RESUMO
AIMS: Iron deficiency (ID) is frequent in heart failure (HF), linked with exercise intolerance and poor prognosis. Intravenous iron repletion improves clinical status in HF patients with left ventricular ejection fraction (LVEF) ≤45%. However, uncertainty exists about the accuracy of serum biomarkers in diagnosing ID. The aims of this study were (i) to identify the iron biomarker with the greatest accuracy for the diagnosis of ID in bone marrow in patients with ischaemic HF, and (ii) to establish the prevalence of ID using this biomarker and its prognostic value in HF patients. METHODS AND RESULTS: Bone marrow was stained for iron in 30 patients with ischaemic HF with LVEF ≤45% and 10 healthy controls, and ID was diagnosed for 0-1 grades (Gale scale). A total of 791 patients with HF with LVEF ≤45% were prospectively followed up for 3 years. Serum ferritin, transferrin saturation, soluble transferrin receptor (sTfR) were assessed as iron biomarkers. Most patients with HF (n = 25, 83%) had ID in bone marrow, but none of the controls (P < 0.001). Serum sTfR had the best accuracy in predicting ID in bone marrow (area under the curve 0.920, 95% confidence interval 0.761-0.987, for cut-off 1.25 mg/L sensitivity 84%, specificity 100%). Serum sTfR was ≥1.25 mg/L in 47% of HF patients, in 56% and 46% of anaemics and non-anaemics, respectively (P < 0.05). The reclassification methods revealed that serum sTfR significantly added the prognostic value to the baseline prognostic model, and to the greater extent than plasma N-terminal pro B-type natriuretic peptide. Based on internal derivation and validation procedures, serum sTfR ≥1.41 mg/L was the optimal threshold for predicting 3-year mortality, independent of other established variables. CONCLUSIONS: High serum sTfR accurately reflects depleted iron stores in bone marrow in patients with HF, and identifies those with a high 3-year mortality.
Assuntos
Anemia Ferropriva , Insuficiência Cardíaca , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/epidemiologia , Biomarcadores , Insuficiência Cardíaca/epidemiologia , Humanos , Receptores da Transferrina , Volume Sistólico , Transferrina , Função Ventricular EsquerdaRESUMO
Iron deficiency (ID) is a common and ominous comorbidity in heart failure (HF) and predicts worse outcomes, independently of the presence of anaemia. Accumulated data from animal models of systemic ID suggest that ID is associated with several functional and structural abnormalities of the heart. However, the exact role of myocardial iron deficiency irrespective of systemic ID and/or anaemia has been elusive. Recently, several transgenic models of cardiac-specific ID have been developed to investigate the influence of ID on cardiac tissue. In this review, we discuss structural and functional cardiac consequences of ID in these models and summarize data from clinical studies. Moreover, the beneficial effects of intravenous iron supplementation are specified.
Assuntos
Anemia Ferropriva/complicações , Insuficiência Cardíaca/fisiopatologia , Coração/fisiopatologia , Deficiências de Ferro , Ferro/sangue , Administração Intravenosa , Animais , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Comorbidade , Feminino , Coração/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/mortalidade , Hepcidinas/metabolismo , Homeostase/fisiologia , Humanos , Ferro/administração & dosagem , Ferro/uso terapêutico , Distúrbios do Metabolismo do Ferro/complicações , Masculino , Camundongos , Camundongos Transgênicos/metabolismo , Modelos Animais , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Receptores da Transferrina/metabolismoRESUMO
(1) Background: Oxidative energy metabolism is presumed to rely on the optimal iron supply. Primary human cardiac myocytes (HCM) exposed to different iron availability conditions during mechanical stretch are anticipated to demonstrate expression changes of genes involved in aerobic and anaerobic metabolic pathways. (2) Methods: HCM were cultured for 48 h either in static conditions and upon mechanical stretch at the optimal versus reduced versus increased iron concentrations. We analyzed the expression of pyruvate kinase (PKM2), lactate dehydrogenase A (LDHA), and mitochondrial complexes Iâ»V at the mRNA and protein levels. The concentration of l-lactate was assessed by means of lactate oxidase method-based kit. (3) Results: Reduced iron concentrations during mechanical work caused a decreased expression of complexes Iâ»V (all p < 0.05). The expression of PKM2 and LDHA, as well as the medium concentration of l-lactate, was increased in these conditions (both p < 0.05). HCM exposed to the increased iron concentration during mechanical effort demonstrated a decreased expression of mitochondrial complexes (all p < 0.01); however, a decrement was smaller than in case of iron chelation (p < 0.05). The iron-enriched medium caused a decrease in expression of LDHA and did not influence the concentration of l-lactate. (4) Conclusions: During mechanical effort, the reduced iron availability enhances anaerobic glycolysis and extracellular lactate production, whilst decreasing mitochondrial aerobic pathway in HCM. Iron enrichment during mechanical effort may be protective in the context of intracellular protein machinery of non-oxidative metabolism with no effect on the extracellular lactate concentration.
RESUMO
Specific skeletal myopathy constitutes a common feature of heart failure, chronic obstructive pulmonary disease, and type 2 diabetes mellitus, where it can be characterized by the loss of skeletal muscle oxidative capacity. There is evidence from in vitro and animal studies that iron deficiency affects skeletal muscle functioning mainly in the context of its energetics by limiting oxidative metabolism in favour of glycolysis and by alterations in both carbohydrate and fat catabolic processing. In this review, we depict the possible molecular pathomechanisms of skeletal muscle energetic impairment and postulate iron deficiency as an important factor causally linked to loss of muscle oxidative capacity that contributes to skeletal myopathy seen in patients with heart failure, chronic obstructive pulmonary disease, and type 2 diabetes mellitus.
