Volum 18, Issue 5 (2026)

Introduction

Acute myocardial infarction (AMI) remains a leading cause of mortality and disability worldwide. Despite advances in reperfusion therapy, the prediction and prevention of adverse post-infarction cardiac remodeling and the development of chronic heart failure continue to be major challenges in cardiology [1]. These processes are underpinned by a complex cascade of molecular and cellular reactions, encompassing inflammation, fibrosis, and neurohormonal activation. In the search for novel diagnostic and prognostic biomarkers, as well as potential therapeutic targets, the somatostatin (SST) ligand-receptor system has garnered increasing research interest.

SST is a peptide hormone with a broad spectrum of inhibitory effects, expressed not only in neuroendocrine cells but also in cardiomyocytes, fibroblasts, and immunocompetent cells [2, 3]. Evidence indicates that SST and its receptors (predominantly subtype 2, SSTR2) play a significant role in regulating the inflammatory response, cell proliferation, and apoptosis. In the setting of ischemic myocardial injury, activation of the endogenous SST system is observed and is considered a potential compensatory mechanism that limits the zone of necrosis and modulates reparative processes [2, 4]. However, the temporal dynamics of endogenous SST levels during the early post-infarction period, as well as their relationship with clinical outcomes and the pattern of myocardial recovery, remain insufficiently elucidated. Although SST has been shown to modulate cytokine secretion, the specific nature of the interaction between the SST system and the cytokine cascade at defined time points following AMI remains unclear.

Contemporary imaging modalities enable non-invasive assessment of SSTR2 receptor activity in the myocardium. The radiopharmaceutical (RP) ^99mTc-Tektrotyd, an SST analog, binds specifically to SSTR2. Consequently, cardiac scintigraphy with ^99mTc-Tektrotyd offers a unique opportunity for the in vivo quantitative evaluation of the density and functional activity of these receptors within the injured area and the peri-infarct region [5]. Accumulation of the RP may serve as an indicator of the intensity of reparative and inflammatory processes. However, correct interpretation of the acquired data necessitates an understanding of the relationship between RP uptake and the levels of its endogenous ligand, SST.

Thus, a set of pertinent scientific questions emerges, the answers to which would facilitate a deeper comprehension of the integrative role of SST in post-infarction remodeling and would allow an assessment of its potential utility for risk stratification and the development of novel therapeutic strategies targeting post-infarction inflammation.

The aim of the study was to evaluate the dynamics of endogenous SST and its association with the intensity of ^99mTc-Tektrotyd uptake and the cytokine profile in patients with primary anterior ST-segment elevation myocardial infarction during the early post-infarction period.

Materials and Methods

General characteristics of the patients and research methods. The study included 22 patients. Their clinical characteristics are presented in Table 1.

Table 1. Clinical characteristics of patients with acute myocardial infarction upon admission to the clinic

Note. Data are presented as n (%) and Me [Q1; Q3]. BMI — body mass index; LVEF — left ventricular ejection fraction; LVEDV — left ventricular end-diastolic volume; LVESV — left ventricular end-systolic volume; CPK-MB — creatine phosphokinase-MB; TnI — troponin I; PCI — percutaneous coronary intervention; TLT — thrombolytic therapy; TIMI (Thrombolysis in Myocardial Infarction) — a scale for assessing coronary artery perfusion after the occlusion point on coronary angiography.

Inclusion criteria were the following: age over 18 years; primary anterior ST-segment elevation myocardial infarction (type 1); signed written informed consent provided by the patient.

Exclusion criteria were the following: prior myocardial infarction; absence of ST-segment elevation; myocarditis; infective endocarditis; inflammatory cardiomyopathy; SST analog therapy; severe renal failure; patient refusal to participate in the study.

During the in-hospital phase, upon admission, all patients underwent laboratory and instrumental evaluation in accordance with the clinical guidelines of the Ministry of Health of the Russian Federation on “Acute ST-segment elevation myocardial infarction” dated 2024 [6]. Percutaneous coronary intervention (PCI) with stenting of the left anterior descending coronary artery (with or without prior thrombolysis) was performed, and conservative medical treatment was administered according to current medical care standards. Additionally, on day 1 (at admission) and day 5, blood samples were collected fr om all patients to determine inflammatory markers. On days 5–6, single-photon emission computed tomography combined with computed tomography (SPECT/CT) using ^99mTc-Tektrotyd was performed.

All procedures performed within the framework of this study complied with the ethical standards of the World Medical Association Declaration of Helsinki (2024). The study was approved by the local ethics committee (protocols No.198 dated May 27, 2020 and No.226 dated February 24, 2022).

