Cardioprotective effect of Tofisopam against isoprenaline-induced myocardial infarction in rats via modulation of NLRP3\IL-1ß\caspase-1 pathway.

Purpose Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Ischemic heart diseases, particularly acute myocardial infarction (MI), represent the most common cause of death. MI is influenced by multiple factors, including the release of inflammatory mediators. A significant percentage of individuals with CVD experience psychological effects, such as anxiety and depression, which are linked to an increased risk of coronary heart disease. Certain anti-anxiety medications have demonstrated immunomodulatory and anti-inflammatory effects. Tofisopam, a 2,3-benzodiazepine with anxiolytic properties, has been shown to exert in vitro anti-inflammatory and immunomodulatory effects. The present study investigates the potential of tofisopam as a protective adjuvant against isoprenaline-induced MI in rats and explores the possible underlying mechanisms. Methods: The study included four groups: a control group, a group pretreated with tofisopam, an isoprenaline toxic group, and an isoprenaline toxic group pretreated with tofisopam. Results: The findings demonstrated that isoprenaline significantly increased cardiac enzyme levels, as well as elevated oxidative and inflammatory stress parameters, along with evident apoptosis in cardiac cells. In contrast, the tofisopam-pretreated group showed a significant reversal of the cardiac damage induced by isoprenaline. Conclusions: Tofisopam protects against isoprenaline-induced MI through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Assessment of left atrial function using two-dimensional speckle tracking echocardiography in cryptogenic stroke patients.

BACKGROUND: Cryptogenic cerebrovascular stroke can be defined as an ischemic stroke that lacks a clear cause, even after a thorough evaluation. It should be distinguished from the embolic stroke of undetermined source (ESUS), a subgroup that includes cardio-embolic sources. This study aims to assess left atrial function through two-dimensional speckle tracking echocardiography (2D-STE) to determine its potential association with cryptogenic stroke and its predictive value for subclinical atrial fibrillation (AF). Our prospective cohort study involved 62 patients with unexplained cerebrovascular stroke or TIA, regardless of gender. Following TEE assessments, 22 patients were excluded due to identified sources of cardio-embolism. The remaining 40 participants were clustered into Group I. Group II, consisted of 40 healthy individuals without significant medical history, served as a control group. Both groups underwent two-dimensional trans-thoracic echocardiography and speckle tracking echocardiography. RESULTS: LA dysfunction parameters exhibited significant differences between Group I and Group II. LV diastolic dysfunction, LAVI, LAEF, and LASr were notably affected in Group I. At the same time, LA diameter in the parasternal long-axis view (PLAX) displayed a significant difference with a p value of 0.001. Within Group I, 14 patients experienced AF episodes (Group Ia, 35%); while, the remaining 26 were categorized as Group Ib (65%). LV diastolic dysfunction displayed a p value < 0.011; while, LAVI, LAEF, and LASr exhibited considerable differences with p values < 0.0001. However, the LA diameter showed no significant variation between the two groups. LASr emerged as the most sensitive and specific parameter for predicting AF, with a cutoff point of ≤ 24.5% and a p value < 0.0001. LAEF showed a cutoff point of ≤ 40.5% and a p value of 0.011. Meanwhile, LAVI demonstrated the lowest sensitivity and specificity, with a mean cutoff point of ≥ 38.5 ml/m2 and a p value of 0.003. CONCLUSIONS: 2D-STE is crucial for assessing LA dysfunction as a potential cryptogenic stroke cause after TEE and ruling out cardio-embolism sources. LASr serves as a key LA cardiopathy indicator, even preceding AF. LASr independently poses an AF risk. While LAEF and LAVI are significant LA dysfunction parameters and AF predictors, they exhibit lower sensitivity and specificity than LASr.

The Relationship of Fetuin-A with Coronary Calcification, Carotid Atherosclerosis, and Mortality Risk in Non-Dialysis Chronic Kidney Disease.

