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Background. Cytokines soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and interleukin 6 (IL-6) are involved in immune response, proliferation, apoptosis, and cardiovascular pathologies. We have previously confirmed that changes of their platelet or plasma contents are associated with pulmonary arterial hypertension (PAH). The positron emission tomography/magnetic resonance imaging (PET/MRI) hybrid imaging provides detailed insight into right ventricle (RV) hemodynamic and metabolic function. Objectives. To evaluate the relationship between RV parameters obtained using PET/MRI and concentrations of plasma and platelet sTWEAK and IL-6 in stable PAH patients. Materials and methods. Eighteen stable PAH patients (48.44 ±16.7 years) had simultaneous PET/MRI scans with 18F-fluorodeoxyglucose (18F-FDG) performed. Its uptake was presented as a standardized uptake value (SUV) for RV and left ventricle (LV). Cytokines concentrations were measured in platelet-poor plasma and platelet lysate. Follow-up time of this study was 58 months; the combined endpoint (CEP) was defined as death or clinical deterioration. Results. We observed significant correlations between platelet sTWEAK levels, plasma IL-6 and PET parameter SUVRV/LV (r = -0.57, p = 0.011; r = 0.50, p = 0.032, respectively). In logistic regression, platelet sTWEAK and IL-6 were both prognostic factors for unfavorable ratio of SUVRV/LV higher than 1 (hazard ratio (HR) = 0.44, 95% confidence interval (95% CI): [0.23; 0.84], p = 0.017; and HR = 3.62, 95% CI: [1.21; 10.17], p = 0.011, respectively). Furthermore, their concentrations were related with prognostically important higher late gadolinium enhancement mass index (LGEMI) and RV global longitudinal strain/systolic pulmonary artery pressure (RV GLS/sPAP) values. Patients who had CEP in follow-up (n = 13) had significantly lower platelet sTWEAK content and higher plasma IL-6 at baseline than stable patients. Lower platelet sTWEAK was related to a worse prognosis in log-rank test (p = 0.006). Platelet sTWEAK and plasma IL-6 together with RV GLS/sPAP, RV ejection fraction (RVEF), mean pulmonary arterial pressure (mPAP), and SUVRV/LV were significantly associated with time to CEP in univariate Cox analysis. Conclusions. The sTWEAK and IL-6 concentrations in PAH patients are linked with metabolic and functional changes of RV visualized in PET/MRI, and both sTWEAK and IL-6 predict clinical deterioration. [ABSTRACT FROM AUTHOR]

Objective: Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). Metabolic alterations may precede haemodynamic and clinical deterioration. Increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) was recently associated with progressive RV dysfunction in MRI, but the prognostic value of their combination has not been established.Methods: Twenty-six clinically stable patients with PAH (49.9±15.2 years) and 12 healthy subjects (control group, 44.7±13.5 years) had simultaneous PET/MRI scans. FDG uptake was quantified as mean standardised uptake value (SUV) for both left ventricle (LV) and RV. Mean follow-up time of this study was 14.2±7.3 months and the clinical end point was defined as death or clinical deterioration.Results: Median SUVRV/SUVLV ratio was 1.02 (IQR 0.42-1.21) in PAH group and 0.16 (0.13-0.25) in controls, p<0.001. In PAH group, SUVRV/SUVLV significantly correlated with RV haemodynamic deterioration. In comparison to the stable ones, 12 patients who experienced clinical end point had significantly higher baseline SUVRV/SUVLV ratio (1.21 (IQR 0.87-1.95) vs 0.53 (0.24-1.08), p=0.01) and lower RV ejection fraction (RVEF) (37.9±5.2 vs 46.8±5.7, p=0.03). Cox regression revealed that SUVRV/SUVLV ratio was significantly associated with the time to clinical end point. Kaplan-Meier analysis showed that combination of RVEF from MRI and SUVRV/SUVLV assessment may help to predict prognosis.Conclusions: Increased RV glucose uptake in PET and decreased RVEF identify patients with PAH with worse prognosis. Combining parameters from PET and MRI may help to identify patients at higher risk who potentially benefit from therapy escalation, but this hypothesis requires prospective validation. [ABSTRACT FROM AUTHOR]

