Endoplasmic reticulum stress and expression of nitric oxide synthases in heart failure with preserved and with reduced ejection fraction - pilot study.

BACKGROUND: Unfolded Protein Response (UPR), endoplasmic reticulum (ER) stress, and inducible nitric oxide synthase (iNOS) overexpression have been found to influence heart failure with preserved ejection fraction (HFpEF) pathogenesis. Their importance in heart failure with reduced ejection fraction (HFrEF) is not entirely established; there is little data involving a detailed comparison between HFpEF and HFrEF from this perspective. This pilot study aimed to compare circulating levels of Glucose-regulated protein 78kDa (GRP78) (ER - stress marker) and all NOS isoforms between both HFpEF and HFrEF and to analyze the correlation between these markers and the clinical characteristics of the patients. METHODS: Forty-two patients with HFpEF and thirty-eight with HFrEF were involved in this study. Clinical characteristics and echocardiographic data were obtained. Basic laboratory tests were performed and ELISA tests for iNOS, endothelial NOS (eNOS), neuronal NOS (nNOS), and GRP78. RESULTS: Patients with HFpEF had lower circulating levels of GRP78 and higher iNOS concentrations when compared to HFrEF patients (P = 0.023, P < 0.0001, accordingly). The subgroup of the HFpEF population with eGFR < 60 mL/min/1.73m2 had higher nNOS and eNOS levels than HFpEF patients with normal GFR (P = 0.049, P = 0.035, respectively). In the HFrEF subgroup, patients with coexistent diabetes mellitus had elevated concentrations of nNOS compared to the subpopulation without diabetes mellitus (P = 0.041). There was a positive correlation between eNOS and nNOS concentrations (ρ = 0.86, P < 0.0001). CONCLUSIONS: In HFpEF, there is a more intensified iNOS overexpression, while in HFrEF, ER stress is more prominent.

Post-myocardial infarction heart failure and long-term high-fat diet: Cardiac endoplasmic reticulum stress and unfolded protein response in Sprague Dawley rat model.

BACKGROUND: Myocardial infarction (MI) significantly contributes to the global mortality rate, often leading to heart failure (HF) due to left ventricular remodeling. Key factors in the pathomechanism of HF include nitrosative/oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. Furthermore, while a high-fat diet (HFD) is known to exacerbate post-MI cardiac remodeling, its impact on these critical factors in the context of HF is not as well understood. AIMS: This study aimed to assess the impact of post-MI HF and HFD on inflammation, nitro-oxidative stress, ER stress, and unfolded protein response (UPR). METHODS: The study was performed on fragments of the left ventricle harvested from 30 male adult Sprague Dawley rats, which were divided into four groups based on diet (normal-fat vs. high-fat) and surgical procedure (sham operation vs. coronary artery ligation to induce MI). We assessed body weight, NT-proBNP levels, protein levels related to nitrosative/oxidative stress, ER stress, UPR, apoptosis, and nitric oxide synthases, through Western Blot and ELISA. RESULTS: HFD and MI significantly influenced body weight and NT-proBNP concentrations. HFD elevated 3-nitrotyrosine and myeloperoxidase levels and altered nitric oxide synthase levels. HFD and MI significantly affected ER stress markers and activated or inhibited UPR pathways. CONCLUSIONS: The study demonstrates significant impacts of post-MI HF and dietary fat content on cardiac function and stress markers in a rat model. The interaction between HFD and MI on UPR activation suggests the importance of dietary management in post-MI recovery and HF prevention.

Zero-fluoroscopy catheter ablation of premature ventricular contractions: comparative outcomes from the right ventricular outflow tract and other ventricular sites.

