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1.
Clin Res Cardiol ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002631

RESUMO

BACKGROUND: Loop diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin-angiotensin system. METHODS: Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score. RESULTS: Baseline median loop diuretic dose was 40 [40-100] mg of furosemide or equivalent. Higher doses of loop diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA use, and lower doses of ACEi reached at 3 and 9 months (all P < 0.01). After propensity adjustment, higher doses of loop diuretics remained significantly associated with poorer uptitration of ACEi (Beta per log doubling of loop diuretic dose: - 1.66, P = 0.021), but not with uptitration of MRAs (P = 0.758). Higher doses of loop diuretics were independently associated with an increased risk of all-cause mortality or HF hospitalization [HR per doubling of loop diuretic dose: 1.06 (1.01-1.12), P = 0.021]. CONCLUSIONS: Higher doses of loop diuretics limited uptitration of ACEi in patients with HFrEF and were associated with a higher risk of death and/or HF hospitalization, independent of their lower likelihood of uptitration and higher baseline risk. This figure was created with images adapted from Servier Medical Art licensed under a Creative Commons Attribution 3.0.

2.
JACC Heart Fail ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32035890

RESUMO

OBJECTIVES: The aims of this study were to compare the characteristics of patients with and without diabetes and to use network analyses to compare biomarker profiles and associated pathways in patients with diabetes compared with those without diabetes, which might offer new avenues for potential therapeutic targets. BACKGROUND: Diabetes adversely affects clinical outcomes and complicates treatment in patients with heart failure (HF). A clear understanding of the pathophysiological processes associated with type 2 diabetes in HF is lacking. METHODS: Network and pathway over-representation analyses were performed to identify unique pathological pathways in patients with and without diabetes using 92 biomarkers from different pathophysiological domains measured in plasma samples from 1,572 patients with HF (31% with diabetes) with reduced ejection fraction (left ventricular ejection fraction <40%). The results were validated in an independent cohort of 729 patients (30% with diabetes). RESULTS: Biomarker profiles were first compared between patients with HF with and without diabetes. Patients with diabetes showed higher levels of galectin-4, growth differentiation factor 15, and fatty acid binding protein 4 and lower levels of paraoxonase 3. Network analyses were then performed, revealing that epidermal growth factor receptor and galectin-3 were the most prominent connecting proteins. Translation of these networks to biologic pathways revealed that diabetes was associated with inflammatory response and neutrophil degranulation. Diabetes conferred worse outcomes after correction for an established risk model (hazard ratio: 1.20; 95% confidence interval: 1.01 to 1.42). CONCLUSIONS: Concomitant diabetes in patients with HF with reduced ejection fraction is associated with distinct pathophysiological pathways related to inflammation, protein phosphorylation, and neutrophil degranulation. These data support the evaluation of anti-inflammatory therapeutic approaches, epidermal growth factor receptor in particular, for patients with HF and diabetes.

4.
Eur J Heart Fail ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32086996

RESUMO

AIMS: Urinary sodium assessment has recently been proposed as a target for loop diuretic therapy in acute heart failure (AHF). We aimed to investigate the time course, clinical correlates and prognostic importance of urinary sodium excretion in AHF. METHODS AND RESULTS: In a prospective cohort of 175 consecutive patients with an admission for AHF we evaluated urinary sodium excretion 6 h after initiation of loop diuretic therapy. Clinical outcome was all-cause mortality or heart failure rehospitalization. Mean age was 71 ± 14 years, and 44% were female. Median urinary sodium excretion was 130 (67-229) mmol at 6 h, 347 (211-526) mmol at 24 h, and decreased from day 2 to day 4. Lower urinary sodium excretion was independently associated with male gender, younger age, renal dysfunction and pre-admission loop diuretic use. There was a strong association between urinary sodium excretion at 6 h and 24 h urine volume (beta = 0.702, P < 0.001). Urinary sodium excretion after 6 h was a strong predictor of all-cause mortality after a median follow-up of 257 days (hazard ratio 3.81, 95% confidence interval 1.92-7.57; P < 0.001 for the lowest vs. the highest tertile of urinary sodium excretion) independent of established risk factors and urinary volume. Urinary sodium excretion was not associated with heart failure rehospitalization. CONCLUSION: In a modern, unselected, contemporary AHF population, low urinary sodium excretion during the first 6 h after initiation of loop diuretic therapy is associated with lower urine output in the first day and independently associated with all-cause mortality.