Transthoracic echocardiography. On admission and on day 5 post-AMI, all patients underwent transthoracic echocardiography (Philips Affiniti 70, the Netherlands) in 2D mode with ECG gating. All examinations were performed by a single operator to eliminate inter-operator variability. Cardiac imaging was conducted fr om standard views (parasternal long-axis and short-axis of the left ventricle (LV), apical 5-, 4-, and 2-chamber, and subcostal) in M- and B-modes. In all cases, image quality was rated as satisfactory or near-satisfactory. LV end-diastolic volume (EDV), end-systolic volume (ESV), and global systolic function (ejection fraction, EF) were calculated over a single cardiac cycle using the modified Simpson’s method (biplane assessment) [7]. The extent and severity of myocardial asynergy were evaluated using the 16-segment LV model, with regional wall motion scored as follows: 1 score signified normokinesis, 2 scores — hypokinesis, 3 — akinesis, and 4 — dyskinesis [8]. The wall motion score index (WMSI) was calculated as the sum of segmental scores divided by the number of segments evaluated [9].

Biochemical analysis. Venous blood sampling was performed on days 1 and 5 post-AMI. To assess the systemic inflammatory response, levels of high-sensitivity C-reactive protein (hs-CRP), and interleukins (IL-6, IL-10, and IL-1β) were measured in blood samples using solid-phase enzyme-linked immunosorbent assay (ELISA) with reagent kits from Vector-Best (Russia).

Plasma SST concentrations were also evaluated on day 1 (prior to PCI) and day 5 post-AMI with solid-phase ELISA, using FineTest reagent kits (Wuhan Fine Biotech Co., Ltd., China).

SPECT/CT with ^99mTc-Tektrotyd. On days 5–6 after the acute coronary event, all patients underwent SPECT/CT with ^99mTc-Tektrotyd (^99mTc-HYNIC-[D-Phe¹, Tyr³-octreotide]; IAE POLATOM, Poland).

Hybrid cardiac imaging and calculation of the maximum standardized uptake value (SUVmax) of ^99mTc-Tektrotyd were performed using a GE Discovery NM/CT 850 SPECT/CT system (GE HealthCare, USA) equipped with low-energy, high-resolution, high-sensitivity collimators. Scintigraphic images were acquired in tomographic mode 3 h after intravenous injection of 550 MBq of ^99mTc-Tektrotyd, using the following parameters: 64 projections, matrix size — 128×128 pixels, pixel size — 1.72 mm, zoom — 1.0, and acquisition time of 15 s per projection. After that, a chest CT scan was performed for attenuation correction using a helical mode with tube voltage of 140 kV, tube current of 30 mA, and slice thickness of 1.25 mm [10]. RP activity in the syringe was measured immediately before and after injection of ^99mTc-Tektrotyd using a dose calibrator with a fixed measurement time.

Image interpretation of the hybrid study and localization of RP uptake were performed using the Volumetrix MI software application on the Advantage Workstation 4.6 (GE HealthCare, USA). The following data were used to calculate SUVmax: patient height and weight, volumetric activity of the RP in the syringe before and after administration, time of RP activity measurement in the syringe, injection time, ^99mTc half-life, and camera sensitivity (160 counts/min/μCi). All necessary data were into the data table. Using the “brush” tool, segmentation of RP uptake zones was performed, with accuracy verified in the axial, sagittal, and coronal planes, as well as segmentation of cardiac CT regions (Figure 1). Upon segmentation completion, the Volumetrix MI application automatically calculated SUVmax according to the following formula:

SUVmax = (Tissue RP concentration (kBq/ml) / Injected activity (kBq)) · Body weight (g).

Figure 1. CT images (upper panel) and scintigraphic images (lower panel) of the heart in the frontal, sagittal, and axial projections (left to right) during myocardial segmentation showing ^99mTc-Tektrotyd uptake. The red cursor is positioned within the left ventricular cavity. White arrows indicate diffuse, moderate-intensity radiopharmaceutical uptake in the projection of the interventricular septum and anterior wall; blue arrows indicate the upper border of the liver

Radionuclide diagnostics were performed within the framework of the scientific protocol and in accordance with ethical requirements.