BACKGROUND: The three-dimensional electroanatomic mapping (EAM) system allows performing catheter ablation (CA) without fluoroscopy in patients with premature ventricular contractions (PVCs). The right ventricle outflow tract (RVOT) location is favorable for performing zero-fluoroscopy CA. Non-RVOT zero-fluoroscopy CA is a challenging procedure. The study aimed to evaluate the efficacy and safety of zero-fluoroscopy CA using the EAM in patients with PVCs from RVOT and non-RVOT. METHODS: Completely zero-fluoroscopy CA of PVCs guided by EAM was performed in 107 patients with PVCs. 54 patients underwent zero-fluoroscopy RVOT CA. The remaining 53 patients underwent zero-fluoroscopy non-RVOT CA. Demographic and clinical baseline characteristics, procedure parameters, and follow-up were obtained from medical records. Primary outcomes were the acute and the permanent success rate (12-month follow-up), complications, and procedure time. RESULTS: There were no significant differences between groups regarding baseline characteristics. Acute procedural success was achieved in 52 patients (94,44%) in the RVOT zero-fluoroscopy CA group and in 45 patients (86,54%) in the non-RVOT zero-fluoroscopy CA group (ns). A long-term success rate was achieved in 50 patients (90,74%) in the RVOT zero-fluoroscopy CA group and in 44 patients (84,62%) in the non-RVOT zero-fluoroscopy CA group (ns). The median procedure time was 80.5 minutes in the RVOT group and 90 minutes in the non-RVOT group (ns). There were two complications in the non-RVOT group (ns). CONCLUSIONS: There were no differences in procedure time efficacy and safety zero-fluoroscopy ablation between RVOT and non-RVOT locations. Non-fluoroscopy CA of PVCs is a feasible, safe, and efficient procedure.

Age- and sex-dependent cardiovascular impact of maternal perinatal stress and altered dopaminergic metabolism in the medulla oblongata of the offspring.

Maternal major depressive disorder with peripartum onset presents health risks to the mother and the developing fetus. Using a rat model of chronic mild stress, we previously reported on the neurodevelopmental impact of maternal perinatal stress on their offspring. This study examined the cardiovascular impact of maternal perinatal stress on their offspring. The cardiovascular impact was assessed in terms of blood pressure and echocardiographic parameters. The results examined by a three-way ANOVA showed a significant association of cardiovascular parameters with maternal perinatal stress and offspring sex and age. Increased blood pressure was observed in adolescent female and adult male offspring of stress-exposed dams. Echocardiography showed an increase in left atrial dimension and a reduction in left ventricular systolic function in adolescent stress-exposed female offspring. Increased interventricular septum thickness at end-diastole and left ventricular diastolic dysfunction were observed in adult stress-exposed male offspring. The underlying mechanisms of cardiovascular impact were examined in stress-exposed adult offspring by assessing the levels of neurotransmitters and their metabolites in the medulla oblongata using high-performance liquid chromatography. A significant decrease in homovanillic acid, a dopamine metabolite and indicator of dopaminergic activity, was observed in adult stress-exposed female offspring. These results suggest a significant sex- and age-dependent impact of maternal stress during the peripartum period on the cardiovascular system in the offspring that extends to adulthood and suggests a multigenerational effect. The presented data urgently need follow-up to confirm their potential clinical and public health relevance.NEW & NOTEWORTHY We demonstrate that maternal perinatal stress is associated with sex- and age-dependent impact on the cardiovascular system in their offspring. The effect was most significant in adolescent female and adult male offspring. Observed changes in hemodynamic parameters and dopaminergic activity of the medulla oblongata are novel results relevant to understanding the cardiovascular impact of maternal perinatal stress on the offspring. The cardiovascular changes observed in adult offspring suggest a potential long-term, multigenerational impact of maternal perinatal stress.

The Role of Epicardial Adipose Tissue in Acute Coronary Syndromes, Post-Infarct Remodeling and Cardiac Regeneration.

Epicardial adipose tissue (EAT) is a fat deposit surrounding the heart and located under the visceral layer of the pericardium. Due to its unique features, the contribution of EAT to the pathogenesis of cardiovascular and metabolic disorders is extensively studied. Especially, EAT can be associated with the onset and development of coronary artery disease, myocardial infarction and post-infarct heart failure which all are significant problems for public health. In this article, we focus on the mechanisms of how EAT impacts acute coronary syndromes. Particular emphasis was placed on the role of inflammation and adipokines secreted by EAT. Moreover, we present how EAT affects the remodeling of the heart following myocardial infarction. We further review the role of EAT as a source of stem cells for cardiac regeneration. In addition, we describe the imaging assessment of EAT, its prognostic value, and its correlation with the clinical characteristics of patients.

Evaluation of Nitrosative/Oxidative Stress and Inflammation in Heart Failure with Preserved and Reduced Ejection Fraction.