5.
Eur J Cardiovasc Nurs ; : 1474515120902317, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31992064

RESUMO

BACKGROUND: Patients' self-care behaviour is still suboptimal in many heart failure (HF) patients and underlying mechanisms on how to improve self-care need to be studied. AIMS: (1) To describe the trajectory of patients' self-care behaviour over 1 year, (2) to clarify the relationship between the trajectory of self-care and clinical outcomes, and (3) to identify factors related to changes in self-care behaviour. METHODS: In this secondary analysis of the COACH-2 study, 167 HF patients (mean age 73 years) were included. Self-care behaviour was assessed at baseline and after 12 months using the European Heart Failure Self-care Behaviour scale. The threshold score of ⩾70 was used to define good self-care behaviour. RESULTS: Of all patients, 21% had persistent poor self-care behaviour, and 27% decreased from good to poor. Self-care improved from poor to good in 10%; 41% had a good self-care during both measurements. Patients who improved self-care had significantly higher perceived control than those with persistently good self-care at baseline. Patients who decreased their self-care had more all-cause hospitalisations (35%) and cardiovascular hospitalisations (26%) than patients with persistently good self-care (2.9%, p < 0.05). The prevalence of depression increased at 12 months in both patients having persistent poor self-care (0% to 21%) and decreasing self-care (4.4% to 22%, both p < 0.05). CONCLUSION: Perceived control is a positive factor to improve self-care, and a decrease in self-care is related to worse outcomes. Interventions to reduce psychological distress combined with self-care support could have a beneficial impact on patients decreasing or persistently poor self-care behaviour.

6.
Clin Res Cardiol ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996990

RESUMO

BACKGROUND: Geographical differences may impact the treatment of heart failure (HF) and the results of clinical trials. We have investigated the differences between geographical areas across Europe in the BIOSTAT-CHF program. METHODS: Patients with worsening HF enrolled in BIOSTAT-CHF were subdivided, according to the European geographical areas, into those from Northern countries (The Netherlands, Norway, Sweden, UK), Central countries (Germany, Poland, Serbia, Slovenia), and Mediterranean countries (France, Greece, Italy). Patients were compared for baseline characteristics, treatment, and outcomes. The primary endpoint was a composite of all-cause mortality or HF hospitalization. RESULTS: Among 2516 patients enrolled in BIOSTAT-CHF, 814 (32.3%) were from Northern European centers, 816 (32.4%) from Central European centers, and 886 (35.2%) from Mediterranean centers. Patients from Northern European centers were older, had more severe signs and symptoms of HF, and with lower incidence of non-cardiac comorbidities such as chronic kidney dysfunction, diabetes and, hypertension, compared to those from the Central and Mediterranean centers. Patients receiving ≥ 50% of the target dose of both ACE-I/ARB after the up-titration phase were higher in the Northern European centers compared with the other regions (60% versus 58.7% in the Central European centers and 46.5% in the Mediterranean ones; p < 0.001). The primary endpoint occurred at a higher rate in the Northern centers (44.3% versus 37.4% in central centers and 39.6% in Mediterranean centers; p = 0.014), this difference became non-significant after the adjustment for important confounders. Importantly, treatment up-titration reduced the event rates regardless of the geographical region (p for interaction > 0.05). CONCLUSION: The BIOSTAT-CHF study showed significant differences in the clinical features, treatment and prognosis in European patients with HF. Patients from the Mediterranean centers less often had the HF treatments up-titrated; however, the treatment up-titration benefited patients irrespective of their geographical region and should be part of the "default" clinical practice.

7.
Eur J Heart Fail ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919934

RESUMO

AIMS: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure. METHODS AND RESULTS: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0-2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84-2.45, P = 2.15 × 10-24 ) in the total cohort, 2.08 (1.72-2.50, P = 1.30 × 10-14 ) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37-2.99, P = 4.37 × 10-4 ) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. CONCLUSIONS: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence.