Statistical analysis. Statistical analysis was performed using Jamovi software (v. 2.6.44). Normality of distribution was assessed using the Shapiro–Wilk test. Given the non-normal distribution of the data, quantitative variables are presented as Me [Q1; Q3], wh ere Me denotes the median, and Q1 and Q3 represent the lower and upper quartiles, respectively; categorical variables are expressed as absolute numbers and percentages. Statistical significance of between-group differences was assessed using the non-parametric Wilcoxon test. The strength and direction of associations between quantitative variables were evaluated using Spearman’s rank correlation coefficient (ρ). Univariate linear regression models were constructed to evaluate the SST effect on cytokine levels and echocardiographic parameters. Differences were considered statistically significant at p<0.05.

Results

Results of in-hospital observation. The median length of hospital stay was 9.0 [8.7; 10.0] days. During the observation period, there was no in-hospital mortality. No major adverse cardiovascular events (MACE) were recorded, nor were there any life-threatening arrhythmias.

Results of transthoracic echocardiography. On admission, 10 patients had a LVEF of 50% or less. All patients had regional wall motion abnormalities of varying severity, localized to the infarct zone. By day 5 of observation, acute LV aneurysm developed in 4 patients. There were no statistically significant changes in LVEF or LVESV by day 5; however, a trend toward an increase in LVEDV was observed (Table 2).

Table 2. Dynamics of global systolic function and left ventricular volumetric parameters in patients with acute myocardial infarction during the early post-infarction period

Note. Data are presented as median [Q1; Q3]. LVEF — left ventricular ejection fraction; LVEDV — left ventricular end-diastolic volume; LVESV — left ventricular end-systolic volume; WMSI — wall motion score index.

Results of quantitative assessment of ^99mTc-Tektrotyd myocardial uptake. On SPECT/CT imaging, ^99mTc-Tektrotyd uptake in the LV myocardium was found in 18 out of 22 patients. In all cases, ^99mTc-Tektrotyd incorporation into the myocardium was diffuse, and its localization corresponded to the infarct zone (Figure 2). The median SUVmax was 2.8 [1.8; 3.1] g/ml.

Figure 2. CT images (upper panel), scintigraphic images (middle panel), and fused hybrid images (lower panel) of the heart in the frontal, sagittal, and axial projections (left to right). The red cursor is positioned within the left ventricular cavity. White arrows indicate diffuse, moderate-intensity radiopharmaceutical uptake in the projection of the interventricular septum and anterior wall; blue arrows indicate the upper border of the liver

Assessment of systemic inflammation and endogenous SST dynamics. Median values of inflammatory markers on days 1 and 5 after AMI onset are presented in Table 3.

Table 3. Levels of endogenous somatostatin and inflammatory biomarkers in patients with acute myocardial infarction on days 1 and 5

Note. Data are presented as Me [Q1; Q3]. SST — somatostatin; IL — interleukin; hs-CRP — high-sensitivity C-reactive protein; * reference values provided by the manufacturer Wuhan Fine Biotech Co., Ltd (China); ** reference values provided by the manufacturer Vector-Best (Russia); *** reference values according to the 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias [11].

Elevated hs-CRP levels [11] were recorded in all patients enrolled in the study. IL-6 concentrations above the reference value (10 pg/ml) were observed in 15 patients (exceeding the normal range by 2- to 7-fold); IL-10 and IL-1β concentrations were within reference ranges in all subjects. Changes in cytokine concentrations from the acute phase to the proliferative phase were individually variable. Specifically, hs-CRP concentrations decreased by day 5 in only 5 patients, increased in 4 patients, and remained unchanged in 13 patients. A reduction in IL-6 levels was observed in all subjects; however, only 16 patients reached values within the reference range. IL-10 and IL-1β concentrations did not change significantly.

The dynamics of endogenous SST were also variable. During the acute phase of AMI, SST concentrations below 20 pg/ml were noted in 10 patients, while the remainder were within reference values. By day 5, however, SST levels had increased in 10 patients, remained unchanged in 2 patients, and decreased in 10 patients.

Correlation analysis revealed a moderate negative association between SST concentration and IL-1β levels on day 1 post-AMI, as well as between day-1 SST and day-5 LVEDV and WMSI. No correlation was found between SST concentration and markers of myocardial necrosis or injury, nor with the standardized uptake value of ^99mTc-Tektrotyd (Table 4). Additionally, a positive correlation was observed between peak troponin I (TnI) and day-1 IL-6 concentration (ρ=0.424; p=0.001), which was expected and reflects the relationship between infarct size and systemic inflammation.

Table 4. Spearman correlation analysis between endogenous somatostatin concentration, IL-1β, and standardized uptake value of ^99mTc-Tektrotyd

Note. IL — interleukin; LVEDV — left ventricular end-diastolic volume; WMSI — wall motion score index; SUVmax — standardized value of ^99mTc-Tektrotyd accumulation in the left ventricular myocardium; TnI — troponin I; CPK-MB — creatine phosphokinase-MB.

