The diagnosis of heart failure with preserved left ventricle ejection fraction (HFpEF) remains a challenge, with score-based algorithms showing varying diagnostic performance and biomarkers sometimes inconclusive. This study aimed to examine whether circulating histones and histone complexes, which recently emerged as robust biomarkers of inflammation and stroke, show distinct profiles in plasma from healthy individuals, HF with reduced EF (HFrEF), and HFpEF patients. We evaluated the plasma histone profile of 30 sex/age-matched healthy individuals, 22 HFpEF and 25 HFrEF prior any therapeutic intervention. ImageStreamX-based detection approach was used to measure the levels of circulating particles positive for core histones H2A, H2B, H3, H4, histone variants macroH2A1.1 and macroH2A1.2. While we found increased levels of most of the histones and histone complexes in both HFpEF and HFrEF patients, H2A was significantly elevated only in HFpEF, compared to healthy individuals (p-value = 0.002) and to HFrEF (p-value = 0.00008). In line with these findings, H2A showed positive correlation with EF (r = 0.493). We identified a plasma histone profile able to detect HF and differentiate between HFpEF and HFrEF using a high throughput and imaging flow cytometry-adapted liquid biopsy.

• Klíčová slova
• Heart failure, Histones, Liquid biopsy, Plasma, Preserved ejection fraction, Reduced ejection fraction,
• Publikační typ
• časopisecké články MeSH

AIMS: In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients. METHODS AND RESULTS: We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6 months and LV ejection fraction <40% persisting after at least 1 week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5 years. LVRR was defined as the combined presence of (1) LVEF ≥ 50% or increase in LVEF ≥ 10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi) ≥ 10% or (3) LVEDDi ≤ 33 mm/m2. LVRR was observed in 46% patients at 1 year, in 60% at 2 years and 50% at 5 years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P < 0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1 year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P = 0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P < 0.05 for all). CONCLUSIONS: LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2 years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up.

• Klíčová slova
• Dilated cardiomyopathy, Endomyocardial biopsy, Left ventricular systolic dysfunction, Mortality, Reverse remodelling,
• MeSH
• dilatační kardiomyopatie * MeSH
• dysfunkce levé srdeční komory * komplikace   MeSH
• funkce levé komory srdeční fyziologie   MeSH
• lidé MeSH
• prognóza MeSH
• srdeční selhání * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Acute heart failure (AHF) is a common and severe condition with a poor prognosis. Its course is often complicated by worsening renal function (WRF), exacerbating the outcome. The population of AHF patients experiencing WRF is heterogenous, and some novel possibilities for its analysis have recently emerged. Clustering is a machine learning (ML) technique that divides the population into distinct subgroups based on the similarity of cases (patients). Given that, we decided to use clustering to find subgroups inside the AHF population that differ in terms of WRF occurrence. We evaluated data from the three hundred and twelve AHF patients hospitalized in our institution who had creatinine assessed four times during hospitalization. Eighty-six variables evaluated at admission were included in the analysis. The k-medoids algorithm was used for clustering, and the quality of the procedure was judged by the Davies-Bouldin index. Three clinically and prognostically different clusters were distinguished. The groups had significantly (p = 0.004) different incidences of WRF. Inside the AHF population, we successfully discovered that three groups varied in renal prognosis. Our results provide novel insight into the AHF and WRF interplay and can be valuable for future trial construction and more tailored treatment.

• Klíčová slova
• acute heart failure, artificial intelligence, cardiorenal syndrome, clustering, machine learning,
• MeSH
• akutní nemoc MeSH
• kreatinin MeSH
• ledviny fyziologie   MeSH
• lidé MeSH
• srdeční selhání * MeSH
• strojové učení MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kreatinin MeSH

Heart failure has a five-year mortality rate approaching 50%. Inducing angiogenesis following a myocardial infarction is hypothesized to reduce cardiomyocyte death and tissue damage, thereby preventing heart failure. Herein, a novel nano-in-gel delivery system for vascular endothelial growth factor (VEGF), composed of star-shaped polyglutamic acid-VEGF nanoparticles in a tyramine-modified hyaluronic acid hydrogel (nano-VEGF-HA-TA), is investigated. The ability of the nano-VEGF-HA-TA system to induce angiogenesis is assessed in vivo using a chick chorioallantoic membrane model (CAM). The formulation is then integrated with a custom-made, clinically relevant catheter suitable for minimally invasive endocardial delivery and the effect of injection on hydrogel properties is examined. Nano-VEGF-HA-TA is biocompatible on a CAM assay and significantly improves blood vessel branching (p < 0.05) and number (p < 0.05) compared to a HA-TA hydrogel without VEGF. Nano-VEGF-HA-TA is successfully injected through a 1.2 m catheter, without blocking or breaking the catheter and releases VEGF for 42 days following injection in vitro. The released VEGF retains its bioactivity, significantly improving total tubule length on a Matrigel® assay and human umbilical vein endothelial cell migration on a Transwell® migration assay. This VEGF-nano in a HA-TA hydrogel delivery system is successfully integrated with an appropriate device for clinical use, demonstrates promising angiogenic properties in vivo and is suitable for further clinical translation.

