Anatolian Journal of Cardiology最新文献

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known for their benefits in conditions like cardiovascular diseases in type 2 diabetes and obesity. They also show promise for aging-related conditions with minimal side effects. However, their impact on cardiovascular risk is still debated. Notably, some long-acting GLP-1RAs cause a sustained increase in heart rate on the first day of use without a clear mechanism. To understand their short-term effects, we examined acute GLP-1R agonism on the electrical activity of elderly hearts.

Methods: In this study, we utilized in vivo electrocardiography, in vitro cellular electrophysiology experiments, and biochemical measurements on heart preparations from 6-month-old (Adult) and 24-month-old (aged) BALB/c mice.

Results: A single liraglutide injection (0.3 mg/kg) induced repetitive, self-sustained arrhythmogenic electrocardiograms in aged mice (24 months old) but had no effect on adults (6 months old) within the first 10 minutes. Acute application of liraglutide to isolated ventricular cardiomyocytes from aged mice significantly prolonged the late phase of action potential repolarization (APR90). This was due to suppressed K+ currents and increased persistent Na+currents (Late-INa), primarily through delayed recovery from inactivation of Na+ currents. Additionally, liraglutide increased Ca2+ spark frequency and wave formation by enhancing Ca2+ release from the sarcoplasmic reticulum, affecting both Na+ and Ca2+ regulation in aging cells. Liraglutide also induced casein kinase 2 (CK2) hyperphosphorylation in aged cardiomyocytes, which a CK2 inhibitor could reverse, normalizing APR90 by reducing Late-INa and enhancing K+ currents.

Conclusion: These findings reveal that acute GLP-1R agonism can disrupt electrical signaling and induce arrhythmia in aged mice through CK2 hyperphosphorylation, providing new insights into the cardiovascular effects of GLP-1RAs in the elderly.

Background: The current study aims to identify the key pathways and potential therapeutic targets for pulmonary arterial hypertension (PAH) and to further evaluate the anti-PAH effects of isorhamnetin.

Methods: The dataset of gene expression profiling for PAH (GSE113439) was downloaded from the gene expression omnibus (GEO) database. Isorhamnetin target genes were extracted from the comparative toxicogenomics database (CTD). Various bioinformatics methods were employed to identify the core pathways associated with PAH and potential intervention targets. Molecular docking was conducted between the interacting target and the candidate compound, isorhamnetin.

Results: One thousand nine hundred sixty-two upregulated genes and 642 downregulated genes were identified. Molecular complex detection analyses revealed that the significant biological processes associated with upregulated genes included DNA damage response, mitotic cell cycle, and chromosome organization. In contrast, the signifi ant biological processes related to downregulated genes encompassed cellular response to growth factor stimulus, response to growth factor, and blood vessel development. Immune infilt ation analysis indicated that PAH is associated with signifi ant changes in the distribution of immune cells and differential expression of immune checkpoints. Furthermore, 58 isorhamnetin targets were extracted from the CTD, and we identified 1 interacting gene, NFE2L2, among the differentially expressed genes (DEGs), DEGs related to ferroptosis, and isorhamnetin targets. Isorhamnetin demonstrated strong affinities with vascular endothelial growth factor (VEGF) receptors and transcription factors (ATM and ZNF24) associated with VEGFs, as well as the ferroptosis protein NFE2L2.

Conclusions: Pulmonary arterial hypertension is characterized by a series of abnormalities in downstream molecular signaling pathways, including DNA damage, immune dysregulation, VEGF signaling deficienc , and the ferroptosis process. These may represent the core pathophysiological mechanisms of PAH. Ferroptosis-related genes, such as NFE2L2 and TF (ATM, ZNF24) associated with VEGFs, are potential therapeutic targets that contribute to the mechanisms mentioned above. Isorhamnetin is a promising candidate compound for the treatment of PAH.