A comprehensive analysis of correlations between the studied parameters is presented as a heatmap (Figure 3).

Figure 3. Spearman correlation heatmap between the standardized uptake value of ^99mTc-Tektrotyd, echocardiographic parameters, and cytokine levels on days 1 and 5 after acute myocardial infarction. SUVmax — standardized uptake value of ^99mTc-Tektrotyd in the myocardium; LVEF — left ventricular ejection fraction; LVEDV — left ventricular end-diastolic volume; LVESV — left ventricular end-systolic volume; WMSI — wall motion score index; SST — somatostatin; IL — interleukin; hs-CRP — high-sensitivity C-reactive protein. The color scale from −1 to 1 represents Spearman’s correlation coefficient; * p<0.05, ** p<0.01, *** p<0.001; (1) — day 1 after acute myocardial infarction (prior to percutaneous coronary intervention), (5) — day 5 after acute myocardial infarction

Univariate linear regression models were constructed to analyze the direct relationship between endogenous SST concentration and other correlates. Sequential calculation of the contribution of each studied parameter to the model demonstrated a significant association between SST and IL-1β levels on both day 1 and day 5 (p<0.05), whereas echocardiographic parameters showed only a trend toward linear dependence (Table 5).

Table 5. Results of univariate linear regression analysis (somatostatin, day 1)

Note. IL — interleukin; LVEDV — left ventricular end-diastolic volume; WMSI — wall motion score index; DW — Durbin–Watson autocorrelation test.

The results of multivariate linear regression analysis are presented in Table 6, which included parameters that showed a correlation with SST concentration on day 1.

Table 6. Results of multivariate linear regression analysis (somatostatin, day 1)

Note. IL — interleukin; LVEDV — left ventricular end-diastolic volume; WMSI — wall motion score index.

The final multivariate linear regression model included IL-1β levels on days 1 and 5 post-AMI (R²= 0.660; adjR²=0.624; F-test=18.4; p=0.001). Thus, higher SST levels were associated with lower IL-1β concentrations both on day 1 (expβ=−0.451; p=0.027) and on day 5 (expβ=−0.440; p=0.028).

Discussion

In this research, the endogenous SST dynamics were studied for the first time in patients with primary anterior ST-segment elevation myocardial infarction. The peptide–receptor relationship was examined using SSTR-directed imaging. The associations between serum SST concentration, echocardiographic parameters, and IL-1β were identified. It was demonstrated that SST concentration was not associated with the standardized uptake value of the SST analog ^99mTc-Tektrotyd in the LV myocardium, but it negatively correlated with the level of the pro-inflammatory cytokine IL-1β, as well as with LVEDV and WMSI. The association between SST concentration and IL-1β was confirmed in both univariate and multivariate linear regression models.

Ischemic and reperfusion injury is accompanied by a complex cascade of metabolic, inflammatory, and neuroendocrine responses aimed at limiting ischemic damage and restoring myocardial structural integrity [2]. Our data on the dynamics of inflammatory markers in AMI demonstrate a partial reduction in pro-inflammatory markers (IL-6) in the absence of significant regression of systemic inflammation (hs-CRP), without activation of the anti-inflammatory response (IL-10). This indicates an ongoing, individually variable inflammation with a predominantly pro-inflammatory phenotype. This may partly explain why anti-inflammatory therapeutic strategies for post-infarction inflammation, as proposed in the COLCOT [12], CANTOS [13], VCU-ART [14], and ASSAIL-MI [15] trials, have not yet been incorporated into routine clinical practice.

Analysis of endogenous serum SST concentrations at time points corresponding to the inflammatory phase (day 1) and the proliferative phase (day 5) revealed not only variability in baseline values but also divergent, individually variable dynamics. It should be noted that interpretation of these findings must take into account the physiological characteristics of SST as a multi-target peptide [2]. Its systemic concentration reflects a complex balance between secretion from various sources, tissue uptake, enzymatic degradation, and individual fluctuations. Unfortunately, there are no direct data in the international literature to allow a detailed comparison of this result. However, key findings from Sütő et al. [16] demonstrate a reduction in plasma SST levels in patients with coronary artery stenosis and a significant increase following stenting. Furthermore, the authors noted that baseline SST levels also decreased with age. These results are consistent with the concept of a cardioprotective and anti-inflammatory role of SST in the setting of ischemic and reperfusion injury [2, 4, 17].