Heart failure (HF) is a complex syndrome characterized by impaired cardiac function. Two common subtypes of HF include heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). In this study, we aimed to evaluate and compare the plasma levels of 3-nitrotyrosine (3-NT)-as a marker of nitrosative/oxidative stress and myeloperoxidase (MPO)-as an indicator of inflammation between HFpEF and HFrEF. Twenty-seven patients diagnosed with HFpEF and twenty-two with HFrEF were enrolled in this study. Additionally, forty-one patients were recruited for the control group. An echocardiographic assessment was conducted, followed by the collection of blood samples from all participants. Subsequently, the levels of 3-NT and MPO were quantified using the ELISA method. Comprehensive clinical characteristics and medical histories were obtained. Circulating levels of 3-NT were significantly higher in the HFpEF patients than in the control and the HFrEF groups. Nitrosative/oxidative stress is significantly intensified in HFpEF but not in HFrEF.

Efficacy of Catheter Ablation Using the Electroanatomical System without the Use of Fluoroscopy in Patients with Ventricular Extrasystolic Beats.

BACKGROUND: Catheter ablation (CA) has become safe and efficient for the treatment of patients with ventricular extrasystolic beats (VEBs). The three-dimensional electroanatomic mapping (EAM) system allows the elimination of fluoroscopy time during CA procedures. Non-fluoroscopy CA is a challenging procedure requiring intimate knowledge of cardiac anatomy in patients with VEBs. The study aimed to evaluate the efficacy and safety of the non-fluoroscopy CA using the EAM system in patients with VEBs. METHODS: Completely fluoroless CA of VEBs guided by EAM was performed in 86% (94 out of 109) of consecutive patients with VEBs. The remaining 15 patients underwent conventional fluoroscopy-guided CA. Demographic and clinical baseline characteristics, procedure parameters, and following complications were obtained from the medical records. Primary outcomes were the acute procedural success rate, the permanent success rate (6-month follow-up), complications, and procedure time. RESULTS: There were no significant differences between groups regarding baseline characteristics. Acute procedural success was achieved in 85 patients (90%) in the non-fluoroscopy group and in 14 patients (93%) in the fluoroscopy group (ns). A long-term success rate was achieved in 82 patients (87%) in the non-fluoroscopy group and in 14 (82%) patients in the fluoroscopy group (ns). The median procedure time was 85 min in the non-fluoroscopy group and 120 min in the fluoroscopy group (p = 0.029). There was only one major complication in the non-fluoroscopy group (ns). CONCLUSIONS: Completely fluoroless CA of VEBs guided by EAM is a feasible, safe, and efficient procedure.

Biochemical and clinical evaluation of endothelial injury after distal or traditional transradial access in percutaneous interventions.

BACKGROUND: Distal transradial access (dTRA) has been proposed as an alternative to traditional transradial access (TRA) in cardiac catheterization. AIMS: The study aimed to compare these two transradial approaches: TRA and dTRA in terms of clinical and biochemical aspects. METHODS: Two hundred patients who qualified for the elective coronary procedure were included. The patients were assigned to one of the groups depending on their vascular access. The groups were compared in terms of perceived pain using the Visual Analogue Scale (VAS), time of gaining access, need for conversion, and local complications. Additionally, in forty patients circulating endothelial injury markers: endothelin 1 (ET-1), interleukin 8 (IL-8), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were assessed. RESULTS: Successful cannulation was obtained in 84 (100%) in the TRA group and in 98 (84%) subjects in the dTRA (P <0.001). dTRA was associated with higher level of pain perceived at the time of gaining vascular approach than TRA; median VAS score (interquartile range [IQR]): 4 (2-5) vs. 2 (2-4) (P = 0.04). The mean time (standard deviation [SD]) needed to cannulate the artery in dTRA was longer than in TRA: 81 (8) seconds vs. 50 (4) seconds (P = 0.04). ET-1 concentration was (SD) 2.08 (0.19) pg/ml [dTRA] vs. 2.00 (0.29) [TRA] pg/ml (P = 0.83); sVCAM-1: 12.71 (3.97) ng/ml vs. 12.86 (4.29) ng/ml (P = 0.98); IL-8: 8.81 (0.42) ng/ml vs. 9.15 (0.52) ng/ml (P = 0.62). Th number of complications after procedures did not differ between these two approaches. CONCLUSIONS: Cannulation of dTRA is associated with a lower success rate and higher pain perceived. dTRA is not inferior to TRA when safety issues and vascular injury are considered.