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1.
J Card Fail ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038532

RESUMO

BACKGROUND: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV-status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and post-discharge clinical outcomes, in the ASCEND-HF trial. METHODS AND RESULTS: KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. 6,373 (89.2%), and 6,354 (89.0%), patients had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with NT-proBNP, and with measures of decongestion such as body weight change and urine output (r<0.3 for all). Duarte-ePV was trending towards an association with worse 30-day (adjusted-OR 1.07, 95%CI 1.00-1.15, p=0.058), but not 180-day outcomes (adjusted-HR 1.03, 95%CI 0.97-1.09, p=0.289). Continuous KH-ePVS>0 (per 10 unit increase) was associated with improved 30-day outcomes (adjusted-OR 0.75, 95%CI 0.62-0.91, p=0.004). Continuous KH-ePVS was not associated with 180-day outcomes (adjusted-HR 1.05, 95%CI 0.98-1.12, p=0.139). CONCLUSIONS: Baseline PV estimates had a weak association with in-hospital measures of decongestion. Duarte-ePV, trended towards an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.

2.
Am Heart J ; 229: 40-51, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32916607

RESUMO

BACKGROUND: The timing of enrolment following an acute coronary syndrome (ACS) may influence cardiovascular (CV) outcomes and potentially treatment effect in clinical trials. Understanding the timing and type of clinical events after an ACS will allow for clinicians to better tailor evidence-based treatments to optimize therapeutic effect. Using a large contemporary trial in patients with type 2 diabetes mellitus (T2DM) post-ACS, we examined the impact of timing of enrolment on subsequent CV outcomes. METHODS: EXAMINE was a randomized trial of alogliptin versus placebo in 5,380 patients with T2DM and a recent ACS from October 2009 to March 2013. The primary outcome was a composite of CV death, nonfatal myocardial infarction (MI), or nonfatal stroke. The median follow-up was 18 months. In this post hoc analysis, we examined the occurrence of subsequent CV events by timing of enrollment divided by tertiles of time from ACS to randomization: 8-34, 35-56, and 57-141 days. RESULTS: Patients randomized early (compared to the latest times) had less comorbidities at baseline including a history of heart failure (HF; 24.7% vs 33.0%), prior coronary artery bypass graft (9.6% vs 15.9%), or atrial fibrillation (5.9% vs 9.4%). Despite the reduced comorbidity burden, the risk of the primary outcome was highest in patients randomized early compared to the latest time (adjusted hazard ratio 1.47; 95% CI 1.21-1.74). Similarly, patients randomized early had an increased risk of recurrent MI (adjusted hazard ratio 1.51; 95% CI 1.17-1.96) and HF hospitalization (1.49; 95% CI 1.05-2.10). CONCLUSIONS: In a contemporary cohort of T2DM with a recent ACS, the risk for recurrent CV events including MI and HF hospitalization is elevated early after an ACS. Given the emergence of antihyperglycemic therapies that reduce the risk of MI and HF among patients with T2DM at high CV risk, future studies evaluating the initiation of these therapies in the early period following an ACS are warranted given the large burden of potentially modifiable CV events.

