Background and Objectives: Iron deficiency (ID) is a common comorbidity in patients with heart failure. It is associated with reduced physical performance, frequent hospitalisations for heart failure decompensation, and high cardiovascular and overall mortality. The aim was to determine the prevalence of ID in patients with advanced heart failure on the waiting list for heart transplantation. Methods and Materials: We included 52 patients placed on the waiting list for heart transplantation in 2021 at our centre. The cohort included seven patients with LVAD (left ventricle assist device) as a bridge to transplantation implanted before the time of results collection. In addition to standard tests, the parameters of iron metabolism were monitored. ID was defined as a ferritin value <100 µg/L, or 100−299 µg/L if transferrin saturation (T-sat) is <20%. Results: ID was present in 79% of all subjects, but only in 35% of these patients anaemia was expressed. In the group without LVAD, ID was present in 82%, a median (lower−upper quartile) of ferritin level was 95.4 (62.2−152.1) µg/mL and mean T-sat was 0.18 ± 0.09. In LVAD group, ID was present in 57%, ferritin level was 268 (106−368) µg/mL and mean T-sat was 0.14 ± 0.04. Haemoglobin concentration was the same in patients with or without ID (133 ± 16) vs. (133 ± 23). ID was not associated with anaemia defined with regard to patient’s gender. In 40.5% of cases, iron deficiency was accompanied by chronic renal insufficiency, compared to 12.5% of the patients without ID. In the patients with LVAD, ID was present in four out of seven patients, but the group was too small for reliable statistical testing due to low statistical power. Conclusions: ID was present in the majority of patients with advanced heart failure and was not always accompanied by anaemia and renal insufficiency. Research on optimal markers for the diagnosis of iron deficiency, especially for specific groups of patients with heart failure, is still ongoing.

• Klíčová slova
• advanced heart failure, anaemia, ferritin, iron deficiency, transferrin saturation,
• MeSH
• anemie z nedostatku železa * komplikace   epidemiologie   MeSH
• anemie * komplikace   MeSH
• deficit železa * MeSH
• ferritiny MeSH
• lidé MeSH
• srdeční selhání * komplikace   epidemiologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ferritiny MeSH

While anti-cancer therapies, including chemotherapy, immunotherapy, radiotherapy, and targeted therapy, are constantly advancing, cardiovascular toxicity has become a major challenge for cardiologists and oncologists. This has led to an increasing demand of cardio-oncology units in Europe and a growing interest of clinicians and researchers. The Heart Failure 2019 meeting of the Heart Failure Association of the European Society of Cardiology in Athens has therefore created a scientific programme that included four dedicated sessions on the topic along with several additional lectures. The major points that were discussed at the congress included the implementation and delivery of a cardio-oncology service, the collaboration among cardio-oncology experts, and the risk stratification, prevention, and early recognition of cardiotoxicity. Furthermore, sessions addressed the numerous different anti-cancer therapies associated with cardiotoxic effects and provided guidance on how to treat cancer patients who develop cardiovascular disease before, during, and after treatment.

• Klíčová slova
• Cancer, Cardiotoxicity, Heart failure,
• MeSH
• kardiologie organizace a řízení   trendy   MeSH
• kardiotoxicita * MeSH
• lidé MeSH
• nádory * komplikace   patofyziologie   terapie   MeSH
• srdeční selhání * komplikace   patofyziologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

End of life is an unfortunate but inevitable phase of the heart failure patients' journey. It is often preceded by a stage in the progression of heart failure defined as advanced heart failure, and characterised by poor quality of life and frequent hospitalisations. In clinical practice, the efficacy of treatments for advanced heart failure is often assessed by parameters such as clinical status, haemodynamics, neurohormonal status, and echo/MRI indices. From the patients' perspective, however, quality-of-life-related parameters, such as functional capacity, exercise performance, psychological status, and frequency of re-hospitalisations, are more significant. The effects of therapies and interventions on these parameters are, however, underrepresented in clinical trials targeted to assess advanced heart failure treatment efficacy, and data are overall scarce. This is possibly due to a non-universal definition of the quality-of-life-related endpoints, and to the difficult standardisation of the data collection. These uncertainties also lead to difficulties in handling trade-off decisions between quality of life and survival by patients, families and healthcare providers. A panel of 34 experts in the field of cardiology and intensive cardiac care from 21 countries around the world convened for reviewing the existing data on quality-of-life in patients with advanced heart failure, discussing and reaching a consensus on the validity and significance of quality-of-life assessment methods. Gaps in routine care and research, which should be addressed, were identified. Finally, published data on the effects of current i.v. vasoactive therapies such as inotropes, inodilators, and vasodilators on quality-of-life in advanced heart failure patients were analysed.