Introduction: In the course of acute myocardial infarction (AMI) cardiomyocyte injury, activation and destruction of endothelial cells together with inflammation lead to miRNA expression alterations. Aim: To assess levels of circulating cardiac-specific (miR-1) and endothelial-specific (miR-126) miRNAs in the acute phase of AMI and after a follow-up period. Material and methods: Seventeen AMI patients (mean age: 64.24 ±13.83 years, mean left ventricle ejection fraction (LVEF): 42.6 ±9.65%), treated with primary percutaneous coronary intervention within the first 12 h, had plasma miRNAs isolated (quantitative real-time PCR, Exiqon) on admission and after 19.2 ±5.9 weeks. Measurements were also performed in a control group of healthy volunteers matched for age and sex. Results: Concentrations of both miRNAs were significantly higher in AMI patients as compared to healthy controls: miR-1: 5.93 (3.15-14.92) vs. 1.46 (0.06-2.96), p = 0.04; miR-126: 4.5 (3.11-7.64) vs. 0.54 (0.36-0.99), p = 0.00003, respectively. Levels of both miRNAs significantly decreased after the follow-up period: miR-1: 5.93 (3.15-14.92) vs. 1.34 (0.04-2.34), p = 0.002; miR-126: 4.5 (3.11-7.64) vs. 1.18 (0.49-1.68), p = 0.0005). Moreover, miR-1 correlated positively with maximal troponin I concentration (r = 0.59, p = 0.02) and negatively with LVEF (r = --0.76, p = 0.0004). Conclusions: In our study, miR-1 emerged as a marker of cardiomyocyte injury and loss of myocardial contractility, whereas dynamics of miR-126 concentration may reflect endothelial activation and damage in the most extreme stage of atherosclerosis, followed by angiogenesis in ischemic myocardium. However, to fully elucidate the role of miR-1 and miR-126 as biomarkers of AMI and future therapeutic targets, further research is required. [ABSTRACT FROM AUTHOR]

Inflammatory processes and platelet activity play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). Enhanced IL-6 signaling and higher concentration of stromal-derived factor alpha (SDF-1) have been previously shown to be linked with prognosis in PAH. We hypothesized that platelets of PAH patients have higher content of IL-6 and SDF-1 and thus are involved in disease progression. We enrolled into study 22 PAH patients and 18 healthy controls. Patients with PAH presented significantly higher plasma concentrations and platelet contents of IL-6, sIL-6R, and SDF-1 than healthy subjects (platelet content normalized to protein concentration: IL-6 (0.85*10–10 [0.29 – 1.37] vs. 0.45*10–10 [0.19–0.65], sIL-6R 1.54*10–7 [1.32–2.21] vs. 1.14*10–7 [1.01–1.28] and SDF-1 (2.72*10–7 [1.85–3.23] vs. 1.70*10–7 [1.43–2.60], all p < 0.05). Patients with disease progression (death, WHO class worsening, or therapy escalation, n = 10) had a significantly higher platelet SDF-1/total platelet protein ratio (3.68*10–7 [2.45–4.62] vs. 1.69*10–7 [1.04–2.28], p = 0.001), with no significant differences between plasma levels. Kaplan–Meier analysis revealed that patients with higher platelet SDF-1/total platelet protein ratio had more frequently deterioration of PAH in the follow-up (15.24 ± 4.26 months, log-rank test, p = 0.01). Concentrations of IL-6, sIL-6 receptor and SDF-1 in plasma and platelets are elevated in PAH patients. Higher content of SDF-1 in platelets is associated with poorer prognosis. Our study, despite of limitation due to small number of enrolled patients, suggests that activated platelets may be an important source of cytokines at the site of endothelial injury, but their exact role in the pathogenesis of PAH requires further investigation. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of the study was to determine clinical and prognostic role of repeated heart-type fatty acid binding protein (hFABP) measurements in acute decompensated HF (ADHF) patients. Methods In seventy-seven ADHF patients (III and IV NYHA class, mean age 70 ± 12.7 years, mean left ventricle ejection fraction [LVEF] 29.73 ± 13.3%) plasma hFABPs concentrations (SunRed Biological Technology) were measured twice − on admission and at discharge (mean time of hospitalization 10.7 ± 4.9 days). Combined end point (CEP), assessed after mean 9.2 ± 7.3 months, was defined as death or the need of HF re-hospitalization. Results Median hFABP concentration on admission was significantly lower than at discharge. hFABP concentrations on admission