8.
Eur J Heart Fail ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919958

RESUMO

BACKGROUND: To assess the prognostic value of mineralocorticoid receptor antagonist (MRA) initiation and change in serum potassium (K+ ) during follow-up in patients post-acute myocardial infarction with left ventricular dysfunction or chronic heart failure (HF) and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Risk scores for predicting cardiovascular death (primary outcome), hospitalization for HF and all-cause death were developed. K+ and other relevant time-updated clinical and biological variables were added to conventional prognostic factors when constructing these new models. EPHESUS (n = 6632) was the derivation cohort, while EMPHASIS-HF (chronic HF, n = 2737) was used as external validation cohort. The final cardiovascular death risk score included medical history, clinical and biological parameters (e.g. K+ , below or above the normal range of 4-5 mmol/L, estimated glomerular filtration rate, and anaemia), as well as aspects of treatment (any diuretic usage, MRA use or discontinuation, and beta-blocker use). The risk score performed well in both the derivation and validation cohorts and outperformed the MAGGIC score. A web-based calculator was created to allow easy determination of the risk score (http://cic-p-nancy.fr/CardiovascularriskscoreCalculator/). CONCLUSION: Adding time-updated variables, including K+ and MRA treatment, improved risk prediction of cardiovascular death (on top of the MAGGIC score) in patients with HF eligible for renin-angiotensin system inhibitors and MRA therapy. This new risk score including MRA usage and K+ may be of value in helping physicians to better use MRAs, avoid unnecessary and potentially detrimental permanent discontinuations, and therefore improving cardiovascular outcomes in patients with chronic HFrEF or HF after acute myocardial infarction with left ventricular dysfunction.

9.
Eur J Heart Fail ; 22(1): 81-89, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793144

RESUMO

AIMS: Heart failure (HF) patients are at high-risk of cardiovascular (CV) events, including CV death. Nonetheless, a substantial proportion of these patients die from non-CV causes. Identifying patients at higher risk for each individual event may help selecting patients for clinical trials and tailoring cardiovascular therapies. The aims of the present study are to: (i) characterize patients according to CV vs. non-CV death; (ii) develop models for the prediction of the respective events; (iii) assess the models' performance to differentiate CV from non-CV death. METHODS AND RESULTS: This study included 2309 patients with HF from the BIOSTAT-CHF (a systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) study. Competing-risk models were used to assess the best combination of variables associated with each cause-specific death. Results were validated in an independent cohort of 1738 HF patients. The best model to predict CV death included low blood pressure, estimated glomerular filtration rate ≤ 60 mL/min, peripheral oedema, previous HF hospitalization, ischaemic HF, chronic obstructive pulmonary disease, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin (c-index = 0.73). The non-CV death model incorporated age > 75 years, anaemia and elevated NT-proBNP (c-index = 0.71). Both CV and non-CV death rose by quintiles of the risk scores; yet these models allowed the identification of patients in whom absolute CV death rates clearly outweigh non-CV death ones. These findings were externally replicated, but performed worse in a less severely diseased population. CONCLUSIONS: Risk models for predicting CV and non-CV death allowed the identification of patients at higher absolute risk of dying from CV causes (vs. non-CV ones). Troponin helped in predicting CV death only, whereas NT-proBNP helped in the prediction of both CV and non-CV death. These findings can be useful both for tailoring therapies and for patient selection in HF trials in order to attain CV event enrichment.

10.
Eur J Heart Fail ; 22(1): 70-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31692186

RESUMO

AIMS: To provide insights into pathogenesis of disease progression and potential novel treatment targets for patients with heart failure by investigation of the plasma proteome using network analysis. METHODS AND RESULTS: The plasma proteome of 50 patients with heart failure who died or were rehospitalised were compared with 50 patients with heart failure, matched for age and sex, who did not have an event. Peptides were analysed on two-dimensional liquid chromatography coupled to tandem mass spectrometry (2D LC ESI-MS/MS) in high definition mode (HDMSE). We identified and quantified 3001 proteins, of which 51 were significantly up-regulated and 46 down-regulated with more than two-fold expression changes in those who experienced death or rehospitalisation. Gene ontology enrichment analysis and protein-protein interaction networks of significant differentially expressed proteins discovered the central role of metabolic processes in clinical outcomes of patients with heart failure. The findings revealed that a cluster of proteins related to glutathione metabolism, arginine and proline metabolism, and pyruvate metabolism in the pathogenesis of poor outcome in patients with heart failure who died or were rehospitalised. CONCLUSIONS: Our findings show that in patients with heart failure who died or were rehospitalised, the glutathione, arginine and proline, and pyruvate pathways were activated. These pathways might be potential targets for therapies to improve poor outcomes in patients with heart failure.

