Effect of KuanXiong Aerosol on Intraoperative Myocardial Ischemia Reperfusion Arrhythmia: A Propensity Score-Matched Case-Control Study

Effect of KuanXiong Aerosol on Intraoperative Myocardial Ischemia Reperfusion Arrhythmia: A Propensity Score-Matched Case-Control Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Effect of KuanXiong Aerosol on Intraoperative Myocardial Ischemia Reperfusion Arrhythmia: A Propensity Score-Matched Case-Control Study JiaLin Yuan, SangYu Liang, JingYan Huang, QiuXiong Chen, LinYan Li, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8928474/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Objective Myocardial intraoperative reperfusion arrhythmia (RA) is very common during the procedure of percutaneous coronary intervention (PCI). This study aimed to investigate whether pre-administering of KuanXiong Aerosol (KXA) can reduce the risk of RA. Methods In this retrospective case - control study, patients diagnosed with acute myocardial infarction (AMI) who underwent PCI at Guangdong Provincial Hospital of Chinese Medicine from January 1, 2018 to December 31, 2023 were included. Clinical data were collected and propensity score match (PSM) was employed to balance baseline characteristics between KXA and control groups. Results A total of 2,168 cases of AMI patients were recruited, among whom 227 experienced reperfusion arrhythmia and 66 experienced major adverse cardiovascular events (MACE). Pre-administering of KXA was associated with a significant reduction in risk of RA ( P < 0.001), consistent after PSM. The incidence of MACE also reduced following KXA administration ( P = 0.034). Conclusion To our knowledge, this is the first study to demonstrate that KXA may have the potential to reduce the risk of intraoperative RA, and decrease incidence of MACE. Health sciences/Cardiology Health sciences/Diseases Health sciences/Medical research Acute myocardial infarction Reperfusion arrhythmia KuanXiong Aerosol Case-control study MACE Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Acute myocardial infarction (AMI) is characterized by myocardial ischemia due to reduced coronary blood flow, leading to a series of pathophysiological changes and myocardial injuries. With the population aging, the incidence and prevalence of AMI are increasing annually, posing a significant threat to human health [ 1 ] . Currently, myocardial reperfusion through coronary artery bypass grafting or percutaneous coronary intervention (PCI) is the main strategy for the treatment of AMI [ 2 ] . Although these interventions alleviate symptoms, reduce myocardial infarct size, and preserve ventricular function, they can paradoxically induce further cardiomyocyte injury. This abnormal phenomenon is called myocardial ischemia-reperfusion injury (MI/RI), which can induce arrhythmia, cardiac arrest and expansion of the infarcted area [ 3 , 4 ] . RA was previously used as a marker to assess the early reperfusion, but subsequent research have proved that RA is not a reliable marker of successful thrombolysis. Instead, it indicates further injury and higher mortality [ 5 , 6 ] . KXA is derived from the "Crying - to - Laughter Powder" described in the ancient Chinese medicinal book called "Ancient and Modern Medical Mirror", and was developed by the Chinese Academician Chen Keji. KXA has been used to treat angina attacks in patients with coronary heart disease (CAD), exhibiting anti-angina effects comparable to nitroglycerin. Its composition consists of five Chinese medicinal herbs, including Asarum Root, Galangal, Long Pepper, Sandalwood and Borneol [ 7 ] . Recent clinical trials [ 8 – 10 ] have shown that KXA can improve the exercise tolerance in patients with CAD, reduce myocardial energy consumption, and decrease the resistance index of coronary micro-circulation. Moreover, KXA has been reported to improve coronary micro-circulation in patients with AMI [ 11 ] , potentially by enhancing vascular endothelial function [ 12 ] . In vivo experiments have [ 13 ] also shown that early administration of KXA can inhibit cardiomyocyte pyroptosis and reduce myocardial injury in AMI-induced rat models. Based on these findings, we hypothesize that KXA may mitigate myocardial ischemia and reperfusion injury and subsequently reduce occurrence of RA. To test this hypothesis, we conducted a preliminary investigation and, building on these results, performed a retrospective case - control design to investigate whether the preoperative administration of KXA has influences the incidence of RA following intraoperative vascular reperfusion in patients with AMI. 2. Methods This study employed a retrospective case-control design using data extracted from electronic medical records. This study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. 2.1. Case Selection From January 1, 2018 to December 31, 2023, we recruited patients diagnosed with AMI were recruited from four medical centers affiliated with Guangdong Provincial Hospital of Chinese Medicine. Patients aged 18 - 80 years, and diagnosed with AMI according to the “2023 ESC Guidelines for the management of acute coronary syndromes” [2] were eligible. Key exclusion criteria included failure of the target artery to be reperfused by PCI, concomitant malignancy, severe liver or kidney disease, primary arrhythmia or congenital heart disease, and systemic immune diseases. These exclusions were applied to minimize potential confounding effects of comorbidities and their associated treatments on the occurrence of RA. To elucidate the effect of KXA on RA, propensity score match (PSM) was performed using SPSS 26.0. Cases and controls were matched 1:1 based on gender, age, TIT and year of admission. Controls were selected from the same source population of AMI patients who underwent PCI during the study period but did not experience RA. This approach minimized confounding factors and ensured comparability between groups for subsequent statistical analyses. 2.2 Materials KXA was manufactured by Zhejiang Sukean Pharmaceutical Co., Ltd., which is located in Zhejiang Province, China. It is a mixture of five herbal ingredients, including Asarum sieboldii Miq. oil, Alpinia officinarum Hance oil, Piper longum L. oil, Santalum album L. oil and Borneol . KXA administration was defined as the inhalation of at least one dose of KXA administered at least half an hour prior to the initiation of PCI procedure, as documented in the electronic medication administration record. 2.3. Ethical Consideration This study was approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (YE2024-176-01). Due to the retrospective nature of this study, the informed consent of subjects was waived by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine. This research was performed in accordance with regulations of the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine and the Declaration of Helsinki. 2.4. Definition Patients meeting the inclusion criteria for this study were screened and recruited after applying the exclusion criteria. Clinical data were subsequently collected from the medical record system. The occurrence of RA during PCI, and MACE during hospitalization were recorded. RA was defined as arrhythmia caused by increased myocardial perfusion after coronary occlusion, including bradycardia, atrioventricular block, accelerated idioventricular rhythm, premature ventricular contractions, persistent or non - persistent ventricular tachycardia, atrial fibrillation, and ventricular fibrillation [14,15] . MACE was defined as all - cause death, recurrent myocardial infarction, and stroke. Total ischaemic time (TIT) was calculated as the interval between symptom onset and the initiation of PCI, representing the duration from the onset of symptoms to the resumption of blood flow. Infarct - related artery (IRA) was defined as the coronary artery responsible for the acute coronary syndrome that was blocked or stenosed by atheroma and thrombosis. IRA was categorized into left main coronary artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX), or right coronary artery (RCA) based on the primary affected artery. If multiple arteries were severely stenosed or occluded, only the artery that responsible for AMI was recorded. Thrombolysis in myocardial infarction (TIMI) 0 was defined as no perfusion or complete coronary occlusion or absence of perfusion. Hypertension was defined as a systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) is ≥90 mmHg on repeated office or clinic measurements [16] . Diabetes mellitus (DM) was defined as a group of metabolic disorders caused by chronic hyperglycemia resulting from multiple etiological factors. Mild to moderate chronic kidney disease (CKD) was defined as a creatinine clearance of 30 - 90 mL/min. 2.5. Data collection and imputation Data were extracted by two trained research assistants using a standardized case report form. Outcomes were adjudicated by two independent cardiologists who were blinded to the KXA exposure status. Variables potentially associated with RA were retrieved from the medical electronics system and re-coded into a database (Excel; Microsoft Corporation, Redmond, WA). Variable Troponin T (TnT) was excluded due to a high missing rate (22.7% missing). Killip class was not included because it was poorly documented in the medical database (88% missing in the diagnosis). The remaining variables with missing values were imputed, including SBP and DBP upon admission (1.06% missing), HR upon admission (0.4% missing), and LVEF (12.07% missing). Multiple imputation by chain equation (MICE) was employed to fill in the missing data, with six imputations performed. MICE uses linear regression to predict missing values based on observed values from the original dataset, and sequentially imputes each variable with missing values [17] . 2.6. Outcome Indicator （ 1 ） Primary outcome indicator ：Occurrence of RA during PCI. （ 2 ） Secondary outcome indicator ：Occurrence of MACE occur during hospitalization. 2.7. Statistical Analysis Means, standard deviations, and medians were reported for continuous variables, while frequencies and percentages were reported for categorical variables. Normality of continuous variables was assessed using the Kolmogrov - Smirnov test to detect compliance with the normal distribution, and parameters with P <0.05 were considered non-normally distributed. Comparisons between groups were performed using the independent - sample t - test for normally distributed continuous variables; the Mann - Whitney U test was used for the comparison of non-normally distributed continuous variables; the Pearson χ 2 test was used for the comparison of nominal or categorical variables. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with RA. Variables with P < 0.05 in the univariate analysis were included in the multivariate model. Unadjusted odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were reported. All statistical analyses were performed using SPSS 26.0 (IBM SPP, Chicago, IL, USA) to perform statistical analyses. A two - sided P <0.05 was considered statistically significant, and P < 0.01 was considered highly significant. 