Immature platelet fraction and immature platelet count as novel biomarkers of elevated platelet reactivity in NSTE-ACS patients receiving dual antiplatelet therapy.

BACKGROUND: Antiplatelet therapy is the cornerstone of treatment for patients presenting with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Some patients may not respond to such therapy adequately, which is associated with a greater risk of ischemic events. Reticulated platelets are the youngest, largest, and most active platelet subtype. They have been initially shown to be associated with an increased risk of cardiovascular (CV) events and increased platelet activity. OBJECTIVES: The aim of the presented study was to evaluate whether the immature platelet fraction (IPF) reflects the response to antiplatelet treatment in invasively managed ACS patients. MATERIAL AND METHODS: This prospective study enrolled ACS patients treated with PCI and dual antiplatelet therapy (DAPT) comprising acetylsalicylic acid (ASA) and clopidogrel or ticagrelor. In all patients, venous blood was collected within 24 h after the procedure. Platelet parameters were measured, including IPF using the Sysmex hematological analyzer and adenosine diphosphate (ADP)-induced platelet reactivity using the Multiplate® Analyzer. RESULTS: A total of 108 patients were enrolled, including 62 with ST-segment elevation ACS (STE-ACS) and 46 with non-ST-segment elevation ACS (NSTE-ACS). Of them, 20.4% had diabetes mellitus, 26.9% had a history of MI and 59.2% of smoking. Spearman's correlation analysis demonstrated that higher IPF and immature platelet count (IPC) values are associated with increased ADP-induced platelet reactivity (respectively: rho = 0.387, 95% confidence interval (95% CI): 0.101-0.615, p = 0.008; and rho = 0.458, 95% CI: 0.185-0.666, p = 0.001) in NSTE-ACS but not in STE-ACS patients. CONCLUSION: Immature platelet count and IPF may be valuable markers of platelet activity in patients with NSTE-ACS treated invasively and receiving DAPT (ClinicalTrials.gov No. NCT06177587).

Hypertrophic Cardiomyopathy versus Storage Diseases with Myocardial Involvement.

One of the main causes of heart failure is cardiomyopathies. Among them, the most common is hypertrophic cardiomyopathy (HCM), characterized by thickening of the left ventricular muscle. This article focuses on HCM and other cardiomyopathies with myocardial hypertrophy, including Fabry disease, Pompe disease, and Danon disease. The genetics and pathogenesis of these diseases are described, as well as current and experimental treatment options, such as pharmacological intervention and the potential of gene therapies. Although genetic approaches are promising and have the potential to become the best treatments for these diseases, further research is needed to evaluate their efficacy and safety. This article describes current knowledge and advances in the treatment of the aforementioned cardiomyopathies.

Immature platelet fraction in cardiovascular diagnostics and antiplatelet therapy monitoring.

Immature platelet fraction (IPF), circulating platelets still containing RNA, can be easily calculated by automated flow cytometry, this makes them an accessible biomarker. Higher IPF concentrations were reported in patients with thrombocytopenia, patients who were smokers, and also those who were diabetics. Several studies have reported their diagnostic and prognostic importance in patients presenting with acute coronary syndromes, especially ST-segment elevation myocardial infarction, where increased IPF level is an independent predictor of cardiovascular death. In addition, higher IPF were reported in patients with inadequate response to either clopidogrel or prasugrel, suggesting their potential role in antiplatelet therapy monitoring. Their prognostic significance was also observed in both coronary artery disease and postcardiac surgery status, where their higher levels correlated with the risk of major adverse cardiac events. The current review aims to present the current evidence on diagnostic, prognostic and potentially therapeutic roles of IPF in cardiovascular medicine.

Predictors of proarrhythmic effect in heart failure patients after 9-week hybrid comprehensive telerehabilitation and their influence on cardiovascular mortality in long-term follow-up: Subanalysis of the TELEREH-HF randomized clinical trial.

