Serum Bicarbonate in Acute Heart Failure: Relationship to Treatment Strategies and Clinical Outcomes

doi:10.1016/j.cardfail.2016.01.007

Journal of Cardiac Failure

Volume 22, Issue 9, September 2016, Pages 738-742

https://doi.org/10.1016/j.cardfail.2016.01.007 Get rights and content

Highlights

•
Elevated serum bicarbonate is a common observation in acute heart failure (AHF) patients.
•
In AHF, bicarbonate increased with diuretics but decreased with ultrafiltration.
•
Bicarbonate change was not associated with clinical signs of decongestion.
•
Adequate decongestion is a key goal in the treatment of patients with AHF.
•
Modest increases in bicarbonate should not prompt decrease or cessation of diuresis.

Abstract

Background

Though commonly noted in clinical practice, it is unknown if decongestion in acute heart failure (AHF) results in increased serum bicarbonate.

Methods and Results

For 678 AHF patients in the DOSE-AHF, CARRESS-HF, and ROSE-AHF trials, we assessed change in bicarbonate (baseline to 72–96 hours) according to decongestion strategy, and the relationship between bicarbonate change and protocol-defined decongestion. Median baseline bicarbonate was 28 mEq/L. Patients with baseline bicarbonate ≥28 mEq/L had lower ejection fraction, worse renal function and higher N-terminal pro–B-type natriuretic peptide than those with baseline bicarbonate <28 mEq/L. There were no differences in bicarbonate change between treatment groups in DOSE-AHF or ROSE-AHF (all P > .1). In CARRESS-HF, bicarbonate increased with pharmacologic care but decreased with ultrafiltration (median +3.3 vs −0.9 mEq/L, respectively; P < .001). Bicarbonate change was not associated with successful decongestion (P > .2 for all trials).

Conclusions

In AHF, serum bicarbonate is most commonly elevated in patients with more severe heart failure. Despite being used in clinical practice as an indicator for decongestion, change in serum bicarbonate was not associated with significant decongestion.

Section snippets

Data Source and Study Population

This analysis was performed with the use of data from 3 National Heart, Lung, and Blood Institute–sponsored Heart Failure Network trials: Diuretic Optimization Strategy Evaluation in Acute Heart Failure (DOSE-AHF), Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), and Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF). The design and primary results of these trials have been published previously.3, 4, 5, 6, 7, 8

All study participants provided

Results

Of 835 unique patients in the DOSE-AHF, CARRESS-HF, and ROSE-AHF trials, 678 patients had a serum bicarbonate level measured at baseline and at follow-up (72 or 96 hours): 225 in DOSE-AHF, 309 in ROSE-AHF, and 144 in CARRESS-HF. Patients with baseline serum bicarbonate above the median (≥28 mEq/L) were significantly more likely to have a reduced ejection fraction, and at baseline they had lower serum sodium and higher blood urea nitrogen, creatinine, and NT-proBNP (Table 1).

No difference could

Discussion

Current treatment strategies in AHF rely predominantly on the use of loop and thiazide diuretics. The mechanisms by which the use of these diuretics results in metabolic alkalosis have been well described.⁹ “Contraction alkalosis,” due to decreased extracellular fluid volume resulting in increased bicarbonate concentration, has only a small effect on serum bicarbonate levels. Diuretic-induced acidification of the distal nephron stimulates increased production of bicarbonate, and decreased

Disclosures

Dr Hernandez has served as a consultant for Amgen and Novartis. The other authors report no relevant disclosures.

Acknowledgments

The authors thank Dr Javed Butler and Dr Horng Chen for their contributions to this manuscript, including assistance with study design, data analysis, and manuscript review.

References (14)

B.A. Bart et al.
Cardiorenal rescue study in acute decompensated heart failure: rationale and design of CARRESS-HF, for the Heart Failure Clinical Research Network
J Card Fail
(2012)
B.F. Palmer
Metabolic complications associated with use of diuretics
Semin Nephrol
(2011)
C. Lucas et al.
Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure
Am Heart J
(2000)
D. Mozaffarian et al.
Heart disease and stroke statistics—2015 update: a report from the American Heart Association
Circulation
(2015)
C. Ronco
Fluid overload: diagnosis and management
(2010)
G.M. Felker et al.
Loop diuretics in acute decompensated heart failure: necessary? Evil? A necessary evil?
Circ Heart Fail
(2009)
G.M. Felker et al.
Diuretic strategies in patients with acute decompensated heart failure
N Engl J Med
(2011)

There are more references available in the full text version of this article.

