Macrophage activation and polarization in post-infarction cardiac remodeling.

Adverse cardiac remodeling leads to impaired ventricular function and heart failure, remaining a major cause of mortality and morbidity in patients with acute myocardial infarction. It have been shown that, even if all the recommended therapies for ST-segment elevation myocardial infarction are performed, one third of patients undergoes progressive cardiac remodeling that represents morphological basis for following heart failure. The need to extend our knowledge about factors leading to different clinical scenarios of myocardial infarction and following complications has resulted in a research of immuno-inflammatory pathways and molecular activities as the basis for post-infarction remodeling. Recently, macrophages (cells of the innate immune system) have become a subject of scientific interest under both normal and pathological conditions. Macrophages, besides their role in host protection and tissue homeostasis, play an important role in pathophysiological processes induced by myocardial infarction. In this article we summarize data about the function of monocytes and macrophages plasticity in myocardial infarction and outline potential role of these cells as effective targets to control processes of inflammation, cardiac remodeling and healing following acute coronary event.

Nonpharmacological Correction of Hypersympatheticotonia in Patients with Chronic Coronary Insufficiency and Severe Left Ventricular Dysfunction.

BACKGROUND: Control of sympathetic hyperactivity is pivotal for treatment of heart failure (HF) in patients with coronary artery disease (CAD). Our earlier studies demonstrated that the auricular pulsed electrical stimulation of the vagus nerve (VNS) beneficially affected condition of CAD patients with HF. The aim of our study was to evaluate changes in heart rate (HR) and the levels of heat shock proteins in peripheral blood lymphocytes in patients with CAD in the course of VNS. METHODS: The study comprised 70 individuals aged 50-68 years with chronic coronary insufficiency, severe left ventricular dysfunction, and NYHA functional class (FC) III-IV HF. Main group included 63 patients who received VNS course (group 1). Control patients (n = 7) received sham therapy (group 2). RESULTS: According to the results of 6-minute walk test and 24-hour ECG monitoring, administration of VNS improved clinical condition of 58 of 63 patients, decreased HF FC, and attenuated HR. Clinical condition in sham therapy group did not change. Immunoenzyme method demonstrated that hsp70 and hsp60 contents in peripheral blood lymphocyte lysate increased by 58% and 48% (P < 0.05), respectively, in patients who initially had HR < 80 bpm. The hsp70 level significantly increased and hsp60 level remained unchanged in patients with initial HR > 80 bpm. CONCLUSIONS: Correction of autonomous nervous status by VNS attenuated HR and improved functional state of the heart in CAD patients. Cardiotropic effect of VNS was the most pronounced in patients with preserved endogenous stress-limiting systems associated with hsp60 and/or hsp70.

Community-Based View on Diagnostic Imaging at the End of COVID-19 Pandemic: Online Survey-Assisted Study.

(1) Background: An online survey-based observational cross-sectional study aimed at elucidating the experience and attitudes of an unstructured population regarding diagnostic imaging. (2) Methods: Invitations to participate were distributed using mixed-mode design to deidentified residents aged 18 years and older. Main outcome measures included morbidity structure and incidence of diagnostic imaging administrations. (3) Results: Respondents (n = 1069) aged 44.3 ± 14.4 years; 32.8% suffered from cardiovascular diseases (CVD); 9.5% had chronic respiratory pathology; 28.9% considered themselves healthy. Respondents with COVID-19 history (49.7%) reported higher rates of computed tomography (CT) (p < 0.0001), magnetic resonance imaging (MRI) (p < 0.001), and ultrasound (p < 0.05). COVID-19 history in CVD respondents shifted imaging administrations towards CT and MRI (p < 0.05). Every tenth respondent received MRI, CT, and ultrasound on a paid basis; 29.0% could not pay for diagnostic procedures; 13.1% reported unavailable MRI. Professional status significantly affected the pattern of diagnostic modalities (p < 0.05). MRI and CT availability differed between respondents in urban and rural areas (p < 0.0001). History of technogenic events predisposed responders to overestimate diagnostic value of fluorography (p < 0.05). (4) Conclusions: Preparedness to future pandemics requires the development of community-based outreach programs focusing on people's awareness regarding medical imaging safety and diagnostic value.

Clinical Significance and Patterns of Potential Drug-Drug Interactions in Cardiovascular Patients: Focus on Low-Dose Aspirin and Angiotensin-Converting Enzyme Inhibitors.