4.
Diabetes Metab ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32919068

RESUMO

AIM: As mineralocorticoid receptor antagonists (MRAs) may possess renoprotective effects in type 2 diabetes (T2D), it was decided to investigate the impact of high-dose MRA on prespecified secondary endpoints-namely, change in urinary albumin-creatinine ratio (UACR) and 24-h ambulatory blood pressure-in the MIRAD trial. METHODS: This was a double-blind clinical trial in which T2D patients at high risk of or with established cardiovascular disease (CVD) were randomized to either high-dose (100-200 mg) eplerenone or a dose-matched placebo as an add-on to background antihypertensive treatment for 26 weeks. Safety was evaluated by the incidence of hyperkalaemia and kidney-related adverse events. RESULTS: A total of 140 patients were enrolled (70 in each group). Baseline UACR was 17 mg/g (geometric mean; 95% CI: 13-22); this decreased by 34% in the eplerenone group compared with the placebo group at week 26 (95% CI: -51% to -12%; P = 0.005). There was no significant decrease in 24-h systolic blood pressure (SBP) due to treatment (-3 mmHg; 95% CI: -6 to 1; P = 0.150). However, the observed change in 24-h SBP correlated with the relative change in UACR in the eplerenone group (r = 0.568, P < 0.001). Mean baseline (± SD) estimated glomerular filtration rate (eGFR) was 85 (± 18.6) mL/min/1.73 m2, and 12 (± 9%) had an eGFR of 41-59 mL/min/1.73 m2. No significant differences in the incidence of mild hyperkalaemia (≥ 5.5 mmol/L; eplerenone vs placebo: 6 vs 2, respectively; P = 0.276) and no severe hyperkalaemia (≥ 6.0 mmol/L) were observed. CONCLUSION: The addition of high-dose eplerenone to T2D patients at high risk of CVD can markedly reduce UACR with an acceptable safety profile.

5.
J Ren Nutr ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32958376

RESUMO

OBJECTIVE: Drinking coffee is one of the most common daily habits, especially in the developed world. Along with caffeine, coffee has various ingredients that have been suggested to have beneficial effects, including antioxidant, antiinflammatory, anticarcinogenic, antithrombotic and antifibrotic effects. In this systematic review and meta-analysis, we investigated the relationship between coffee intake and chronic kidney disease (CKD) related outcomes. DESIGN AND METHODS: Literature search was performed through PubMed/Medline, Web of Science, Embase (Elsevier), and the Cochrane Central Register of Controlled Trials (Wiley) from 1960 to February 2020. Incidence of CKD, the progression of CKD, and CKD-associated mortality have been evaluated in relation to coffee consumption and the amount of consumption. The Newcastle-Ottawa scale was used for quality assessment of included studies. RESULTS: 12 studies were included in the analysis (7 prospective, 5 cross-sectional) involving 505,841 subjects. 7 studies investigated the relationship between coffee consumption and incident CKD and showed that coffee consumption was associated with a significant decrease in the risk for incident CKD outcome (RR 0.86, 95% CI 0.76 to 0.97, P = .01) with a greater decrease in individuals taking ≥2 cups/day compared to those who drank ≤1 cup/day. There was a significantly lower risk of incident end stage kidney disease (ESKD) in coffee users (HR 0.82, 95% CI 0.72 to 0.94, P = .005). Coffee consumption was also associated with a lower risk of albuminuria (OR 0.81, 95% CI 0.68 to 0.97, P = .02). Overall, the risk of death related to CKD was lower in coffee users (HR 0.72, 95% CI 0.54 to 0.96, P = .02). CONCLUSION: Coffee intake was dose-dependently associated with lower incident CKD, ESKD, and albuminuria.