Objective: This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease (CKD). Methods: The study included 135 adult patients with CKD at stages 3-5, who were divided into coronary artery calcification (CAC) and non-CAC groups. We excluded current smokers and individuals with diabetes mellitus, inflammatory conditions, liver diseases, acute kidney failure, chronic hemodialysis, and cancer. We conducted kidney function tests, complete blood counts, and measured serum levels of fetuin-A, tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Cardiac spiral computed tomography was used to calculate the CAC score, employing the Agatston method. Carotid ultrasonography was performed to assess carotid intima-media thickness (CIMT) and to detect the presence of plaques. Results: CAC patients had considerably higher levels of TNF-α (p<0.001), IL-6 (p<0.001), hs-CRP (p=0.006), TC, TG, parathyroid hormone (PTH) (p<0.001) and phosphorus (p<0.001) than non-CAC patients. They also had significantly lower levels of fetuin-A (p<0.001). Fetuin-A was considerably lower in CKD subgroups as CKD progressed. Fetuin-A (p=0.046), age (p=0.009), TNF-α (p=0.027), IL-6 (p=0.005), TG (p=0.002), PTH (p=0.002), and phosphorus (p=0.004) were significant predictors of CAC. CAC and fetuin-A were strong predictors of all-cause mortality and cardiovascular (CV) mortality. Fetuin-A was a significant predictor of CIMT (p=0.045). Conclusion: Fetuin-A reliably predicted CAC and CIMT. Fetuin-A and CAC emerged as significant risk factors for all-cause and CV mortality in non-dialysis CKD.

Does Speckle Tracking Transthoracic Echocardiography Indicate Subtle Changes in Left Ventricular Function in Heart Failure Patients with Reduced Ejection Fraction Treated by Sacubitril-valsartan?

Background: In heart failure patients and reduced ejection fraction (HFrEF), assessing subtle changes in left ventricle (LV) function is crucial for monitoring treatment efficacy. This study aims to determine the effect of valsartan/sacubitril on LV ejection fraction (EF) assessed by two-dimensional (2D) transthoracic echocardiography (TTE) in comparison to that assessed by 2D TTE speckle tracking in patients with HFrEF ≤35% after 6 months of treatment. Patients and Methods: A prospective study will be conducted on 200 heart failure patients with reduced EF (HFrEF) undergoing sacubitril-valsartan treatment. Each participant underwent a comprehensive evaluation, including physical examination, history taking, serial 12-lead electrocardiogram, and 2D echo to evaluate cardiac parameters. In addition, 2D speckle tracking echocardiography (STE) assessments were conducted before and after 6 months of valsartan/sacubitril treatment. Results: The enrolled patients had an average age of 48 years with 63% females. At the beginning of the study, 9 (4.5%) patients were classified as New York Heart Association (NYHA) FC I, 120 (60%) as NYHA FC II, 64 (32%) as NYHA FC III, and 7 (3.5%) as FC IV. Following treatment, 82 (41%) patients improved to NYHA FC I, and 118 (59%) were in NYHA FC II. Notably, 82 (41%) patients showed improved left ventricular EF (LVEF), detected either by traditional TTE or STE, whereas 118 (59%) showed no improvement in EF through traditional TTE. In addition, 74 (37%) patients demonstrated improvement detected by STE. In contrast, 44 (22%) patients demonstrated no improvement in EF detected by either TTE or STE. Conclusion: STE was a more reliable diagnostic method for seeing early LVEF improvement in patients with HFrEF receiving valsartan/sacubitril treatment not seen by conventional TTE.