11.
Int J Cardiol ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31785953

RESUMO

OBJECTIVE: Little is known about the course of echocardiographic parameters used for the evaluation of valvular heart disease (VHD) during pregnancy, hampering interpretation of possible changes (physiological vs. pathophysiological). Therefore we studied the course of these parameters and ventricular function in pregnant women with aortic and pulmonary VHD. METHODS: The cohort comprised 66 pregnant women enrolled in the prospective ZAHARA studies or evaluated by an identical protocol who had pulmonary VHD or aortic VHD (stenosis/prosthetic valve). The control group comprised 46 healthy pregnant women. Echocardiography was performed preconception, during pregnancy and 1 year postpartum. Peak gradient, mean gradient, aortic valve area (AVA)/effective orifice area (EOA), left ventricular ejection fraction (LVEF) and right ventricular function (RVF; TAPSE) were assessed. RESULTS: Peak and mean gradients increased during pregnancy compared to preconception in women with aortic VHD and controls (p < 0.0125), but not in women with pulmonary VHD. AVA/EOA remained unchanged. Preconception and postpartum gradients were comparable in all groups. Mean LVEF was normal in pregnant women with VHD and controls. Mean TAPSE was lower (p < 0.001) in women with pulmonary VHD compared to women with aortic VHD and controls (<20 mm vs. ≥23 mm; p < 0.001). In women with pulmonary VHD a decrease of TAPSE was observed during pregnancy (p = 0.005). CONCLUSION: Physiological changes during pregnancy lead to increased Doppler gradients in women with aortic VHD. This increase was not found in women with pulmonary VHD, probably caused by impaired RVF. Therefore, evaluation of RVF during pregnancy might be important to prevent underestimation of the degree of stenosis.

12.
Eur J Heart Fail ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797504

RESUMO

AIMS: Cathepsin D is a ubiquitous lysosomal protease that is primarily secreted due to oxidative stress. The role of circulating cathepsin D in heart failure (HF) is unknown. The aim of this study is to determine the association between circulating cathepsin D levels and clinical outcomes in patients with HF and to investigate the biological settings that induce the release of cathepsin D in HF. METHODS AND RESULTS: Cathepsin D levels were studied in 2174 patients with HF from the BIOSTAT-CHF index study. Results were validated in 1700 HF patients from the BIOSTAT-CHF validation cohort. The primary combined outcome was all-cause mortality and/or HF hospitalizations. Human pluripotent stem cell-derived cardiomyocytes were subjected to hypoxic, pro-inflammatory signalling and stretch conditions. Additionally, cathepsin D expression was inhibited by targeted short hairpin RNAs (shRNA). Higher levels of cathepsin D were independently associated with diabetes mellitus, renal failure and higher levels of interleukin-6 and N-terminal pro-B-type natriuretic peptide (P < 0.001 for all). Cathepsin D levels were independently associated with the primary combined outcome [hazard ratio (HR) per standard deviation (SD): 1.12; 95% confidence interval (CI) 1.02-1.23], which was validated in an independent cohort (HR per SD: 1.23, 95% CI 1.09-1.40). In vitro experiments demonstrated that human stem cell-derived cardiomyocytes released cathepsin D and troponin T in response to mechanical stretch. ShRNA-mediated silencing of cathepsin D resulted in increased necrosis, abrogated autophagy, increased stress-induced metabolism, and increased release of troponin T from human stem cell-derived cardiomyocytes under stress. CONCLUSIONS: Circulating cathepsin D levels are associated with HF severity and poorer outcome, and reduced levels of cathepsin D may have detrimental effects with therapeutic potential in HF.

