Hemoconcentration-guided Diuresis in Heart Failure

doi:10.1016/j.amjmed.2014.06.009

The American Journal of Medicine

Volume 127, Issue 12, December 2014, Pages 1154-1159

https://doi.org/10.1016/j.amjmed.2014.06.009 Get rights and content

Abstract

One quarter of patients hospitalized for heart failure are readmitted within 30 days, perhaps related to ineffective decongestion. Limited data exist guiding the extent and duration of diuresis in patients hospitalized for heart failure. The objective of this review was to determine the prognostic value of hemoconcentration, or the relative increase in the cellular elements in blood, in patients hospitalized for heart failure and to clarify its role in guiding inpatient diuretic practices. Six post hoc retrospective studies from 2010 to 2013 were available for review. Hemoconcentration was consistently associated with markers of aggressive fluid removal, including higher diuretic dosing and reduced body weight, but increased risk of in-hospital worsening renal function. Despite this, hemoconcentration was associated with improved short-term mortality and rehospitalization. Hemoconcentration is a practical, readily available, noninvasive, economically feasible strategy to help guide diuresis and monitor congestion relief in patients hospitalized for worsening heart failure. Clinicians should strongly consider using changes in hemoglobin and hematocrit as an adjunct to other available measures of decongestion and clinical acumen in inpatient heart failure care.

Section snippets

Concentrating on the Problem: Optimizing Volume and Quality

Despite adequate relief of clinical symptoms during hospitalization and incremental reductions in hospital length of stay,⁴ postdischarge mortality and rehospitalization remain exceedingly high. Approximately 20% to 25% of all hospitalized patients with heart failure are readmitted within 30 days, with more than 60% of them returning to the hospital within the first 15 days.⁵ Of these 30-day readmissions, 35% are related directly to heart failure and may reflect inadequate decongestion during

Pitfalls of Traditional Approaches

Although the type⁹ and intensity¹⁰ of volume removal have become a focus of recent trials, data are scarce regarding the optimal duration and therapeutic targets of inpatient volume reduction therapy. A number of parameters are currently being used empirically in the tailoring of inpatient diuresis, including resting or exertional symptoms, urine output, natriuretic peptide levels,¹¹ orthostasis,¹² renal function,¹³ body weight,¹⁴ and intravascular volume.¹⁵ We currently lack randomized

Hemoconcentration: A Review of the Available Data

Hemoconcentration has been broadly applied to various medical conditions, attempting to serve as a surrogate of intravascular volume status. It is widely accepted in contemporary risk stratification and prognostication in pancreatitis.³³ Over the last decade, hemoconcentration has been introduced as a possible target for therapy in heart failure.³⁴ Hemoconcentration was first evaluated retrospectively in 336 patients hospitalized for heart failure in the ESCAPE trial by Testani et al.³⁵

Hemoconcentration: Considerations and Qualifications

Several retrospective, post hoc studies have shed light on the association between hemoconcentration and clinical outcomes in patients hospitalized for heart failure. However, it is important to recognize that none of these studies have assessed the applicability and routine use of hemoconcentration to guide clinical decision-making compared with usual care in a prospective, randomized fashion. It is plausible that healthier patients (including those with normal or near normal baseline renal

A Proposed Hemoconcentration-Guided Therapeutic Strategy

We have developed a potential algorithm for hemoconcentration-guided therapy that requires further validation and prospective testing (Figure 1). Hemoconcentration must be used in conjunction with other available clinical parameters in the frequent assessment and reassessment of intensity and duration of diuresis.

Conclusions

Hemoconcentration is a practical, readily available, noninvasive, economically feasible strategy to help guide diuresis and monitor congestion relief in patients hospitalized for worsening heart failure. Clinicians should strongly consider using changes in hemoglobin and hematocrit as an adjunct to other available measures of decongestion and clinical acumen in inpatient heart failure care. Hemoconcentration may provide incremental insight into prognosis and whether worsening renal function

References (43)