Background: Coronary artery disease (CAD) is a widespread health issue globally, linked to significant morbidity and mortality. While oxidative stress, dysregulated lipid metabolism, and unhealthy lifestyle choices contribute to CAD, recent research highlights the role of immune responses and inflammation. Malnutrition, a modifiable risk factor, notably impacts CAD prognosis. The prognostic nutritional index (PNI), derived from serum albumin and lymphocyte count, predicts outcomes in various diseases. This study aims to elucidate the relationship between malnutrition, as assessed by the PNI score, and the functional significance of coronary artery stenosis, evaluated by fractional flow reserve (FFR) measurements.

Methods: A retrospective analysis involved 232 patients with single intermediate-grade coronary stenosis who underwent FFR measurement between January 2022 and January 2024. Prognostic nutritional index values were calculated from serum albumin and lymphocyte counts. Patients were divided into 2 groups based on FFR values.

Results: Patients with hemodynamically significant coronary stenosis (FFR ≤ 0.80) exhibited higher inflammatory markers and triglycerides, while those with FFR > 0.80 showed elevated albumin and PNI levels. Triglycerides and PNI emerged as independent predictors of significant coronary stenosis.

Conclusions: This study demonstrates that PNI is independently associated with the functional significance of coronary artery stenosis as determined by FFR. Since lymphocytes, total protein and albumin values, which are readily available from routine blood tests, form the basis for PNI, this index can be easily used in clinical settings to predict hemodynamically significant coronary artery stenosis. However, the results of this study should be further expanded and validated through studies involving larger samples and prospective designs.

Background: An exaggerated hypertensive response (EHR) during exercise is linked to increased cardiovascular risk and mortality. This study aims to assess structural and functional cardiac changes, along with subclinical myocardial damage, using transthoracic echocardiography (ECHO) and 2D longitudinal strain analysis in patients showing a hypertensive response to treadmill exercise.

Methods: Patients without known chronic diseases, presenting to the Cardiology Department at Health Sciences University Gülhane Training and Research Hospital, were divided into 2 groups based on their blood pressure response during treadmill exercise: exaggerated hypertensive response (EHR, n = 42) and normal response (control, n = 44). Left ventricular longitudinal strain was assessed using transthoracic echocardiography, and global longitudinal strain (GLS) was calculated as the average from all segments. Data analysis was performed using SPSS 26.

Results: No significant differences were found between the groups regarding baseline demographic and laboratory parameters (P > .05 for all). However, the EHR group exhibited significantly higher interventricular septum thickness, mitral A velocity, and mitral annulus velocity (a'), while mitral annulus velocity (e') was significantly lower (P < .05 for all). Additionally, left ventricular (LV) mass index, left atrial volume index, mitral E/e' ratio, deceleration time, and relative wall thickness (RWT) were higher in the EHR group, while the mitral E/A ratio was lower (P < .05 for all). The GLS was also significantly lower in the EHR group (P < .05).

Conclusion: Left ventricular geometry parameters, such as LV mass index and RWT, and GLS findings indicating subclinical cardiac damage, were significantly altered in the EHR group, suggesting a higher risk of LV hypertrophy and myocardial dysfunction.

Background: Patients with hypertrophic obstructive cardiomyopathy (HOCM) have few available nonsurgical treatment options. The feasibility of CARTOSound-guided catheter radiofrequency ablation (RFA) has been reported previously; however, relevant data are limited. The objective is to retrospectively evaluate the effectiveness and safety of CARTOSound-guided RFA for patients with HOCM.

Methods: Thirty-seven patients with successive HOCM accompanied by severe left ventricular outflow tract (LVOT) obstruction underwent CARTOSound-guided RFA were reviewed. The intracardiac echocardiography (ICE) images obtained were merged with the CARTO system to create a shell of the left ventricle. The systolic anterior motion-septal contact area marked from the ICE images was considered the target area for the current delivery of RFA. Follow-up data of the LVOT gradient examined before, 1 month, 6 months, 1 year, and every year after catheter-mediated RFA were accessed.

