This was a single-center, retrospective study with a small sample size. We collected data from the Second Hospital of Hebei Medical University between May 2021 and April 2023.

The inclusion criteria for patients were as follows: (1) had primary STEMI, which was diagnosed by experienced cardiologists according to guidelines (1); and (2) underwent reperfusion treatment, including pharmacological thrombolysis therapy and percutaneous coronary intervention (PCI) on infarction-related vessels. Cardiologists determined culprit vessels through patients' symptoms, electrocardiogram, and coronary angiography; (3) all participants completed quantitative resting MPI within 14 days after reperfusion treatment. The exclusion criteria were as follows: (1) patients with reinfarction; (2) patients who did not receive reperfusion treatment in the acute stage; (3) patients whose clinical information was missing, such as resting heart rate and blood pressure; (4) patients did not undergo a resting dynamic scan; and (5) patients whose imaging did not meet the clinical diagnosis.

All patients undergoing MPI provided informed consent. Ultimately, 75 patients were included and 10 were excluded (Figure 1). Among those excluded, three patients had reinfarction, one did not receive reperfusion treatment in the acute stage, two lost biochemical information, one was missing heart rate and blood pressure, two lacked a scan sequence, and one dynamic sequence could not be reconstructed.

Resting dynamic and perfusion scanning was performed on D-SPECT (Spectrum Dynamics, Caesarea, Israel). D-SPECT is a commercially available dedicated cardiac CZT-SPECT system with nine cadmium zinc telluride detection columns. The acquisition procedures and reconstruction parameters were the same as in previous studies (15). The specific imaging process is shown in Figure 2.

Patients were fasted before the examination and a fatty meal was prepared. Technicians conducted quality checks on imaging devices before imaging, while nurses established intravenous access for patients. Patients were made aware of the need to lie on the examination bed, and nuclear medicine physicians measured their blood pressure and heart rate 2–3 times while the patients were calm.

A prescan injection of 0.5–1.0 mCi ^99mTc-sestamibi (^99mTc-MIBI) was administered for cardiac localization, followed by a 7.0–9.0 mCi 2 mL bolus injected at 1 mL/s using a high-pressure syringe pump (ACIST Medical Systems). A 6-min CZT SPECT dynamic imaging acquisition was started at the same time as the bolus injection. Patients then rested for an interval of 1 h, consuming a fatty meal to promote hepatobiliary clearance and reduce infracardiac activity. After 1 h, the tracer was stably distributed on the myocardium, and the resting MPI was performed in both the supine and upright positions.

Both resting dynamic and perfusion sequences were checked for quality and clinical diagnostic requirements before they were reconstructed. Qualified scan sequences were reconstructed, and MBF was measured using QGS-QPS postprocessing commercial software (Cedars-Sinai Medical Center, Los Angeles, CA, USA). Before obtaining SPECT parameters, the endocardial and epicardial contouring and number of boluses were assessed. Dynamic images were corrected by motion correction (MC) and rate pressure product (RPP) correction to obtain the resting MBF. If the product of the resting heart rate and resting systolic blood pressure was greater than 10,000, the resting MBF equaled the product of heart rate and blood pressure divided by 10,000. Quantitative blood flow values were also calculated using the Renkin-Crone formula (16). Postprocessing software was also used to analyze the perfusion images to obtain semiquantitative perfusion parameters and G-MPI results.

The left ventricular bullseye was divided into 17 segments according to the American Heart Association (AHA) (17), each segment with an independent resting MBF. The resting MBF is divided into ischemic MBF and non-ischemic MBF. The ischemic area is dominated by the culprit vessels, and the non-ischemic area is governed by the non-culprit vessels. The segments dominated by the three branches of the coronary artery are prescribed by the AHA. The ischemic MBF is equal to the average resting MBF of each segment of the culprit vascular domination, and the non-ischemic MBF is equal to average resting MBF of each segment of the non-culprit vascular domination. All resting MBFs were measured independently by two physicians, each with at least 10 years of experience in nuclear medicine.

All patients with STEMI were treated with reperfusion therapy and in-hospital medication according to guidelines (1, 18). All general and clinical information came from the hospital's medical records system and standard questionnaires from the Department of Nuclear Medicine. This information included sex, age, risk factors, onset and treatment of STEMI, biochemical indicators during hospitalization, electrocardiogram, CAG, PCI surgical records, and discharge diagnosis. Due to the precision of the cTnI detection method, the peak cTnI was classified into five grades: 0.04–25.00 = grade 1; 25.00–50.00 = grade 2; 50.00–75.00 = grade 3; 75.00–100.00 = grade 4; and >100.00 = grade 5.

Continuous variables were shown as mean ± SD or median (interquartile range). Categorical variables were expressed as percentages. We also used the intraclass correlation coefficient (ICC) to test the consistency of the resting MBF. The resting MBF was the average of the two. The Wilcoxon signed-rank test of two paired samples was used for ischemic MBF and non-ischemic MBF. The resting MBF was analyzed using the receiver operating characteristic (ROC) curve, and the Youden index was calculated to obtain the cutoff value. Multiple linear regression was performed to examine the influence of ischemic, non-ischemic MBF. SPSS (version 26.0) and Prism (version 10.0) software were used. A p-value <0.05 was considered to indicate statistical significance or relevance.