significantly correlated with echocardiographic parameters of LV remodeling. Among fifty-six patients (72.7%) who reached CEP, significantly higher admission and discharge hFABP concentrations were found. Patients with plasma discharge hFABP concentrations higher than 7.8 ng/mL were at higher risk of CEP (log-rank test, p = 0.01). Logistic stepwise regression analysis revealed discharge hFABP, LVEF and left ventricle mass index independent and significant predictors of CEP (p < 0.05). Conclusions In ADHF patients plasma hFABP admission concentrations are related with LV remodeling. Persistently elevated hFABP concentrations have prognostic value, as may reflect continuous myocardial damage despite effective treatment and clinical improvement. Highlights • Mean hFABP levels increase during hospitalization in ADHF patients. • Baseline hFABP measurements correlate with echocardiographic parameters of LV remodeling. • Higher hFABP levels at discharge indicate poor out-of-hospital outcome in patients with ADHF. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by proliferative changes in pulmonary arteries. There is growing evidence suggesting that soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and P-selectin could be involved in PAH development and progression. Here we investigate whether circulating platelets may be a source of sTWEAK and contribute to diminished availability of sTWEAK and P-selectin in PAH patients. We have prospectively enrolled two independent study groups of stable patients with confirmed PAH and age matched controls: derivation (10 PAH; 15 controls) and validation (20 PAH; 12 controls). P-selectin and sTWEAK concentrations were measured in platelet-poor plasma and platelet lysate. To avoid procedural bias, in each group we employed different protocols for platelet isolation. Consistently, both in derivation and validation groups PAH patients presented significantly lower sTWEAK content in platelets than control group with no significant differences in plasma levels. Similarly, patients presented comparable to controls plasma P-selectin concentrations and lower concentration in platelet lysate. Kaplan-Meier analysis revealed that patients with low platelet sTWEAK/total protein concentration ratio had more frequently detoriation of PAH in the follow-up (16.51 ± 3.32 months), log-rank test, p = .03. Patients diagnosed with pulmonary arterial hypertension present diminished sTWEAK and P-selectin storage capacity in platelets. Thrombocytes appear to be a major source of sTWEAK that could be released upon local injury and its decreased availability could have an impact on pathophysiology and prognosis in PAH. [ABSTRACT FROM AUTHOR]

In response to an increased afterload in pulmonary arterial hypertension (PAH), the right ventricle (RV) adapts by remodeling and increasing contractility. The idea of coupling refers to maintaining a relatively constant relationship between ventricular contractility and afterload. Twenty-eight stable PAH patients (mean age 49.5 ± 15.5 years) were enrolled into the study. The follow-up time of this study was 58 months, and the combined endpoint (CEP) was defined as death or clinical deterioration. We used echo TAPSE as a surrogate of RV contractility and estimated systolic pulmonary artery pressure (sPAP) reflecting RV afterload. Ventricular–arterial coupling was evaluated by the ratio between these two parameters (TAPSE/sPAP). In the PAH group, the mean pulmonary artery pressure (mPAP) was 47.29 ± 15.3 mmHg. The mean echo-estimated TAPSE/sPAP was 0.34 ± 0.19 mm/mmHg and was comparable in value and prognostic usefulness to the parameter derived from magnetic resonance and catheterization (ROC analysis). Patients who had CEP (n = 21) had a significantly higher mPAP (53.11 ± 17.11 mmHg vs. 34.86 ± 8.49 mmHg, p = 0.03) and lower TAPSE/sPAP (0.30 ± 0.21 vs. 0.43 ± 0.23, p = 0.04). Patients with a TAPSE/sPAP lower than 0.25 mm/mmHg had worse prognosis, with log-rank test p = 0.001. the echocardiographic estimation of TAPSE/sPAP offers an easy, reliable, non-invasive prognostic parameter for the comprehensive assessment of hemodynamic adaptation in PAH patients. [ABSTRACT FROM AUTHOR]