BACKGROUND: Regular exercise training is beneficial in heart failure (HF) patients. However, its potential proarrhythmic effect is possible but has not been sufficiently investigated. OBJECTIVE: To identify patients at risk for proarrhythmic effect after the 9-week of hybrid comprehensive telerehabilitation (HCTR) program vs the 9-week of usual care (UC) and to investigate its predictors and impact on cardiovascular mortality based on data from the TELEREH-HF RCT. METHODS: Proarrhythmic effect, strictly defined on the basis of available standards was evaluated by comparing 24-h Holter ECG before and after 9-week of HCTR or UC of 773 HF patients (The New York Heart Association class I-III, left ventricular ejection fraction ≤40%). RESULTS: The proarrhytmic effect was found in 78 (20.4%) and in 61 (15.6%) patients in the HCTR and UC group respectively, and the difference between groups was not statistically significant (p = 0.081). However, univariate analysis identified several statistically significant predictors of proarrhythmia in HCTR only vs the UC group. After a multivariate analysis ischaemic aetiology of HF (OR = 2.27, p = 0.008), peak oxygen consumption at baseline <14 ml/kg/min (OR = 2.03, p = 0.012) and level of N-terminal-pro B-type natriuretic peptide (NT-proBNP) in the first and the second tercile (OR = 1.85, p = 0.043) were identified to be independent predictors of proarrhytmic effect of exercise training among the HF patients in HCTR group only. CONSLUSIONS: Patients who underwent a 9-week HCTR were not at a higher risk of proarrhythmic effect after its completion compared to UC. However, predictors of proarrhythmia such as ischemic aetiology of HF, poor physical capacity, lower NT-proBNP level were discovered in the HCTR group only, yet it does not cause a significant risk of cardiovascular mortality including sudden cardiac death in long-term follow-up.

Long-term outcomes and quality of life following implementation of dedicated mitral valve Heart Team decisions for patients with severe mitral valve regurgitation in tertiary cardiovascular care center.

BACKGROUND: This study was purposed to investigate which treatment strategy was associated with the most favourable prognosis for patients with severe mitral regurgitation (MR) following Heart Team (HT)-decisions implementation. METHODS: In this retrospective study, long-term outcomes of patients with severe MR qualified after HT discussion to: optimal medical treatment (OMT) alone, OMT and MitraClip (MC) procedure or OMT and mitral valve replacement (MVR) were evaluated. The primary endpoint was defined as cardiovascular (CV) death and the secondary endpoints included all-cause mortality, myocardial infarctions (MI), strokes, hospitalizations for heart failure exacerbation and CV events during a mean (standard deviation [SD]) follow-up of 29 (15) months. RESULTS: From 2016 to 2019, 176 HT meetings were held and a total of 157 participants (mean age [SD] = 71.0 [9.2], 63.7% male) with severe MR and completely implemented HT decisions (OMT, MC or MVR for 53, 58 and 46 patients, respectively) were included into final analysis. Comparing OMT, MC and MVR groups statistically significant differences between the implemented procedures and occurrence of primary and secondary endpoints with the most frequent in OMT-group were observed (p < 0.05). However, for interventional strategy MC was non-inferior to MVR for all endpoints (p > 0.05). General health status assessed at the end of follow-up were significantly the lowest for MVR, then for MC and the highest for OMT-group (p < 0.01). CONCLUSIONS: In the present study it was demonstrated that after careful HT evaluation of patients with severe MR at high risk of surgery, percutaneous strategy (MC) can be considered as equivalent to surgical treatment (MVR) with non-inferior outcomes.

Gastrointestinal Incretins-Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) beyond Pleiotropic Physiological Effects Are Involved in Pathophysiology of Atherosclerosis and Coronary Artery Disease-State of the Art.

