Angiopoietin-like growth factor-derived peptides as biological activators of adipose-derived mesenchymal stromal cells.

Adipose-derived mesenchymal stromal cells (AD-MSCs) are an essential issue in modern medicine. Extensive preclinical and clinical studies have shown that mesenchymal stromal/stem cells, including AD-MSCs, have specific properties (ability to differentiate into other cells, recruitment to the site of injury) of particular importance in the regenerative process. Ongoing research aims to elucidate factors supporting AD-MSC culture and differentiation in vitro. Angiopoietin-like proteins (ANGPTLs), known for their pleiotropic effects in lipid and glucose metabolism, may play a significant role in this context. Regeneration is a complex and dynamic process controlled by many factors. ANGPTL6 (Angiopoietin-related growth factor, AGF), among many activities modulated the biological activity of stem cells. This study examined the influence of synthesized AGF-derived peptides, designated as AGF9 and AGF27, on AD-MSCs. AGF9 and AGF27 enhanced the viability and migration of AD-MSCs and acted as a chemotactic factor for these cells. AGF9 stimulated chondrogenesis and lipid synthesis during AD-MSCs differentiation, influenced AD-MSCs cytokine secretion and modulated transcriptome for such basic cell activities as migration, transport of molecules, and apoptosis. The ability of AGF9 to modulate the biological activity of AD-MSCs warrants the consideration of this peptide a noteworthy therapeutic agent that deserves further investigation for applications in regenerative medicine.

Advances in myocarditis management in the light of the latest research and recent guidelines of the European Society of Cardiology.

Myocarditis remains an unknown disease with varying clinical manifestations, often leading to heart failure. The latest 2021 and 2022 guidelines of the European Society of Cardiology (ESC) are the first official European documents updating knowledge on the diagnosis and treatment of myocarditis since the 2013 ESC expert consensus statement. These guidelines and new studies allow standardization and improvements to the management of myocarditis. In this review, we discuss the most important aspects of myocarditis diagnosis, therapies and follow-up based on current knowledge.

Immunosuppressive Therapy of Biopsy-Proven, Virus-Negative, Autoimmune/Immune-Mediated Myocarditis-Focus on Azathioprine: A Review of Existing Evidence and Future Perspectives.

The use of immunosuppressive therapy (IT) in biopsy-proven, autoimmune/immune-mediated (AI), virus-negative myocarditis has become the standard of care. In particular, according to recent guidelines, azathioprine (AZA), in association with steroids, is a cornerstone of first-line therapy regimens. IT may have a crucial impact on the natural history of AI myocarditis, preventing its progression to end-stage heart failure, cardiovascular death, or heart transplantation, provided that strict appropriateness and safety criteria are observed. In particular, AZA treatment for AI virus-negative myocarditis requires the consideration of some crucial aspects regarding its pharmacokinetics and pharmacodynamics, as well as a high index of suspicion to detect its overt and/or subclinical side effects. Importantly, besides a tight teamwork with a clinical immunologist/immuno-rheumatologist, before starting IT, it is also necessary to carry out a careful "safety check-list" in order to rule out possible contraindications to IT and minimize patient's risk. The aim of this review is to describe the pharmacological properties of AZA, as well as to discuss practical aspects of its clinical use, in the light of existing evidence, with particular regard to the new field of cardioimmunology.

Adipose-Derived Mesenchymal Stromal Cells in Basic Research and Clinical Applications.

Adipose-derived mesenchymal stromal cells (AD-MSCs) have been extensively studied in recent years. Their attractiveness is due to the ease of obtaining clinical material (fat tissue, lipoaspirate) and the relatively large number of AD-MSCs present in adipose tissue. In addition, AD-MSCs possess a high regenerative potential and immunomodulatory activities. Therefore, AD-MSCs have great potential in stem cell-based therapies in wound healing as well as in orthopedic, cardiovascular, or autoimmune diseases. There are many ongoing clinical trials on AD-MSC and in many cases their effectiveness has been proven. In this article, we present current knowledge about AD-MSCs based on our experience and other authors. We also demonstrate the application of AD-MSCs in selected pre-clinical models and clinical studies. Adipose-derived stromal cells can also be the pillar of the next generation of stem cells that will be chemically or genetically modified. Despite much research on these cells, there are still important and interesting areas to explore.

Personalized Management of Myocarditis and Inflammatory Cardiomyopathy in Clinical Practice.