3. Results 3.1. Baseline patients characteristics A total of 2,388 patients with AMI were identified from January 1, 2018 to December 31, 2023, at the Guangdong Provincial hospital of Chinese Medicine. After exclusions, 2,168 eligible patients were included in the study (see Fig. 1 ). Among the eligible patients, 79.7% were male. The median age was 63 years (54, 74), the median body mass index (BMI) was 24.24kg/m 2 (22.0, 26.7), and the median length of hospitalization was 5 days (4, 7), the proportion of acute ST-elevation myocardial infarction (STEMI) was 37.5%, while non-ST-elevation myocardial infarction (NSTEMI) was 62.5%. Intraoperative RA occurred in 227 patients (10.5%) during PCI. A total of 506 (23.3%) received preoperative KXA, and 66 events (3%) experienced MACE during hospitalization. 3.2. KXA could prevent intraoperative RA Patients were divided into two groups based on occurrence of RA during PCI: the arrhythmic group and the non-arrhythmic group. Comparison between the two groups are presented in Table 1 . No significant differences were observed in gender, age, BMI, smoke status, or heart rate, indicating that the groups were comparable. Table 1 Basic Characteristics based on RA Arrhythmic Group(N = 227) Non-Arrhythmic Group(N = 1941) P Value Basic Gender (Male) b (%) 186 (81.9) 1541 (79.4) 0.367 Age a (Year) 61 (54, 70) 63 (54, 70) 0.293 BMI a (Kg/m 2 ) 24.2 (21.96, 26.38) 24.2 (22.01, 26.81) 0.672 Smoke b (%) 130 (57.3) 1071(55.2) 0.549 Length of Stay a (Day) 6 (4, 8) 5 (4, 7) 0.001 HR a (beats/min) 79 (69, 91) 80 (70, 90) 0.416 SBP a (mmHg) 124 (107, 139) 132 (118, 148) < 0.001 DBP a (mmHg) 73 (64, 87) 78 (69, 89) < 0.001 Diagnosis Type of AMI (STEMI) b (%) 159 (70.0) 655 (33.7) < 0.001 Hypertension b (%) 106 (46.7) 1134 (58.4) 0.001 DM b (%) 72 (31.7) 755 (38.9) 0.035 CKD b (%) 10 (4.4) 137 (7.0) 0.172 TIT≤720min b (%) 157 (69.2) 719 (37.0) < 0.001 Period b (Year) (%) 2018 21 (9.3) 240 (12.4) 0.509 2019 39 (17.2) 281 (14.5) 2020 30 (13.2) 295 (15.2) 2021 40 (17.6) 355 (18.3) 2022 51 (22.5) 364 (18.8) 2023 46 (20.3) 406 (20.9) IRA b (%) LAD 70 (30.8) 981 (50.5) < 0.001 LCX 24 (10.6) 353 (18.2) RCA 132 (58.1) 566 (29.2) LM 1 (0.4) 41 (2.1) TIMI 0 b (%) 176 (77.5) 799 (41.2) < 0.001 Multivessel Disease b (%) 16 (7.0) 336 (17.3) < 0.001 KXA b (%) 16 (7.0) 490 (25.2) < 0.001 β-blockers b (%) 166 (73.1) 1441 (74.2) 0.749 MACE b (%) 14(6.2) 52(2.7) 0.031 a Nonparametric tests were performed for these variables. b Chi-square tests were performed for these variables. Abbreviations: BMI, body mass index; CKD, chronic kidney disease; DBP, diastolic blood pressure; DM, Diabetes mellitus; HR, heart rate; IRA, infarct related artery; KXA, KuanXiong Aerosol; MACE, Major Adverse Cardiovascular Events; SBP, systolic blood pressure; STEMI, ST-elevated myocardial infarction; TIMI, thrombolysis in myocardial infarction; TIT, total ischemia time. Comparative analysis revealed significant differences in variables such as SBP, DBP, length of stay, AMI type (STEMI), comorbidity with hypertension, comorbidity with DM, TIT, IRA, TIMI 0 flow, multivessel disease, KXA administration and MACE. Pearson Chi-square test demonstrated a significant difference in the frequency of KXA administration between the arrhythmic and the non-arrhythmic groups ( χ 2 = 37.609, P < 0.001). To further explore the role of KXA in RA, univariate and multivariate logistic regression were performed. Variables that were statistically significant between baseline groups and could potentially associated with the occurrence of RA were included in the models. Univariate logistic regression analysis indicated that preoperative administration of KXA before PCI was a protective factor against RA (Wald 31.886, crude OR 0.225, 95%CI 0.134–0.377, P < 0.001). After adjusting for potential confounders including SBP, DBP, type of AMI (STEMI), hypertension, DM, TIT, IRA, and multivessel disease through multivariate logistic regression confirmed that KXA remained significantly associated with a reduced risk of RA (Wald 7.610, adjusted OR 0.456, 95%CI 0.261–0.797, P = 0.006). Details can be found in Table 2 . Table 2 Logistic Regression of KXA on the prevention of RA Univariate Logistic Regression Multivariate Logistic Regression Variables Unadjusted OR (95%CI) P Value Variables Adjusted OR (95%CI) P Value SBP 0.983 (0.977–0.989) < 0.001 SBP 0.996 (0.986–1.005) 0.394 DBP 0.980 (0.971–0.990) < 0.001 DBP 0.995 (0.981–1.009) 0.452 STEMI 4.591 (3.404–6.192) < 0.001 STEMI 1.586 (1.070–2.350) 0.022 Hypertension 0.623 (0.473–0.822) 0.001 Hypertension 0.852 (0.627–1.159) 0.309 DM 0.730 (0.544–0.979) 0.036 DM 0.914 (0.663–1.260) 0.582 TIT 3.812 (2.834–5.127) < 0.001 TIT 2.166 (1.537–3.054) < 0.001 IRA† < 0.001 IRA† < 0.001 LAD 2.926 (0.397–21.585) 0.292 LAD 2.255 (0.293–17.366) 0.435 LCX 2.788 (0.367–21.147) 0.321 LCX 2.871 (0.361–22.842) 0.319 RCA 9.562 (1.303–70.142) 0.026 RCA 6.930 (0.905–53.047) 0.062 TIMI 0 4.932 (3.565–6.823) < 0.001 TIMI 0 2.625 (1.768–3.897) < 0.001 Multivessel disease 0.362 (0.215–0.610) < 0.001 Multivessel disease 0.734 (0.422–1.276) 0.273 KXA 0.225 (0.134–0.377) < 0.001 KXA 0.456 (0.261–0.796) 0.006 †The result for LAD, LCX, and RCA were compared with LM. Captions: Length of stay was not included in the logistic regression analysis, as its significance was considered as a result of RA rather than a cause of factort. To minimize the potential confounding effects of gender, age, surgery year, and TIT on the occurrence of intraoperative RA, PSM was performed to select control group of patients at a 1:1 ratio. Patients were matched for the same gender, similar age, surgery performed in the same year, and similar TIT. Age and TIT were included as continuous matching covariates, whereas sex, and year of intervention were matched exactly. The Caliper value was set at 0.1, and the matching order was randomized. After matching, 227 patients with RA were successfully matched in a 1:1 ratio with 227 control patients without RA. The overall balance test indicated good covariate balance ( χ 2 = 0.311, P = 0.856). Moreover, the Relative Multivariate Imbalance L1 decreased from 0.312 to 0.203 after matching. These result indicate an overall good matching performance. No variables in the matching process had |d| > 0.25, indicating adequate balance across all variables after the match. After matching the absolute standardized differences for age and TIT were reduced to 2.9% and 5.7%, respectively, compared with 5.9% and 76.1% before the match, indicating excellent balance of the two variables between the two groups was very good. The histogram of the distribution of SD, the univariate SD scatter plot, and SD comparisons are presented in Fig. 2 . A paired chi - square test (McNemar Test) revealed a significant difference in the frequency of preoperative use of KXA between the two groups ( P < 0.001). Furthermore, univariate binary logistic regression analysis identified preoperative use of KXA use as a protective factor (Wald 4.059, OR 0.518, 95%CI 0.273 ~ 0.982, P = 0.044), corresponding to a 1.93-fold reduction in the risk of intraoperative RA. Details are presented in Table 3 . Table 3 Association between preoperative use of KXA and occurrence of intraoperative RA (2×2 table) Preoperative use of KXA Total No Yes Intraoperative reperfusion arrhythmia No 198 (87.2%) 29 (12.8%) 227 (100%) Yes 211 (93.0%) 16 (7.0%) 227 (100%) Total 409 (90.1%) 45 (9.9%) 454 (100%) The risk of intraoperative RA in the two groups is shown in Fig. 3 . In comparison with patients who did not receive KXA, those administered KXA had a significantly lower risk of intraoperative RA (36% vs 52%, P < 0.001). 3.3. Effect of KXA on the risk of MACE Pearson Chi-square test showed that preoperative KXA use was associated with a significantly reduced risk of MACE ( χ 2 = 7.724, P = 0.005). The proportion of MACE was 3.6% (60/1662) in the non-user group and 1.2% (6/506) in the user group (see Fig. 4 ). To further explore the role of preoperatively KXA administration on MACE, the enrolled population was stratified into two groups based on preoperative KXA use. Baseline characteristics and outcome comparisons between the two groups are presented in Table 4 . Table 4 Basic Characteristics based on KXA KXA Group(N = 506) Control Group(N = 1662) P Value Basic Gender (Male) b (%) 390 (77.1) 1337 (80.4) 0.113 Age a (Year) 63 (55, 71) 62 (54, 70) 0.156 BMI a (Kg/m 2 ) 24.2 (21.8, 26.6) 24.3 (22.0, 26.8) 0.276 Smoke b (%) 239 (47.2) 728 (43.8) 0.191 Length of Stay a (Day) 5 (4, 7) 5 (4, 7) 0.249 HR a (beats/min) 79 (70, 90) 80 (70, 90) 0.935 SBP a (mmHg) 135 (120, 153) 130 (116, 146) < 0.001 DBP a (mmHg) 80 (70, 90) 78 (68, 89) 0.008 Diagnosis STEMI b (%) 74 (14.6) 740 (44.5) < 0.001 Hypertension b (%) 321 (63.4) 919 (55.3) < 0.001 DM b (%) 210 (41.5) 617 (37.1) 0.085 CKD b (%) 5 (1.0) 27 (1.6) 0.407 TIT≤720min b (%) 46 (9.1) 830 (49.9) < 0.001 Period b (%) (Year) 2018 41 (8.1) 220 (13.2) 0.034 2019 77 (15.2) 243 (14.6) 2020 79 (15.6) 246 (14.8) 2021 97 (19.2) 298 (17.9) 2022 111 (21.9) 304 (18.3) 2023 101 (20.0) 351 (21.1) Examination LVEF b (%) 58 (48, 66) 59 (49, 66) 0.817 β-blockers b (%) 354 (70.0) 1253 (75.4) 0.015 MACE b (%) 6 (1.2) 60 (3.6) 0.005 a Nonparametric tests were applied for these variables. b Chi-square tests were performed for these variables. Abbreviations: BMI, body mass index; CKD, chronic kidney disease; DBP, diastolic blood pressure; DM, Diabetes mellitus; HR, heart rate; KXA, KuanXiong Aerosol; LVEF, left ventricular ejection fraction; MACE, Major Adverse Cardiovascular Events; SBP, systolic blood pressure; STEMI, ST-elevated myocardial infarction; TIT, total ischemia time. There were significant differences between groups in variables of SBP, DBP, STEMI, Hypertension, TIT, Period, β-blockers, and MACE. The proportions of STEMI and TIT≤720min were significantly higher in the non - KXA group ( P < 0.001). To minimize potential bias of STEMI, we then conducted univariate and multivariate logistic regression were subsequently performed based on these comparison. Details are presented in Table 5 . Table 5 Logistic Regression of KXA on the prevention of MACE Univariate Logistic Regression Multivariate Logistic Regression Variables Unadjusted OR (95%CI) P Value Variables Adjusted OR (95%CI) P Value SBP 0.981 (0.970–0.992) 0.001 SBP 0.985 (0.970–1.001) 0.068 DBP 0.976 (0.960–0.993) 0.005 DBP 0.993 (0.970–1.018) 0.589 STEMI 2.640 (1.598–4.359) < 0.001 STEMI 2.132 (1.201–3.786) 0.010 Hypertension 1.515 (0.902–2.546) 0.117 Hypertension 2.053 (1.196–3.521) 0.009 Period † 0.069 Period † 0.194 2019 0.813 (0.201–3.284) 0.772 2019 0.903 (0.222–3.673) 0.886 2020 2.463 (0.785–7.729) 0.122 2020 2.507 (0.790–7.954) 0.119 2021 1.669 (0.518–5.378) 0.391 2021 1.581 (0.483–5.172) 0.449 2022 3.253 (1.099–9.627) 0.033 2022 2.817 (0.926–8.568) 0.068 2023 2.358 (0.780–7.129) 0.129 2023 2.105 (0.683–6.482) 0.195 TIT 1.493 (0.915–2.439) 0.109 TIT 0.779 (0.439–1.382) 0.392 BB 0.690 (0.410–1.161) 0.162 BB 0.804 (0.466–1.387) 0.433 KXA 0.320 (0.138–0.746) 0.008 KXA 0.382 (0.157–0.930) 0.034 †This variable was compared on the basis of 2018 (year). Before adjustment, significant differences were observed in variables of SBP, DBP, STEMI and KXA. After adjustment for confounding factors, KXA remained independently and negatively associated with MACE (adjusted OR 0.382, 95%CI 0.157–0.930, P = 0.034). This indicated that compared with patients who didn’t receive KXA, those treated with KXA had a 61.8% lower risk of developing MACE. 4. Discussion KXA is often used in China for treatment of angina pectoris and has