Assuntos
Suscetibilidade a Doenças , Metabolismo Energético , Deficiências de Ferro , Músculo Esquelético/metabolismo , Estresse Fisiológico , Animais , Doença Crônica , Humanos , Doenças Musculares/etiologia , Doenças Musculares/metabolismo , Doenças Musculares/terapia , Oxirredução , Oxigênio/metabolismoRESUMO
OBJECTIVE: Introduction: Implantable cardioverter-defibrillators (ICD) improve prognosis in patients with malignant ventricular arrhythmias. Patients with ICD represent a significant proportion of all Emergency Department (ED) admissions. The number of these visits due to the high-energy therapy or antitachycardia pacing (ATP) delivered by the implanted cardioverter-defibrillator is constantly increasing. The aim: To present the prevalence and type of therapeutic interventions of an ICD in patients admitted to ED in 2014-2017 at two medical centers covering approx. 400 000 residents. PATIENTS AND METHODS: Materials and methods: The patients' documentation was analyzed to find patients admitted to emergency department because of the suspicion of the ventricular arrhythmias' therapy delivered by ICD. RESULTS: Results: In most cases adequate high-energy therapies due to life-threatening ventricular arrhythmias were the reason for hospitalization. We identified 126 patients aged 63.0±12.0 years, 108 (86&) of male and 18 (14&) of female. Among 171 ED admissions 6 were associated with ATP and 149 with high-energy therapy, 10 cases presented with VT without therapies, 5 with fantom shocks and in one case the patient had only a pacemaker but not ICD. The number of ICD shocks ranged from 1 to 108. Inadequate ICD discharges were found in 26 (17.4&) of high energy therapies. CONCLUSION: Conclusions:1. The number of patients with ICD admitted to Emergency Department due to the initiation of high-energy or anti-tachyarrhythmic therapy has been steadily increasing in recent years. 2. In most cases, the reason for the admissions are adequate high-energy therapies, i.e. ICD discharges that disrupt the potentially life threatening arrhythmia. 3. Accurate medical history, the possibility of assessing the heart rate stored in the ICD memory during its intervention form the basis for establishing a plan of action in patients with ICD.
Assuntos
Arritmias Cardíacas/terapia , Desfibriladores Implantáveis , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Idoso , Cardioversão Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Terapia de Ressincronização Cardíaca/métodos , Ferritinas/sangue , Insuficiência Cardíaca Sistólica , Distúrbios do Metabolismo do Ferro , Ferro , Comorbidade , Ecocardiografia/métodos , Metabolismo Energético/fisiologia , Feminino , Insuficiência Cardíaca Sistólica/diagnóstico , Insuficiência Cardíaca Sistólica/epidemiologia , Insuficiência Cardíaca Sistólica/metabolismo , Insuficiência Cardíaca Sistólica/terapia , Hemoglobinas , Humanos , Ferro/análise , Deficiências de Ferro , Distúrbios do Metabolismo do Ferro/sangue , Distúrbios do Metabolismo do Ferro/epidemiologia , Distúrbios do Metabolismo do Ferro/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Índice de Gravidade de Doença , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Nowadays, when the majority of patients with acute myocardial infarction (AMI) are treated with primary percutaneous coronary intervention and modern pharmacotherapy, risk stratification becomes a challenge. Simple and easily accessible parameters that would help in a better determination of prognosis are needed. The aim of the study was to estimate the prevalence of high mean corpuscular volume (MCV, defined as MCV > 92 fL) and to establish its prognostic value in non-anemic patients with AMI. METHODS: We retrospectively analyzed the data of 248 consecutive non-anemic patients hospitalized due to AMI (median age: 65 [59-76] years, men: 63%, ST segment elevation myocardial infarction: 31%, and median left ventricular ejection fraction [LVEF]: 50%). RESULTS: The prevalence of high MCV was 39 ± 6% (± 95% confidence interval) in the entire AMI population. High MCV was more prevalent in males, patients with low body mass index, non-diabetics and cigarette smokers (all p < 0.05). During the 180-day follow-up, there were 38 (15%) events, defined as another AMI or death. In a multivariable Cox proportional hazard model, female gender (p < 0.01), low LVEF (p < 0.001), previous AMI (p < 0.05), arterial hypertension (p < 0.05), and high MCV (p < 0.001) were prognosticators of pre-defined events. CONCLUSIONS: In non-anemic patients with AMI, high MCV is an independent prognostic factor of poor outcome defined as another AMI or death.
RESUMO
In heart failure, impairment of cardiac muscle function leads to numerous neurohormonal and metabolic disorders, including an imbalance between anabolic and catabolic processes, in favour of the latter. These disorders cause loss of muscle mass with structural and functional changes within the skeletal muscles, known as skeletal myopathy. This phenomenon constitutes an important mechanism that participates in the pathogenesis of chronic heart failure. both its clinical symptoms and the progression of the disease. Attempts to reverse the above-mentioned pathologic processes by exploiting the anabolic action of androgenic hormones could provide a potentially attractive treatment option. The current concepts of anabolic androgen deficiency and resultant skeletal myopathy in patients with heart failure are reviewed, and the potential role of anabolic-androgenic hormones as an emerging therapeutic option for targeting heart failure is discussed.