• Klíčová slova
• angiogenic growth factor, catheter delivery, chick chorioallantoic membrane model, hyaluronic acid hydrogel, nanoparticle-loaded hydrogel, protein delivery, sustained release, vascular endothelial growth factor nanoparticles,
• Publikační typ
• časopisecké články MeSH

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

• MeSH
• bezpečnost pacientů MeSH
• kardiotonika škodlivé účinky   terapeutické užití   MeSH
• kontrakce myokardu účinky léků   MeSH
• lidé MeSH
• simendan škodlivé účinky   terapeutické užití   MeSH
• srdeční selhání diagnóza   farmakoterapie   mortalita   patofyziologie   MeSH
• vazodilatace účinky léků   MeSH
• vazodilatancia škodlivé účinky   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kardiotonika MeSH
• simendan MeSH
• vazodilatancia MeSH

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

• Klíčová slova
• Acute heart failure, advanced heart failure, haemodynamics, inodilator, inotrope, neurohormone, regulatory clinical trial,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Viral infections are considered the most frequent cause of myocarditis and dilated cardiomyopathy (DCM). MATERIAL AND METHODS: We investigated the changes in viral presence and the impact of viral genome persistence in the myocardium on echocardiographic parameters, functional status and some laboratory parameters in a 6-month follow-up. Fifty-four patients with recent onset DCM, left ventricular ejection fraction < 40% and biopsy-proven myocarditis (> 14 mononuclear leukocytes/mm2 and/or > 7 T-lymphocytes/mm2) were enrolled. Polymerase chain reaction (PCR) was performed to detect pathogens in the myocardium. Patients were divided according to the administered therapy: standard heart failure medication (46 patients) and immunosuppressive therapy (8 patients). RESULTS: In the standard heart failure medication group viral clearance was observed in 13 patients and viral persistence in 24 patients in the follow-up period. Comparing both groups, there was no statistically significant difference - LVEF improvement of 12.0 ±11.4% vs. 18.3 ±12.6%, decrease in NYHA class of 0.7 ±0.7 vs. 1.0 ±0.7, decline in NT-proBNP of 1335 ±1933 ng/l vs. 1942 ±3242 ng/l and decrease in infiltrating leukocytes of 11.1 ±15.8 vs. 6.7 ±23.0 cells/mm2 and T-lymphocytes of 5.8 ±15.1 vs. 1.8 ±10.9 cells/mm2 (all p = NS). A decrease in PCR positive patients from 37 to 29 was observed. The number of PVB19 positive PCR findings decreased from 5 to 4 in patients with immunosuppressive therapy. CONCLUSIONS: A decrease in the number of positive PCR findings in control endomyocardial biopsy was observed. Viral genome persistence was not associated with worse outcome in short-term follow-up.

• Klíčová slova
• dilated cardiomyopathy, endomyocardial biopsy, inflammatory cardiomyopathy, myocarditis, polymerase chain reaction,
• Publikační typ
• časopisecké články MeSH

AIMS: The prognosis after hospitalization for acute decompensated heart failure (ADHF) remains poor, especially <30 days post-discharge. Evidence-based medications with prognostic impact administered at discharge improve survival and hospital readmission, but robust studies comparing pre-discharge with post-discharge initiation are rare. The PARADIGM-HF trial established sacubitril/valsartan as a new evidence-based therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (<40%) (rEF). In common with other landmark studies, it enrolled patients who were ambulatory at the time of inclusion. In addition, there is also still limited knowledge of initiation and up-titration of sacubitril/valsartan in ACEi/ARB- naïve patients and in de novo HF with rEF patients. METHODS AND RESULTS: TRANSITION is a multicentre, open-label study in which ~1000 adults hospitalized for ADHF with rEF are randomized to start sacubitril/valsartan in a pre-discharge arm (initiated ≥24 h after haemodynamic stabilization) or a post-discharge arm (initiated within Days 1-14 after discharge). The protocol allows investigators to select the appropriate starting dose and dose adjustments according to clinical circumstances. Over a 10 week treatment period, the primary and secondary objectives assess the feasibility and safety of starting sacubitril/valsartan in-hospital, early after haemodynamic stabilization. Exploratory objectives also include assessment of HF signs and symptoms, readmissions, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels, and health resource utilization parameters. CONCLUSIONS: TRANSITION will provide new evidence about initiating sacubitril/valsartan following hospitalization for ADHF, occurring either as de novo ADHF or as deterioration of chronic HF, and in patients with or without prior ACEI/ARB therapy. The results of TRANSITION will thus be highly relevant to the management of patients hospitalized for ADHF with rEF.