been shown to rapidly relieve the symptoms and accelerate ST segment normalization, with efficacy comparable to that of nitroglycerin [ 18 ] . Previous studies [ 12 , 19 ] have also reported its therapeutic effects in myocardial bridge, acute myocardial infarction and other cardiac diseases. In this study, pre-reperfusion administration of KXA before PCI significantly reduce the risk of intraoperative RA to 48.2% compared with those patients who did not receive KXA. After PSM matching the for gender, age, year of surgery, and TIT, the difference between the case and control groups remained statistically significant, suggesting that KXA may inhibit the occurrence of intraoperative RA. Moreover, preoperatively KXA administration was also associated with a reduced risk of in-hospital MACE. This protective effect may be attributable to the ability of KXA to ameliorate MI/RI. In addition, patients with RA had a longer length of hospital stay and a higher incidence of MACE. Clinical studies have shown that RA can lead to larger infarct size and adverse prognosis [ 20 ] . Compared to patients who didn’t present ventricular tachycardia or ventricular fibrillation (VT/VF), those who developed with VT/VF after PCI had a significantly increased mortality rate (3.6% vs 33.3%) [ 21 ] . Regarding prolongation hospitalization, patients with CAD often require extended in-hospital monitoring following PCI - related ventricular arrhythmia, probably due to the longer procedural duration of intervention and observation [ 22 , 23 ] . Although several studies [ 21 , 24 ] have reported that RA can significantly influence in - hospital mortality, the PAMI trial [ 15 ] (Primary Angioplasty in Myocardial Infarction Trial) didn’t demonstrate a clear association between RA and poor in-hospital prognosis. In our study, the definition of RA differed slightly from that used in previous reports, as it encompassed not only ventricular arrhythmia but also atrial bradycardia and atrioventricular block. These arrhythmias often bring potential harm and may require intervention such as permanent pacemaker implantation [ 25 ] . In our cohort, a greater proportion of patients in the arrhythmic group had a shorter TIT (≤ 12 h, 69.2% vs 37.0%, P < 0.001). This difference may be explained by the higher prevalence of STEMI in the arrhythmic group, resulting in earlier reperfusion of cardiomyocytes relative to patients without arrhythmia. With the therapeutic time window, delayed achievement of revascularization is associated with a progressively increased risk of RA [ 26 ] . However, once this window has elapsed, the probability of RA will gradually decreases [ 27 ] , whereas mortality increases with further delays in revascularization [ 28 ] . This is likely caused by increased sympathetic activation after AMI, and the ischemia-induced shortening of the electrical refractory periods in the injured myocardium [ 29 ] . In the absence of timely reperfusion, irreversible myocardial injury and apoptosis ensue, ultimately abolishing the myocardium’s ability to generate electrical signals. Additionally, we found a significantly higher proportion of STEMI cases and a shorter TIT in the non-KXA group, indicating that the KXA group comprised a substantially greater proportion of NSTEMI patients. This imbalance may be attributable to clinicians, practice patterns, whereby clinicians preferentially administered KXA after hemodynamic stabilization or were reluctant to pre-administered KXA before PCI in critically ill STEMI patients. After all, none of the current guidelines have mentioned the application of KXA before PCI so far. Nevertheless, our analysis revealed that KXA administration was associated with a reduced the risk of MACE, and this result remained robust after adjusting for other covariates. The mechanism of KXA in mitigating MI/RI may be mediated through improvement of vascular endothelial function. Several clinical studies [ 30 , 31 ] have found that KXA increases circulating nitric oxide (NO) levels while reducing endothelin-1 (ET-1) concentrations in patients with CAD. NO and ET-1 are mainly released by vascular endothelial cells, reflecting vascular endothelial function. NO is a classical endothelium-derived vasodilator that relaxs vascular smooth muscle by activating guanylate cyclase, thereby reducing perivascular resistance, enhancing coronary blood flow, improving myocardial perfusion in the ischemic regions, and inhibiting platelet aggregation and the aggregation of inflammatory cells [ 32 ] . In contrast, ET-1 can antagonize the effect of NO by, promoting vasoconstriction and thrombogenesis [ 33 ] . Likewise, improved survival has been associated with higher NO bioavailability and lower ET-1 levels. Moreover, NO is a well-known cardioprotective molecule acting through the cGMP/PKG signaling pathway, and represents a central component of both the RISK (reperfusion injury salvage kinase) and SAFE (survivor activating factor enhancement) cardioprotective pathways [ 34 ] . Through interaction with mitochondria, NO could activate mK ATP channels and prevent the generation of reactive oxygen species, ultimately conferring vasoprotective and cardioprotective effects [ 35 ] . Network pharmacology analyses [ 36 ] showed that the mechanism of angina pectoris in CAD may involve the VEGF signaling pathway, and VEGF can stimulate endothelial cells to produce NO [ 22 ] , which improves vascular perfusion, suppresses thrombosis and inflammation, reduces reperfusion injury [ 37 ] , and suppresses ventricular arrhythmia caused by myocardial reperfusion [ 38 ] . In conclude, our result indicated that KXA may have the potential to prevent intraoperative RA and reduce the occurrence of MACE. These protective effects are likely mediated, at least in part, through activation of the NO-cGMP pathway. This study has some limitations. First, its retrospective case-control design is inherently subject to retrospective bias. For example, misclassification of AMI subtype may have occurred, and although the database indicated that KXA was administered preoperatively, initiation after surgery cannot be completely excluded. Secondly, intraoperative RA occurred was identified solely based on surgical records; therefore, underreporting is possible, and some RA events may not have been adequately documented. Given the relatively low incidence of RA was observed, this potential misclassification bias cannot be rule out. Thirdly, despite using PSM and multi-variable adjustment, unmeasured or residual confounding factors (e.g., detailed medication history, socioeconomic status) could still exist, potentially biasing the estimated effects. Finally, patients were recruited from multiple sub - centers of one hospital of Guangdong Provincial Hospital of Chinese Medicine. Limiting the generalizability of the findings to other regions or populations Consequently, a definitive casual relationship between the preoperative KXA use and intraoperative RA cannot be established. Larger-scale, nationwide, longitudinal and prospective studies will be needed to clarify the role of KXA in MI/RI. 5. Conclusion KXA may help prevent intraoperative RA, ameliorate MI/RI, and diminish the risk of MACE during hospitalization in patients with AMI. To our knowledge, this is the first study to reveal the efficacy of KXA in the context of MI/R injury. Declarations Funding: National High-Level Key Disciplines in Traditional Chinese Medicine Author Contribution Jia-Lin Yuan was responsible for the study design and methodology, clinical data collection, and writing of the initial draft of the manuscript. SangYu Liang and JingYan Huang assisted with the clinical data collection. Liu He and Qiu-Xiong Chen conceived the research idea and overall dirction, and supervised and guided the research process. Lin-Yan Li and Liu He reviewed, revised, and polished the manuscript. Data Availability The data that support the findings of this study are available from Guangdong Provincial Hospital of Chinese Medicine but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with the permission of Guangdong Provincial Hospital of Chinese Medicine. References Moran, A. E. et al. The Global Burden of Ischemic Heart Disease in 1990 and 2010. CIRCULATION. ;129(14):1493 – 501.10.1161/CIRCULATIONAHA.113.004046. (2014). Byrne, R. A. et al. 2023 ESC Guidelines for the management of acute coronary syndromes. 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Cardiac arrhythmias in the emergency settings of acute coronary syndrome and revascularization: an European Heart Rhythm Association (EHRA) consensus document, endorsed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Acute Cardiovascular Care Association (ACCA). EP Europace. ;21(10):1603 – 4.10.1093/europace/euz163. (2019). Unger, T. et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. HYPERTENSION. ;75(6):1334 – 57.10.1161/HYPERTENSIONAHA.120.15026. (2020). Romaniuk, H., Patton, G. C. & Carlin, J. B. Multiple Imputation in a Longitudinal Cohort Study: A Case Study of Sensitivity to Imputation Methods. AM J EPIDEMIOL. ;180(9):920 – 32.10.1093/aje/kwu224. (2014). Li-zhi, L. I. et al. Effect of Kuanxiong Aerosol on Coronary Heart Disease Angina Patients:a Multicenter Randomized Controlled Clinical Study. Chin. J. Integr. Traditional Western Med. 34 (04), 396–401 (2014). Xiao-shu, Y. I. N. & Jing-wei, Z. H. E. N. G. ZHANG Yong-hong. Clinical study of wide chest aerosol in the treatment of patients with coronary artery muscle bridge. Jilin Med. J. 42 (7), 1569–1571 (2021). van der Weg, K. et al. Bursts of reperfusion arrhythmias occur independently of area at risk size and are the first marker of reperfusion injury. INT J CARDIOL. ;271:240 – 6.10.1016/j.ijcard.2018.05.083. (2018). Mehta, R. H. Incidence of and Outcomes Associated With Ventricular Tachycardia or Fibrillation in Patients Undergoing Primary Percutaneous Coronary Intervention. JAMA. ;301(17):1779.10.1001/jama.2009.600. (2009). Konig, S. et al. Incidence and characteristics of ventricular tachycardia in patients after percutaneous coronary revascularization of chronic total occlusions. PLOS ONE. ;14(11):e225580.10.1371/journal.pone.0225580. (2019). Chu, S. & ARRHYTHMIA ASSOCIATED WITH ACUTE CORONARY SYNDROME. : OCCURRENCE, RISK FACTORS, THERAPY AND PROGNOSIS: A SINGLE-CENTRE STUDY. HEART. ;98(Suppl 2):E275.10.1136/heartjnl-2012-302920v.14. (2012). Paranskaya, L. et al. Ventricular tachycardia and sudden death after primary PCI-reperfusion therapy. Herzschrittmachertherapie + Elektrophysiologie. ;22(4):243 – 8.10.1007/s00399-011-0160-z. (2011). Misumida, N. et al. Frequency and Significance of High-Degree Atrioventricular Block and Sinoatrial Node Dysfunction in Patients With Non-ST-Elevation Myocardial Infarction. The American Journal of Cardiology. ;122(10):1598 – 603.10.1016/j.amjcard.2018.08.001. (2018). Kumar, S. et al. Effect of reperfusion time on inducible ventricular tachycardia early and spontaneous ventricular arrhythmias late after ST elevation myocardial infarction treated with primary percutaneous coronary intervention. HEART RHYTHM. ;8(4):493 – 9.10.1016/j.hrthm.2010.11.046. (2011). Khederlou, H., Azimi Pirsaraei, S. V., Rabbani, E. & Motedayen, M. Correlations between Cardiovascular Risk Factors and Ventricular Arrhythmias Following Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction. Journal