6.
PLoS One ; 15(8): e0236934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750075

RESUMO

BACKGROUND: Potassium disturbances are associated with adverse prognosis in patients with chronic conditions. Its prognostic implications in stable patients attending the emergency department (ED) is poorly described. AIMS: This study aimed to assess the prevalence of dyskalemia, describe its predisposing factors and prognostic associations in a population presenting the ED without unstable medical illness. METHODS: Post-hoc analysis of a prospective, cross-sectional, multicenter study in the ED of 11 French academic hospitals over a period of 8 weeks. All adults presenting to the ED during this period were included, except instances of self-drug poisoning, inability to complete self-medication questionnaire, presence of an unstable medical illness and decline to participate in the study. All-cause hospitalization or deaths were assessed. RESULTS: A total of 1242 patients were included. The mean age was 57.2±22.3 years, 51% were female. The distribution according to potassium concentrations was: hypokalemia<4mmol/L(n = 620, 49.9%), normokalemia 4-5mmol/L(n = 549, 44.2%) and hyperkalemia >5mmol/L(n = 73, 0,6%). The proportion of patients with a kalemia<3.5mmol/L was 8% (n = 101). Renal insufficiency (OR [95% CI] = 3.56[1.94-6.52], p-value <0.001) and hemoglobin <12g/dl (OR [95% CI] = 2.62[1.50-4.60], p-value = 0.001) were associated with hyperkalemia. Female sex (OR [95% CI] = 1.31[1.03-1.66], p-value = 0.029), age <45years (OR [95% CI] = 1.69 [1.20-2.37], p-value = 0.002) and the use of thiazide diuretics (OR [95% CI] = 2.04 [1.28-3.32], p-value = 0.003), were associated with hypokalemia<4mmol/l. Two patients died in the ED and 629 (52.7%) were hospitalized. Hypokalemia <3.5mmol/L was independently associated with increased odds of hospitalization or death (OR [95% CI] = 1.47 [1.00-2.15], p-value = 0.048). CONCLUSIONS: Hypokalemia is frequently found in the ED and was associated with worse outcomes in a low-risk ED population.


Assuntos
Serviços Médicos de Emergência , Hipopotassemia/epidemiologia , Idoso , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Hipopotassemia/complicações , Hipopotassemia/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
7.
Eur J Heart Fail ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32809261

RESUMO

AIMS: The associations between potassium level and outcomes, the effect of sacubitril-valsartan on potassium level, and whether potassium level modified the effect of sacubitril-valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM-HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non-cardiovascular death and heart failure hospitalization, were examined. METHODS AND RESULTS: A total of 8399 patients were randomized to either enalapril or sacubitril-valsartan. Potassium level at randomization and follow-up was examined as a continuous and categorical variable (≤3.5, 3.6-4.0, 4.1-4.9, 5.0-5.4 and ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+ ≥5.5 mmol/L and hypokalaemia as K+ ≤3.5 mmol/L. Compared with potassium 4.1-4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84-3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10-1.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non-cardiovascular death and heart failure hospitalization. Sacubitril-valsartan had no effect on potassium overall. The benefit of sacubitril-valsartan over enalapril was consistent across the range of baseline potassium levels. CONCLUSIONS: Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.

8.
BMJ Open ; 10(8): e039277, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847923

RESUMO

INTRODUCTION: Hyperkalaemia is a common electrolyte disorder and can be life-threatening. In the emergency room (ER), interventions aim to protect patients from the immediate dangers of elevated serum potassium by redistributing potassium ions from the bloodstream into the cells via intravenous insulin or nebulised beta2-agonists. However, to date, evidence for acute management of hyperkalaemia is limited. The aim of this randomised controlled trial is therefore to compare three strategies, namely insulin/glucose intravenous infusion, nebulised salbutamol or a combination of nebulised salbutamol and insulin/glucose intravenous infusion to reduce serum potassium concentration at 60 min as a first-line treatment in patients admitted to the ER with serum potassium concentrations superior or equal to 6 mmol/L. METHODS AND ANALYSIS: INSAKA is a prospective, multicentre, controlled, open-label, parallel-group, randomised in a 1:1:1 ratio clinical trial. Patients will be eligible for randomisation if they have serum potassium concentrations superior or equal to 6 mmol/L measured in the ER. Patients will receive either: (1) 10 mg of nebulised salbutamol, (2) 10 units of short-acting insulin in an intravenous bolus with 500 mL of 10% glucose or (3) 10 units of short-acting insulin in an intravenous bolus with 500 mL of 10% glucose combined with 10 mg of nebulised salbutamol. The primary endpoint will be the mean change in the absolute serum potassium level from baseline to 60 min measured in mmol/L. We plan to include 525 patients. ETHICS AND DISSEMINATION: The INSAKA trial will be conducted in accordance with the International Council on Harmonization Good Clinical Practices. All trial documents and procedures have been reviewed and approved by the Ethics Committee Sud Méditerranée III (approval ID number: 19.07.16.36428). The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, broadcast media, print media and the internet. TRIAL REGISTRATION: EudraCT number: 2019-002710-39, Clinicaltrials.gov identifier: NCT04012138.