Myocarditis is an inflammatory heart disease induced by infectious and non-infectious causes frequently triggering immune-mediated pathologic mechanisms leading to myocardial damage and dysfunction. In approximately half of the patients, acute myocarditis resolves spontaneously while in the remaining cases, it may evolve into serious complications including inflammatory cardiomyopathy, arrhythmias, death, or heart transplantation. Due to the large variability in clinical presentation, unpredictable course of the disease, and lack of established causative treatment, myocarditis represents a challenging diagnosis in modern cardiology. Moreover, an increase in the incidence of myocarditis and inflammatory cardiomyopathy has been observed in recent years. However, there is a growing potential of available non-invasive diagnostic methods (biomarkers, serum anti-heart autoantibodies (AHA), microRNAs, speckle tracking echocardiography, cardiac magnetic resonance T1 and T2 tissue mapping, positron emission tomography), which may refine the diagnostic workup and/or noninvasive follow-up. Personalized management should include the use of endomyocardial biopsy and AHA, which may allow the etiopathogenetic subsets of myocarditis (infectious, non-infectious, and/or immune-mediated) to be distinguished and implementation of disease-specific therapies. In this review, we summarize current knowledge on myocarditis and inflammatory cardiomyopathy, and outline some practical diagnostic, therapeutic, and follow-up algorithms to facilitate comprehensive individualized management of these patients.

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.

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.

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.

Efficacy of immunosuppressive therapy in myocarditis: A 30-year systematic review and meta analysis.

AIMS: Myocarditis is an inflammation of the heart muscle, due to infectious, toxic or autoimmune causes. Literature reported controversial results in relation to the effect of immunosuppression (IS)/immunomodulation (IM). We aimed at assessing the effect of IS/IM by meta analysis. METHODS AND RESULTS: Using the P.R.I.S.M.A. approach, two researchers searched for relevant studies on PubMed, Embase, and the Central Registry of Controlled Trials of the Cochrane Library. Proposed MeSH terms were: "immunotherapy OR immune therapy OR immune modeling OR Immunosuppressive Agents" AND "combination OR combined with OR plus" AND "myocarditis OR cardiomyopathies OR inflammatory cardiomyopathy". The language was restricted to English. Reference lists of included articles and those relevant to the topic were hand searched for the identification of additional, potentially relevant articles. The cutoff date was from 1987 until 30th Nov 2019. Reported survival or mortality events or change of left ventricular ejection fraction (LVEF) after IS/IT were primary outcomes of the study; in addition, improvement of New York Heart Association class, follow-up biopsy (Bx) findings, viral genome clearance on Bx and recurrence of myocarditis were recorded if reported. Statistical analysis was conducted using Review Manager 5.3; 5452 studies were screened, of these 73 were assessed for eligibility, including 8 randomized control studies, 26 retrospective studies, 2 prospective studies and 1 case control study, 34 case reports and 2 case series. In prospective studies, the difference in mortality between the IS and control groups tended to be lower in the combined IS groups (12.5% vs. 18.2%) (95% CI of odds ratio 0.7(0.3, 1.64)) and the pooled difference of the increase of LVEF between the IS and control groups tended to be higher in the combined IS groups (95% CI 7.26 (-2.29, 16.81)). In retrospective studies, the difference of survival between the IS and control group was significantly in favor of IS (95%CI Hazard ratio 0.82(0.69, 0.96)). CONCLUSIONS: A tailored IS may be considered in myocarditis, depending on the phase of the disease, and the type of underlying autoimmune or immune-mediated form.

Clinically Suspected Myocarditis in the Course of Severe Acute Respiratory Syndrome Novel Coronavirus-2 Infection: Fact or Fiction?

Cardiac complications, including clinically suspected myocarditis, have been described in novel coronavirus disease 2019. Here, we review current data on suspected myocarditis in the course of severe acute respiratory syndrome novel coronavirus-2 (SARS-CoV-2) infection. Hypothetical mechanisms to explain the pathogenesis of troponin release in patients with novel coronavirus disease 2019 include direct virus-induced myocardial injury (ie, viral myocarditis), systemic hyperinflammatory response (ie, cytokine storm), hypoxemia, downregulation of angiotensin-converting enzyme 2, systemic virus-induced endothelialitis, and type 1 and type 2 myocardial infarction. To date, despite the fact that millions of SARS-CoV-2 infections have been diagnosed worldwide, there is no definitive proof that SARS-CoV-2 is a novel cardiotropic virus causing direct cardiomyocyte damage. Diagnosis of viral myocarditis should be based on the molecular assessment of endomyocardial biopsy or autopsy by polymerase chain reaction or in-situ hybridization. Blood, sputum, or nasal and throat swab virology testing are insufficient and do not correlate with the myocardial involvement of a given pathogen. Data from endomyocardial biopsies and autopsies in clinically suspected SARS-CoV-2 myocarditis are scarce. Overall, current clinical epidemiologic data do not support the hypothesis that viral myocarditis is caused by SARS-CoV-2, or that it is common. More endomyocardial biopsy and autopsy data are also needed for a better understanding of pathogenesis of clinically suspected myocarditis in the course of SARS-CoV-2 infection, which may include virus-negative immune-mediated or already established subclinical autoimmune forms, triggered or accelerated by the hyperinflammatory state of severe novel coronavirus disease 2019.