Coronary artery disease (CAD), which is the manifestation of atherosclerosis in coronary arteries, is the most common single cause of death and is responsible for disabilities of millions of people worldwide. Despite numerous dedicated clinical studies and an enormous effort to develop diagnostic and therapeutic methods, coronary atherosclerosis remains one of the most serious medical problems of the modern world. Hence, new markers are still being sought to identify and manage CAD optimally. Trying to face this problem, we have raised the question of the most predominant gastrointestinal hormones; glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), mainly involved in carbohydrates disorders, could be also used as new markers of incidence, clinical course, and recurrence of CAD and are related to extent and severity of atherosclerosis and myocardial ischemia. We describe GIP and GLP-1 as expressed in many animal and human tissues, known to be connected to inflammation and related to enormous noncardiac and cardiovascular (CV) diseases. In animals, GIP and GLP-1 improve endothelial function and lead to reduced atherosclerotic plaque macrophage infiltration and stabilize atherosclerotic lesions by directly blocking monocyte migration. Moreover, in humans, GIPR activation induces the pro-atherosclerotic factors ET-1 (endothelin-1) and OPN (osteopontin) but also has anti-atherosclerotic effects through secretion of NO (nitric oxide). Furthermore, four large clinical trials showed a significant reduction in composite of CV death, MI, and stroke in long-term follow-up using GLP-1 analogs for DM 2 patients: liraglutide in LEADER, semaglutide in SUSTAIN-6, dulaglutide in REWIND and albiglutide in HARMONY. However, very little is known about GIP metabolism in the acute phase of myocardial ischemia or for stable patients with CAD, which constitutes a direction for future research. This review aims to comprehensively discuss the impact of GIP and GLP-1 on atherosclerosis and CAD and its potential therapeutic implications.

NT-proBNP increase during stress echocardiography predicts significant changes in ischemic mitral regurgitation severity in patients qualified for surgical revascularization.

BACKGROUND: In many patients, significant changes in ischemic mitral regurgitation (IMR) severity during exercise can be observed independent of the degree of IMR at rest. This study aimed to investigate the correlations between N-terminal fragment B-type natriuretic peptide (NT-proBNP) and echocardiography measurements at rest and at peak exercise in patients with moderate IMR who qualified for surgical revascularization. METHODS: A total of 100 patients eligible for coronary artery bypass grafting, were included in this prospective study. All patients underwent exercise echocardiography. Additionally, the levels of NT-proBNP were measured at rest and after peak exercise. RESULTS: A positive correlation of absolute NT-proBNP levels with effective regurgitant orifice area (EROA) were observed and with tricuspid regurgitant peak gradient (TRPG) at peak exercise. Absolute ΔNT-proBNP during exercise and the tenting area at rest were independent predictors of severe IMR at peak exercise. The level of absolute ΔNT-proBNP during exercise and coaptation height at rest were the most important predictors of significant increases in TRPG. The best cutoff value for ΔNT-proBNP as a predictor for increases in EROA at peak exercise was 68.9 pg/mL and to predict an increase in TRPG ≥ 50 mmHg at peak exercise was 68 pg/mL. CONCLUSIONS: The level of ΔNT-proBNP during exercise was the most important parameter in predicting significant changes in IMR severity and pulmonary pressure. Based on the present data, it can be speculated that integration of the assessment of NT-proBNP at rest and at exercise might improve patient selection for valve surgery.

Sex Differences in Incidence, Clinical Characteristics and Outcomes in Children and Young Adults Hospitalized for Clinically Suspected Myocarditis in the Last Ten Years-Data from the MYO-PL Nationwide Database.

There is a widespread lack of systematic knowledge about myocarditis in children and young adults in European populations. The MYO-PL nationwide study aimed to evaluate sex differences in the incidence, clinical characteristics, management and outcomes of all young patients with a clinical diagnosis of myocarditis, hospitalized in the last ten years. The study involved data (from the only public healthcare insurer in Poland) of all (n = 3659) patients aged 0-20 years hospitalized for myocarditis in the years 2011-2019. We assessed clinical characteristics, management and five-year outcomes. Males comprised 75.4% of the study population. The standardized incidence rate of myocarditis increased over the last ten years and was, on average, 7.8 and 2.5 (in males and females, respectively). It was the highest (19.5) in males aged 16-20 years. The highest rates of hospital admissions occurred from late autumn to early spring. Most myocarditis-directed diagnostic procedures, including laboratory tests, echocardiography, coronary angiography, cardiac magnetic resonance and endomyocardial biopsy, were performed in a low number of patients, particularly in females. Most patients required rehospitalization for cardiovascular reasons. The results of this large epidemiological study showed an increasing incidence of myocarditis hospitalizations in young patients over last ten years and that it was sex-, age- and season-dependent. Survival in young patients with myocarditis was age- and sex-related and usually it was worse than in the national population. The general management of myocarditis requires significant improvement.