• Klíčová slova
• Advanced heart failure, Levosimendan, Nesiritide, Nitroprusside, Quality of life, Trade-off,
• MeSH
• hospitalizace trendy   MeSH
• kvalita života psychologie   MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• progrese nemoci * MeSH
• srdeční selhání mortalita   psychologie   terapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

OBJECTIVES: The purpose of this study was to compare the prognostic impact of clinical and biomarker correlates of resting heart rate (HR) and chronotropic incompetence in heart failure (HF) patients. BACKGROUND: The mechanisms and underlying pathophysiological influences of HR abnormalities in HF are incompletely understood. METHODS: In a prospective pilot study, 81 patients with advanced systolic HF (97% were receiving beta-blockers) and 25 age-, sex-, and body-size matched healthy controls underwent maximal cardiopulmonary exercise testing with sampling of neurohormones and biomarkers. RESULTS: Two-thirds of HF patients met criteria for chronotropic incompetence. Resting HR and HR reserve (HRR, a measure of chronotropic response) were not correlated with each other and were associated with distinct biomarker profiles. Resting HR correlated with increased myocardial stress (B-type natriuretic peptide [BNP]: r = 0.26; pro-A-type natriuretic peptide: r = 0.24; N-terminal-proBNP: r = 0.32) and inflammation (leukocyte count: r = 0.28; high-sensitivity C-reactive protein assay: r = 0.25). In contrast, HRR correlated with the neurohumoral response to HF (copeptin: r = -0.33; norepinephrine: r = -0.29) but not with myocyte stress or injury reflected by natriuretic peptides or hs-troponin I. Patients in the lowest chronotropic incompetence quartile (HRR ≤0.38) displayed more advanced HF, reduced exercise capacity, ventilatory inefficiency, and poorer quality of life. Over a median follow-up of 17 months, the combined endpoint of death or urgent transplant/assist device implantation occurred more frequently in patients with higher resting HR (>67 beats/min) or lower HRR, with both markers providing additive prognostic information. CONCLUSIONS: Increased resting HR and chronotropic incompetence may reflect different pathophysiological processes, provide incremental prognostic information, and represent distinct therapeutic targets.

• Klíčová slova
• biomarkers, chronotropic incompetence, exercise, heart failure, heart rate,
• MeSH
• chronická nemoc MeSH
• lidé středního věku MeSH
• lidé MeSH
• odpočinek MeSH
• pilotní projekty MeSH
• prognóza MeSH
• prospektivní studie MeSH
• srdeční frekvence fyziologie   MeSH
• srdeční selhání patofyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

AIMS: Danon disease (DD) is a rare X-linked disorder caused by mutations in the lysosomal-associated membrane protein type 2 gene (LAMP2). DD is difficult to distinguish from other causes of dilated or hypertrophic cardiomyopathy (HCM) in female patients. As DD female patients regularly progress into advanced heart failure (AHF) aged 20-40 years, their early identification is critical to improve patient survival and facilitate genetic counselling. In this study, we evaluated the prevalence of DD among female patients with non-ischemic cardiomyopathy, who reached AHF and were younger than 40 years. METHODS AND RESULTS: The study cohort comprised 60 female patients: 47 (78%) heart transplant recipients, 2 (3%) patients treated with ventricular assist device, and 11 (18%) patients undergoing pre-transplant assessment. Aetiology of the cardiomyopathy was known in 15 patients (including two DD patients). LAMP2 expression in peripheral white blood cells (WBC) was tested by flow cytometry (FC) in the remaining 45 female patients. Whole exome sequencing was used as an alternative independent testing method to FC. Five additional female DD patients (two with different novel LAMP2 mutations) were identified by FC. The total prevalence of DD in this cohort was 12%. HCM phenotype (57% vs. 9%, * P = 0.022) and delta waves identified by electrocardiography (43% vs. 0%, ** P = 0.002) were significantly more frequent in DD female patients. CONCLUSIONS: Danon disease is an underdiagnosed cause of AHF in young female patients. LAMP2 expression testing in peripheral WBCs by FC can be used as an effective screening/diagnostic tool to identify DD in this patient population.