Are adipokines associated with atrial fibrillation in type 2 diabetes?

INTRODUCTION: The potential effect of adipokines on the development of AF is yet to be established. The aim of this study was to investigate the association of baseline serum adipokines with 1) the presence of AF at baseline and 2) future risk of AF development. MATERIAL AND METHODS: The current study is a sub-analysis of the prospective, randomised AVOCADO (Aspirin Vs./Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes) trial. The AVOCADO study included patients with type 2 DM burdened with at least two additional cardiovascular risk factors and receiving acetylsalicylic acid. In patients included in the current analysis adipokines and inflammatory biomarker levels were measured. Information on the subsequent AF diagnosis was collected after a median of 5.4 years of follow-up. RESULTS: A total of 273 patients with type 2 DM (median age 68 years; 52% male) were included in the initial analysis comparing patients with and without AF at baseline. Patients with diagnosed AF (12%) had higher levels of serum resistin [8.5 (5.8-10.5) vs. 6.9 (5.6-8.7) ng/mL; p = 0.034], adiponectin [6.9 (5.6-8.7) vs. 2.7 (1.8-4.2) ng/mL; p = 0.032], and N-terminal pro-B-type natriuretic peptide [336 (148-473) vs. 108 [45-217]; p < 0.001) than non-AF patients. There were no significant differences in serum leptin, IL-6, and TNF-alpha concentrations between the two groups. From subjects without known AF at study entry, 19% developed AF at follow-up. In logistic regression analysis, baseline adipokine levels did not predict AF development. CONCLUSION: In type 2 DM, patients with AF have higher resistin and adiponectin concentrations than patients with no AF. None of the studied adipokines proved a predictor of future AF development.

Resistin is a prognostic factor for death in type 2 diabetes.

PURPOSE: To investigate the association of leptin, resistin, and tumour necrosis factor α (TNF-α) with prognosis in type 2 diabetes (T2D). METHODS: Analysis included 284 T2D patients. Apart from routine laboratory parameters, baseline leptin, resistin, and TNF-α concentrations were measured. Patients were followed for a median of 5.4 years. The primary endpoint was all-cause death at follow-up. The secondary endpoint was a composite of death, acute coronary syndrome, and stroke or transient ischemic attack. RESULTS: At baseline, median age was 68 years, and 48% of patients were female. Data on the primary endpoint were obtained for all patients: 32 (11%) died during follow-up. Data on the secondary endpoint were available for 230 patients, of whom 45 (20%) reached the secondary endpoint. In univariate analyses, older age, heart failure, lower-glomerular filtration rate, and higher resistin, TNF-α and NT-proBNP concentrations were predictors of the study endpoints. Of these variables, only resistin remained an independent predictor of both study endpoints in multivariate models. In receiver-operating characteristic analysis, area under the curve for resistin was 0.7. Resistin concentration of greater than or equal to 11.4 ng/mL had sensitivity of 41% and specificity of 91% for prediction of death at follow-up (Youden's index). CONCLUSIONS: Higher resistin is associated with reduced survival in T2D, irrespectively of TNF-α. Resistin concentration of above 11 ng/mL indicates T2D patients at an increased risk of unfavourable outcomes. Leptin was not a prognostic factor. These results suggest that in T2D, association of resistin with unfavourable outcomes might, at least in part, result from its pro-inflammatory properties.

Clinical characteristics and thromboembolic risk of atrial fibrillation patients with and without congestive heart failure. Results from the CRATF study.

