Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated pulmonary vascular resistance (PVR), right ventricular (RV) failure, and death in the absence of appropriate treatment. The progression and prognosis are strictly related to the etiology, biochemical parameters, and treatment response. The gold-standard test remains right-sided heart catheterization, but dynamic monitoring of systolic pressure in the pulmonary artery is performed using echocardiography. However, simple and easily accessible non-invasive assays are also required in order to monitor this pathology. In addition, research in this area is in continuous development. In recent years, more and more biomarkers have been studied and included in clinical guidelines. These biomarkers can be categorized based on their associations with inflammation, endothelial cell dysfunction, cardiac fibrosis, oxidative stress, and metabolic disorders. Moreover, biomarkers can be easily detected in blood and urine and correlated with disease severity, playing an important role in diagnosis, prognosis, and disease progression.

Background and Aims: Leptin, one of the best-known adipocytes, together with the renin-angiotensin-aldosterone system and galectin-3 are important players in inflammation, arterial hypertension and heart failure pathophysiology. Moreover, uninucleotide A1166C polymorphism is associated with hypertension and poor prognosis in heart failure. The aim of the study was to investigate a possible relationship between leptin serum values, specific heart failure biomarkers and the presence of AT1 receptor A1166C polymorphism in overweight and obese heart failure patients. Methods: The study included 88 consecutive overweight and obese patients admitted for decompensated heart failure. NT-proBNP, MR-proANP, galectin-3 and leptin levels were determined on the arrival day. Genotyping of the A1166C allele – AT1 receptor gene was performed in all patients in order to find variants. Results: We found a strong positive correlation (r = 0.347, p = 0.001) between leptin serum concentrations and BMI. Leptin levels were not correlated with heart failure biomarkers (NT-proBNP, MR-proANP and galectin-3). All homozygote CC variants were hypertensive, but we registered no significant difference in genetic AC and AA variants distribution between hypertensive and normotensive. Leptin was not significantly modified by the presence of potentially pathogenic A1166C–AT 1 receptor genotypes (AC + CC). But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations. Conclusion: Overweight and obese patients with heart failure display high leptin serum levels. Leptin does not offer incremental prognostic value in heart failure overweight and obese patients. But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations, suggesting a worse prognosis probably due to more advanced cardiac fibrosis.

Background. Pulmonary arterial hypertension (PAH) is characterized by several maladaptive mechanisms: endothelial dysfunction, oxidative stress, inflammation, pathological remodeling of the pulmonary arterioles, and cellular hypoxia. These mechanisms all favor progressive pulmonary vasculopathy and progressive right ventricle (RV) dysfunction. Aim. This study aims to characterize the experimental model of monocrotaline-induced PAH in rats. Subsequently, by administering Sildenafil, Rosuvastatin, and Magnesium sulfate, we assessed the animals via ultrasonography and assayed biochemical parameters to evaluate the efficacy of the treatment. Methods. 42 male Wistar rats were randomly allocated into six equal groups (n=7) and received a single subcutaneous MCT injection (60 mg/kg dose). Drug therapy with Sildenafil, Rosuvastatin, and Magnesium sulfate in different combinations was initiated 14 days after MCT injection. Fulton Index, RV anterior wall thickness, RV internal diameter, and pulmonary arterial acceleration time/ejection time (PAAT/ PAET) were measured. The following biochemical parameters were also measured: endothelin 1(ET1), brain natriuretic peptide (BNP), nitric oxide (NO) metabolites, vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). Results. MCT-PAH was a successful experimental model that has fulfilled anatomical, pressure, and biochemical characteristics supporting this fact. Sildenafil monotherapy does not provide any substantial benefit in reducing MCT-PAH. The additive effects of Rosuvastatin + Sildenafil or Sildenafil + Magnesium sulfate significantly reduced the degree of RV hypertrophy and improved RV systolic pressures. However, there were also modest decreases in biochemical parameters compared to Sildenafil alone. The triple drug combination Sildenafil + Rosuvastatin + Magnesium sulfate shows significant results (p<0,001) compared to the previously described drug combinations. The lowest biochemical parameters were recorded: RV anterior wall thickness, RV internal diameter values, and a significant PAAT/PAET ratio improvement. Thanks to their benefits on vascular pathological remodeling, triple drug combinations implicitly reduce ET1, VEGF, NO metabolites, and iNOS values with statistical significance. Conclusions. The beneficial pleiotropic effects of Rosuvastatin combined with Magnesium sulfate (thanks to its potent vasodilator and antioxidant effects) demonstrated its efficacy in this study by improving RV systolic pressures, RV hypertrophy, oxidative stress, and myocardial dysfunction biomarkers.