9.
Heart Fail Rev ; 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32783110

RESUMO

Treatment of patients with heart failure with reduced ejection fraction (HFrEF) with currently available therapies reduces morbidity and mortality. However, implementation of these therapies is a problem with only few patients achieving guideline-recommended maximal doses of therapy. In an effort to improve guideline adherence and uptitration, several trials have investigated a biomarker-guided strategy (using natriuretic peptide targets in specific), but although conceptually promising, these trials failed to show a consistent beneficial effect on outcomes. In this review, we discuss different methodological issues that may explain the failure of these trials and offer potential solutions. Moreover, alternative approaches to increase heart failure guideline adherence are evaluated.

10.
Biol Sex Differ ; 11(1): 47, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831121

RESUMO

BACKGROUND: Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. METHODS: A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. RESULTS: We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83-2.63), p = 0.18. CONCLUSION: In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.

12.
Clin Res Cardiol ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32789678

RESUMO

BACKGROUND: Patients with diabetes who had a recent myocardial infarction (MI) are at high risk of cardiovascular events. Therefore, risk assessment is important for treatment and shared decisions. We used data from EXAMINE trial to investigate whether a multi-proteomic approach would provide specific proteomic signatures and also improve the prognostic capacity for determining the risk of cardiovascular death, MI, stroke, heart failure [HF], all-cause death, and combinations of these outcomes. METHODS: 93 circulating proteins (92 from the Olink® CVDII plus troponin) were assessed in 5131 patients. Cox, competing risks, and reclassification measures were applied. RESULTS: The clinical model showed good discrimination and calibration for all outcomes. On top of the clinical model that included age, sex, smoking, diabetes duration, history of MI (prior to the index MI of inclusion), history of HF hospitalization, history of stroke, atrial fibrillation, hypertension, systolic blood pressure, statin therapy, estimated glomerular filtration rate, and study treatment (alogliptin or placebo), troponin and BNP added prognostic information to the composite of cardiovascular death, MI, or stroke (∆C-index + 5%) and cardiovascular death alone (∆C-index + 7%). Troponin, BNP, and TRAILR2 added prognostic information on all-cause death and the composite of cardiovascular death or HF hospitalization. HF hospitalization alone was improved by adding BNP and Gal-9. For MI, troponin, FGF23, and AMBP added prognostic value; whereas for stroke, only troponin added prognostic value (multi-proteomics improved C-index > 3% [p < 0.001] for all the studied outcomes). The addition of the final biomarker selection to the clinical model improved event reclassification (cNRI from + 23% to + 64%). Specifically, the addition of the biomarkers allowed a better classification of patients at low risk (as having "true" low risk) and patients and high risk (as having "true" high risk). These results were consistent for all the studied outcomes with even more marked differences in the fatal events. CONCLUSIONS: The addition of multi-proteomic biomarkers to a clinical model in this population with diabetes and a recent MI allowed a better risk prediction and event reclassification, potentially helping for better risk assessment and targeted treatment decisions. T2D type 2 diabetes, MI myocardial infarction, CV cardiovascular, HFH heart failure hospitalization, Δ delta, cNRI continuous net reclassification index, BNP brain natriuretic peptide, TRAILR2 trail receptor 2 (or death receptor 5), Gal-9 galectin-9, FGF23 fibroblast growth factor 23.

