Dataset Information

A combined clinical and biomarker approach to predict diuretic response in acute heart failure.

ABSTRACT:

Background

Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF).

Methods and results

We investigated explanatory and predictive models for diuretic response--weight loss at day 4 per 40 mg of furosemide--in 974 patients with AHF included in the PROTECT trial. Biomarkers, addressing multiple pathophysiological pathways, were determined at baseline and after 24 h. An explanatory baseline biomarker model of a poor diuretic response included low potassium, chloride, hemoglobin, myeloperoxidase, and high blood urea nitrogen, albumin, triglycerides, ST2 and neutrophil gelatinase-associated lipocalin (r(2) = 0.086). Diuretic response after 24 h (early diuretic response) was a strong predictor of diuretic response (? = 0.467, P < 0.001; r(2) = 0.523). Addition of diuretic response after 24 h to biomarkers and clinical characteristics significantly improved the predictive model (r(2) = 0.586, P < 0.001).

Conclusions

Biomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h.

SUBMITTER: ter Maaten JM

PROVIDER: S-EPMC4735256 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

A combined clinical and biomarker approach to predict diuretic response in acute heart failure.

ter Maaten Jozine M JM Valente Mattia A E MA Metra Marco M Bruno Noemi N O'Connor Christopher M CM Ponikowski Piotr P Teerlink John R JR Cotter Gad G Davison Beth B Cleland John G JG Givertz Michael M MM Bloomfield Daniel M DM Dittrich Howard C HC van Veldhuisen Dirk J DJ Hillege Hans L HL Damman Kevin K Voors Adriaan A AA

Clinical research in cardiology : official journal of the German Cardiac Society 20150818 2

<h4>Background</h4>Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF).<h4>Methods and results</h4>We investigated explanatory and predictive models for diuretic response--weight loss at day 4 per 40 mg of furosemide--in 974 patie ...[more]

PMID: 26280875

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Project description:Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use.In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.In the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 ?mol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 ?mol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 ?mol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 ?mol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.).

Project description:BACKGROUND:Despite the fact that loop diuretics are a landmark in acute heart failure (AHF) treatment, few trials exist that evaluate whether the duration and timing of their administration and drug amount affect outcome. In this study, we sought to evaluate different loop diuretic infusion doses in relation to outcome and to diuretic response (DR), which was serially measured during hospitalization. METHODS:This is a post-hoc analysis of a DIUR-HF trial. We divided our sample on the basis of intravenous diuretic dose during hospitalization. Patients taking less than 125 mg of intravenous furosemide (median value) were included in the low dose group (LD), patients with a diuretic amount above this threshold were inserted in the high dose group (HD). The DR formula was defined as weight loss/40 mg daily of furosemide and it was measured during the first 24 h, 72 h, and over the whole infusion period. Outcome was considered as death due to cardiovascular causes or heart failure hospitalization. RESULTS:One hundred and twenty-one AHF patients with reduced ejection fractions (EF) were evaluated. The cardiovascular (CV) death/heart failure (HF) re-hospitalization rate was significantly higher in the HD group compared to the LD group (75% vs. 22%; p < 0.001). Both low DR, measured during the entire infusion period (HR 3.25 (CI: 1.92-5.50); p < 0.001) and the intravenous diuretic HD (HR 5.43 [CI: 2.82-10.45]; p < 0.001) were related to outcome occurrence. Multivariable analysis showed that DR (HR 3.01 (1.36-6.65); p = 0.006), intravenous diuretic HD (HR 2.83 (1.24-6.42); p=0.01) and worsening renal function (WRF) (HR 2.21 (1.14-4.28); p = 0.01) were related to poor prognosis. CONCLUSIONS:HD intravenous loop diuretic administration is associated with poor prognosis and less DR. Low DR measured during the whole intravenous administration better predicts outcome compared to DR measured in the early phases. ClinicalTrials.gov Acronym and Identifier Number: DIUR-HF; NCT01441245; registered on 23 September 2011.

Project description:BackgroundLoop diuretics are common therapy for emergency department (ED) patients with acute heart failure (AHF). Diuretic resistance (DR) is a term used to describe blunted natriuretic response to loop diuretics. It would be important to detect DR prior to it becoming clinically apparent, so early interventions can be initiated. However, several definitions have been proposed, and it is not clear if they identify similar patients. We compared these definitions and described the clinical characteristics of patients who fulfilled them.MethodsTo qualify for this secondary analysis of 1033 ED patients with AHF, all patients needed to receive intravenous diuretics in the ED and have urine available within 24 h of their ED evaluation. A poor diuretic response, suggesting DR, was characterized by (1) a fractional sodium excretion (FeNa) of less than 0.2%; (2) spot urinary sodium of less than 50 meq/L; and (3) a urinary Na/K ratio <1.0. McNemar's test was used to compare the different cohorts identified by the three definitions. Secondary analyses evaluated associations between each DR definition and hospital length of stay (LOS), ED revisits and rehospitalizations for AHF, and mortality using the Wilcoxon rank-sum tests and linear regression or Pearson chi-square test and logistic regression, as appropriate.ResultsThe median age of the 187 patients was 64, and 50% were African-American. There were 5.9% of patients with a FeNa less than 0.2%, 17.1% had urinary sodium less than 50 meq/L, and 10.7% had a urinary Na/K ratio <1.0. The three definitions identified significantly different patients with very little overlap (p < 0.02 for all comparisons). There were 37 (19.8%) patients who were readmitted to the ED or hospital or died within 30 days of ED evaluation. Patients with spot urinary sodium less than 50 meq/L were more likely to be readmitted (p = 0.03).ConclusionsThe patient proportion with poor natriuresis and DR varies depending on the definition used. Early ED therapy would be impacted at different rates if clinical decisions are made based on these definitions. These findings need to be further explored in a prospective ED-based study.Trial registrationClinicalTrials.gov, NCT00508638.

Dataset Information

A combined clinical and biomarker approach to predict diuretic response in acute heart failure.

Background

Methods and results

Conclusions

Publications

A combined clinical and biomarker approach to predict diuretic response in acute heart failure.

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