13.
Eur J Heart Fail ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797505

RESUMO

AIMS: Recently, bio-adrenomedullin (bio-ADM) was proposed as a congestion marker in heart failure (HF). In the present study, we aimed to study whether bio-ADM levels at discharge from a hospital admission for worsening HF could provide additional information on (residual) congestion status, diuretic dose titration and clinical outcomes. METHODS AND RESULTS: Plasma bio-ADM was measured in 1236 acute HF patients in the PROTECT trial at day 7 or discharge. Median discharge bio-ADM was 33.7 [21.5-61.5] pg/mL. Patients with higher discharge bio-ADM levels were hospitalised longer, had higher brain natriuretic peptide levels, and poorer diuretic response (all P < 0.001). Bio-ADM was the strongest predictor of discharge residual congestion (clinical congestion score > 3) (odds ratio 4.35, 95% confidence interval 3.37-5.62; P < 0.001). Oedema at discharge was one of the strongest predictors of discharge bio-ADM (ß = 0.218; P < 0.001). Higher discharge loop diuretic doses were associated with a poorer diuretic response during hospitalisation (ß = 0.187; P < 0.001) and higher bio-ADM levels (ß = 0.084; P = 0.020). High discharge bio-ADM levels combined with higher use of loop diuretics were independently associated with a greater risk of 60-day HF rehospitalisation (hazard ratio 4.02, 95% confidence interval 2.23-7.26; P < 0.001). CONCLUSION: In hospitalised HF patients, elevated pre-discharge bio-ADM levels were associated with higher discharge loop diuretic doses and reflected residual congestion. Patients with combined higher bio-ADM levels and higher loop diuretic use at discharge had an increased risk of rehospitalisation. Assessment of discharge bio-ADM levels may be a readily applicable marker to identify patients with residual congestion at higher risk of early hospital readmission.

14.
J Am Coll Cardiol ; 74(23): 2893-2904, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31806133

RESUMO

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.

15.
Eur J Heart Fail ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808274

RESUMO

AIMS: Severe deficiency of the essential trace element selenium can cause myocardial dysfunction although the mechanism at cellular level is uncertain. Whether, in clinical practice, moderate selenium deficiency is associated with worse symptoms and outcome in patients with heart failure is unknown. METHODS AND RESULTS: BIOSTAT-CHF is a multinational, prospective, observational cohort study that enrolled patients with worsening heart failure. Serum concentrations of selenium were measured by inductively coupled plasma mass spectrometry. Primary endpoint was a composite of all-cause mortality and hospitalization for heart failure; secondary endpoint was all-cause mortality. To investigate potential mechanisms by which selenium deficiency might affect prognosis, human cardiomyocytes were cultured in absence of selenium, and mitochondrial function and oxidative stress were assessed. Serum selenium concentration (deficiency) was <70 µg/L in 485 (20.4%) patients, who were older, more often women, had worse New York Heart Association class, more severe signs and symptoms of heart failure and poorer exercise capacity (6-min walking test) and quality of life (Kansas City Cardiomyopathy Questionnaire). Selenium deficiency was associated with higher rates of the primary endpoint [hazard ratio (HR) 1.23; 95% confidence interval (CI) 1.06-1.42] and all-cause mortality (HR 1.52; 95% CI 1.26-1.86). In cultured human cardiomyocytes, selenium deprivation impaired mitochondrial function and oxidative phosphorylation, and increased intracellular reactive oxygen species levels. CONCLUSIONS: Selenium deficiency in heart failure patients is independently associated with impaired exercise tolerance and a 50% higher mortality rate, and impaired mitochondrial function in vitro, in human cardiomyocytes. Clinical trials are needed to investigate the effect of selenium supplements in patients with heart failure, especially if they have low plasma concentrations of selenium.

16.
Eur J Heart Fail ; 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31863682

RESUMO

AIMS: Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serum NGAL (sNGAL) or urine NGAL (uNGAL) is superior to creatinine for predicting short-term outcomes in AHF. METHODS AND RESULTS: The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF-related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr (area under the curve [AUC]; admission sNGAL 0.61 [95% confidence interval (CI) 0.55-0.67] and 0.59 [95% CI 0.54-0.65], peak sNGAL 0.60 [95% CI 0.54-0.66] and 0.57 [95% CI 0.52-0.63], admission sCr 0.60 [95% CI 0.54-0.64] and 0.59 [95% CI 0.53-0.64] [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55-0.67, and 0.59, 95% CI 0.54-0.65; peak sNGAL: 0.60, 95% CI 0.54-0.66, and 0.57, 95% CI 0.52-0.63; admission sCr: 0.60, 95% CI 0.54-0.64, and 0.59, 95% CI 0.53-0.64, at 30 and 60 days, respectively], peak sCr 0.61 [95% CI 0.55-0.67] and 0.59 [95% CI 0.54-0.64] at 30 and 60 days, respectively). NGAL was not predictive of the composite endpoint in multivariate analysis. CONCLUSIONS: Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events.