of Tehran University Heart Center. ;18(2):122 – 8.10.18502/jthc.v18i2.13322. (2023). Moriyama, N. et al. Impact of Late Ventricular Arrhythmias on Cardiac Mortality in Patients with Acute Myocardial Infarction. J INTERV CARDIOL. ;2019(2019):1-9.10.1155/2019/5345178. (2019). Oikawa, J. et al. Risk Factors of In-Hospital Lethal Arrhythmia Following Acute Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention - Insight From the J-MINUET Study. Circ Rep. ;2(1):17-23.10.1253/circrep.CR-19-0081. (2019). LI, Rong-rong, Z. H. A. N. G., Wen-hu, M. A. & Yong-qiang Application Effect of Broad Chest Aerosol in Patients with Stable Angina Pectoris of Coronary Heart Disease. Practical Clin. J. Integr. Traditional Chin. Western Med. 23 (10), 45–48 (2023). Jin-yan, F. A. N. G. et al. Randomized Controlled Trial of Kuanxiong Aerosol Combined Conventional Treatment on Stable Angina Pectoris of Coronary Heart Disease with Cold Coagulation and Blood Stasis Syndrome. Chin. J. Integr. Traditional Western Med. 42 (2), 172–175 (2022). Palmer, R. M. J., Ferrige, A. G. & Moncada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (London). ;327(6122):524 – 6.10.1038/327524a0. (1987). Cahill, P. A. & Redmond, E. M. Vascular endothelium – Gatekeeper of vessel health. ATHEROSCLEROSIS. ;248:97-109.10.1016/j.atherosclerosis.2016.03.007. (2016). Andreadou, I. et al. The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. BRIT J PHARMACOL. ;172(6):1587 – 606.10.1111/bph.12811. (2015). Jones, S. P. & Bolli, R. The ubiquitous role of nitric oxide in cardioprotection. J MOL CELL CARDIOL. ;40(1):16-23.10.1016/j.yjmcc.2005.09.011. (2006). Zhang, Y. Z., Zeng, R. X., Zhou, Y. S. & Zhang, M. Z. Kuanxiong Aerosol () in Treatment of Angina Pectoris: A Literature Review and Network Pharmacology. CHIN J INTEGR MED. ;27(6):470 – 80.10.1007/s11655-021-2867-y. (2021). Papapetropoulos, A., García-Cardeña, G., Madri, J. A. & Sessa, W. C. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. The Journal of clinical investigation. ;100(12):3131 – 9.10.1172/jci119868. (1997). Pabla, R. & Curtis, M. J. Effects of NO Modulation on Cardiac Arrhythmias in the Rat Isolated Heart. CIRC RES. ;77(5):984 – 92.10.1161/01.RES.77.5.984. (1995). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers invited by journal 27 Mar, 2026 Editor assigned by journal 27 Mar, 2026 Editor invited by journal 04 Mar, 2026 Submission checks completed at journal 03 Mar, 2026 First submitted to journal 03 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8928474","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":614065909,"identity":"846dd983-0fe1-4242-ae18-0826b2d79a7a","order_by":0,"name":"JiaLin Yuan","email":"","orcid":"","institution":"Guangdong Provincial Hospital of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"JiaLin","middleName":"","lastName":"Yuan","suffix":""},{"id":614065912,"identity":"eba4961b-bcb8-4f89-9276-8338a598e056","order_by":1,"name":"SangYu Liang","email":"","orcid":"","institution":"Guangdong Provincial Hospital of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"SangYu","middleName":"","lastName":"Liang","suffix":""},{"id":614065913,"identity":"c0b79756-0722-44a4-8314-da189cf9849d","order_by":2,"name":"JingYan Huang","email":"","orcid":"","institution":"Guangdong Provincial Hospital of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"JingYan","middleName":"","lastName":"Huang","suffix":""},{"id":614065914,"identity":"f713acf3-916f-4b15-9ed9-2d73dc8dd1f0","order_by":3,"name":"QiuXiong Chen","email":"","orcid":"","institution":"Guangdong Provincial Hospital of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"QiuXiong","middleName":"","lastName":"Chen","suffix":""},{"id":614065915,"identity":"14dad5c6-cd7e-42dc-b233-f1721bbf32a9","order_by":4,"name":"LinYan Li","email":"","orcid":"","institution":"City University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"LinYan","middleName":"","lastName":"Li","suffix":""},{"id":614065916,"identity":"82679dd1-11a9-4dc6-a52a-9bf210b79195","order_by":5,"name":"Liu He","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEUlEQVRIiWNgGAWjYBACPmYGNgaGin8MDOwNIL4ERJiHgSFBAocWNrCWMweAqg6AtUgQ1gJCjG1A5RIJDAhr8Gph5zF78IHtDgP/zNdpEgw1FnUGNxIYH7xtY8iTbMDlMB5zwxk8zxgkbuduk2A4JiEB1MJsOLeNoVgap194zKR5JJjrN0gDtTA2gLWwSfO2MSTOw6fljwEzg4HkWbgW9t8EtTAkHGYwkOBF2MIM0jIbpxa2MsmeA2kMEmdyN1skHJOQnHnmYbPknHMSiTNxeJ+f//A2iZ//bBj4289uvPGhpo6f73jywQ9vymwSZxzAYQ0SYAFHjcIBRpDxuGIFFTB/AJHyONwzCkbBKBgFIxcAAJniT2IGttAAAAAAAElFTkSuQmCC","orcid":"","institution":"City University of Hong Kong","correspondingAuthor":true,"prefix":"","firstName":"Liu","middleName":"","lastName":"He","suffix":""}],"badges":[],"createdAt":"2026-02-20 18:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8928474/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8928474/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105844682,"identity":"476089dd-4d21-4191-a2cb-3e1c054fcb3c","added_by":"auto","created_at":"2026-03-31 17:33:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":152474,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaption: A total of 2168 patients with AMI were recruited in this study. A pair of 227 RA vs control cases were selected for further analysis.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8928474/v1/c91d125d84ee353ba15bdda8.png"},{"id":105904560,"identity":"cba4c125-fef2-4ad8-9fc0-8849cb706e7d","added_by":"auto","created_at":"2026-04-01 10:09:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":93004,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges of difference of variables after and before PSM\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaption: A, distribution of SD; B, difference in standard deviations; C, univariate SD scatter plot. All four variables reach balance after PSM.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8928474/v1/3ef4e79efe4e434142934c9f.png"},{"id":105844684,"identity":"601268ec-fb4e-46c3-a2d1-429531d3a3ed","added_by":"auto","created_at":"2026-03-31 17:33:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":20156,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistogram of association between preoperative use of KuanXiong aerosol and occurrence of intraoperative reperfusion arrhythmia;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaption: Compared to the unused population, patients who were administered KXA had lower risk of intraoperative reperfusion arrhythmia.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8928474/v1/f2f42f2a07a8e465d9c6c206.png"},{"id":105844685,"identity":"385c9b54-0a1d-4a7b-9d85-a79e4845a44a","added_by":"auto","created_at":"2026-03-31 17:33:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":73521,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePie graph of association between preoperative use of KuanXiong aerosol and occurrence of major adverse cardiovascular event.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaption: Patients who were administered KXA before the surgery had lower risk of major adverse cardiovascular event.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8928474/v1/30036947ec6c16ee8350c720.png"},{"id":106402094,"identity":"82033f81-695b-42dc-a248-04b61e64d39d","added_by":"auto","created_at":"2026-04-08 09:11:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1442073,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8928474/v1/3cc5a0e1-7f4e-4268-82a7-a87bf617d669.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of KuanXiong Aerosol on Intraoperative Myocardial Ischemia Reperfusion Arrhythmia: A Propensity Score-Matched Case-Control Study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAcute myocardial infarction (AMI) is characterized by myocardial ischemia due to reduced coronary blood flow, leading to a series of pathophysiological changes and myocardial injuries. With the population aging, the incidence and prevalence of AMI are increasing annually, posing a significant threat to human health \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Currently, myocardial reperfusion through coronary artery bypass grafting or percutaneous coronary intervention (PCI) is the main strategy for the treatment of AMI\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Although these interventions alleviate symptoms, reduce myocardial infarct size, and preserve ventricular function, they can paradoxically induce further cardiomyocyte injury. This abnormal phenomenon is called myocardial ischemia-reperfusion injury (MI/RI), which can induce arrhythmia, cardiac arrest and expansion of the infarcted area \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRA was previously used as a marker to assess the early reperfusion, but subsequent research have proved that RA is not a reliable marker of successful thrombolysis. Instead, it indicates further injury and higher mortality\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eKXA is derived from the \"Crying - to - Laughter Powder\" described in the ancient Chinese medicinal book called \"Ancient and Modern Medical Mirror\", and was developed by the Chinese Academician Chen Keji. KXA has been used to treat angina attacks in patients with coronary heart disease (CAD), exhibiting anti-angina effects comparable to nitroglycerin. Its composition consists of five Chinese medicinal herbs, including Asarum Root, Galangal, Long Pepper, Sandalwood and Borneol \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRecent clinical trials\u003csup\u003e[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e have shown that KXA can improve the exercise tolerance in patients with CAD, reduce myocardial energy consumption, and decrease the resistance index of coronary micro-circulation. Moreover, KXA has been reported to improve coronary micro-circulation in patients with AMI\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, potentially by enhancing vascular endothelial function\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. In vivo experiments have\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e also shown that early administration of KXA can inhibit cardiomyocyte pyroptosis and reduce myocardial injury in AMI-induced rat models.\u003c/p\u003e \u003cp\u003eBased on these findings, we hypothesize that KXA may mitigate myocardial ischemia and reperfusion injury and subsequently reduce occurrence of RA. To test this hypothesis, we conducted a preliminary investigation and, building on these results, performed a retrospective case - control design to investigate whether the preoperative administration of KXA has influences the incidence of RA following intraoperative vascular reperfusion in patients with AMI.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThis study employed a retrospective case-control design using data extracted from electronic medical records.\u003c/p\u003e\n\u003cp\u003eThis study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e2.1. Case Selection\u003c/h4\u003e\n\u003cp\u003eFrom January 1, 2018 to December 31, 2023, we recruited patients diagnosed with AMI were recruited from four medical centers affiliated with Guangdong Provincial Hospital of Chinese Medicine.