Objective: This study assessed the patterns and clinical significance of potential drug-drug interactions (pDDIs) in patients with diseases of the cardiovascular system. Methods: Electronic health records (EHRs), established in 2018-2023, were selected using the probability serial nested sampling method (n = 1030). Patients were aged 27 to 95 years (65.0% men). Primary diagnosis of COVID-19 was present in 17 EHRs (1.7%). Medscape Drug Interaction Checker was used to characterize pDDIs. The Mann-Whitney U test and chi-square test were used for statistical analysis. Results: Drug numbers per record ranged from 1 to 23 in T-List and from 1 to 20 in P-List. In T-List, 567 drug combinations resulted in 3781 pDDIs. In P-List, 584 drug combinations resulted in 5185 pDDIs. Polypharmacy was detected in 39.0% of records in T-List versus 65.9% in P-List (p-value < 0.05). The rates of serious and monitor-closely pDDIs due to 'aspirin + captopril' combinations were significantly higher in P-List than in T-List (p-value < 0.05). The rates of serious pDDIs due to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations were significantly lower in P-List compared with the corresponding rates in T-List (p-value < 0.05). Serious pDDIs due to administration of aspirin with fosinopril, perindopril, and ramipril were detected less frequently in T-List (p-value < 0.05). Conclusions: Obtained data may suggest better patient adherence to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations, which are potentially superior to the combinations of aspirin with fosinopril, perindopril, and ramipril. An abundance of high-order pDDIs in real-world clinical practice warrants the development of a decision support system aimed at reducing pharmacotherapy-associated risks while integrating patient pharmacokinetic, pharmacodynamic, and pharmacogenetic information.

Transthoracic echocardiography in the detection of chronic total coronary artery occlusion.

AIMS: The aim of our study was to detect chronic total occlusion of the left anterior descending coronary artery (LAD), circumflex coronary artery (Cx), and right coronary artery (RCA) using transthoracic echocardiography (TTE) in 110 consecutive patients who underwent coronary angiography for investigation of angina. METHODS AND RESULTS: Coronary blood flow direction was assessed in the epicardial collaterals [distal LAD (dLAD), obtuse marginal branches and right posterior descending artery (PDA)] and intramyocardial collaterals [LAD septal branch (SB LAD) and RCA septal branch (SB RCA)]. The sensitivity and specificity of retrograde flow for identification of the occluded LAD by TTE in the dLAD only were 78 and 96%, respectively, and those in both dLAD and SB LAD were 89 and 96%, respectively. The retrograde SB LAD flow detects proximal LAD occlusion with 88% sensitivity and 75% specificity. The sensitivity and specificity of retrograde flow for identification of the occluded RCA by TTE in the PDA only were 79 and 97%, respectively, and those in both PDA and SB RCA were 89 and 97%, respectively. The retrograde SB RCA flow does not allow us to differentiate between proximal and non-proximal RCA occlusion. Transthoracic echocardiography is not a method for diagnosing Cx occlusions as the success in visualizing the Cx epicardial collaterals was achieved in 31% of cases only. CONCLUSION: TTE is a sensitive and highly specific non-invasive method for diagnosis of LAD and RCA occlusions, based on the detection of the coronary blood flow direction in the epicardial and intramyocardial collaterals.

Serum Soluble ST2 and Adverse Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: To assess the dynamics of serum levels of soluble isoform of suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and their correlations with the development of adverse left ventricular remodeling (LVR) through 6 months in patients with primary myocardial infarction with ST-segment elevation (STEMI). METHODS: Subjects were 31 patients with STEMI (median age: 58 years), who underwent percutaneous coronary intervention (PCI) during the first 24 hours of the onset of myocardial infarction (MI). Blood samples and parameters of echocardiography were assessed at days 1, 3, 7, and 14 and 6 months after STEMI. RESULTS: Serum levels of sST2 and NT-proBNP decreased during the 6-month period. Levels of sST2 decreased by 48% from admission to day 7, and levels of NT-proBNP decreased by 40% from day 7 to 6 months after STEMI. Serum levels of sST2 at day 1 (r = 0.5, P < .05) and day 3 (r = 0.4, P < .05) were associated with adverse LVR by 6 months after STEMI. Logistic regression analysis showed that a high concentration of sST2 at day 7 increased the risk of adverse LVR (95% confidence interval [CI], 0.5-0.9; areas under curve [AUC] = 0.8; P = .002), with 92% sensitivity and 70% specificity. A multivariate analysis model revealed that adverse LVR was associated with the level of sST2 (P = .003) and with complete revascularization (P = .01) at the admission. CONCLUSIONS: The dynamics of serum levels of sST2 and NT-proBNP were different. The level of sST2 normalized by the 7th day; NT-proBNP decreased only by the end of the 6-month period after MI. Increased serum levels of sST2 by the 7th day of MI were associated with the development of adverse LVR by the end of the 6-month period.

Relationships of growth factors, proinflammatory cytokines, and anti-inflammatory cytokines with long-term clinical results of autologous bone marrow mononuclear cell transplantation in STEMI.