In our study, there was a difference between ischemic MBF and non-ischemic MBF after reperfusion treatment for patients with STEMI. We found that ischemic MBF was lower than non-ischemic MBF. In addition, the resting MBF in ischemic areas after reperfusion therapy was still low. Thus, we thought that STEMI reperfusion therapy solves the problem of epicardial blood vessel patency. However, why is the blood flow low in the area dominated by culprit vessels after treatment? This may be due to the recovery of coronary blood flow after treatment for STEMI, which requires a certain amount of time, as well as the impairment of the epicardial vessels, coronary microcirculation, and myocardium.

After STEMI reperfusion therapy, the culprit vessels already demonstrate patency. However, patients with STEMI have an instrumental injury to the epicardial vessels due to catheters, balloons, and stents, which may injure endothelial cells, causing the microthrombus to fall off, thus decreasing myocardial perfusion (20).

On the one hand, the decrease in resting MBF may be related to impaired microcirculation. Microembolization washout after thrombolysis treatment and transmural myocardial infarction may cause structural damage, leading to vascular obstruction (21). Moreover, interstitial edema, inflammatory cell infiltration, and platelet aggregation can also damage microcirculation patency (21). The effects of functional damage may occur after PCI, resulting in transient vascular contraction in epicardial vessels and microcirculation (22, 23). On the other hand, patients may have microcirculation injuries before STEMI, and most patients present with hypertension, smoking, hyperlipidemia, and diabetes, which may harm microcirculation (24, 25). Furthermore, microvascular structures may sustain further severe injury during subacute AMI through leakage of the red blood cells in blood vessels and leakage into the intercellular space of the myocardial body, forming intramyocardial hemorrhage (IMH) (26).

AMI mediates ischemia, and reperfusion causes edema of the myocardium, resulting in temporary impairment of cell function (27). A swollen myocardium and adjacent vessel compression may also affect blood flow patency. On the other hand, swelling may decrease tracer uptake, which further leads to the underestimation of resting MBF. In contrast, because of prolonged ischemia, some myocardium may undergo necrosis (26). Thus, there may be no or significantly reduced blood flow to the local myocardium.

Conversely, non-ischemic MBF is greater than ischemic MBF, possibly because the distal myocardium has a compensatory effect, resulting in increased resting MBF (28). However, this view needs to be confirmed by long-term imaging follow-up in the later stage.

Most studies have paid less attention to the clinical significance of resting MPI in ischemic disease (29). However, only resting MPI combined with clinical features enables the diagnosis of obstructive CAD (30). In clinical application, patients with acute coronary syndrome (ACS) in the acute period cannot undergo stressing MPI (31). For STEMI, cardiologists use electrocardiogram and coronary angiography to locate the ischemic area. In our research, we applied resting MBF to identify ischemia. According to the ROC analysis, the AUCs were 0.666 and 0.671 with or without RPP correction. To some extent, MBF is able to identify residual ischemia in patients with STEMI.

In our study, the SRS and male sex were inversely related to the ischemic MBF.

The SRS indicates the degree of ischemia and infarct (32) and is often correlated with fixed ischemia. Previously, cardiologists and nuclear physicians mainly relied on SRS, TPD, and gated parameters to analyze the severity of myocardial infarction, prognostic information, and treatment decisions (9–12). Current CZT-SPECT systems enable the measurement of MBF, which is also proportional with regional myocardial perfusion (3, 33). SRS is derived from semiquantitative and visual analysis, which has limitations in multivessel diseases or balanceable ischemia (6). However, MBF, as a quantitative parameter, excludes the influence of human factors and is semiquantitative. It may be more sensitive for assessing and identifying ischemic areas than semiquantitative parameters (Figure 5). In our study, the higher the SRS, the lower the resting MBF. To some extent, ischemia-related MBF can reflect the severity of myocardial infarction.

Generally, male individuals have a greater risk of cardiovascular disease than female individuals (34, 35). Our study had the same characteristics as the general population distribution; male prevalence was greater, and female patients comprised only 9.33% of the study population. In a previous study, there was no significant difference in infarct size and cardiac impairment between women and men with AMI (36). However, the male sex was found to be an identical risk factor for coronary reduced flow and coronary microvascular disease (CMD) after myocardial infarction with thrombolysis (37). In our multiple linear analysis, the male sex had an inverse relationship with ischemic MBF.

RPP and resting MBF are directly proportional, and currently available postprocessing software generally recommends RPP correction when measuring MFR. Moreover, some studies have also suggested that MFR without RPP correction also has prognostic value (38). In our study, only resting MBF was involved. There were statistically significant differences in ischemic MBF and non-ischemic MBF, both before and after RPP correction. In addition, there were small differences in the AUC and cutoff values before and after the correction. Furthermore, an excessively high heart rate and systolic blood pressure may overestimate resting MBF (15, 39), and we believe that RPP correction is optional for resting MPI only.

Resting MBF may also be affected by the degree of response to reperfusion treatment and individual differences.

The present study has some limitations. First, our assessment of myocardial infarction was performed after treatment, not before. Second, the study size was small. In the future, we can combine multiple medical centers to include more samples for research. Third, the long-term prognostic value of resting MBF was not discussed in this study, and we will follow patients and explore the prognostic value of resting MBF in patients with STEMI. Fourth, our study did not assess MFR, mainly because of the high risk of stress after STEMI. Finally, this study involved only the resting MBF and did not compare to the indices of microvascular resistance (IMR) (40, 41) and invasive resting flow (42). In the future, we will include a subcohort of patients with uncomplicated STEMI for MFR measurements. If possible, we will conduct comparisons of non-invasive resting flow and invasive resting flow to further investigate hemodynamics.