• Klíčová slova
• Acute decompensated heart failure, Acute heart failure, Discharge, Hospitalization, LCZ696, Sacubitril/valsartan,
• MeSH
• akutní nemoc MeSH
• aminobutyráty aplikace a dávkování   MeSH
• antagonisté receptorů pro angiotenzin aplikace a dávkování   MeSH
• bifenylové sloučeniny MeSH
• fixní kombinace léků MeSH
• funkce levé komory srdeční účinky léků   fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• propuštění pacienta * MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• srdeční selhání farmakoterapie   patofyziologie   MeSH
• tepový objem účinky léků   fyziologie   MeSH
• tetrazoly aplikace a dávkování   MeSH
• valsartan MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• znovupřijetí pacienta * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• aminobutyráty MeSH
• antagonisté receptorů pro angiotenzin MeSH
• bifenylové sloučeniny MeSH
• fixní kombinace léků MeSH
• sacubitril and valsartan sodium hydrate drug combination MeSH Prohlížeč
• tetrazoly MeSH
• valsartan MeSH

Inflammatory cardiomyopathy is defined as inflammation of the heart muscle associated with impaired function of the myocardium. In our region, its etiology is most often viral. Viral infection is a possible trigger of immune and autoimmune mechanisms which contributed to the damage of myocardial function. Myocarditis is considered the most common cause of dilated cardiomyopathy. Typical manifestation of this disease is heart failure, chest pain, or arrhythmias. The most important noninvasive diagnostic method is magnetic resonance imaging, but the gold standard of diagnostics is invasive examination, endomyocardial biopsy. In a significant proportion of cases with impaired left ventricular systolic function, recovery occurs spontaneously in several weeks and therefore it is appropriate to postpone critical therapeutic decisions about 3-6 months after start of the treatment. Therapy is based on standard heart failure treatment; immunosuppressive or antimicrobial treatment may be considered in some cases depending on the results of endomyocardial biopsy. If severe dysfunction of the left ventricle persists, device therapy may be needed.

• MeSH
• antibakteriální látky terapeutické užití   MeSH
• antiflogistika terapeutické užití   MeSH
• biopsie metody   MeSH
• kardiomyopatie diagnóza   terapie   MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• myokarditida diagnóza   terapie   MeSH
• srdeční resynchronizační terapie metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• antiflogistika MeSH

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction-LVEF <40 %) with heart failure symptoms ≤ 6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm(2) and/or >7 T-lymphocytes/mm(2) in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm(2) and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm(2) (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = -0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = -0.33; p = 0.038 and R = -0.45; p = 0.003) and with the change in LVEDV (R = -0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment option in patients with recent onset biopsy-proven inflammatory cardiomyopathy.

• Klíčová slova
• Echocardiography, Endomyocardial biopsy, Inflammatory cardiomyopathy, Left ventricular dysfunction, Myocarditis,
• MeSH
• biologické markery krev   MeSH
• biopsie MeSH
• časové faktory MeSH
• chemotaxe leukocytů MeSH
• dopplerovská echokardiografie * MeSH
• dospělí MeSH
• dysfunkce levé srdeční komory diagnóza   diagnostické zobrazování   farmakoterapie   patologie   MeSH
• funkce levé komory srdeční * účinky léků   MeSH
• kardiomyopatie diagnóza   diagnostické zobrazování   farmakoterapie   patologie   MeSH
• kardiovaskulární látky terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• myokard metabolismus   patologie   MeSH
• myokarditida diagnóza   diagnostické zobrazování   farmakoterapie   patologie   MeSH
• natriuretický peptid typu B krev   MeSH
• obnova funkce MeSH
• odds ratio MeSH
• peptidové fragmenty krev   MeSH
• prediktivní hodnota testů MeSH
• rizikové faktory MeSH
• srdeční selhání diagnóza   diagnostické zobrazování   farmakoterapie   patologie   MeSH
• T-lymfocyty patologie   MeSH
• tepový objem * účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• kardiovaskulární látky MeSH
• natriuretický peptid typu B MeSH
• peptidové fragmenty MeSH
• pro-brain natriuretic peptide (1-76) MeSH Prohlížeč