Melatonin enhances captopril mediated cardioprotective effects and improves mitochondrial dynamics in male Wistar rats with chronic heart failure.

Mitochondrial dysfunction is a recent emerging research scope that proved to be involved in many cardiovascular diseases culminating in chronic heart failure (CHF), which remains one of the primary causes of morbidity and mortality. This study investigated the added cardio-protective effects of exogenous melatonin administration to conventional captopril therapy in isoproterenol (ISO) exposed rats with CHF. Five groups of Wistar rats were recruited; (I): Control group, (II): (ISO group), (III): (ISO + captopril group), (IV): (ISO + melatonin group) and (V): (ISO + melatonin/captopril group). Cardiac function parameters and some oxidant, inflammatory and fibrotic markers were investigated. Moreover; mRNA expression of mitochondrial mitophagy [parkin & PTEN induced kinase 1 (PINK1)], biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)], fusion [mitofusin 2 (Mfn2)] and fission [dynamin-related protein 1 (DRP-1)] parameters in rat's myocardium were evaluated. Rats' myocardium was histo-pathologically and immunohistochemically evaluated for Beclin1 and Sirt3 expression. The present study revealed that captopril and melatonin ameliorated cardiac injury, oxidative stress biomarkers, and pro-inflammatory cytokines in ISO-exposed rats. These protective effects could be attributed to mitochondrial dynamic proteins control (i.e. enhanced the mRNA expression of parkin, PINK1, PGC-1α and Mfn2, while reduced DRP-1 mRNA expression). Also, Beclin1 and Sirt3 cardiac immunoreactivity were improved. Combined captopril and melatonin therapy showed a better response than either agent alone. Melatonin enhanced myocardial mitochondrial dynamics and Sirt3 expression in CHF rats and may represent a promising upcoming therapy added to conventional heart failure treatment.

Relationship between inflammatory markers and coronary slow flow in type 2 diabetic patients.

BACKGROUND: Diabetes is a serious and quickly expanding global health problem. Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Coronary slow flow (CSF) is characterised by delayed distal perfusion during coronary angiography with normal coronary arteries. This study aimed to investigate the correlation between CSF and inflammatory markers regarding glycemic status in T2DM. METHODS: This cross-sectional study included 120 patients who were divided equally into 4 groups according to their glycemic control and presence or absence of coronary slow flow: Group I included patients with T2DM with good glycemic control without CSF; Group II included patients with T2DM with good glycemic control and CSF; Group III included patients with T2DM with poor glycemic control without CSF; and Group IV included patients with T2DM with poor glycemic control and CSF. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), platelets, hematocrit, and haemoglobin were also evaluated as risk factors for coronary slow flow. RESULTS: This study showed that body mass index (BMI), hematocrit level, NLR, and CRP demonstrated a moderate but significant correlation (r = 0.53) with CSF in poorly controlled T2DM. NLR cutoff > 2.1 could predict CSF in poorly controlled T2DM with a modest sensitivity and specificity. A 1.9 increase in HbA1c increases the likelihood of coronary slow flow. Dylipidemia increases the likelihood of coronary slow flow by 0.18 times. Other predictors for coronary slow flow include NLR, PLR, CRP, platelets, hematocrit, and hemoglobin. The effect of the predictors is still statistically significant after being adjusted for glycemic status, age, and sex (p < 0.001). CONCLUSIONS: Poor glycemic control increases the incidence of CSF. This supports the hypothesis that CSF is related to endothelial dysfunction as poor glycemic control causes endothelial dysfunction due to inflammation. TRIAL REGISTRATION: ZU-IRB#9419-3-4-2022 Registered 3 April 2022, email.  IRB_123@medicine.zu.edu.eg .

Left atrial longitudinal strain analysis in long Covid-19 syndrome.

It is known that during the active course of Coronavirus disease 2019 (COVID-19), myocardial injury has an established pathological base, while its myocardial injury post-recovery is still obscured.The aim of this study was to evaluate the longitudinal left atrial strain (LAS) using speckle tracking echocardiography (STE) in COVID-19-recovered patients who are previously healthy without confounder comorbidities to detect the potential cardiac dysfunction.200 patients were prospectively included and examined 4?12 weeks after recovery from COVID-19 infection. 137 participants with comorbidities or previous history of cardiopulmonary disease were excluded from the analysis. A total of 63 patients who fulfilled our inclusion criteria were recruited into two groups according to thepresence or absence of persistent dyspnoea and exercise intolerance. Clinical, laboratory & comprehensive echocardiographic examinations were done for all. We observed that 31.7% of the previously healthy individuals developed dyspnoea & exercise intolerance post-COVID-19 infection. There were significantly impaired LAS parameters in the symptomatic group (LA reservoir, contraction & conduit strain, 22.7%, -6.6% & -16.1% versus 40%, -12%, and ? 27% in the asymptomatic group with P < 0.000). Only LA reservoir strain and LA stiffness can independently predict the development of dyspnoea & exercise intolerance post-COVID-19 at cut-off values of 30% & 24.5% respectively with a sensitivity of 90% and a specificity of 91%, P < 0.001. These impaired LAS parameters could explain the developed symptoms post-COVID-19 recovery, even before disturbed conventional diastolic echocardiographic parameters.LAS parameters are significantly associated with the developed exertional dyspnoea & exercise intolerance post-COVID-19. LA reservoir strain & LA stiffness could provide a simple, easily available tool that points to early LV diastolic dysfunction and may direct the therapy in this subset of the population.

Tissue tracking of segmental strain as a predictor of provoked dynamic left ventricular outflow tract obstruction.

BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) is commonly observed in patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy (LVH). Some patients develop LVOTO provoked by physical exertion, and hence termed dynamic LVOTO (DLVOTO). However, its precise prevalence and mechanism are still unclear. AIM: Two-dimensional speckle tracking echocardiography (2D STE) seems to be helpful for the detection of early LV structural abnormalities. This study aimed to examine the possible role of segmental as well as global longitudinal strain in identifying DLVOTO non-HCM patients as detected by dobutamine stress echocardiography (DSE). METHODS AND RESULTS: Two hundred and fifty patients without structural heart disease had undergone conventional transthoracic echocardiography, 2D STE, and DSE. All patients with non-ischemic evidence were divided into two groups according to the DSE results; DLVOTO (+) and DLVOTO (-). Among 250 patients, 50 patients (36%) had shown DLVOTO after DSE (15 males, 35 females; mean age 55±7years). They were compared with 90 non -LVOTO obstruction patients (43 males, 47 females; mean age 57±6years). Based on multivariate logistic regression analysis, the independent predictors of provoked DLVOTO during DSE were resting basal septal longitudinal strain BS-LS average (p < 0.001), resting LA reservoir strain (p < 0.001), and systolic LVOT diameter (p = 0.03). Resting BS-LS average with cut-off - 17.5% was recognized as a critical indicator of DLVOTO, with sensitivity 78%, and specificity 95% (better than systolic LVOT diameter of sensitivity 76%, and specificity 15% and resting LA reservoir strain which showed poor AUC at ROC curve 0.007). CONCLUSION: We demonstrate that provoked LVOTO during DSE in non HCM symptomatic patients is directly correlated to resting regional LS, where the increased BS-LS of ≥ -17.5% was a key determinant of LVOT gradient provocation. Assessment of baseline BS-LS average might be a bedside simple tool for detection of patients with DLVOTO not able to do DSE.