Study Population
This is a retrospective cohort study conducted between January 2014 and September 2018. Out of 5663 consecutive patients who underwent coronary angiography in the Hangzhou First People's Hospital Heart Center, 409 patients with CSFP were assessed for eligibility. In total, 369 patients were enrolled in the analysis and divided into two groups according to the experimental design. A flow diagram of the progress through the phases is shown in Fig. 1.
Ethics and consent statements
Since this is a retrospective cohort study, ethical and informed consent is not required.
Definitions
CSFP is defined as primary CSFP[2], which essentially is a delay in contrast injection into the coronary arteries. It is important to identify primary CSFP from delayed progression of contrast agents in coronary reperfusion therapy (such as angioplasty or stent implantation for acute myocardial infarction) or from other secondary causes of coronary slow flow. Conditions associated with secondary coronary slow flow include the following categories: coronary ectasia, coronary spasm, embolism, heart failure, angioplasty and stenting of acute myocardial infarction, valvular heart disease and connective tissue disorders.
Corrected TIMI frame count (CTFC)[11] represents the number of frames required to reach the distal boundary marker of the coronary artery. Not only is CTFC a simple, repeatable, objective, quantitative coronary index, but it also standardizes TIMI grading and facilitates angiography time comparisons between flow tests.
Criteria for inclusion and exclusion
Inclusion criteria
Patients with primary CSFP
Patients who underwent interventional therapy showed CSFP on coronary angiography after 1 month
Exclusion criteria
Previous myocardial infarction or interventional therapy
Heart pump failure
Severe liver or kidney failure
Life expectancy of less than 5 years
Preoperative examination
Venous blood samples are extracted within 24 hours of admission. White blood cells, red blood cells, platelets, total cholesterol, low-density lipoprotein, high-density lipoprotein, C-reactive protein, creatinine, uric acid, admission blood glucose, glycosylated hemoglobin, electrocardiogram and echocardiography must be completed and reviewed prior to coronary angiography.
Coronary angiography and evaluation of coronary flow velocity
Selective coronary angiography was performed by two experienced interventional cardiologists using a standard Judkins’ technique. When evaluating the results of coronary angiography, the left anterior descending (LAD) and the left circumflex (LCX) should be projected in at least four angles; the right coronary artery (RCA), in at least two angles. The first frame used to evaluate each TFC is when the dye enters the artery completely, and the last frame is when the dye enters the distal marker branch. In our study, the filming speed was 15 frames per second. The calculation of CTFC was performed by an observer who was blinded to the clinical details. The standard numbers of CTFC frames are defined as 36.2 ± 2.6 frames for LAD, 22.2 ± 4.1 frames for LCX, and 20.4 ± 3.0 frames or RCA. Researchers with TFC of any of the three vessels greater than twice the standard deviation of the normal published range were defined as patients with slow coronary blood flow.
Endpoint
The mean follow-up time for all patients was 24 months. Data related to clinical outcomes were obtained mainly through telephone follow-up and partly by reviewing outpatient records. The endpoints of the study included cardiovascular events requiring hospitalization or death. The former includes the occurrence of ACS, heart failure requiring hospitalization, and angina requiring revascularization[12]. All deaths are considered cardiogenic unless an unequivocal noncardiac cause was established.
Statistics
Before statistical analysis, all continuous variables were plotted and tested for normality and homogeneity of variance. Depending on the results, continuous variables are expressed as the means ± standard deviations (or medians and interquartile ranges). Categorical variables are expressed in terms of frequencies and percentages. Differences were compared between the two groups. Continuous data were compared by the T test or the Mann-Whitney U test (according to data characteristics), and categorical variables were tested by the chi-square test and Fisher’s exact test.
To compare the relationships between prognosis and factors, log-rank tests and Cox regression methods were performed. Log-rank tests are accurate based on hypergeometric probability. Time-to-event curves (i.e., age, treatment, diabetes, smoking and BMI) were evaluated by the Kaplan-Meier method. To identify independent risk factors for prognosis, a single-factor regression analysis was conducted on independent variables one by one, and corresponding p-values were recorded. Independent variables with p values less than 0.1 were incorporated into the final regression equation to identify clinical predictors.
Receiver operating characteristic (ROC) curves were constructed for the prediction of endpoint events. Different prediction parameters were analyzed by the logistic regression model, and the prediction probability was calculated for ROC analysis. The area under the curve (AUC) and the sensitivity and specificity of predicting RP were calculated. AUC = 1.00 indicates the highest accuracy, while AUC = 0.50 indicates no accuracy. A p-value of < 0.05 (2-sided) was considered statistically significant. All statistical analyses were carried out using SPSS software (version 23.0).