a normal distribution were expressed by median (interquartile range), and a non-parametric test (Mann-Whitney U test) was used for comparisons between the 2 groups. Categorical variables were presented as the number of cases (percentage) and used the chi-square test or Fisher exact test for significance testing. In the univariate logistic regression analysis, indicators with P<0.05 were selected for inclusion in the multivariate logistic regression analysis using the stepwise forward regression method. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the C₂HEST score for the occurrence of NOAF during the hospitalization of patients. The restricted cubic spline model was used to investigate the dose-response relationship between the C₂HEST score and the risk of developing NOAF during hospitalization. When P<0.05, the difference was considered statistically significant.

Results

BASELINE DATA COMPARISON BETWEEN GROUPS:

A total of 665 patients were enrolled in this study. The average age was 63.31±13.09 years old, and male patients accounted for 73.08%. During hospitalization, a total of 63 patients (9.47%) developed NOAF. Compared with the NSTEMI patients without NOAF, the patients with NOAF had higher C2HEST score, age, NT-proBNP level, CRP level, and KILLIP class. The proportions of heart failure, hyperthyroidism, and COPD were also higher, while the left ventricular ejection fraction (LVEF) was lower. These differences were statistically significant (P<0.05; Table 1).

LOGISTIC REGRESSION ANALYSIS OF NOAF IN PATIENTS WITH NSTEMI:

All variables were included in the univariate logistic regression analysis. The results showed that heart failure, hyperthyroidism, COPD, age, KILLIP class >1, C2HEST score, NT-proBNP, CRP, and LVEF were all associated with NOAF (Table 2). To avoid the interference of multicollinearity and confounding factors, we excluded the variables related to C2HEST score. Then, the remaining variables with P<0.05 in the univariate regression analysis were included in the multivariate logistic regression analysis using the stepwise forward regression method. The results indicated that C2HEST score (OR=1.95, 95% CI: 1.63–2.33) was the only independent risk factor for the occurrence of NOAF during hospitalization in patients with NSTEMI (Table 3). Restricted cubic spline analysis showed a linear dose-response relationship between C2HEST score and NOAF in patients with NSTEMI (P for nonlinear >0.05, P for overall <0.001; Figure 2).

ROC CURVE ANALYSIS OF NOAF IN PATIENTS WITH NSTEMI:

The ROC curve was used to evaluate the ability of the C2HEST score to identify NOAF during hospitalization in patients with NSTEMI. The results showed that the area under the ROC curve (AUC) of the C2HEST score was 0.775 (95% CI: 0.724–0.836), cut-off value was 2.5, corresponding specificity was 69.9%, and sensitivity was 76.2%. This indicates that the C2HEST score has a high identification efficiency for NOAF (Figure 3, Table 4).

Discussion

LIMITATIONS:

Several limitations are inherent in this study. First, the sample size was rather small, and the study was a single-center investigation. To validate this study’s conclusions, a larger sample size and multicenter studies are needed in the future. Second, despite the exclusion of patients with a definite AF history during the patient recruitment phase, the potential for misclassifying NOAF was unavoidable. This is because there may have been patients with undiagnosed AF among the study participants, especially those with occult paroxysmal AF, who may not have been accurately identified. Furthermore, as a retrospective study, patients did not receive continuous ECG monitoring, which may have also led to the omission of some cases of NOAF. Third, all types of NOAF have an impact on prognosis. Our study did not focus on the association between NOAF in the chronic phase of MI and C₂HEST score, which may need to be explored in future studies with long-term post-hospitalization follow-up. Finally, this study included only patients with NSTEMI who successfully underwent PCI. Therefore, some of the conclusions drawn from this study may not be applicable to patients with other types of diseases.

Conclusions

An elevated C2HEST score was found to be an independent risk factor for the development of NOAF in patients with NSTEMI. There was a linear dose-response relationship between C2HEST score and NOAF. The C2HEST score may serve as a useful risk assessment tool for NOAF in patients with NSTEMI.