13.
Theranostics ; 10(19): 8665-8676, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754270

RESUMO

Rationale: To test whether novel biomarkers, such as microribonucleic acids (miRNAs), and nonstandard predictive models, such as decision tree learning, provide useful information for medical decision-making in patients on hemodialysis (HD). Methods: Samples from patients with end-stage renal disease receiving HD included in the AURORA trial were investigated (n=810). The study included two independent phases: phase I (matched cases and controls, n=410) and phase II (unmatched cases and controls, n=400). The composite endpoint was cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. miRNA quantification was performed using miRNA sequencing and RT-qPCR. The CART algorithm was used to construct regression tree models. A bagging-based procedure was used for validation. Results: In phase I, miRNA sequencing in a subset of samples (n=20) revealed miR-632 as a candidate (fold change=2.9). miR-632 was associated with the endpoint, even after adjusting for confounding factors (HR from 1.43 to 1.53). These findings were not reproduced in phase II. Regression tree models identified eight patient subgroups with specific risk patterns. miR-186-5p and miR-632 entered the tree by redefining two risk groups: patients older than 64 years and with hsCRP<0.827 mg/L and diabetic patients younger than 64 years. miRNAs improved the discrimination accuracy at the beginning of the follow-up (24 months) compared to the models without miRNAs (integrated AUC [iAUC]=0.71). Conclusions: The circulating miRNA profile complements conventional risk factors to identify specific cardiovascular risk patterns among patients receiving maintenance HD.

14.
Clin Res Cardiol ; 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770373

RESUMO

BACKGROUND: Right ventricular (RV) dysfunction and RV-pulmonary artery (PA) uncoupling are associated with the development of pulmonary congestion during exercise. However, there is limited information regarding the association between these right-sided cardiac parameters and pulmonary congestion in acutely decompensated heart failure (HF). METHODS: We performed an individual patient meta-analysis from four cohort studies of hospitalized patients with HF who had available lung ultrasound (B-lines) data on admission and/or at discharge. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE), RV-PA coupling was defined as the ratio of TAPSE to PA systolic pressure (PASP). RESULTS: Admission and discharge cohort included 319 patients (75.8 ± 10.1 years, 46% women) and 221 patients (77.9 ± 9.0 years, 47% women), respectively. Overall, higher TAPSE was associated with higher ejection fraction, lower PASP, b-type natriuretic peptide and B-line counts. By multivariable analysis, worse RV function or RV-PA coupling was associated with higher B-line counts on admission and at discharge, and with a less reduction in B-line counts from admission to discharge. Higher B-line counts at discharge were associated with a higher risk of the composite of all-cause mortality and/or HF re-hospitalization [adjusted-HR 1.13 (1.09-1.16), p < 0.001]. Furthermore, the absolute risk increase related to high B-line counts at discharge was higher in patients with lower TAPSE. CONCLUSIONS: In patients with acutely decompensated HF, impaired RV function and RV-PA coupling were associated with severe pulmonary congestion on admission, and less resolution of pulmonary congestion during hospital stay. Worse prognosis related to residual pulmonary congestion was enhanced in patients with RV dysfunction. TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure.

15.
Eur J Emerg Med ; 27(5): 329-337, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32852924

RESUMO

Hyperkalemia is a common electrolyte disorder observed in the emergency department. It is often associated with underlying predisposing conditions, such as moderate or severe kidney disease, heart failure, diabetes mellitus, or significant tissue trauma. Additionally, medications, such as inhibitors of the renin-angiotensin-aldosterone system, potassium-sparing diuretics, nonsteroidal anti-inflammatory drugs, succinylcholine, and digitalis, are associated with hyperkalemia. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened a conference in 2018 to identify evidence and address controversies on potassium management in kidney disease. This review summarizes the deliberations and clinical guidance for the evaluation and management of acute hyperkalemia in this setting. The toxic effects of hyperkalemia on the cardiac conduction system are potentially lethal. The ECG is a mainstay in managing hyperkalemia. Membrane stabilization by calcium salts and potassium-shifting agents, such as insulin and salbutamol, is the cornerstone in the acute management of hyperkalemia. However, only dialysis, potassium-binding agents, and loop diuretics remove potassium from the body. Frequent reevaluation of potassium concentrations is recommended to assess treatment success and to monitor for recurrence of hyperkalemia.