M. Gheorghiade et al.
Rehospitalization for heart failure: problems and perspectives
J Am Coll Cardiol
(2013)
K.F. Adams et al.
Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE)
Am Heart J
(2005)
G.C. Fonarow et al.
Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry
J Am Coll Cardiol
(2007)
C.M. O'Connor et al.
Demographics, clinical characteristics, and outcomes of patients hospitalized for decompensated heart failure: observations from the IMPACT-HF registry
J Card Fail
(2005)
G.M. Felker et al.
Diuretics and ultrafiltration in acute decompensated heart failure
J Am Coll Cardiol
(2012)
C.W. Yancy et al.
2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
J Am Coll Cardiol
(2013)
A. Bayes-Genis et al.
Serial NT-proBNP monitoring and outcomes in outpatients with decompensation of heart failure
Int J Cardiol
(2007)
A. Morello et al.
Association of atrial fibrillation and amino-terminal pro-brain natriuretic peptide concentrations in dyspneic subjects with and without acute heart failure: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study
Am Heart J
(2007)
R.D. Kociol et al.
Troponin elevation in heart failure prevalence, mechanisms, and clinical implications
J Am Coll Cardiol
(2010)
S. Anwaruddin et al.
Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study
J Am Coll Cardiol
(2006)

J.M. Testani et al.

Clinical characteristics and outcomes of patients with improvement in renal function during the treatment of decompensated heart failure

J Card Fail

(2011)

J.D. Baillargeon et al.

Hemoconcentration as an early risk factor for necrotizing pancreatitis

Am J Gastroenterol

(1998)

A. Boyle et al.

Redefining the therapeutic objective in decompensated heart failure: hemoconcentration as a surrogate for plasma refill rate

J Card Fail

(2006)

C. Davila et al.

Clinical correlates of hemoconcentration during hospitalization for acute decompensated heart failure

J Card Fail

(2011)

P. van der Meer et al.

The predictive value of short-term changes in hemoglobin concentration in patients presenting with acute decompensated heart failure

J Am Coll Cardiol

(2013)

J. Oh et al.

Hemoconcentration is a good prognostic predictor for clinical outcomes in acute heart failure: data from the Korean Heart Failure (KorHF) Registry

Int J Cardiol

(2013)

J.M. Testani et al.

Timing of hemoconcentration during treatment of acute decompensated heart failure and subsequent survival: importance of sustained decongestion

J Am Coll Cardiol

(2013)

H. Bueno et al.

Trends in length of stay and short-term outcomes among Medicare patients hospitalized for heart failure, 1993-2006

JAMA

(2010)

K. Dharmarajan et al.

Diagnoses and timing of 30-day readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia

JAMA

(2013)

M. Metra et al.

Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the PROTECT Study

Eur Heart J

(2011)

M. Vaduganathan et al.

Thirty-day readmissions: the clock is ticking

JAMA

(2013)

Cited by (39)