• Klíčová slova
• Advanced heart failure, Danon disease, Lysosomal-associated membrane protein type 2, Screening, White blood cells,
• MeSH
• fenotyp MeSH
• glykogenóza typu IIb * komplikace   diagnóza   epidemiologie   MeSH
• hypertrofická kardiomyopatie * komplikace   diagnóza   epidemiologie   MeSH
• lidé MeSH
• membránový protein 2 asociovaný s lyzozomy genetika   MeSH
• srdeční selhání * diagnóza   epidemiologie   etiologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• LAMP2 protein, human MeSH Prohlížeč
• membránový protein 2 asociovaný s lyzozomy MeSH

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.

• Klíčová slova
• Acute heart failure, Advanced heart failure, Dobutamine, Inodilators, Inotropes, Levosimendan, Milrinone, Norepinephrine,
• MeSH
• agonisté adrenergních beta-receptorů terapeutické užití   MeSH
• kardiotonika terapeutické užití   MeSH
• konsensus MeSH
• lékařská praxe - způsoby provádění MeSH
• lidé MeSH
• srdeční selhání farmakoterapie   MeSH
• výběr pacientů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté adrenergních beta-receptorů MeSH
• kardiotonika MeSH

BACKGROUND: Heart failure (HF) is a frequent cause of morbidity and mortality of end-stage kidney disease (ESKD) patients on hemodialysis. It is not easy to distinguish HF from water overload. The traditional HF definition has low sensitivity and specificity in this population. Moreover, many patients on hemodialysis have exercise limitations unrelated to HF. Therefore, we postulated two new HF definitions ((1) Modified definition of the Acute Dialysis Quality Improvement working group; (2) Hemodynamic definition based on the calculation of the effective cardiac output). We hypothesize that the newer definitions will better identify patients with higher number of endpoints and with more advanced structural heart disease. METHODS: Cohort, observational, longitudinal study with recording predefined endpoints. Patients (n = 300) treated by hemodialysis in six collaborating centers will be examined centrally in a tertiary cardiovascular center every 6-12 months lifelong or till kidney transplantation by detailed expert echocardiography with the calculation of cardiac output, arteriovenous dialysis fistula flow volume calculation, bio-impedance, and basic laboratory analysis including NTproBNP. Effective cardiac output will be measured as the difference between measured total cardiac output and arteriovenous fistula flow volume and systemic vascular resistance will be also assessed non-invasively. In case of water overload during examination, dry weight adjustment will be recommended, and the patient invited for another examination within 6 weeks. A composite major endpoint will consist of (1) Cardiovascular death; (2) HF worsening/new diagnosis of; (3) Non-fatal myocardial infarction or stroke. The two newer HF definitions will be compared with the traditional one in terms of time to major endpoint analysis. DISCUSSION: This trial will differ from others by: (1) detailed repeated hemodynamic assessment including arteriovenous access flow and (2) by careful assessment of adequate hydration to avoid confusion between HF and water overload.

• Klíčová slova
• Hemodialysis, arteriovenous access, effective cardiac output, heart failure,
• MeSH
• chronická renální insuficience * komplikace   MeSH
• chronické selhání ledvin * diagnóza   terapie   komplikace   MeSH
• dialýza ledvin škodlivé účinky   MeSH
• lidé MeSH
• longitudinální studie MeSH
• pozorovací studie jako téma MeSH
• srdeční selhání * diagnóza   etiologie   terapie   MeSH
• voda MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• voda MeSH

BACKGROUND: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. METHODS AND RESULTS: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. CONCLUSIONS: The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.