Background/Objectives: Cardiovascular diseases are the most important cause of mortality in chronic obstructive pulmonary disease (COPD). Speckle-tracking echocardiography (2D-STE) can be used for assessing atrial and ventricular function, and its role in COPD is underexplored. The main objective of this study was to investigate prognostic associations in patients with COPD using 2D-STE echocardiography and laboratory biomarkers. Methods: The study included 70 participants, divided into two groups: 55 patients diagnosed with COPD and 15 healthy controls. All four cardiac chambers were analyzed with standard ultrasound and 2D-STE techniques. We measured NT-proBNP and several oxidative stress biomarkers: reduced glutathione (GSH), the GSH/GSSG ratio, malondialdehyde (MDA), and Caspase-3. Results: An NT-proBNP level above 325 pg/mL independently predicts advanced COPD stages (GOLD grades 3 and 4), with statistically significant results at a 95% confidence interval (CI) (p = 0.001). Additionally, 2D-STE identified reduced right ventricular (RV) and left ventricular (LV) strain in COPD patients before changes in LV ejection fraction. RV and LV strain measurements (RV4CLS < −16.15%, RVFWSL < −18.6%, LV GLS < −19.45%) along with PASP > 37.5 mmHg are independent predictors of advanced COPD stages, demonstrating significance at a 95% CI (p = 0.001). A positive correlation was observed between NT-proBNP, ultrasound parameters assessing RV systolic function, LV longitudinal strain impairment, and PASP. Conclusions: NT-proBNP serves as an independent biomarker of pulmonary hypertension and secondary right heart overload and independently predicts advanced COPD stages (GOLD grades 3 and 4) alongside RV and LV strain measurements.

Heart failure continues to be a major worldwide medical issue, associated with high morbidity and mortality. The need for ideal biomarkers to aid the diagnosis and prognosis in certain situations, such as obesity or atrial fibrillation is still ongoing. Obese patients are commonly hyperleptinemic. The aim of the study is to assess the role of several biomarkers in overweight and obese patients diagnosed with heart failure, depending on the presence or absence of atrial fibrillation and also their relationship with leptin. The study included 88 overweight and obese patients, with a body mass index (BMI) ≥25 kg/m2, admitted for worsening heart failure. Of these, 52.2% had atrial fibrillation. Dosage of NT-proBNP was performed using the chemiluminescence method. MR-proANP, galectin-3 and leptin were dosed using the ELISA method. A value of P [0.05 was defined as statistically significant. The values of natriuretic peptides NT-proBNP and MR-proANP were significantly increased. Only NT-proBNP was significantly influenced by renal function. No statistically significant correlation was found between heart failure-specific biomarkers and leptin secretion. There were no significant differences in the biomarkers levels between the 2 groups of patients. No statistically significant correlation was found between heart failure-specific biomarkers and leptin secretion. Obese patients with heart failure had significantly increased values of all the studied parameters, but the presence of atrial fibrillation did not influence their levels. High leptin levels were not directly correlated with the levels of heart failure-specific biomarkers.

Previous experimental findings have led to considerable interest in the beneficial effects on pulmonary hypertension (PH) produced by sildenafil and in the pleiotropic effects of rosuvastatin and their positive role in the process of pulmonary angiogenesis. However, magnesium sulfate, the most abundant intracellular cation, is essential in vascular endothelial functionality due to its anti-inflammatory and vasodilatory effects. Therefore, the present study aims to assess these treatment regimens and how they could potentially provide some additional benefits in PH therapy. Fourteen days after chronic-hypoxia PH was induced, rosuvastatin, sildenafil and magnesium sulfate were administered for an additional fourteen days to male Wistar rats. The Fulton Index, right ventricle (RV) anterior wall thickness, RV internal diameter and pulmonary arterial (PA) acceleration time/ejection time were evaluated, and another four biochemical parameters were calculated: brain natriuretic peptide, vascular endothelial growth factor, nitric oxide metabolites and endothelin 1. The present study demonstrates that sildenafil and rosuvastatin have modest effects in reducing RV hypertrophy and RV systolic pressure. The drug combination of sildenafil + rosuvastatin + magnesium sulfate recorded statistically very highly significant results on all parameters; through their positive synergistic effects on vascular endothelial function, oxidative stress and pathological RV remodeling, they attenuated PH in the chronic hypoxia pulmonary hypertension (CHPH) rat model.