Congestive heart failure (CHF) and atrial fibrillation (AF) frequently coexist and are associated with increased risk of cardiovascular events.To compare baseline characteristics, comorbidities and pharmacotherapy in AF patients with concomitant CHF to those without CHF.The study included 3506 real-life AF patients with (37.1%) and without CHF - participants of the multicentre, retrospective MultiCenter expeRience in AFib patients Treated with OAC (CRAFT) trial (NCT02987062).All patients were treated with non-vitamin K antagonist oral anticoagulants (NOAC) or vitamin K antagonists (VKA). The frequency of NOAC among patients with and without CHF was 45.6% and 43.2%, respectively (P = .17). Patients with CHF were older (73.3 vs 64.7 years, P <.001), less likely to be women (37.4% vs 42%, P = .007), had higher CHA2DS2-VASc score (3.8 ±â€Š1.7 vs 2.6 ±â€Š1.8, P <.001), more often had permanent AF (53.0% vs 13.4%, P <.001), chronic obstructive pulmonary disease (16.7% vs 4.9%, P <.001), coronary artery disease (64.3% vs 29.8%, P <.001), peripheral vascular disease (65.3% vs 31.4%, P <.001), chronic kidney disease (43.1% vs 10.0%, P <.001), liver fibrosis (5.7% vs 2.6%, P <.001), neoplasm (9.6% vs 7.3%, P = .05), history of composite of stroke, transient ischemic attack or systemic embolization (16.2% vs 10.7%, P <.001), pacemaker (27.4% vs 22.1%, P = .004), implantable cardioverter-defibrillator (22.7% vs 0.8%, P <.001) or transaortic valve implantation (4.0% vs 0.8%, P <.001), cardiac resynchronization therapy (8.7% vs 0.3%, P <.001), composite of kidney transplantation, hemodialysis or creatinine level > 2.26 mg/dL (3.6% vs 0.8%, P <.001) and had less often hypertension (69.4% vs 72.5%, P = .05).Patients with AF and CHF had a higher thromboembolic risk and had more concomitant diseases.

Melanization of Bomirski hamster amelanotic melanoma cells (Ab line) depends on the type of culture medium.

INTRODUCTION: The effect of melanogenesis intensity on melanoma biology remains an open question, and the biological differences between melanotic and amelanotic melanoma cells have not yet been satisfactorily documented. As a result, the melanization of melanoma cells in in vitro cultures is not considered among experimental procedures. The aim of this study was to investigate the effect of the medium used to culture Bomirski amelanotic Ab melanoma cells on the melanogenesis process. MATERIAL AND METHODS: Amelanotic melanoma cells (Ab) were cultured in two media recommended for in vitro melanoma cell cultures, RPMI and DMEM. The melanization was evaluated by determining the melanin and tyrosinase presence in the cells using spectrophotometrical and western blot methods, respectively. Changes in Ab melanoma cells' ultrastructure were determined using electron microscopy (EM). RESULTS: The medium with higher level of tyrosine (DMEM) induced significant melanization of amelanotic melanoma cells (Ab) after only 24 h, while the RPMI medium, with a lower level of tyrosine, weakly affected melanin production. Melanization of Ab cells was paralleled by an increase in the amount of tyrosinase protein. Induced melanization was easily observed on EM-micrographs in the form of newly formed melanosomes containing melanin pigment. Melanosomes at stages from one (I) to four (IV) were observed. CONCLUSIONS: Culture medium has an important effect on the in vitro biology of amelanotic melanoma cells, since it can affect the rate of cellular melanization. The appropriate medium should be carefully selected, taking into account the known biology of the melanoma cells being used.

Heart failure patients with a previous coronary revascularization: results from the ESC-HF Registry.

BACKGROUND: Coronary revascularization is common in heart failure (HF). AIMS: Clinical characteristic and assessment of in-hospital and long-term outcomes in patients hospitalized for HF with or without a previous percutaneous coronary intervention (PCI) or a coronary artery bypass grafting (CABG). METHODS: The primary endpoint (PE) (all-cause death) and the secondary endpoint (SE) (all-cause death or hospitalization for HF-worsening) were assessed at one-year in 649 inpatients of the ESC-HF Pilot Survey. Additionally, occurrence of death during index hospitalization was evaluated. RESULTS: PCI/CABG-patients (32.7%) were more frequently male, smokers, had myocardial infarction, hypertension (HT), peripheral artery disease and diabetes. The non-PCI/CABG-patients more often had a cardiogenic shock and died in-hospital. The PE occurred in 33 of the 212 PCI/CABG-patients (15.6%) and in 56 of the 437 non-PCI/CABG-patients (12.8%; P=0.3). The SE occurred in 82 of the 170 PCI/CABG-patients (48.2%) and in 122 of the 346 non-PCI/CABG-patients (35.3%; P=0.01). Independent predictors of the PE in the PCI/CABG-patients were: lower left ventricular ejection fraction, use of antiplatelets; in the non-PCI/CABG-patients were: age, ACS at admission. Independent predictors of the SE in the PCI/CABG-patients were: diabetes, NYHA (New York Heart Association) class at admission, HT; in the non-PCI/CABG-patients were: NYHA class, haemoglobin at admission. Serum sodium concentration at admission was a predictor of the PE and the SE in both groups. Heart rate at discharge was a predictor of the PE and the SE in the non-PCI/CABG patients. CONCLUSIONS: The revascularized HF patients had a similar mortality and higher risk of death or hospitalizationsat 12 months compared with the non-PCI/CABG-patients. The revascularized patients had more comorbidities, while the non-PCI/CABG-patients had a higher incidence of cardiogenic shock and in-hospital mortality.

