Study population and data collection
This was a single-center retrospective study, and the clinical data were extracted from hospital electronic medical records. The data of patients who were diagnosed with AMI and hospitalized in the Department of Cardiovascular Disease at Sir Run Run Hospital, Nanjing Medical University from June 1, 2016, to March 10, 2021 was collected. The patients were divided into two groups according to lactulose supplementation. In detail, among the AMI patients with lactulose supplementation, the patients who received a 667mg/ml lactulose oral solution once a day orally from the date of admission and continued during hospitalization were enrolled and analyzed. Then, the groups were compared regarding clinical characteristics and the incidence of post-MI MACEs.
The following variables were collected: demographic information, biochemical variables, medical and surgical history, concomitant medications, biochemical variables, and Killip classification on hospital admission. Collection of clinical information and laboratory examinations were performed on admission to our hospital, according to the standards of practice. All biochemical indicators were selected as the first biochemical result after admission.
The study protocol, as well as the exemption from informed consent, were approved by the ethics committee of Sir Run Run Hospital (ethical approval code: 2021-SR-024). The study protocol complied with the requirements of the Helsinki Declaration of the World Medical Association and the International Ethics Guide for Human Biomedical Research of the Council for International Organizations of Medical Sciences.
Diagnosis and definitions of AMI
AMI was diagnosed according to the International Classification of Diseases, 10th Revision guidelines, with the following criteria: detection of troponin with at least one value above the 99th percentile of the upper reference limit together with evidence of myocardial ischemia with at least one of the following: (1) symptoms of ischemia, including chest pain, chest tightness, and other symptoms; (2) acute electrocardiographic changes of new ischemia (ST segment and T wave changes or new left bundle branch block); (3) new pathological Q-waves on electrocardiography; or (4) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality[18].
Outcome events
MACEs during hospitalization, which included onset of heart failure (HF), presence of reinfarction, postoperative arrhythmia, cardiac death, and stroke, were investigated. HF was diagnosed mainly by clinical manifestations such as dyspnea, hemoptysis, fatigue, S3 gallop, jugular venous distention, moist rales and edema; in combination of chest X-ray findings showing signs of redistribution of blood or of interstitial or alveolar pulmonary edema, or UCG findings showing left ventricular enlargement, increased systolic volume, or left ventricular ejection fraction ≤ 40%. Reinfarction was defined as an increase in cardiac troponin I (cTnI) level to at least five times the upper limit of the reference range, with or without ST segment elevation, together with at least one of the following: symptoms of ischemia (chest pain or dyspnea), ECG changes indicating new ischemia (new ST-T changes or left bundle branch block), new pathological Q waves on ECG, or ultrasonic cardiograph (UCG) findings showing new loss of viable myocardium or new regional wall motion abnormality. Postoperative arrhythmia was defined as ECG changes showing any one of: malignant ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation), new persistent atrial flutter or atrial fibrillation, second-degree type II or third-degree atrioventricular conduction block, or frequent ventricular premature contractions, non-fatal cardiac arrest or cardiac arrest. Cardiac death was defined as death due to AMI, malignant arrhythmia (ventricular tachycardia, ventricular fibrillation), or HF. Stroke was identified as an acute neurological deficit lasting > 24 hours and affecting the ability to perform daily activities with confirmation by imaging techniques [19–23]. In addition, we investigated time to first MACE, and the length of hospital stay was considered the number of days from the date of admission to the date of discharge. Moreover, the proportion of patients who developed pneumonia during hospitalization was also studied.
Statistical analysis
Statistical analyses of the data were performed using R software (version 4.0.4, The R Foundation for Statistical Computing, Vienna, Austria) with the corresponding R packages. All tests were two-sided, and a value of P < 0.05, was considered statistically significant. Continuous variables were presented as means and standard deviations, and significant differences between the two groups were determined using Student’s t-test. Categorical variables were described using counts and percentages, and the groups were compared using a chi-square test (α = 0.05).
To determine the relationship between lactulose and MACEs post-AMI and investigate the influence of lactulose on the occurrence of pulmonary infections during hospitalization, univariate, multivariate, and multiple stepwise logistic regression analyses were performed. Odds ratios (ORs) with 95% confidence intervals (CIs) are presented. Univariate linear regression was used to analyze the effect of lactulose on the length of hospital stay. To investigate the influence of lactulose on the number of days from the date of admission to the date of occurrence of MACEs during hospitalization, univariate and multiple stepwise Cox regression analyses were performed. Hazard ratios (HRs) with 95% confidence intervals (CIs) are presented.