16.
ESC Heart Fail ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32602236

RESUMO

AIMS: How general practitioners (GPs) manage dyskalaemia is currently unknown. This study aimed at describing GP practices regarding hypokalaemia or hyperkalaemia diagnosis and management in their outpatients. METHODS AND RESULTS: A telephone survey was conducted among French GPs with a 20-item questionnaire (16 closed-ended questions and 12 open-ended questions) regarding their usual management of hypokalaemia or hyperkalaemia patients, both broadly and more specifically in patients with heart failure and/or chronic kidney disease and/or in patients treated with angiotensin-converting enzyme/angiotensin receptor blockers or mineralocorticoid receptor antagonists. We aimed to interview 500 GPs spread geographically throughout France. This descriptive survey results are presented as mean ± standard deviation (if normally distributed or as median and inter-quartile range if the distribution was skewed). Categorical variables are expressed as frequencies and proportions (%). A total of 500 GPs participated in the study. Dyskalaemia thresholds (for diagnosis and intervention) and management patterns were highly heterogeneous. The mean ± SD (range) potassium level leading to 'intervene' was 5.32 ± 0.34 mmol/L (4.5-6.5) for hyperkalaemia and 3.23 ± 0.34 mmol/L (2.0-6.5) for hypokalaemia. Potassium levels leading to refer the patient to the emergency department (ED) were 6.14 ± 0.55 (4.5-10) and 2.69 ± 0.42 mmol/L (1-4), respectively. Potassium binders (51-65%) or potassium supplements (67-74%) were frequently used to manage hyperkalaemia or hypokalaemia. GPs uncommonly referred their dyskalaemic patients to cardiologists or nephrologists (or to the emergency department, if the latter was deemed necessary owing to the severity of the dyskalaemia). We identified an association between the close vicinity of GP office from an ED and 'referring a heart failure patient' (19.2% with ED vs. 8.6% without ED) and referring a heart failure and chronic kidney disease patient on mineralocorticoid receptor antagonist (16.7% with ED vs. 9.3% without ED). Although the majority (67%) of GPs had an electrocardiogram on hand, it was rarely used (14%) in dyskalaemic patients. Subgroup analyses considering gender, age of the participating GPs, and high-income/low-income regions did not identify specific patterns regarding the multidimensional aspect of dyskalaemia management. CONCLUSIONS: Owing to the considerable heterogeneity of French GP practices toward dyskalaemia diagnosis and management approaches, there is a likely need to standardize (potentially enabled by therapeutic algorithms) practices.

17.
Trials ; 21(1): 601, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611377

RESUMO

BACKGROUND: Septic shock remains a significant cause of death in critically ill patients. During septic shock, some patients will retain microcirculatory disorders despite optimal hemodynamic support (i.e., fluid resuscitation, vasopressors, inotropes). Alterations in the microcirculation are a key pathophysiological factor of organ dysfunction and death in septic shock patients. Ilomedin is a prostacyclin analog with vasodilatory effect and anti-thrombotic properties (i.e., inhibition of platelet aggregation) preferentially at the microcirculatory level. We hypothesize that early utilization of intravenous Ilomedin in septic shock patients with clinical persistence of microperfusion disorders would improve the recovery of organ dysfunction. METHODS: The I-MICRO trial is a multicenter, prospective, randomized, double-blinded, placebo-controlled study. We plan to recruit 236 adult patients with septic shock and persistent microcirculatory disorders (i.e., skin mottling or increased capillary refill time) despite hemodynamic support. Participants will be randomized to receive a 48-h intravenous infusion of either Ilomedin or placebo starting at the earliest 6 h and later 24 h after septic shock. The primary outcome will be the change (delta) of sequential organ failure assessment (SOFA) score between randomization and day 7. Secondary outcomes will include mean SOFA score during the first 7 days after randomization, mortality at day 28 post-randomization, number of ventilation-free survival days in the 28 days post-randomization, number of renal replacement therapy-free survival days in the 28 days post-randomization, number of vasopressor-free survival days in the 28 days post-randomization, and mottling score at day 1 after randomization. DISCUSSION: The trial aims to provide evidence on the efficacy and safety of Ilomedin in patients with septic shock and persistent microcirculatory disorders. TRIAL REGISTRATION: NCT NCT03788837 . Registered on 28 December 2018.