Evaluating knowledge, attitude, and physical activity levels related to cardiovascular disease in Egyptian adults with and without cardiovascular disease: a community-based cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) represents a significant health challenge in Egypt, yet there exists limited understanding regarding the knowledge, attitudes, and physical activity levels associated with CVD. These factors play a pivotal role in developing effective prevention and management strategies. Hence, this cross-sectional study aimed to evaluate Egyptian adults' knowledge, attitudes, and physical activity (KAP) levels. METHODS: Data were collected using a previously validated questionnaire encompassing demographic characteristics, CVD knowledge (including risk factors and symptoms), attitudes toward CVD, and self-reported physical activity levels. The survey was distributed among social media channels, and trained researchers administered the questionnaire via face-to-face interviews with adult patients with and without CVD admitted to Cairo University Hospital clinics. RESULTS: The study involved 591 participants, of whom 21.7% had CVD. Overall, participants exhibited poor knowledge regarding CVD, with a mean score of 21 ± 7 out of 40, equivalent to 52.5%. Attitudes toward CVD were moderate, with a mean score of 66.38 ± 8.7 out of 85, approximately 78%. Physical activity levels per week were also moderate, averaging 1188 MET-min with a range of 1121-18,761. Subgroup analysis revealed that individuals with CVD had lower average knowledge, attitude, and physical activity levels than those without CVD. Working in the healthcare field was a predictor of higher knowledge score (standard error (SE) 5.89, 95% confidence interval (CI) 4.61 to 7.17, P < 0.001), while those with CVD and smokers were predictors of lower attitude score (SE -4.08, 95% CI -6.43 to -1.73, P < 0.001) and (SE -2.54, 95% CI -4.69 to -0.40, P = 0.02), respectively. CONCLUSION: The study findings highlight a significant disparity in knowledge, attitudes, and physical activity levels related to CVD in Egypt. Targeted interventions aimed at improving awareness, fostering positive attitudes, and promoting physical activity among individuals at risk for CVD are crucial for effective prevention and management.

Clinicopathological characteristics and predictors of outcome of rapidly progressive glomerulonephritis: a retrospective study.

BACKGROUND: Globally, there are regional and time-based variations in the prevalence, etiology, and prognosis of rapidly progressive glomerulonephritis (RPGN). Prognosis of RPGN is poor, with a higher risk of death and end stage renal disease (ESRD) even with immunosuppressive medications. In the Middle East and North Africa, the studies on this disease are very limited. Therefore, we determined the predictors of outcome of RPGN. METHODS: We retrospectively assessed 101 adult patients over age of 18, diagnosed with RPGN based on renal biopsy illustrating crescents in ≥ 50% of the glomeruli. Patients who had crescents in their renal biopsies that were < 50% and those who refused to consent to a renal biopsy were excluded. We categorized the patients into 3 groups based on immunohistochemistry; type I, type II and type III. Then, depending on renal loss, we divided them into ESRD and non-ESRD groups. The clinical history and physical examination were retrieved. Additionally, 24-hour urine protein, urine analysis, renal function tests, serum albumin, complete blood count, antinuclear antibodies, anti-double stranded DNA antibodies, ANCA antibodies and serum complement levels were checked. Each patient underwent a kidney biopsy for immunohistochemistry and light microscopy. The percentage of crescentic glomeruli, number of sclerosed glomeruli, tertiary lymphoid organ (TLO), neutrophil infiltration, endocapillary or mesangial hypercellularity, interstitial fibrosis with tubular atrophy (IFTA) were analyzed. Primary outcomes (remission, ESRD and mortality) and secondary outcomes were assessed. RESULTS: Type II was the most frequent cause of RPGN (47.5%), followed by type III (32.7%) and type I (19.8%). 32 patients (31.7%) died during follow up, whereas 60 patients (59.4%) developed ESRD. In 41 patients (40.6%), remission occurred. Oliguria, serum creatinine, and need for HD at presentation were significantly increased in ESRD group compared to non-ESRD group (P < 0.001 for each). Mesangial proliferation, IFTA, TLO formation, sclerotic glomeruli and fibrous crescents were also significantly increased in ESRD group in comparison to non-ESRD group (P < 0.001 for each). Glomerulosclerosis (P = 0.036), and IFTA (P = 0.008) were predictors of ESRD. Infections (P = 0.02), respiratory failure (P < 0.001), and heart failure (P = 0.004) were mortality risk factors. CONCLUSION: Type II RPGN was the most common. Infection was the most frequent secondary outcome. Oliguria, glomerulosclerosis, the requirement for hemodialysis at presentation, IFTA and TLO formation were predictors of ESRD. Respiratory failure, heart failure and infections were significant predictors of mortality.