• Klíčová slova
• Chronic advanced heart failure, Levosimendan, Repetitive inodilator therapy,
• MeSH
• chronická nemoc MeSH
• hydrazony aplikace a dávkování   MeSH
• lidé MeSH
• pyridaziny aplikace a dávkování   MeSH
• simendan MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• srdeční selhání farmakoterapie   MeSH
• stupeň závažnosti nemoci MeSH
• vazodilatancia aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• Názvy látek
• hydrazony MeSH
• pyridaziny MeSH
• simendan MeSH
• vazodilatancia MeSH

BACKGROUND: The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. METHODS AND RESULTS: In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome (P=0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L-1, 68-101 mg·dL-1) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L-1, 108-142 mg·dL-1; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P=0.002). CONCLUSIONS: Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia.

• Klíčová slova
• cachexia, glucagon/glucagon‐like peptide, glucose, heart failure, insulin, metabolism, obesity paradox, right ventricular dysfunction, starvation,
• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dysfunkce pravé srdeční komory krev   diagnóza   patofyziologie   MeSH
• funkce pravé komory srdeční MeSH
• glukagon krev   MeSH
• glukózový toleranční test MeSH
• homeostáza MeSH
• inzulin krev   MeSH
• kachexie krev   diagnóza   patofyziologie   MeSH
• Kaplanův-Meierův odhad MeSH
• krevní glukóza metabolismus   MeSH
• Langerhansovy ostrůvky metabolismus   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční selhání krev   diagnóza   patofyziologie   MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• glukagon MeSH
• inzulin MeSH
• krevní glukóza MeSH

BACKGROUND: Growth differentiation factor (GDF)-15 is a pleiotropic cytokine that is associated with appetite-suppressing effects and weight loss in patients with malignancy. OBJECTIVES: This study aims to investigate the relationships between GDF-15 levels, anorexia, cachexia, and clinical outcomes in patients with advanced heart failure with reduced ejection fraction (HFrEF). METHODS: In this observational, retrospective analysis, a total of 344 patients with advanced HFrEF (age 58 ± 10 years, 85% male, 67% NYHA functional class III), underwent clinical and echocardiographic examination, body composition evaluation by skinfolds and dual-energy x-ray absorptiometry, circulating metabolite assessment, Minnesota Living with Heart Failure Questionnaire, and right heart catheterization. RESULTS: The median GDF-15 level was 1,503 ng/L (Q1-Q3: 955-2,332 ng/L) (reference range: <1,200 ng/L). Higher GDF-15 levels were associated with more prevalent anorexia and cachexia. Patients with higher GDF-15 had increased circulating free fatty acids and beta-hydroxybutyrate, lower albumin, cholesterol, and insulin/glucagon ratio, consistent with a catabolic state. Patients with higher GDF-15 had worse congestion and more severe right ventricular dysfunction. In multivariable Cox analysis, elevated GDF-15 was independently associated with risk of the combined endpoint of death, urgent transplantation, or left ventricular assist device implantation, even after adjusting for coexisting anorexia and cachexia (T3 vs T1 HR: 2.31 [95% CI: 1.47-3.66]; P < 0.001). CONCLUSIONS: In patients with advanced HFrEF, elevated circulating GDF-15 levels are associated with a higher prevalence of anorexia and cachexia, right ventricular dysfunction, and congestion, as well as an independently increased risk of adverse events. Further studies are warranted to determine whether therapies altering GDF-15 signaling pathways can affect metabolic status and clinical outcomes in advanced HFrEF.

• Klíčová slova
• anorexia, cachexia, growth differentiation factor-15, heart failure, right ventricular dysfunction,
• MeSH
• biologické markery krev   MeSH
• hmotnostní úbytek * fyziologie   MeSH
• kachexie * krev   etiologie   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nechutenství * etiologie   krev   epidemiologie   MeSH
• retrospektivní studie MeSH
• růstový diferenciační faktor 15 * krev   MeSH
• senioři MeSH
• srdeční selhání * krev   komplikace   patofyziologie   MeSH
• tepový objem fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• biologické markery MeSH
• GDF15 protein, human MeSH Prohlížeč
• růstový diferenciační faktor 15 * MeSH