Results: The symptoms of 30 patients (81.1%) improved during the follow-up after RFA. The symptoms of all 30 patients were alleviated from the New York Heart Association (NYHA) class IV/III/II to the NYHA class II/I. A sustained and significant gradient reduction was observed in 28 patients (75.7%). The invasive pressure gradient of LVOT was 84.43 ± 27.55 mm Hg before RFA and 42.78 ± 36.38 mm Hg after RFA (P < .001), with a decrease of 41.65 ± 19.72 mm Hg. The median drop in pressure gradient was 36.0% (1.0-67.0%).

Conclusions: Catheter-mediated RFA is an effective and safe treatment for patients with HOCM. However, its long-term efficacy and safety should be validated in the future by conducting multicenter clinical trials with large sample sizes.

Background: Acute coronary syndromes are the leading cause of mortality worldwide. Electrical risk score (ERS) is a novel electrocardiographic risk scoring system. The prognostic importance of ERS in non-ST elevation myocardial infarction (NSTEMI) patients is unknown. We aimed to determine the association of ERS with in-hospital prognosis in NSTEMI patients undergoing coronary angiography (CAG).

Methods: A total of 427 consecutive NSTEMI patients undergoing CAG were enrolled in this study. Six parameters comprised ERS: pulse rate >75, left ventricular hypertrophy according to Sokolow-Lyon criteria, QRS transition zone ≥V4, corrected QT (QTc) interval >450 for men and >460 for women, T peak to T end interval (Tp-e) >89 ms, and frontal QRS-T angle >90°. The ERS was calculated according to the number of abnormal findings in electrocardiogram. The study population was divided into 2 groups as ERS <3 and ≥3.

Results: No significant difference was found between ERS ≥3 and <3 groups in terms of demographic characteristics. However, patients with ERS ≥3 had significantly higher maximum troponin (P < .001), thrombolysis in myocardial infarction (P = .002), and global registry of acute coronary events (P < .001) risk scores and 3-vessel disease frequency (P = .001), whereas they had lower left ventricular ejection fraction (P < .001). These patients also had higher frequency of in-hospital mortality (P < .001) and adverse events. Multiple logistic regression analysis demonstrated that ERS (OR = 1.790, 95% CI: 1.036-3.095, P = .037) was an independent predictor of in-hospital mortality.

Conclusion: The frequency of in-hospital adverse events and mortality was significantly higher in NSTEMI patients with an ERS ≥3 at admission. This simple electrocardiographic risk marker may help identify patients at higher cardiac risk in patients presenting with NSTEMI and identify patients who may need early coronary intervention.

Background: The purpose of this study was to probe the specific role of long noncoding RNA taurine upregulation 1 (LncRNA TUG1) in viral myocarditis (VMC).

Methods: The mouse model of VMC was induced by Coxsackievirus type B3 (CVB3). LncRNA TUG1 was subsequently silenced, and micro-140-3p (miR-140-3p) was overexpressed in VMC mice. GenePharma synthesized wild-type and mutant LncRNA TUG1 or CXCL8 (C-X-C Motif Chemokine Ligand 8, Interleukin-8) fragments containing the miR-140-3p binding site and cloned them into the pmirGLO luciferase reporter vector. Dual luciferase reporter assays were performed to test the activity of LncRNA TUG1 or CXCL8 fragments containing miR-140-3p mimic and mimic NC. The effects of silencing LncRNA TUG1 on cell proliferation, apoptosis, and inflammation in the VMC mouse model and in vitro were investigated by flow cytometry, enzyme linked immunosorbent assay, and western blot.

Results: In the VMC mouse model, LncRNA TUG1 and CXCL8 were upregulated, while miR-140-3p was downregulated. Suppressing LncRNA TUG1 led to inhibition of CXCL8 by promoting miR-140-3p. Suppressing LncRNA TUG1 or CXCL8 or restoring miR-140-3p were observed to increase cell viability and decrease apoptosis rate of cardiomyocytes.

Conclusion: LncRNA TUG1 knockdown suppresses inflammation and damage of VMC cardiomyocytes via the miR-140-3p/CXCL8 axis.