The quality of life in patients with at least moderate ischemic mitral regurgitation qualified to cardiosurgery treatment.

B a c k g r o u n d: To assess and compare mid-term outcomes and the quality of life (QoL) in patients with multivessel coronary artery disease (MVD) and moderate ischemic mitral regurgitation (IMR), treated with either coronary artery bypass grafting (CABG; group I) or CABG + mitral annuloplasty (CABG+MA; group II) in 12-months follow-up after surgery. M e t h o d s: We prospectively analyzed 74 patients (50.7% female, 66 [67-72] years) with at least moderate IMR, 3-24 weeks after myocardial infarction (MI). The effective regurgitation orifice (ERO) was used for a quantitative IMR assessment. To evaluate QoL we used a Short Form-36 (SF-36) questionnaire. R e s u l t s: Patients in group II spent more time in the hospital, expired more infection complications and received more often in-hospital complications requiring use amines and intra-aortic balloon pump as compared to those in group I. Analysis of SF-36 showed that all patients treated surgically notable improved their QoL during 12 months of follow-up. C o n c l u s i o n s: We observed a significant improvement in QoL among patients with MVD in 12 months follow-up after surgery irrespective of treatment type.

Stress Echocardiography Protocol for Deciding Type of Surgery in Ischemic Mitral Regurgitation: Predictors of Mitral Regurgitation Recurrence following CABG Alone.

PURPOSE: Although coronary artery bypass grafting alone (CABGa), or, with mitral annuloplasty (CABGmp), is considered the best therapeutic strategy for patients with ischemic mitral regurgitation (IMR), some recurrences are still reported. The aim of this study was to evaluate the use of the mitral deformation indices (MDI) as a predictor of recurrence of mitral regurgitation in a 12-month follow-up after CABG alone. METHODS: A total of 145 patients after myocardial infarction with significant IMR, eligible for CABG, were prospectively enrolled in the study. Mitral valve morphology, left ventricle function, IMR degree as assessed by effective regurgitation orifice area (ERO), myocardial viability, and MDI were assessed prior to surgery. Patients were referred for CABGa (gr.1; n = 90) or CABGmp (gr.2; n = 55) based on clinical assessment, and the results of rest and stress echocardiography (exercise echocardiography and low dose dobutamine echocardiography-DBX). One year after surgery, each patient underwent the evaluation of cardiovascular events. Univariable logistic regression analysis was used to identify the factors of recurrence of IMR in 1 year follow-up. Serial echo examinations were performed in all patients at discharge, and at 1 and 12 months after surgery. RESULTS: Logistic regression analysis revealed that in CABGa, group preoperative changes of tenting area (TA) and coaptation high (CH) during DBX remained the predictors of the recurrence of IMR in 12 months follow-up. TAdbx > 1 cm2 provided a sensitivity of 90% and specificity of 29%, (AUC 0.6436). The best cut-off value for CHdbx was 0.4 cm (sensitivity 90%, specificity 34%; AUC 0.6432). In both groups (CABGa vs. CABGmp) no significant differences were observed in 12-month mortality (1.2% vs. 0%; p = 1.0), hospitalizations due to the heart failure (HF) exacerbation (5.9% vs. 8.5%; p = 0.72), and in the incidence of the composite endpoint (deaths/CV hosp/stroke) (7% vs. 8.5%; p = 0.742). CONCLUSIONS: The preoperative assessment of MDI changes during dbx can be used to identify patients with IMR qualified to CABG alone at increased risk of recurrence of IMR in 1 year follow-up. Mitral deformation analysis should be used for a better qualification of patients with IMR to the exact surgical approach.