Early glomerular filtration rate decline is associated with hemoglobin rise following dapagliflozin initiation in heart failure with reduced ejection fraction
2023, Revista Espanola de Cardiologia
Los inhibidores del cotransportador 2 de sodio-glucosa (iSGLT2) inducen cambios a corto plazo en la función renal y la hemoglobina y su fisiopatología se comprende de manera incompleta. Nuestro objetivo es evaluar la relación entre los cambios de la tasa de filtrago glomerular estimado (TFGre) y la hemoglobina tras el inicio de dapagliflozina en pacientes estables con insuficiencia cardiaca y fracción de eyección reducida (IC-FEr).
Este análisis post hoc de un ensayo clínico aleatorizado evaluó el efecto de la dapagliflozina sobre el consumo máximo de oxígeno a 1 y 3 meses en pacientes ambulatorios con IC-FEr estable (ensayo DAPA-VO₂, NCT04197635). Se utilizó un análisis de regresión lineal mixta para evaluar la relación entre los cambios en la TFGe y la hemoglobina a 1 y 3 meses.
Se evaluó a 87 pacientes. La media de edad era 67,0 ± 10,5 años, y 21 pacientes (24,1%) eran mujeres. Las medias basales de TFGe y hemoglobina fueron de 66,9 ± 20,7 ml/min/1,73 m² y 14,3 ± 1,7 g/dl respectivamente. En comparación con el placebo, la TFGe no cambió significativamente en el grupo de dapagliflozina, pero la hemoglobina aumentó significativamente a 1 y 3 meses. A 1 mes, el aumento de la hemoglobina se relacionó con la disminución de la TFGe solo en el grupo de dapagliflozina (p < 0,001). A los 3 meses no había asociación significativa (p = 0,123). Los cambios de la TFGe a 1 y 3 meses no se asociaron con cambios en el consumo pico de oxígeno, la calidad de vida o los péptidos natriuréticos.
En pacientes con IC-FEr estable, los cambios en la TFGe a 1 mes inducidos por la dapagliflozina están en relación inversa con cambios en la hemoglobina. Esta asociación no se observa a los 3 meses.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce short-term changes in renal function and hemoglobin. Their pathophysiology is incompletely understood. We aimed to evaluate the relationship between 1- and 3-month estimated glomerular filtration rate (eGFR) and hemoglobin changes following initiation of dapagliflozin in patients with stable heart failure with reduced ejection fraction (HFrEF).
This is a post hoc analysis of a randomized clinical trial that evaluated the effect of dapagliflozin on 1- and 3-month peak oxygen consumption in outpatients with stable HFrEF (DAPA-VO₂ trial, NCT04197635). We used linear mixed regression analysis to assess the relationship between eGFR and hemoglobin changes across treatment arms.
A total of 87 patients were evaluated in this substudy. The mean age was 67.0 ± 10.5 years, and 21 (24.1%) were women. The mean baseline eGFR and hemoglobin were 66.9 ± 20.7 mL/min/1.73m² and 14.3 ± 1.7 g/dL, respectively. Compared with placebo, eGFR did not significantly change at either time points in the dapagliflozin group, but hemoglobin significantly increased at 1 and 3 months. At 1 month, the hemoglobin increase was related to decreases in eGFR only in the dapagliflozin arm (P < .001). At 3 months, there was no significant association in either treatment arms (P = .123). Changes in eGFR were not associated with changes in peak oxygen consumption, quality of life, or natriuretic peptides.
In patients with stable HFrEF, 1-month changes in eGFR induced by dapagliflozin are inversely related to changes in hemoglobin. This association was no longer significant at 3 months.
Full English text available from:www.revespcardiol.org/en
Relative Blood Volume Profiles Hours After Loop Diuretic Administration: A Systematic Review and Meta-analysis
2023, CJC Open
Plasma refill rates can be estimated by combining measurements of urine output with relative blood volume profiles. Change in plasma refill rates could guide decongestive loop diuretic therapy in acute heart failure. The objective of the study was to assess average relative blood volume profiles generated from 2 or 3 follow-up measurements obtained hours after loop diuretic administration in subjects with vs without baseline congestion.
A systematic review was conducted of articles written in English, French, Spanish, and German, using MEDLINE (1964 to 2019), Cochrane Reviews (1996 to 2019), and Embase (1974 to 2019). Search terms included the following: diuretics, hemoconcentration, plasma volume, and blood volume. We included studies of adults given a loop diuretic with at least one baseline and one follow-up measurement. A single author extracted subject- or group-level blood volume measurements, aggregated them when needed, and converted them to relative changes.
Across all 16 studies that met the prespecified inclusion criteria, relative blood volume maximally decreased 9.2% (6.6% to 12.0%) and returned to baseline after 3 or more hours. Compared to subjects without congestion, those with congestion experienced smaller decreases in relative blood volume across all follow-up periods (P = 0.001) and returned to baseline within the final follow-up period.
Single doses of loop diuretics produce measurable changes in relative blood volume that follow distinct profiles for subjects with vs without congestion. Measured alongside urine output, these profiles may be used to estimate plasma refill rates—potential patient-specific targets for decongestive therapy across serial diuretic doses.
Le taux de remplissage plasmatique peut être estimé en combinant les mesures de la diurèse et les profils volémiques relatifs. Chez les personnes atteintes d’insuffisance cardiaque aiguë, une variation du taux de remplissage plasmatique pourrait guider un traitement décongestif par un diurétique de l’anse. L’étude avait pour objectif d’évaluer les profils volémiques relatifs moyens obtenus dans le cadre de deux ou trois mesures de suivi réalisées quelques heures après l’administration d’un diurétique de l’anse à des sujets présentant ou non une congestion initiale.