\u003c/p\u003e\n\u003cp\u003ePatients aged 18 - 80 years, and diagnosed with AMI according to the \u0026ldquo;2023 ESC Guidelines for the management of acute coronary syndromes\u0026rdquo;\u003csup\u003e[2]\u003c/sup\u003e were eligible. Key exclusion criteria included failure of the target artery to be reperfused by PCI, concomitant malignancy, severe liver or kidney disease, primary arrhythmia or congenital heart disease, and systemic immune diseases. These exclusions were applied to minimize potential confounding effects of comorbidities and their associated treatments on the occurrence of RA.\u003c/p\u003e\n\u003cp\u003eTo elucidate the effect of KXA on RA, propensity score match (PSM) was performed using SPSS 26.0. Cases and controls were matched 1:1 based on gender, age, TIT and year of admission. Controls were selected from the same source population of AMI patients who underwent PCI during the study period but did not experience RA. This approach minimized confounding factors and ensured comparability between groups for subsequent statistical analyses.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e2.2 Materials\u003c/h4\u003e\n\u003cp\u003eKXA was manufactured by Zhejiang Sukean Pharmaceutical Co., Ltd., which is located in Zhejiang Province, China. It is a mixture of five herbal ingredients, including \u003cem\u003eAsarum\u0026nbsp;\u003c/em\u003e\u003cem\u003esieboldii\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eMiq. oil, \u003cem\u003eAlpinia officinarum Hance\u003c/em\u003e oil, \u003cem\u003ePiper longum\u003c/em\u003e L. oil, \u003cem\u003eSantalum album\u003c/em\u003e L. oil and \u003cem\u003eBorneol\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eKXA administration was defined as the inhalation of at least one dose of KXA administered at least half an hour prior to the initiation of PCI procedure, as documented in the electronic medication administration record.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e2.3. Ethical Consideration\u003c/h4\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (YE2024-176-01). Due to the retrospective nature of this study, the informed consent of subjects was waived by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine. This research was performed in accordance with regulations of the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine and the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e2.4. Definition\u003c/h4\u003e\n\u003cp\u003ePatients meeting the inclusion criteria for this study were screened and recruited after applying the exclusion criteria. Clinical data were subsequently collected from the medical record system. The occurrence of RA during PCI, and MACE during hospitalization were recorded.\u003c/p\u003e\n\u003cp\u003eRA was defined as arrhythmia caused by increased myocardial perfusion after coronary occlusion, including bradycardia, atrioventricular block, accelerated idioventricular rhythm, premature ventricular contractions, persistent or non - persistent ventricular tachycardia, atrial fibrillation, and ventricular fibrillation\u003csup\u003e[14,15]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eMACE was defined as all - cause death, recurrent myocardial infarction, and stroke.\u003c/p\u003e\n\u003cp\u003eTotal ischaemic time (TIT) was calculated as the interval between symptom onset and the initiation of PCI, representing the duration from the onset of symptoms to the \u0026nbsp; resumption of blood flow.\u003c/p\u003e\n\u003cp\u003eInfarct - related artery (IRA) was defined as the coronary artery responsible for the acute coronary syndrome that was blocked or stenosed by atheroma and thrombosis. IRA was categorized into left main coronary artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX), or right coronary artery (RCA) based on the primary affected artery. If multiple arteries were severely stenosed or occluded, only the artery that responsible for AMI was recorded.\u003c/p\u003e\n\u003cp\u003eThrombolysis in myocardial infarction (TIMI) 0 was defined as no perfusion or complete coronary occlusion or absence of perfusion.\u003c/p\u003e\n\u003cp\u003eHypertension was defined as a systolic blood pressure (SBP) \u0026ge;140 mmHg and/or diastolic blood pressure (DBP) is \u0026ge;90 mmHg on repeated office or clinic measurements\u0026nbsp;\u003csup\u003e[16]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eDiabetes mellitus (DM) was defined as a group of metabolic disorders caused by chronic hyperglycemia resulting from multiple etiological factors.\u003c/p\u003e\n\u003cp\u003eMild to moderate chronic kidney disease (CKD) was defined as a creatinine clearance of 30 - 90 mL/min.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e2.5. Data collection and imputation\u003c/h4\u003e\n\u003cp\u003eData were extracted by two trained research assistants using a standardized case report form. Outcomes were adjudicated by two independent cardiologists who were blinded to the KXA exposure status. Variables potentially associated with RA were retrieved from the medical electronics system and re-coded into a database (Excel; Microsoft Corporation, Redmond, WA).\u003c/p\u003e\n\u003cp\u003eVariable Troponin T (TnT) was excluded due to a high missing rate (22.7% missing). Killip class was not included because it was poorly documented in the medical database (88% missing in the diagnosis).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe remaining variables with missing values were imputed, including SBP and DBP upon admission (1.06% missing), HR upon admission (0.4% missing), and LVEF (12.07% missing).\u003c/p\u003e\n\u003cp\u003eMultiple imputation by chain equation (MICE) was employed to fill in the missing data, with six imputations performed. MICE uses linear regression to predict missing values based on observed values from the original dataset, and sequentially imputes each variable with missing values\u003csup\u003e[17]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e2.6. Outcome Indicator\u003c/h4\u003e\n\u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003cstrong\u003ePrimary outcome indicator\u003c/strong\u003e：Occurrence of RA during PCI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003cstrong\u003eSecondary outcome indicator\u003c/strong\u003e：Occurrence of MACE occur during hospitalization.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e2.7. Statistical Analysis\u003c/h4\u003e\n\u003cp\u003eMeans, standard deviations, and medians were reported for continuous variables, while frequencies and percentages were reported for categorical variables. Normality of continuous variables was assessed using the Kolmogrov - Smirnov test to detect compliance with the normal distribution, and parameters with \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 were considered non-normally distributed. Comparisons between groups were performed using the independent - sample t - test for normally distributed continuous variables; the Mann - Whitney U test was used for the comparison of non-normally distributed continuous variables; the Pearson \u0026chi;\u003csup\u003e2\u003c/sup\u003e test was used for the comparison of nominal or categorical variables.\u003c/p\u003e\n\u003cp\u003eUnivariate and multivariate logistic regression analyses were conducted to identify factors associated with RA. Variables with \u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05 in the univariate analysis were included in the multivariate model. Unadjusted odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were reported.\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using SPSS 26.0 (IBM SPP, Chicago, IL, USA) to perform statistical analyses. A two - sided \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 was considered statistically significant, and \u003cem\u003eP\u003c/em\u003e\u0026lt; 0.01 was considered highly \u0026nbsp;significant.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Baseline patients characteristics\u003c/h2\u003e \u003cp\u003eA total of 2,388 patients with AMI were identified from January 1, 2018 to December 31, 2023, at the Guangdong Provincial hospital of Chinese Medicine. After exclusions, 2,168 eligible patients were included in the study (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong the eligible patients, 79.7% were male. The median age was 63 years (54, 74), the median body mass index (BMI) was 24.24kg/m\u003csup\u003e2\u003c/sup\u003e (22.0, 26.7), and the median length of hospitalization was 5 days (4, 7), the proportion of acute ST-elevation myocardial infarction (STEMI) was 37.5%, while non-ST-elevation myocardial infarction (NSTEMI) was 62.5%.\u003c/p\u003e \u003cp\u003eIntraoperative RA occurred in 227 patients (10.5%) during PCI. A total of 506 (23.3%) received preoperative KXA, and 66 events (3%) experienced MACE during hospitalization.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.2. KXA could prevent intraoperative RA\u003c/h2\u003e \u003cp\u003ePatients were divided into two groups based on occurrence of RA during PCI: the arrhythmic group and the non-arrhythmic group. Comparison between the two groups are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. No significant differences were observed in gender, age, BMI, smoke status, or heart rate, indicating that the groups were comparable.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBasic Characteristics based on RA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArrhythmic Group(N\u0026thinsp;=\u0026thinsp;227)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-Arrhythmic Group(N\u0026thinsp;=\u0026thinsp;1941)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eBasic\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (Male)\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e186 (81.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1541 (79.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003csup\u003ea\u003c/sup\u003e (Year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (54, 70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (54, 70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003csup\u003ea\u003c/sup\u003e (Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.2 (21.96, 26.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.2 (22.01, 26.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.672\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoke\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130 (57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1071(55.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of Stay\u003csup\u003ea\u003c/sup\u003e (Day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (4, 8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (4, 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR\u003csup\u003ea\u003c/sup\u003e (beats/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (69, 91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (70, 90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.416\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP\u003csup\u003ea\u003c/sup\u003e (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (107, 139)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132 (118, 148)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP\u003csup\u003ea\u003c/sup\u003e (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (64, 87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (69, 89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of AMI (STEMI)\u003csup\u003eb\u003c/sup\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e655 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106 (46.