Atherosclerosis Pathways are Activated in Pericoronary Adipose Tissue of Patients with Coronary Artery Disease.

PURPOSE: Perivascular release of inflammatory mediators may accelerate coronary lesion formation and contribute to plaque instability. Accordingly, we compared gene expression in pericoronary adipose tissue (PCAT) in patients with advanced coronary artery disease (CAD) and non-CAD controls. PATIENTS AND METHODS: PCAT samples were collected during coronary bypass grafting from CAD patients (n = 21) and controls undergoing valve replacement surgery, with CAD excluded by coronary angiography (n = 19). Gene expression was measured by GeneChip™ Human Transcriptome Array 2.0. Obtained list of 1348 transcripts (2.0%) that passed the filter criteria was further analyzed by Ingenuity Pathway Analysis software, identifying 735 unique differentially expressed genes (DEGs). RESULTS: Among the CAD patients, 416 (30.9%) transcripts were upregulated, and 932 (69.1%) were downregulated, compared to controls. The top upregulated genes were involved in inflammation and atherosclerosis (chemokines, interleukin-6, selectin E and low-density lipoprotein cholesterol (LDL-C) receptor), whereas the downregulated genes were involved in cardiac ischaemia and remodelling, platelet function and mitochondrial function (miR-3671, miR-4524a, multimerin, biglycan, tissue factor pathway inhibitor (TFPI), glucuronidases, miR-548, collagen type I, III, IV). Among the top upstream regulators, we identified molecules that have proinflammatory and atherosclerotic features (High Mobility Group Box 2 (HMGB2), platelet-derived growth platelet (PDGF) and evolutionarily conserved signaling intermediate in Toll pathways (ESCIT)). The activated pathway related to DEGs consisted of molecules with well-established role in the pathogenesis of atherosclerosis (TFPI, plasminogen activator, plasminogen activator, urokinase receptor (PLAUR), thrombomodulin). Moreover, we showed that 22 of the altered genes form a pro-atherogenic network. CONCLUSION: Altered gene expression in PCAT of CAD patients, with genes upregulation and activation of pathway involved in inflammation and atherosclerosis, may be involved in CAD development and progression.

Occurrence, Trends, Management and Outcomes of Patients Hospitalized with Clinically Suspected Myocarditis-Ten-Year Perspectives from the MYO-PL Nationwide Database.

The epidemiology of myocarditis is unknown and based mainly on small single-centre studies. The study aimed to evaluate the current incidence, clinical characteristics, management and outcomes of patients hospitalized due to myocarditis in a general population. The study was registered in ClinicalTrials.gov (NCT04827706). The nationwide MYO-PL (the occurrence, trends, management and outcomes of patients with myocarditis in Poland) database (years 2009-2020) was created to identify hospitalization records with a primary diagnosis of myocarditis according to the International Classification of Diseases and Related Health Problems, 10th Revision (ICD 10), derived from the database of the national healthcare insurer. We identified 19,978 patients who were hospitalized with suspected myocarditis for the first time, of whom 74% were male. The standardized incidence rate of myocarditis ranged from 1.15 to 14 per 100,000 people depending on the age group and was the highest in patients aged 16-20 years. The overall incidence increased with time. The performance of the recommended diagnostic tests (in particular, endomyocardial biopsy) was low. Relative five-year survival ranged from 0.99 to 0.56-worse in younger females and older males. During a five-year follow-up, 6% of patients (3.7% and 6.9% in females and males, respectively) were re-hospitalized for myocarditis. Surprisingly, females more frequently required hospitalization due to heart failure/cardiomyopathy (10.5%) and atrial fibrillation (5%) than compared to males (7.3% and 2.2%, respectively) in the five-year follow up. In the last ten years, the incidence of suspected myocarditis increased, particularly in males. Survival rates for patients with myocarditis were worse than in the general population. Management of myocarditis requires significant improvement.

District versus academic hospitals: clinical outcomes of patients with atrial fibrillation.