Immediate, short-term, and long-term effects of balloon mitral valvuloplasty on the left atrial global longitudinal strain and its correlation to the outcomes in patients with severe rheumatic mitral stenosis.

BACKGROUND: Left atrial global longitudinal strain (LA GLS) has been used as a new assessment tool for left atrial function. This article aims to investigate the effect of balloon mitral valvuloplasty (BMV) in patients with severe rheumatic mitral stenosis on LA GLS and its relation to the mitral valve area achieved after the procedure. The study included 95 patients with severe mitral stenosis who fulfilled the criteria for BMV (case group) and 80 normal healthy subjects (control group). All included participants underwent complete echocardiographic examinations. For the case group, LA GLS was assessed by 2D speckle-tracking Echocardiography before valvuloplasty, immediately after, within 24 h, at 6 months, and at 12 months, and the results were compared. RESULTS: The impaired left-atrium strain in patients with severe mitral stenosis was improved immediately after BMV, and the improvement continued at 6 and 12 months post-BMV (23.1% ± 4.2 vs. 36.0% ± 4.9, 36.2% ± 4.5, and 40.1% ± 9.5, respectively p < 0.01). After BMV, there was a significant decrease in left atrial volume (76.3 ± 12.4 ml/m2 vs. 68.6 ± 10.4 ml/m2, p < 0.01) and a significant increase in the area occupied by the mitral valve (1.02 ± 0.18 cm2 vs. 1.60 ± 0.31 cm, p < 0.01). The immediate LA GLS and the mitral valve area were positively correlated (r = 0.64, p < 0.01). Furthermore, the immediate LA GLS was associated with significantly improved function class (p < 0.01). CONCLUSIONS: LA GLS can indicate left atrial (mainly reservoir) function. The improvement observed in patients after BMV may indicate that LA GLS can be used to evaluate the progress after BMV. TRIAL REGISTRATION: The study was approved by the local ethics committee of the Faculty of Medicine in Minia University (Registration No. MUFMIRB 324-4-2022). Institutional Review Board, Faculty of Medicine, Minia University, Egypt. 324-4-2022, 24 18 April, 2022.

Additive value of 3D-echo in prediction of immediate outcome after percutaneous balloon mitral valvuloplasty.

BACKGROUND: Results of percutaneous balloon mitral valvuloplasty (BMV) are basically dependent on suitable patient selection. Currently used two-dimensional (2D) echocardiography (2DE) scores have many limitations. Three-dimensional (3D) echocardiography (3DE)-based scores were developed for better patient selection and outcome prediction. We aimed to compare between 3D-Anwar and 2D-Wilkins scores in mitral assessment for BMV, and investigate the additive value of 3DE in prediction of immediate post-procedural outcome. Fifty patients with rheumatic mitral stenosis and candidates for BMV were included. Patients were subjected to 2D- and real-time 3D-transthoracic echocardiography (TTE) before and immediately after BMV for assessing MV area (MVA), 2D-Wilkins and 3D-Anwar score, commissural splitting, and mitral regurgitation (MR). Transesophageal echocardiography (TEE) was also undertaken immediately before and intra-procedural. Percutaneous BMV was performed by either multi-track or Inoue balloon technique. RESULTS: The 2DE underestimated post-procedural MVA than 3DE (p = 0.008). Patients with post-procedural suboptimal MVA or significant MR had higher 3D-Anwar score compared to 2D-Wilkins score (p = 0.008 and p = 0.03 respectively). The 3D-Anwar score showed a negative correlation with post-procedural MVA (r = - 0.48, p = 0.001). Receiver operating characteristic (ROC) curve analysis for both scores revealed superior prediction of suboptimal results by 3D-Anwar score (p < 0.0001). The 3DE showed better post-procedural posterior-commissural splitting than 2DE (p = 0.004). Results of both multi-track and Inoue balloon were comparable except for favorable posterior-commissural splitting by multi-track balloon (p = 0.04). CONCLUSION: The 3DE gave valuable additive data before BMV that may predict immediate post-procedural outcome and suboptimal results.