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1134 (58.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (31.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e755 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e137 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTIT\u0026le;720min\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e157 (69.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e719 (37.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003ePeriod\u003csup\u003eb\u003c/sup\u003e (Year) (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e240 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.509\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e281 (14.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e295 (15.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e355 (18.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e364 (18.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e406 (20.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eIRA\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e981 (50.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLCX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e353 (18.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRCA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e132 (58.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e566 (29.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (2.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTIMI 0\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e176 (77.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e799 (41.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultivessel Disease\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e336 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKXA\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e490 (25.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-blockers\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166 (73.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1441 (74.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.749\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMACE\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52(2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e Nonparametric tests were performed for these variables.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003eb\u003c/sup\u003e Chi-square tests were performed for these variables.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: BMI, body mass index; CKD, chronic kidney disease; DBP, diastolic blood pressure; DM, Diabetes mellitus; HR, heart rate; IRA, infarct related artery; KXA, KuanXiong Aerosol; MACE, Major Adverse Cardiovascular Events; SBP, systolic blood pressure; STEMI, ST-elevated myocardial infarction; TIMI, thrombolysis in myocardial infarction; TIT, total ischemia time.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eComparative analysis revealed significant differences in variables such as SBP, DBP, length of stay, AMI type (STEMI), comorbidity with hypertension, comorbidity with DM, TIT, IRA, TIMI 0 flow, multivessel disease, KXA administration and MACE.\u003c/p\u003e \u003cp\u003ePearson Chi-square test demonstrated a significant difference in the frequency of KXA administration between the arrhythmic and the non-arrhythmic groups (\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;37.609, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). To further explore the role of KXA in RA, univariate and multivariate logistic regression were performed. Variables that were statistically significant between baseline groups and could potentially associated with the occurrence of RA were included in the models.\u003c/p\u003e \u003cp\u003eUnivariate logistic regression analysis indicated that preoperative administration of KXA before PCI was a protective factor against RA (Wald 31.886, crude OR 0.225, 95%CI 0.134\u0026ndash;0.377, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After adjusting for potential confounders including SBP, DBP, type of AMI (STEMI), hypertension, DM, TIT, IRA, and multivessel disease through multivariate logistic regression confirmed that KXA remained significantly associated with a reduced risk of RA (Wald 7.610, adjusted OR 0.456, 95%CI 0.261\u0026ndash;0.797, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006). Details can be found in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic Regression of KXA on the prevention of RA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eUnivariate Logistic Regression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003eMultivariate Logistic Regression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnadjusted OR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted OR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.983 (0.977\u0026ndash;0.989)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.996 (0.986\u0026ndash;1.005)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.394\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.980 (0.971\u0026ndash;0.990)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.995 (0.981\u0026ndash;1.009)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.452\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTEMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.591 (3.404\u0026ndash;6.192)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSTEMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.586 (1.070\u0026ndash;2.350)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.623 (0.473\u0026ndash;0.822)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.852 (0.627\u0026ndash;1.159)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.309\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.730 (0.544\u0026ndash;0.979)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.914 (0.663\u0026ndash;1.260)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTIT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.812 (2.834\u0026ndash;5.127)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTIT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.166 (1.537\u0026ndash;3.054)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIRA\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIRA\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.926 (0.397\u0026ndash;21.585)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.255 (0.293\u0026ndash;17.366)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.435\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLCX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.788 (0.367\u0026ndash;21.147)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLCX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.871 (0.361\u0026ndash;22.842)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRCA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.562 (1.303\u0026ndash;70.142)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRCA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.930 (0.905\u0026ndash;53.047)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTIMI 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.932 (3.565\u0026ndash;6.823)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTIMI 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.625 (1.768\u0026ndash;3.897)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultivessel disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.362 (0.215\u0026ndash;0.610)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMultivessel disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.734 (0.422\u0026ndash;1.276)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.273\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKXA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.225 (0.134\u0026ndash;0.377)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKXA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.456 (0.261\u0026ndash;0.796)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u0026dagger;The result for LAD, LCX, and RCA were compared with LM.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eCaptions: Length of stay was not included in the logistic regression analysis, as its significance was considered as a result of RA rather than a cause of factort.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTo minimize the potential confounding effects of gender, age, surgery year, and TIT on the occurrence of intraoperative RA, PSM was performed to select control group of patients at a 1:1 ratio. Patients were matched for the same gender, similar age, surgery performed in the same year, and similar TIT. Age and TIT were included as continuous matching covariates, whereas sex, and year of intervention were matched exactly. The Caliper value was set at 0.1, and the matching order was randomized.\u003c/p\u003e \u003cp\u003eAfter matching, 227 patients with RA were successfully matched in a 1:1 ratio with 227 control patients without RA. The overall balance test indicated good covariate balance (\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.311, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.856). Moreover, the Relative Multivariate Imbalance L1 decreased from 0.312 to 0.203 after matching. These result indicate an overall good matching performance. No variables in the matching process had |d| \u0026gt; 0.25, indicating adequate balance across all variables after the match. After matching the absolute standardized differences for age and TIT were reduced to 2.9% and 5.7%, respectively, compared with 5.9% and 76.1% before the match, indicating excellent balance of the two variables between the two groups was very good. The histogram of the distribution of SD, the univariate SD scatter plot, and SD comparisons are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA paired chi - square test (McNemar Test) revealed a significant difference in the frequency of preoperative use of KXA between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Furthermore, univariate binary logistic regression analysis identified preoperative use of KXA use as a protective factor (Wald 4.059, OR 0.518, 95%CI 0.273\u0026thinsp;~\u0026thinsp;0.982, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.044), corresponding to a 1.93-fold reduction in the risk of intraoperative RA. Details are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between preoperative use of KXA and occurrence of intraoperative RA (2\u0026times;2 table)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ePreoperative use of KXA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntraoperative reperfusion arrhythmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e198 (87.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e227 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e211 (93.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (7.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e227 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e409 (90.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45 (9.