Cited by (19)

Serum Chloride and Heart Failure
2023, Kidney Medicine
Despite significant advances in management, heart failure continues to impose a significant epidemiologic burden with high prevalence and mortality rates. For decades, sodium has been the serum electrolyte most commonly associated with outcomes; however, challenging the conventional paradigm of sodium’s influence, recent studies have identified a more prominent role in serum chloride in the pathophysiology of heart failure. More specifically, hypochloremia is associated with neurohumoral activation, diuretic resistance, and a worse prognosis in patients with heart failure. This review examines basic science, translational research, and clinical studies to better characterize the role of chloride in patients with heart failure and additionally discusses potential new therapies targeting chloride homeostasis that may impact the future of heart failure care.
Multinephron Segment Diuretic Therapy to Overcome Diuretic Resistance in Acute Heart Failure: A Single-Center Experience
2022, Journal of Cardiac Failure
Citation Excerpt :
A major barrier to MSDT is the absence of safety data. Concerns include hyponatremia, hypokalemia, hypochloremia, metabolic alkalosis, and worsening kidney function.8,13,34,35 We found serum electrolytes, serum bicarbonate, and kidney function did not worsen with MSDT.
The concept of multinephron segment diuretic therapy (MSDT) has been recommended in severe diuretic resistance with only expert opinion and case-level evidence. The purpose of this study was to investigate the safety and efficacy of MSDT, combining 4 diuretic classes, in acute heart failure (AHF) complicated by diuretic resistance.
A retrospective analysis was conducted in patients hospitalized with AHF at a single medical center who received MSDT, including concomitant carbonic anhydrase inhibitor, loop, thiazide, and mineralocorticoid receptor antagonist diuretics. Subjects served as their own controls with efficacy evaluated as urine output and weight change before and after MSDT. Serum chemistries, renal replacement therapies, and in-hospital mortality were evaluated for safety. Patients with severe diuretic resistance before MSDT were analyzed as a subcohort. A total of 167 patients with AHF and diuretic resistance received MSDT. MSDT was associated with increased median 24-hour urine output in the first day of therapy compared with the previous day (2.16 L [0.95–4.14 L] to 3.08 L [1.74–4.86 L], P = .003) in the total cohort and in the Severe diuretic resistance cohort (0.91 L [0.43–1.43 L] to 2.08 L [1.13–3.96 L], P < .001). The median cumulative weight loss at day 7 or discharge was –7.4 kg (–15.3 to –3.4 kg) (P = .02). Neither serum sodium, chloride, potassium, bicarbonate, or creatinine changed significantly relative to baseline (P > .05 for all).
In an AHF cohort with diuretic resistance, MSDT was associated with increased diuresis without changes in serum chemistries or kidney function. Prospective studies of MSDT in AHF and diuretic resistance are warranted.
Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review
2020, Journal of the American College of Cardiology
Citation Excerpt :
A second mechanism involves increased luminal solute and fluid delivery to distal segments, which increases transepithelial solute flux and obligates new protein synthesis (57). A third mechanism involves systemic metabolic effects, including metabolic alkalosis (58) and hypokalemia, which strongly activate the sodium-chloride cotransporter (59–62). It seems likely that distal convoluted tubule remodeling is a consequence of increased NaCl movement through cells, because it also occurs when genetic mutations activate NCC (63).
Expansion of extracellular fluid volume is central to the pathophysiology of heart failure. Increased extracellular fluid leads to elevated intracardiac filling pressures, resulting in a constellation of signs and symptoms of heart failure referred to as congestion. Loop diuretics are one of the cornerstones of treatments for heart failure, but in contrast to other therapies, robust clinical trial evidence to guide the use of diuretics is sparse. A nuanced understanding of renal physiology and diuretic pharmacokinetics is essential for skillful use of diuretics in the management of heart failure in both the inpatient and outpatient settings. Diuretic resistance, defined as an inadequate quantity of natriuresis despite an adequate diuretic regimen, is a major clinical challenge that generally portends a poor prognosis. In this review, the authors discuss the fundamental mechanisms and physiological principles that underlie the use of diuretic therapy and the available data on the optimal use of diuretics.
Development and validation of a novel combinatorial nomogram model to predict in-hospital deaths in heart failure patients
2024, BMC Cardiovascular Disorders
Diuretic Treatment in Patients with Heart Failure: Current Evidence and Future Directions – Part I: Loop Diuretics
2024, Current Heart Failure Reports
Nomograms for Predicting the Risk of Acute Heart Failure in ICU Patients with Atrial Fibrillation
2023, Research Square

View all citing articles on Scopus

: Funding Sources: DOSE-AHF, CARRESS-HF, and ROSE-AHF were funded by the National Heart, Lung, and Blood Institute. Dr Cooper is supported by grant T32HL069749-11A1 from the National Institute of Health. The content of this paper is the responsibility solely of the authors and does not necessarily represent the official views of the National Institutes of Health.

View full text

Brief ReportSerum Bicarbonate in Acute Heart Failure: Relationship to Treatment Strategies and Clinical Outcomes

Highlights

Abstract

Background

Methods and Results

Conclusions

Section snippets

Data Source and Study Population

Results

Discussion

Disclosures

Acknowledgments

J Card Fail

Semin Nephrol

Am Heart J

Heart disease and stroke statistics—2015 update: a report from the American Heart Association

Circulation

Fluid overload: diagnosis and management

Loop diuretics in acute decompensated heart failure: necessary? Evil? A necessary evil?

Circ Heart Fail

Diuretic strategies in patients with acute decompensated heart failure

N Engl J Med

Brief Report
Serum Bicarbonate in Acute Heart Failure: Relationship to Treatment Strategies and Clinical Outcomes