Introduction: Atrial fibrillation (AF) is associated with increased hospitalization. Objectives: We aimed to compare long-term outcomes in patients with AF hospitalized in academic and district hospitals. Patients and methods: This retrospective observational study included data from the Multicenter Experience in Atrial Fibrillation Patients Treated with Oral Anticoagulants (CRAFT; NCT02987062) study which included AF patients hospitalized between 2011 and 2016 in academic and district hospitals. The primary end point was a major adverse event (MAE) defined as all-cause death and thromboembolic and hemorrhagic events during the median 4-year follow-up. Results: We analyzed 2983 patients with AF: 2271 (76%) from academic and 712 (24%) from district hospitals. Patients treated in district hospitals, as compared with patients treated in academic hospitals, more often experienced MAEs (53% vs 37%; P <⁠0.001), all-cause death (40% vs 24%; P <⁠0.001), and thromboembolic events (13% vs 7.8%; P <⁠0.001), with similar rates of hemorrhagic events (15% vs 15%; P = 1.00). In multivariable logistic regression, female sex, coronary artery disease, smoking, and antiplatelet drug therapy were associated with greater likelihood of thromboembolic events in academic hospitals. Heart failure, renal failure, and vitamin K antagonist (in academic hospitals), and coronary artery disease (in district hospitals) were associated with greater likelihood of hemorrhagic events. District (vs academic) conditions were associated with higher risk of MAEs and all-cause death in men and those with low risk of bleeding, and with higher incidence of thromboembolic events in women, elderly patients, and those with high risk of bleeding and with diabetes. Conclusions: Patients with AF treated at district hospitals had worse long-term outcomes than those treated in academic conditions.

Relationship between diabetes mellitus and atrial fibrillation prevalence in the Polish population: a report from the Non-invasive Monitoring for Early Detection of Atrial Fibrillation (NOMED-AF) prospective cross-sectional observational study.

BACKGROUND: The global burden of atrial fibrillation (AF) and diabetes mellitus (DM) is constantly rising, leading to an increasing healthcare burden of stroke. AF often remains undiagnosed due to the occurrence in an asymptomatic, silent form, i.e., silent AF (SAF). The study aims to evaluate the relationships between DM and AF prevalence using a mobile long-term continuous ECG telemonitoring vest in a representative Polish and European population ≥ 65 years for detection of AF, symptomatic or silent. METHODS: A representative sample of 3014 participants from the cross-sectional NOMED-AF study was enrolled in the analyses (mean age 77.5, 49.1% female): 881 (29.2%) were diagnosed with DM. AF was screened using a telemonitoring vest for a mean of 21.9 ± 9.1days. RESULTS: Overall, AF was reported in 680 (22.6%) of the whole study population. AF prevalence was higher among subjects with concomitant DM (DM+) versus those without DM (DM-) [25%, 95% CI 22.5-27.8% vs 17%; 95% CI 15.4-18.5% respectively, p < 0.001]. DM patients were commonly associated with SAF [9%; 95% CI 7.9-11.4 vs 7%; 95% CI 5.6-7.5 respectively, p < 0.001], and persistent/permanent AF [12.2%; 95% CI 10.3-14.3 vs 6.9%; 95% CI 5.9-8.1 respectively, p < 0.001] compared to subjects without DM. The prolonged screening was associated with a higher percentage of newly established AF diagnosis in DM+ vs DM- patients (5% vs 4.5% respectively, p < 0.001). In addition to shared risk factors, DM+ subjects were associated with different AF and SAF independent risk factors compared to DM- individuals, including thyroid disease, peripheral/systemic thromboembolism, hypertension, physical activity and prior percutaneous coronary intervention/coronary artery bypass graft surgery. CONCLUSIONS: AF affects 1 out of 4 subjects with concomitant DM. The higher prevalence of AF and SAF among DM subjects than those without DM highlights the necessity of active AF screening specific AF risk factors assessment amongst the diabetic population. TRIAL REGISTRATION: NCT03243474.

Resistin is Associated with Inflammation and Renal Function, but not with Insulin Resistance in Type 2 Diabetes.

The aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function.

Prostacyclin Analogues Inhibit Platelet Reactivity, Extracellular Vesicle Release and Thrombus Formation in Patients with Pulmonary Arterial Hypertension.

(1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce vasodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with prostacyclin analogues and not receiving prostacyclin analogues. (3) Methods: Venous blood was collected from 42 patients treated with prostacyclin analogues (49.5 ± 15.9 years, 81% female) and 38 patients not receiving prostacyclin analogues (55.5 ± 15.6 years, 74% female). Platelet reactivity was analyzed by impedance aggregometry using arachidonic acid (AA; 0.5 mM), adenosine diphosphate (ADP; 6.5 µM), and thrombin receptor-activating peptide (TRAP; 32 µM) as agonists. In a subset of patients, concentrations of extracellular vesicles (EVs) from all platelets (CD61+), activated platelets (CD61+/CD62P+), leukocytes (CD45+), and endothelial cells (CD146+) were analyzed by flow cytometry. Platelet-rich thrombus formation was measured using a whole blood perfusion system. (4) Results: Compared to controls, PAH patients treated with prostacyclin analogues had lower platelet reactivity in response to AA and ADP (p = 0.01 for both), lower concentrations of platelet and leukocyte EVs (p ≤ 0.04), delayed thrombus formation (p ≤ 0.003), and decreased thrombus size (p = 0.008). Epoprostenol did not affect platelet reactivity but decreased the concentrations of platelet and leukocyte EVs (p ≤ 0.04). Treprostinil decreased platelet reactivity in response to AA and ADP (p ≤ 0.02) but had no effect on the concentrations of EVs. All prostacyclin analogues delayed thrombus formation and decreased thrombus size (p ≤ 0.04). (5) Conclusions: PAH patients treated with prostacyclin analogues had impaired platelet reactivity, EV release, and thrombus formation, compared to patients not receiving prostacyclin analogues.

Positron emission tomography in clinically suspected myocarditis - STREAM study design.

AIM: Myocarditis is an inflammatory disease associated with increased glucose uptake. The hypothesis of this study assumes that 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) may improve specificity and sensitivity in the diagnosis of myocarditis and referral for endomyocardial biopsy (EMB), adding additional information for post-discharge risk stratification. The aim of the study is to assess the diagnostic and prognostic feasibility of FDG-PET/CT in comparison to cardiac magnetic resonance (CMR) (alone or in combination) in patients with clinically suspected myocarditis undergoing EMB. METHODS: Fifty hospitalized patients with clinically suspected myocarditis who meet the inclusion/exclusion criteria will be enrolled in a prospective, observational, multicentre, cohort study (NCT04085718). The primary endpoint is the sensitivity and specificity of FDG-PET/CT imaging in the diagnosis of myocarditis. The main secondary endpoints include correlation of FDG-PET/CT imaging with CMR, echocardiography, and EMB results. The patients will undergo the following evaluations: clinical examination, blood tests (including biomarkers of fibrosis and anti-heart autoantibodies (AHA)), ECG, 24 h Holter ECG, echocardiography, CMR, as well as resting single photon emission computed tomography (SPECT) to assess possible myocardial perfusion defects, cardiac FDG-PET/CT and right ventricular EMB. After 6-months a follow-up visit will be performed (including 24 h Holter ECG, echocardiography and CMR). Investigators evaluating individual studies (CMR, SPECT, FDG-PET/CT and EMB) are to be blinded to the other tests' results. CONCLUSION: We believe that FDG-PET/CT alone or in combination with CMR may be a useful tool for improving diagnostic accuracy in patients with clinically suspected myocarditis.

Echocardiographic photorealistic imaging of leiomyomatosis intravascularis.

We present a case of patient with leiomyomatosis intravascularis. To diagnose, we used 3D photorealistic imaging which allowed us better visualisation of pathological structures as well as planning the surgical procedure in greater detail. The main advantage of this technique is the possibility to move the virtual light source and thus visualize the specific part of the heart.