18.
Eur J Heart Fail ; 21(12): 1553-1560, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769140

RESUMO

AIMS: In acute heart failure (AHF), relationships between changes in B-type natriuretic peptide (BNP) and worsening renal function (WRF) and its prognostic implications have not been fully determined. We investigated the relationship between WRF and a decrease in BNP with in-hospital and 1-year mortality in AHF. METHODS AND RESULTS: The Acute Kidney Injury NGAL Evaluation of Symptomatic heart faIlure Study (AKINESIS) was a prospective, international, multicentre study of AHF patients. Severe WRF (sWRF) was a sustained increase of ≥44.2 µmol/L (0.5 mg/dL) or ≥50% in creatinine, non-severe WRF (nsWRF) was a non-sustained increase of ≥26.5 µmol/L (0.3 mg/dL) or ≥50% in creatinine, and WRF with clinical deterioration was nsWRF with renal replacement therapy, inotrope use, or mechanical ventilation. Decreased BNP was defined as a ≥30% reduction in the last measured BNP compared to admission BNP. Among 814 patients, the incidence of WRF was not different between patients with or without decreased BNP (nsWRF: 33% vs. 31%, P = 0.549; sWRF: 11% vs. 9%, P = 0.551; WRF with clinical deterioration: 8% vs. 10%, P = 0.425). Decreased BNP was associated with better in-hospital and 1-year mortality regardless of WRF, while WRF was associated with worse outcomes only in patients without decreased BNP. In multivariate Cox regression analysis, decreased BNP, sWRF, and WRF with clinical deterioration were significantly associated with 1-year mortality. CONCLUSIONS: Decreased BNP was associated with better in-hospital and long-term outcomes. WRF was only associated with adverse outcomes in patients without decreased BNP.

19.
Eur J Intern Med ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31708361

RESUMO

BACKGROUND: Knowledge on the association between heart failure (HF) etiologies, precipitant causes and clinical outcomes may help in ascertaining patient's risk and in selecting tailored therapeutic strategies. METHODS: The prognostic value of both HF etiologies and precipitants for worsening HF were analyzed using the index cohort of BIOSTAT-CHF. The studied HF etiologies were: a) ischemic HF; b) dilated cardiomyopathy; c) hypertensive HF; d) valvular HF; and e) other/unknown. The precipitating factors for worsening HF were: a) atrial fibrillation; b) non-adherence; c) renal failure; d) acute coronary syndrome; e) hypertension; and f) Infection. The primary outcome was the composite of all-cause death or HF hospitalization. RESULTS: Among 2465 patients included in the study, 45% (N = =1102) had ischemic HF, 23% (N = =563) dilated cardiomyopathy, 15% (N = =379) other/unknown, 10% (N = =237) hypertensive and 7% (N = =184) valvular HF. Patients with ischemic HF had the worst prognosis, whereas patients with dilated cardiomyopathy had the best prognosis. From the precipitating factors for worsening HF, renal failure was the one independently associated with worse prognosis (adjusted HR (95%CI) = =1.48 (1.04-2.09), p < 0.001). We found no interaction between HF etiologies and precipitating factors for worsening HF with regard to the study outcomes (p interaction > 0.10 for all). Treatment up-titration benefited patients regardless of their underlying etiology or precipitating cause (p interaction > 0.10 for all). CONCLUSIONS: In BIOSTAT-CHF, patients with HF of an ischemic etiology, and those with worsening HF precipitated by renal failure (irrespective of the underlying HF etiology), had the highest rates of death and HF hospitalization, but still benefited equally from treatment up-titration.

20.
Circulation ; 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31736337

RESUMO

Background: Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction (HFpEF), the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women, compared with men. Methods: In a pre-specified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial which compared sacubitril-valsartan and valsartan in patients with HFpEF. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Results: Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older, had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI 0.59-0.90) in women and 1.03 (0.84-1.25) in men; P interaction=0.017. The benefit from sacubitril-valsartan was due to reduction in heart failure hospitalization. The improvement in NYHA class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in KCCQ-CSS was less in women than in men. The difference in adverse events, between sacubitril-valsartan and valsartan, was similar in women and men. Conclusions: As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. While the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01920711.

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