Experimental and clinical data indicate that SST is one of the regulators of the inflammatory response. Activation of the somatostatinergic system can lim it exudation by suppressing leukocyte migration and adhesion, inhibit the proliferation of immunocompetent cells [18], and reduce the production of key pro-inflammatory mediators such as IL-1β, IL-6, TNF-α, and interferon-γ [19]. This effect is primarily mediated through activation of SSTR2 on macrophages, T lymphocytes, fibroblasts, and endothelial cells via three pathways. The first pathway involves activation of intracellular signaling cascades through inhibition of adenylyl cyclase and reduction of cyclic adenosine monophosphate levels, which subsequently suppresses activation of a major driver of pro-inflammatory cytokine synthesis — the transcription factor NF-κB [17]. It should be stated that reduced NF-κB transcription serves as a signal for shifting macrophage polarization from the M1 to the M2 phenotype [20]. The second pathway involves suppression of NLRP3 inflammasome activation in macrophages via attenuation of pyroptosis [21]. The third one consists of reduced chemotaxis and phagocytic activity of neutrophils and macrophages [22]. Thus, the negative association between SST and IL-1β levels in AMI reinforces the potential biological significance of SST as an anti-inflammatory and immunomodulatory peptide.

The concept of a cardioprotective effect of SST is also reflected in the results of correlation analysis between day-1 SST levels and day-5 echocardiographic parameters. However, we were unable to confirm this relationship in regression analysis, most likely due to the small sample size. It is known that the severity of systolic dysfunction and LV geometry alterations following infarction are determined by the volume of necrotic myocardium [23]. In turn, the WMSI is considered the most optimal tool for assessing the extent of myocardial damage. It is also preferred over global LV function assessment, as it has been recognized as a powerful predictor of adverse outcomes, particularly heart failure-related rehospitalization [24]. The mechanisms underlying the limitation of infarct size (previously demonstrated by our group in an experimental study [4]) and early remodeling may be mediated through modulation of inflammation, blockade of catecholamine release [25], and stabilization of cardiac sympathetic nervous system tone.

In recent years, there has been growing interest in molecular imaging methods based on SST analogs to assess inflammatory processes in the cardiovascular system. Radiolabeled SST analogs have high affinity for SSTR2, which is abundantly expressed on the surface of activated CD68⁺ macrophages [26]. This approach has already demonstrated utility in visualizing vascular inflammation, post-infarction inflammation, myocarditis, and sarcoidosis. Thus, it offers opportunities for non-invasive monitoring of anti-inflammatory therapy and risk stratification [10, 25, 27]. One of the key objectives of our study was to establish a possible peptide–receptor relationship between systemic circulating SST levels and the intensity of myocardial receptor expression as assessed by SSTR2-targeted imaging. However, no such associations were observed. From our point of view, this finding has a clear pathophysiological rationale and indicates that the systemic and local components of the somatostatinergic system in AMI function as parallel, rather than interconnected, processes within the same pathological event. Circulating SST concentration represents a humoral response to stress and injury, governed by complex non-linear neuroendocrine regulation. In contrast, SUVmax reflects the density of infiltrating inflammatory cells expressing SSTR2 on their membrane surface. At the same time, the question of possible compensatory SSTR2 overexpression in response to endogenous ligand deficiency remains open and requires further research in larger clinical cohorts and with extended long-term follow-up.

Further research should be aimed at determining the therapeutic efficacy of SST analogs, elucidating the cellular mechanisms of octreotide action, and identifying optimal therapeutic windows for its application in the setting of acute coronary ischemia.

Study limitations. This work has several limitations. Firstly, it is a single-center study performed on a small patient cohort, which limits statistical power and precludes the formation of subgroups for subanalysis, as well as multivariate regression analysis incorporating a large number of confounders. Secondly, the study does not include a control group, which restricts comparison of the somatostatinergic response and does not allow for the identification of specific biochemical patterns characteristic of post-infarction changes.

Conclusion

In the early post-infarction period, endogenous SST demonstrates a negative association with the level of the pro-inflammatory cytokine IL-1β and with LV remodeling parameters, underscoring its important anti-inflammatory role. The absence of a direct association between SST concentration and ^99mTc-Tektrotyd SUVmax indicates the complex nature of the peptide–receptor interaction and requires further research. The obtained data expand current knowledge regarding the role of the somatostatinergic system in the regulation of post-infarction inflammation and open up prospects for the development of targeted cardioprotective strategies and personalized patient selection for SST-directed therapy.

Study funding. The research was supported by a grant from the Russian Science Foundation (grant No.25-25-00040).

Conflict of interest. The authors declare no conflict of interest.