Introduction Even though thrombocytopenia following transcatheter aortic valve implantation (TAVI) has been described, further investigation of this phenomenon is needed. Aims To determine which factors may explain the fall in platelet count that occurs after implantation of a TAVI device, including markers of platelet and blood coagulation activation. Material and methods 32 patients without previous indications for dual antiplatelet therapy (mean age 78.5 ± 7.9 years, 62% females) with severe aortic valve stenosis (mean gradient 54.6 ± 16.9 mm Hg) who qualified for TAVI procedure (Edwards Sapien XT) were prospectively analyzed. Platelet counts were analyzed before the surgery, on the day of the procedure and for the three following postoperative days (POD 1 to 3). To assess platelet activation P-selectin (PS, serum) and platelet factor 4 (PF-4, CTAD plasma) were measured, whereas for the evaluation of coagulation activation prothrombin fragments 1 + 2 (F1 + 2, plasma) were assessed before the procedure, on POD-1 and POD-3 (ELISA). Results During the postoperative period a significant platelet count drop, the most evident on POD-2, was observed followed by a platelet count raise. The platelet count drop correlated directly with the amount of iodinated contrast agent ( r = 0.42, p = 0.016) and inversely with baseline mean platelet volume ( r = − 0.37, p = 0.046). Neither clinical nor perioperative parameters, except contrast medium, influenced platelet count decrease. No significant differences regarding the concentration of the evaluated markers in patients with and without thrombocytopenia were found. PF-4 and F1 + 2 significantly changed during the study ( p < 0.05). Greater acute PF-4 decrease correlated with greater acute platelet count drop ( r = 0.48, p = 0.043), and during the study slower PF-4 increase correlated with higher platelet count increase on POD-3 ( r = − 0.505, p = 0.032). Lower baseline PS correlated with lower baseline platelet count and higher platelet count increase on POD-3 ( r = 0.45, p = 0.04 and =− 0.55, p = 0.02, respectively). No significant correlations between F1 + 2 concentrations and platelet count changes have been found. Conclusions Platelet reduction shortly after TAVI procedure is related to the amount of contrast agent applied during the procedure. Platelet activation and blood coagulation along with impaired baseline platelet renewal might be the mechanisms of thrombocytopenia following TAVI procedure. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to determine the value of the Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and CardShock scoring systems in predicting the risk of in-hospital, 30 day and 3 year mortality in patients with cardiogenic shock (CS)., Methods: This was a single-centre observational study conducted between May 2016 and December 2017. Data from consecutive patients with CS admitted to the intensive cardiac care unit (ICCU) were included in the analysis., Results: The study group comprised 63 patients with CS {median age 71.0 [interquartile range (IQR), 59-82]; 42 men}: 32 patients with ischaemic and 31 with non-ischaemic aetiology. The median APACHE II, SOFA and CardShock scores were 13 (IQR, 9.9-19.0) points, 8.0 (IQR, 6.0-10.0) points and 3.0 (IQR, 2.0-5.0) points, respectively. The in-hospital, 30 day and 3 year mortality rates were 39.7%, 41.3% and 77.8%, respectively. APACHE II and SOFA scores were significantly higher in the group of patients who died at 30 days (P = 0.043 and P = 0.045, respectively). The CardShock score was higher in patients with CS who died in hospital (P = 0.007) and within 30 days (P = 0.004). No score was statistically significant for 3 year mortality. Area under the curve (AUC) analysis showed that the CardShock score had the highest value in predicting in-hospital and 30 day mortality relative to APACHE II and SOFA, with a cut-off score of 5 points [AUC: 0.70; 95% confidence interval (CI): 0.59-0.81; P = 0.001] and 4 points (AUC: 0.71; 95% CI: 0.60-0.82; P < 0.001), respectively. The Bayesian Weibull model demonstrated the utility of all scales in estimating short-term risk in patients with CS, with the impact of APACHE II and SOFA on patient life expectancy decreasing to a non-significant level at approximately 32 days and CardShock at 33 days. The forest plots derived from the Bayesian logistic regression analysis show significant estimated coefficients