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e454 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe risk of intraoperative RA in the two groups is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In comparison with patients who did not receive KXA, those administered KXA had a significantly lower risk of intraoperative RA (36% vs 52%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Effect of KXA on the risk of MACE\u003c/h2\u003e \u003cp\u003ePearson Chi-square test showed that preoperative KXA use was associated with a significantly reduced risk of MACE (\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;7.724, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005). The proportion of MACE was 3.6% (60/1662) in the non-user group and 1.2% (6/506) in the user group (see Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo further explore the role of preoperatively KXA administration on MACE, the enrolled population was stratified into two groups based on preoperative KXA use. Baseline characteristics and outcome comparisons between the two groups are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBasic Characteristics based on KXA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKXA Group(N\u0026thinsp;=\u0026thinsp;506)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group(N\u0026thinsp;=\u0026thinsp;1662)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eBasic\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (Male)\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e390 (77.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1337 (80.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003csup\u003ea\u003c/sup\u003e (Year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (55, 71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (54, 70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003csup\u003ea\u003c/sup\u003e (Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.2 (21.8, 26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.3 (22.0, 26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoke\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e239 (47.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e728 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.191\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of Stay\u003csup\u003ea\u003c/sup\u003e (Day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4, 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (4, 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR\u003csup\u003ea\u003c/sup\u003e (beats/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (70, 90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (70, 90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.935\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP\u003csup\u003ea\u003c/sup\u003e (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e135 (120, 153)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130 (116, 146)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP\u003csup\u003ea\u003c/sup\u003e (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 (70, 90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (68, 89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTEMI\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (14.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e740 (44.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e321 (63.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e919 (55.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e210 (41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e617 (37.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTIT\u0026le;720min\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e830 (49.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003ePeriod\u003csup\u003eb\u003c/sup\u003e (%) (Year)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e220 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e243 (14.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e246 (14.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e298 (17.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111 (21.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e304 (18.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e351 (21.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExamination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (48, 66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (49, 66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.817\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-blockers\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e354 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1253 (75.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMACE\u003csup\u003eb\u003c/sup\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e Nonparametric tests were applied for these variables.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003eb\u003c/sup\u003e Chi-square tests were performed for these variables.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: BMI, body mass index; CKD, chronic kidney disease; DBP, diastolic blood pressure; DM, Diabetes mellitus; HR, heart rate; KXA, KuanXiong Aerosol; LVEF, left ventricular ejection fraction; MACE, Major Adverse Cardiovascular Events; SBP, systolic blood pressure; STEMI, ST-elevated myocardial infarction; TIT, total ischemia time.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThere were significant differences between groups in variables of SBP, DBP, STEMI, Hypertension, TIT, Period, β-blockers, and MACE. The proportions of STEMI and TIT\u0026le;720min were significantly higher in the non - KXA group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eTo minimize potential bias of STEMI, we then conducted univariate and multivariate logistic regression were subsequently performed based on these comparison. Details are presented in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic Regression of KXA on the prevention of MACE\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eUnivariate Logistic Regression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003eMultivariate Logistic Regression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnadjusted OR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted OR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.981 (0.970\u0026ndash;0.992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.985 (0.970\u0026ndash;1.001)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.976 (0.960\u0026ndash;0.993)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.993 (0.970\u0026ndash;1.018)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.589\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTEMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.640 (1.598\u0026ndash;4.359)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSTEMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.132 (1.201\u0026ndash;3.786)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.515 (0.902\u0026ndash;2.546)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.053 (1.196\u0026ndash;3.521)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeriod\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeriod\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.813 (0.201\u0026ndash;3.284)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.772\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.903 (0.222\u0026ndash;3.673)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.886\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.463 (0.785\u0026ndash;7.729)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.507 (0.790\u0026ndash;7.954)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.669 (0.518\u0026ndash;5.378)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.581 (0.483\u0026ndash;5.172)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.449\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.253 (1.099\u0026ndash;9.627)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.817 (0.926\u0026ndash;8.568)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.358 (0.780\u0026ndash;7.129)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.129\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.105 (0.683\u0026ndash;6.482)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.195\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTIT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.493 (0.915\u0026ndash;2.439)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTIT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.779 (0.439\u0026ndash;1.382)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.392\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.690 (0.410\u0026ndash;1.161)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.804 (0.466\u0026ndash;1.387)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.433\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKXA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.320 (0.138\u0026ndash;0.746)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKXA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.382 (0.157\u0026ndash;0.930)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u0026dagger;This variable was compared on the basis of 2018 (year).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBefore adjustment, significant differences were observed in variables of SBP, DBP, STEMI and KXA. After adjustment for confounding factors, KXA remained independently and negatively associated with MACE (adjusted OR 0.382, 95%CI 0.157\u0026ndash;0.930, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034). This indicated that compared with patients who didn\u0026rsquo;t receive KXA, those treated with KXA had a 61.8% lower risk of developing MACE.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eKXA is often used in China for treatment of angina pectoris and has been shown to rapidly relieve the symptoms and accelerate ST segment normalization, with efficacy comparable to that of nitroglycerin\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Previous studies\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e have also reported its therapeutic effects in myocardial bridge, acute myocardial infarction and other cardiac diseases.\u003c/p\u003e \u003cp\u003eIn this study, pre-reperfusion administration of KXA before PCI significantly reduce the risk of intraoperative RA to 48.2% compared with those patients who did not receive KXA. After PSM matching the for gender, age, year of surgery, and TIT, the difference between the case and control groups remained statistically significant, suggesting that KXA may inhibit the occurrence of intraoperative RA. Moreover, preoperatively KXA administration was also associated with a reduced risk of in-hospital MACE. This protective effect may be attributable to the ability of KXA to ameliorate MI/RI.