The influence of the atrial fibrillation episode duration on the endothelial function in patients treated with pulmonary veins isolation.

BACKGROUND: Atrial fibrillation (AF) is associated with endothelial dysfunctions. OBJECTIVES: The aim of the study was to assess the influence of the duration of an AF episode on the endothelial function. MATERIAL AND METHODS: The study included 65 patients with persistent AF qualified for the percutaneous pulmonary veins isolation. Patients were divided into three subgroups with increasing time of the duration of AF episode, as follow: ≤ 7 months (n = 24 patients), from 7 to 14 months (n = 18 patients) and ≥ 14 months (n = 23 patients). Concentrations of endothelin-1 (ET-1), thrombomodulin (TM) and VEGF in serum were measured. RESULTS: Median age in the whole study group was 56 years with 84.6% of males. Patients with longer lasting AF episode had a higher body mass index and less incidence of heart failure. Median values of ET1, TM and VEGF were 3.1 (2.5-3.5) pg/mL, 3126.0 (2827.2-3594.1) pg/mL and 464.6 (323.6-630.1), respectively. Among increasing tertiles of AF episode duration, median ET-1 serum concentrations were as follows: 3.3 (2.8-3.7) pg/mL, 3.06 (2.6-3.4) pg/mL, 2.7 (2.3-3.2) pg/mL, p = 0.019, respectively. There was also a trend towards negative association of serum VEGF level with AF episode duration. Serum biomarkers' levels were not associated with total AF duration. CONCLUSIONS: AF episode duration may be associated with the endothelial function, assessed by serum biomarkers. ET-1 serum concentrations are significantly lower in patients with longer AF. ET-1, TM and VEGF have no correlation with total AF duration.

Heart failure in elderly patients: differences in clinical characteristics and predictors of 1-year outcome in the Polish ESC-HF Long-Term Registry.

INTRODUCTION    Heart failure (HF) is the leading cause of hospitalization in elderly patients. OBJECTIVES    The aim of the study was to examine the clinical profile and 1-year outcomes of elderly patients (aged ≥65 years) compared with younger patients (aged <65 years) hospitalized for HF decompensation, as well as clinical differences among elderly patients aged 65-74 years and those aged ≥75 years. PATIENTS AND METHODS    The primary endpoint (PE; all-cause death) and the secondary endpoint (SE; all-cause death or rehospitalization for HF worsening) were assessed at 1 year in a group of 765 hospitalized Polish participants of the ESC-HF Long-Term Registry. RESULTS    The PE was observed in 9.1% of patients aged <65 years; 18.5% of those aged ≥65 years (P = 0.0001); 14.5% of those aged 65-74 years; and 21.6% of those aged ≥75 years (P = 0.07). The SE occurred in 28.0% of patients aged <65 years; 36.1% of those aged ≥65 years (P = 0.04); 29.2% of those aged 65-74 years; and 41.2% of those aged ≥75 years (P = 0.01). Independent predictors of the PE in patients aged ≥65 years were as follows: chronic obstructive pulmonary disease (COPD), systolic blood pressure (SBP), New York Heart Association (NYHA) class, ß-blocker use; in patients aged 65-74 years: coronary revascularization, NYHA class, sodium, and creatinine; in patients aged ≥75 years: NYHA class and SBP. Independent predictors of the SE in patients aged ≥65 years were as follows: COPD, NYHA class, potassium, SBP, and physical activity; in patients aged <65 years: chronic kidney disease (CKD), NYHA, and SBP; in patients aged 65-74 years: NYHA and creatinine; and in patients aged ≥75 years, previous HF hospitalization, coronary artery disease, CKD, COPD, alcohol consumption, smoking, NYHA, and SBP. CONCLUSIONS    Elderly patients with HF differed from younger patients in terms of long-term outcome and prognostic factors. There were also important differences within the elderly group itself.