with 94% highest density interval (HDI) for in-hospital and 30 day mortality. The use of invasive or non-invasive ventilation, a higher heart rate and a less negative fluid balance showed an unfavourable prognosis. Survival was associated with being in the pre-CS class, with a higher glomerular filtration rate and a higher platelet count., Conclusions: APACHE II and SOFA could be used for the risk stratification of patients with CS admitted to the ICCU. CardShock proved to be a more appropriate tool for assessing short-term prognosis in patients with CS of all aetiologies, suggesting that there is potential for its promotion for use in daily clinical practice., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: In the course of acute myocardial infarction (AMI) cardiomyocyte injury, activation and destruction of endothelial cells together with inflammation lead to miRNA expression alterations., Aim: To assess levels of circulating cardiac-specific (miR-1) and endothelial-specific (miR-126) miRNAs in the acute phase of AMI and after a follow-up period., Material and Methods: Seventeen AMI patients (mean age: 64.24 ±13.83 years, mean left ventricle ejection fraction (LVEF): 42.6 ±9.65%), treated with primary percutaneous coronary intervention within the first 12 h, had plasma miRNAs isolated (quantitative real-time PCR, Exiqon) on admission and after 19.2 ±5.9 weeks. Measurements were also performed in a control group of healthy volunteers matched for age and sex., Results: Concentrations of both miRNAs were significantly higher in AMI patients as compared to healthy controls: miR-1: 5.93 (3.15-14.92) vs. 1.46 (0.06-2.96), p = 0.04; miR-126: 4.5 (3.11-7.64) vs. 0.54 (0.36-0.99), p = 0.00003, respectively. Levels of both miRNAs significantly decreased after the follow-up period: miR-1: 5.93 (3.15-14.92) vs. 1.34 (0.04-2.34), p = 0.002; miR-126: 4.5 (3.11-7.64) vs. 1.18 (0.49-1.68), p = 0.0005). Moreover, miR-1 correlated positively with maximal troponin I concentration ( r = 0.59, p = 0.02) and negatively with LVEF ( r = -0.76, p = 0.0004)., Conclusions: In our study, miR-1 emerged as a marker of cardiomyocyte injury and loss of myocardial contractility, whereas dynamics of miR-126 concentration may reflect endothelial activation and damage in the most extreme stage of atherosclerosis, followed by angiogenesis in ischemic myocardium. However, to fully elucidate the role of miR-1 and miR-126 as biomarkers of AMI and future therapeutic targets, further research is required., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia Sp. z o. o.)

Introduction: MicroRNAs (miRNAs) are small RNAs that play an important role in the regulation of gene expression. miRNA dysregulation has been associated with phenotypic changes, including cardiovascular diseases (CVDs)., Objectives: The aim of the study was to obtain a list of single nucleotide polymorphisms (SNPs) related to CVDs, with computationally predicted effect on miRNA binding sites, which would verify the hypothesis that miRNA dysregulation can lead to the development of CVDs., Materials and Methods: SNPs, CVDs, and miRNAs were the 3 factors subjected to analysis. Based on the publicly available databases, we created a set of SNPs associated with the phenotype of interest and of SNPs located in known miRNA binding sites. We then merged the records assigned by the same SNP, which allowed us to indicate miRNA target sites, whose variants may be associated with CVDs. The results were supplemented with the additional data such as miRNA and mRNA coexpression, differences in the expression between various tissues, and Expression Quantitative Trait Locus analysis. Only in-silico methods, on the basis of publically available information tools and databases, were used., Results: We obtained a list of 47 entries, constituting unique miRNA-SNP allele-phenotype linkages., Conclusions: Computational approach supports the hypothesis of the linkage between alterations in miRNA function and numerous CVDs. Given the high frequency of SNP incidence, this pathomechanism may be common in the population. Although the obtained results need to be further experimentally validated, limiting the number of interactions to the most probable ones will facilitate the identification of clinically significant associations.