\u003c/p\u003e \u003cp\u003eIn addition, patients with RA had a longer length of hospital stay and a higher incidence of MACE. Clinical studies have shown that RA can lead to larger infarct size and adverse prognosis\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Compared to patients who didn\u0026rsquo;t present ventricular tachycardia or ventricular fibrillation (VT/VF), those who developed with VT/VF after PCI had a significantly increased mortality rate (3.6% vs 33.3%)\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRegarding prolongation hospitalization, patients with CAD often require extended in-hospital monitoring following PCI - related ventricular arrhythmia, probably due to the longer procedural duration of intervention and observation\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Although several studies\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e have reported that RA can significantly influence in - hospital mortality, the PAMI trial\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e (Primary Angioplasty in Myocardial Infarction Trial) didn\u0026rsquo;t demonstrate a clear association between RA and poor in-hospital prognosis. In our study, the definition of RA differed slightly from that used in previous reports, as it encompassed not only ventricular arrhythmia but also atrial bradycardia and atrioventricular block. These arrhythmias often bring potential harm and may require intervention such as permanent pacemaker implantation\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our cohort, a greater proportion of patients in the arrhythmic group had a shorter TIT (\u0026le;\u0026thinsp;12 h, 69.2% vs 37.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This difference may be explained by the higher prevalence of STEMI in the arrhythmic group, resulting in earlier reperfusion of cardiomyocytes relative to patients without arrhythmia.\u003c/p\u003e \u003cp\u003eWith the therapeutic time window, delayed achievement of revascularization is associated with a progressively increased risk of RA\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. However, once this window has elapsed, the probability of RA will gradually decreases\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e, whereas mortality increases with further delays in revascularization\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. This is likely caused by increased sympathetic activation after AMI, and the ischemia-induced shortening of the electrical refractory periods in the injured myocardium\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. In the absence of timely reperfusion, irreversible myocardial injury and apoptosis ensue, ultimately abolishing the myocardium\u0026rsquo;s ability to generate electrical signals.\u003c/p\u003e \u003cp\u003eAdditionally, we found a significantly higher proportion of STEMI cases and a shorter TIT in the non-KXA group, indicating that the KXA group comprised a substantially greater proportion of NSTEMI patients. This imbalance may be attributable to clinicians, practice patterns, whereby clinicians preferentially administered KXA after hemodynamic stabilization or were reluctant to pre-administered KXA before PCI in critically ill STEMI patients. After all, none of the current guidelines have mentioned the application of KXA before PCI so far. Nevertheless, our analysis revealed that KXA administration was associated with a reduced the risk of MACE, and this result remained robust after adjusting for other covariates.\u003c/p\u003e \u003cp\u003eThe mechanism of KXA in mitigating MI/RI may be mediated through improvement of vascular endothelial function. Several clinical studies\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e have found that KXA increases circulating nitric oxide (NO) levels while reducing endothelin-1 (ET-1) concentrations in patients with CAD. NO and ET-1 are mainly released by vascular endothelial cells, reflecting vascular endothelial function. NO is a classical endothelium-derived vasodilator that relaxs vascular smooth muscle by activating guanylate cyclase, thereby reducing perivascular resistance, enhancing coronary blood flow, improving myocardial perfusion in the ischemic regions, and inhibiting platelet aggregation and the aggregation of inflammatory cells \u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. In contrast, ET-1 can antagonize the effect of NO by, promoting vasoconstriction and thrombogenesis \u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e. Likewise, improved survival has been associated with higher NO bioavailability and lower ET-1 levels. Moreover, NO is a well-known cardioprotective molecule acting through the cGMP/PKG signaling pathway, and represents a central component of both the RISK (reperfusion injury salvage kinase) and SAFE (survivor activating factor enhancement) cardioprotective pathways\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. Through interaction with mitochondria, NO could activate mK\u003csub\u003eATP\u003c/sub\u003e channels and prevent the generation of reactive oxygen species, ultimately conferring vasoprotective and cardioprotective effects\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNetwork pharmacology analyses\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e showed that the mechanism of angina pectoris in CAD may involve the VEGF signaling pathway, and VEGF can stimulate endothelial cells to produce NO\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e, which improves vascular perfusion, suppresses thrombosis and inflammation, reduces reperfusion injury\u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e, and suppresses ventricular arrhythmia caused by myocardial reperfusion\u003csup\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn conclude, our result indicated that KXA may have the potential to prevent intraoperative RA and reduce the occurrence of MACE. These protective effects are likely mediated, at least in part, through activation of the NO-cGMP pathway.\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, its retrospective case-control design is inherently subject to retrospective bias. For example, misclassification of AMI subtype may have occurred, and although the database indicated that KXA was administered preoperatively, initiation after surgery cannot be completely excluded. Secondly, intraoperative RA occurred was identified solely based on surgical records; therefore, underreporting is possible, and some RA events may not have been adequately documented. Given the relatively low incidence of RA was observed, this potential misclassification bias cannot be rule out. Thirdly, despite using PSM and multi-variable adjustment, unmeasured or residual confounding factors (e.g., detailed medication history, socioeconomic status) could still exist, potentially biasing the estimated effects. Finally, patients were recruited from multiple sub - centers of one hospital of Guangdong Provincial Hospital of Chinese Medicine. Limiting the generalizability of the findings to other regions or populations Consequently, a definitive casual relationship between the preoperative KXA use and intraoperative RA cannot be established. Larger-scale, nationwide, longitudinal and prospective studies will be needed to clarify the role of KXA in MI/RI.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eKXA may help prevent intraoperative RA, ameliorate MI/RI, and diminish the risk of MACE during hospitalization in patients with AMI. To our knowledge, this is the first study to reveal the efficacy of KXA in the context of MI/R injury.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNational High-Level Key Disciplines in Traditional Chinese Medicine\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJia-Lin Yuan was responsible for the study design and methodology, clinical data collection, and writing of the initial draft of the manuscript. SangYu Liang and JingYan Huang assisted with the clinical data collection. Liu He and Qiu-Xiong Chen conceived the research idea and overall dirction, and supervised and guided the research process. Lin-Yan Li and Liu He reviewed, revised, and polished the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from Guangdong Provincial Hospital of Chinese Medicine but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with the permission of Guangdong Provincial Hospital of Chinese Medicine.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMoran, A. E. et al. The Global Burden of Ischemic Heart Disease in 1990 and 2010. CIRCULATION. ;129(14):1493\u0026thinsp;\u0026ndash;\u0026thinsp;501.10.1161/CIRCULATIONAHA.113.004046. (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eByrne, R. A. et al. 2023 ESC Guidelines for the management of acute coronary syndromes. 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(1995).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Acute myocardial infarction, Reperfusion arrhythmia, KuanXiong Aerosol, Case-control study, MACE","lastPublishedDoi":"10.21203/rs.3.rs-8928474/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8928474/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eMyocardial intraoperative reperfusion arrhythmia (RA) is very common during the procedure of percutaneous coronary intervention (PCI). This study aimed to investigate whether pre-administering of KuanXiong Aerosol (KXA) can reduce the risk of RA.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this retrospective case - control study, patients diagnosed with acute myocardial infarction (AMI) who underwent PCI at Guangdong Provincial Hospital of Chinese Medicine from January 1, 2018 to December 31, 2023 were included. Clinical data were collected and propensity score match (PSM) was employed to balance baseline characteristics between KXA and control groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 2,168 cases of AMI patients were recruited, among whom 227 experienced reperfusion arrhythmia and 66 experienced major adverse cardiovascular events (MACE). Pre-administering of KXA was associated with a significant reduction in risk of RA (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), consistent after PSM. The incidence of MACE also reduced following KXA administration (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTo our knowledge, this is the first study to demonstrate that KXA may have the potential to reduce the risk of intraoperative RA, and decrease incidence of MACE.\u003c/p\u003e","manuscriptTitle":"Effect of KuanXiong Aerosol on Intraoperative Myocardial Ischemia Reperfusion Arrhythmia: A Propensity Score-Matched Case-Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-31 17:33:49","doi":"10.21203/rs.3.rs-8928474/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-17T12:16:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"79636618020932721723798906905977674206","date":"2026-05-08T02:16:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-27T11:52:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-27T08:47:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-04T13:28:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-03T23:14:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-03-03T18:37:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"13e0f219-ba5b-4279-bc6f-2747ad62e3b6","owner":[],"postedDate":"March 31st, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-17T12:16:28+00:00","index":108,"fulltext":""},{"type":"reviewerAgreed","content":"79636618020932721723798906905977674206","date":"2026-05-08T02:16:39+00:00","index":107,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":65339788,"name":"Health sciences/Cardiology"},{"id":65339789,"name":"Health sciences/Diseases"},{"id":65339790,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-03-31T17:33:49+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-31 17:33:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8928474","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8928474","identity":"rs-8928474","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}