Diuretic Response in Acute Heart Failure
Diuretic Response in Acute Heart Failure
Aim Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome.
Methods and Results We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses.We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was –0.38 (–0.80 to –0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11–1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14– 1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24–2.01, P < 0.001) in multivariable models. The proposed metric—weight loss indexed to diuretic dose—better captures a dose–response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal.
Conclusions Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study.
Heart failure (HF) is a growing public health problem and the leading cause of hospitalization in Europe and the USA. Loop diuretics are a cornerstone of acute heart failure (AHF) therapy—administered to up to 90% of hospitalized patients —and while some observational data suggest higher doses are associated with worse outcomes, others found no difference after case matching. The question of whether diuretics cause poor outcome or merely reflect disease severity remains unanswered; data on optimal posology and administration are conflicting at best, although the prospective Diuretic Optimization Strategies Evaluation (DOSE) trial suggests that safety concerns associated with high-dose diuretics may be unfounded.
A frequently mentioned complication of diuretic therapy in AHF is diuretic resistance, which is associated with worsening renal function (WRF) and cardiorenal syndromes. Existing definitions of resistance—which include congestion refractory to 'standard' diuretic therapy, reduced diuresis and natriuresis upon repeated dosing, and persistent congestion despite increasing (≥80 mg oral furosemide) daily diuretic doses —are of limited use. Despite the clinical importance of the issue, few studies have explicitly examined the importance of effective decongestion using diuretics within the setting of AHF.
Heart failure guidelines recommend using weight loss to monitor volume status, and correlations between weight loss and outcomes have been reported. However, post-discharge changes in body weight only predicted rehospitalization and were unrelated to mortality in one study, highlighting the limitations of examining body weight alone, while others found diuretic dose did not predict weight loss. This is perhaps unsurprising, considering both the non-linear dose–response relationship and the diuretic resistance commonly seen in HF. A simple, continuous, quantitative measure for diuretic response—combining decongestive effect and diuretic dose—may help better unravel diuretic 'resistance' and open new avenues towards individualized, tailored treatment. The aim of this study was to define a clinically applicable measure for diuretic response, characterize the unresponsive patient, and determine the prognostic significance of diuretic response.
Abstract and Introduction
Abstract
Aim Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome.
Methods and Results We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses.We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was –0.38 (–0.80 to –0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11–1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14– 1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24–2.01, P < 0.001) in multivariable models. The proposed metric—weight loss indexed to diuretic dose—better captures a dose–response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal.
Conclusions Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study.
Introduction
Heart failure (HF) is a growing public health problem and the leading cause of hospitalization in Europe and the USA. Loop diuretics are a cornerstone of acute heart failure (AHF) therapy—administered to up to 90% of hospitalized patients —and while some observational data suggest higher doses are associated with worse outcomes, others found no difference after case matching. The question of whether diuretics cause poor outcome or merely reflect disease severity remains unanswered; data on optimal posology and administration are conflicting at best, although the prospective Diuretic Optimization Strategies Evaluation (DOSE) trial suggests that safety concerns associated with high-dose diuretics may be unfounded.
A frequently mentioned complication of diuretic therapy in AHF is diuretic resistance, which is associated with worsening renal function (WRF) and cardiorenal syndromes. Existing definitions of resistance—which include congestion refractory to 'standard' diuretic therapy, reduced diuresis and natriuresis upon repeated dosing, and persistent congestion despite increasing (≥80 mg oral furosemide) daily diuretic doses —are of limited use. Despite the clinical importance of the issue, few studies have explicitly examined the importance of effective decongestion using diuretics within the setting of AHF.
Heart failure guidelines recommend using weight loss to monitor volume status, and correlations between weight loss and outcomes have been reported. However, post-discharge changes in body weight only predicted rehospitalization and were unrelated to mortality in one study, highlighting the limitations of examining body weight alone, while others found diuretic dose did not predict weight loss. This is perhaps unsurprising, considering both the non-linear dose–response relationship and the diuretic resistance commonly seen in HF. A simple, continuous, quantitative measure for diuretic response—combining decongestive effect and diuretic dose—may help better unravel diuretic 'resistance' and open new avenues towards individualized, tailored treatment. The aim of this study was to define a clinically applicable measure for diuretic response, characterize the unresponsive patient, and determine the prognostic significance of diuretic response.
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