AIM: The aim of the study was to test the hypothesis suggesting that the pre-intervention levels of proinflammatory cytokines, anti-inflammatory cytokines, and angiogenic growth factors predict the long-term clinical results of autologous bone marrow-derived mononuclear cell (ABMMC) transplantation in patients with primary ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: From 2003 to 2006, a total of 62 patients with primary STEMI were enrolled in an open randomized study registered under the title ESTABOMA. Patients were randomized into two groups: group 1 included patients treated with percutaneous coronary intervention (PCI) and ABMMC transplantation (n = 28); group 2 comprised patients treated only with PCI (n = 34). Follow-up study was performed 7.96 ± 0.96 years after STEMI and involved physical examination, six-minute walk test, echocardiography, and determination of brain natriuretic peptide (BNP) levels. The total and cardiovascular mortality rates were higher in group 1 compared with group 2: 36% (n = 10) vs. 12% (n = 4) (p = 0.02) and 29% (n = 8) vs. 6% (n = 2) (p = 0.03), respectively. Lower levels of proinflammatory cytokines were observed in group 1 after PCI and ABMMC transplantation. Serum levels of FGF, VEGF, and IL-10, determined before PCI and ABMMC transplantation were prognostically significant long-term indicators of unfavorable course of CAD after STEMI.

Platelet hemostasis in patients with metabolic syndrome and type 2 diabetes mellitus: cGMP- and NO-dependent mechanisms in the insulin-mediated platelet aggregation.

Patients with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) have high risk of microcirculation complications and microangiopathies. An increase in thrombogenic risk is associated with platelet hyperaggregation, hypercoagulation, and hyperfibrinolysis. Factors leading to platelet activation in MetS and T2DM comprise insulin resistance, hyperglycemia, non-enzymatic glycosylation, oxidative stress, and inflammation. This review discusses the role of nitric oxide (NO) in the regulation of platelet adhesion and aggregation processes. NO is synthesized both in endotheliocytes, smooth muscle cells, macrophages, and platelets. Modification of platelet NO-synthase (NOS) activity in MetS patients can play a central role in the manifestation of platelet hyperactivation. Metabolic changes, accompanying T2DM, can lead to an abnormal NOS expression and activity in platelets. Hyperhomocysteinemia, often accompanying T2DM, is a risk factor for cardiovascular accidents. Homocysteine can reduce NO production by platelets. This review provides data on the insulin effects in platelets. Decrease in a number and sensitivity of the insulin receptors on platelets in T2DM can cause platelet hyperactivation. Various intracellular mechanisms of anti-aggregating insulin effects are discussed. Anti-aggregating effects of insulin are mediated by a NO-induced elevation of cGMP and upregulation of cAMP- and cGMP-dependent pathways. The review presents data suggesting an ability of platelets to synthesize humoral factors stimulating thrombogenesis and inflammation. Proinflammatory cytokines are considered as markers of T2DM and cardiovascular complications and are involved in the development of dyslipidemia and insulin resistance. The article provides an evaluation of NO-mediated signaling pathway in the effects of cytokines on platelet aggregation. The effects of the proinflammatory cytokines on functional activity of platelets are demonstrated.

Reduced coronary flow reserve in the coronary sinus is a predictor of hemodynamically significant stenoses of the left coronary artery territory.

AIM AND METHODS: The role of transesophageal Doppler assessment of coronary flow reserve (CFR) in the coronary sinus (CS) in the diagnostics of significant left coronary artery (LCA) stenoses was studied in 65 CAD patients with angiographically proven >50% stenotic atherosclerosis of the LCA territory (38--with isolated left anterior descending artery (LAD) or left circumflex artery (Cx) stenosis; 27--with both LAD and Cx stenoses) and 31 healthy volunteers (all men). Dipyridamole was used as a stress agent. The antegrade phase of coronary flow in the CS moving into the right atrium was analysed. CFR in the CS was calculated in two ways: (1) as ratio of hyperemic to baseline peak antegrade flow velocity (CFRp); (2) as ratio of hyperemic to baseline volumetric blood flow velocity (CFRv). The level of CFR <2.0 in both ways of calculation was diagnosed as reduced. RESULTS: CAD patients compared with healthy volunteers had significantly lower CFRp (1.51+/-0.44 and 2.57+/-0.79; p<0.001) and CFRv (2.21+/-1.18 and 5.43+/-2.83; p < 0.001) in the CS. CFRp <2.0 in the CS was a predictor of significant stenoses of the LCA with sensitivity of 89% and specificity of 76%, while CFRv <2.0 was a predictor of significant stenoses of the LCA with sensitivity of 49% and specificity of 97%. CFRp <2.0 in the CS was registered in 96% of CAD patients with two-vessel lesion and in 84% of CAD patients with one-vessel lesion, while CFRv <2.0 in the CS was revealed in 85% of CAD patients with two-vessel lesion and only in 26% of CAD patients with one-vessel lesion. Sensitivity and specificity of CFRv <2.0 in the CS in the diagnostics of significant two-vessel lesion of the LCA were 85% and 84%, respectively. CONCLUSIONS: Thus, the reduced CFR in the CS is a sensitive and specific predictor of LCA stenoses. A decrease of both CFRp <2 and CFRv <2.0 in the CS is a predictor of significant two-vessel lesion of the LCA, while a decrease of only CFRp <2.0 in the CS is a predictor of significant one-vessel lesion of the LCA.