18.
Cells ; 9(7)2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664340

RESUMO

Circulating levels of soluble interleukin 1 receptor-like 1 (sST2) are increased in heart failure and associated with poor outcome, likely because of the activation of inflammation and fibrosis. We investigated the pathogenic role of sST2 as an inductor of cardiac fibroblasts activation and collagen synthesis. The effects of sST2 on human cardiac fibroblasts was assessed using proteomics and immunodetection approaches to evidence the upregulation of neuropilin-1 (NRP-1), a regulator of the profibrotic transforming growth factor (TGF)-ß1. In parallel, sST2 increased fibroblast activation, collagen and fibrosis mediators. Pharmacological inhibition of nuclear factor-kappa B (NF-κB) restored NRP-1 levels and blocked profibrotic effects induced by sST2. In NRP-1 knockdown cells, sST2 failed to induce fibroblast activation and collagen synthesis. Exogenous NRP-1 enhanced cardiac fibroblast activation and collagen synthesis via NF-κB. In a pressure overload rat model, sST2 was elevated in association with cardiac fibrosis and was positively correlated with NRP-1 expression. Our study shows that sST2 induces human cardiac fibroblasts activation, as well as the synthesis of collagen and profibrotic molecules. These effects are mediated by NRP-1. The blockade of NF-κB restored NRP-1 expression, improving the profibrotic status induced by sST2. These results show a new pathogenic role for sST2 and its mediator, NRP-1, as cardiac fibroblast activators contributing to cardiac fibrosis.

19.
Arch Cardiovasc Dis ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32660835

RESUMO

Renal function is often affected in patients with chronic heart failure with reduced ejection fraction (HFrEF). The complex interplay between heart and renal dysfunction makes renal function and potassium monitoring mandatory. Renin-angiotensin-aldosterone system (RAAS) blockers are a life-saving treatment for patients with HFrEF, regardless of worsening renal function. Uptitration to the maximum-tolerated dose should be a constant goal. This simple fact is all too often forgotten (only 30% of patients with heart failure receive the target dosage of RAAS blockers), and the RAAS blocker effect on renal function is sometimes misunderstood. RAAS blockers are not nephrotoxic drugs as they only have a functional effect on renal function. In many routine clinical cases, RAAS blockers are withheld or stopped because of this misunderstanding, combined with suboptimal assessment of the clinical situation and underestimation of the life-saving effect of RAAS blockers despite worsening renal function. In this expert panel, which includes heart failure specialists, geriatricians and nephrologists, we propose therapeutic management algorithms for worsening renal function for physicians in charge of outpatients with chronic heart failure. Firstly, the essential variables to take into consideration before changing treatment are the presence of concomitant disorders that could alter renal function status (e.g. infection, diarrhoea, hyperthermia), congestion/dehydration status, blood pressure and intake of nephrotoxic drugs. Secondly, physicians are invited to adapt medication according to four clinical scenarios (patient with congestion, dehydration, hypotension or hyperkalaemia). Close biological monitoring after treatment modification is mandatory. We believe that this practical clinically minded management algorithm can help to optimize HFrEF treatment in routine clinical practice.

20.
Int Urol Nephrol ; 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32661618

RESUMO

Chronic kidney disease is prevalent, affecting more than one in ten adults. In this population, metabolic acidosis is considered a key underlying pathophysiological feature, tying together bone mineral disorders, sarcopenia, insulin resistance, vascular calcification, pro-inflammatory and pro-thrombotic states. This review aims to address the paucity of literature on alkalinizing agents, a promising treatment option that has known adverse effects.

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