Une revue systématique d’articles rédigés en anglais, en français, en espagnol et en allemand a été effectuée au moyen des bases de données MEDLINE (1964 à 2019), Cochrane Reviews (1996 à 2019) et Embase (1974 à 2019). Les termes de recherche comprenaient : diurétiques, hémoconcentration, volume plasmatique et volume sanguin. Nous avons inclus des études portant sur des adultes ayant reçu un diurétique de l’anse chez qui au moins une mesure initiale et une mesure de suivi avaient été effectuées. Un seul auteur a recueilli des mesures du volume sanguin individuelles ou de groupe, les a regroupées, au besoin, et converties en variations relatives.
Parmi les 16 études qui répondaient aux critères d’inclusion prédéfinis, le volume sanguin relatif a diminué de 9,2 % (de 6,6 % à 12,0 %) et est revenu aux valeurs initiales après trois heures ou plus. Les sujets qui présentaient une congestion ont connu des diminutions du volume sanguin relatif inférieures à celles de ceux n’en présentant pas lors de toutes les périodes de suivi (p = 0,001); le volume sanguin relatif est revenu aux valeurs initiales durant la période finale de suivi.
Des doses uniques de diurétique de l’anse produisent des changements mesurables du volume sanguin relatif selon des profils distincts chez les sujets présentant une congestion, comparativement à ceux n’en présentant pas. Utilisés en association avec les mesures de la diurèse, ces profils peuvent servir à estimer le taux de remplissage plasmatique, qui constitue potentiellement une cible particulière au patient qui reçoit une série de doses d’un diurétique comme traitement décongestif.
Treatment of Cardiorenal Syndrome
2019, Cardiology Clinics
Citation Excerpt :
When achieved, hemoconcentration has been shown to be associated with increased fluid removal, high-diuretic doses, and reduced body weight, while carrying an increased risk of in-hospital WRF. Even with changes in renal function, hemoconcentration has improved short-term mortality and rates of readmission, suggesting that not all fluctuations in creatinine correlate to a poor prognosis.9 Regardless of the diuretic regimen, diuretic resistance is common, especially in patients with severe HF symptoms, and has been reported to occur in 30% of patients with HF on diuretic therapy.10
Worsening renal function during decongestion among patients hospitalized for heart failure: Findings from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial
2018, American Heart Journal
Citation Excerpt :
Given variability in assessment of clinical congestion, and issues regarding the feasibility, invasive nature of PAC, other objective markers of decongestion have been evaluated.19 Attainment of hemoconcentration during an acute HF hospitalization has been associated with more aggressive diuretic use, weight loss, reductions in filling pressures, and, importantly, improvement in short term mortality.8,20,21 Similarly, higher levels of plasma volume, estimated non-invasively, have been independently associated with increased cardiovascular mortality9,22,23 and a decrease of the estimated plasma volume during a hospitalization for HF and beyond the hospitalization were associated with better outcomes.9,23
Worsening renal function (WRF) can occur throughout a hospitalization for acute heart failure (HF). However, decongestion can be measured in different ways and the prognostic implications of WRF in the setting of different measures of decongestion are unclear.
Patients (N = 433) from the ESCAPE were classified by measures of decongestion during hospitalization: hemodynamic (right atrial pressure ≤8 mmHg and/or wedge pressure ≤15 mmHg at discharge), clinical (≤1 sign of congestion at discharge), hemoconcentration (any increase in hemoglobin) and estimated plasma volume using the Hakim formula (5% reduction in plasma volume). WRF was defined as creatinine increase ≥0.3 mg/dl during hospitalization. The association between WRF and 180-day all-cause death was assessed.
Successful decongestion was observed in 124 (60%) patients by hemodynamics, 204 (49%) by clinical exam, 173 (47%) by hemoconcentration, and 165 (45%) by plasma volume. There was no agreement between the hemodynamic assessment and other decongestion measures in up to 43% of cases. Persistent congestion with concomitant WRF at discharge was associated with worse outcomes compared to patients without congestion and WRF. Among patients decongested at discharge, in-hospital WRF was not significantly associated with 180-day all-cause death, when using hemodynamic, clinical or estimated plasma volume as measures of decongestion (P > .05 for all markers).
In patients hospitalized for HF, although there was disagreement across common measures of decongestion, in-hospital WRF was not associated with increased hazard of all-cause mortality among patients successfully decongested at discharge.
Putting creatinine and hemoconcentration in their place as prognostic predictors in the conundrum of acute heart failure
2018, Revista Portuguesa de Cardiologia
Integrative Assessment of Congestion in Heart Failure Throughout the Patient Journey
2018, JACC: Heart Failure
Congestion is one of the main predictors of poor patient outcome in patients with heart failure. However, congestion is difficult to assess, especially when symptoms are mild. Although numerous clinical scores, imaging tools, and biological tests are available to assist physicians in ascertaining and quantifying congestion, not all are appropriate for use in all stages of patient management. In recent years, multidisciplinary management in the community has become increasingly important to prevent heart failure hospitalizations. Electronic alert systems and communication platforms are emerging that could be used to facilitate patient home monitoring that identifies congestion from heart failure decompensation at an earlier stage. This paper describes the role of congestion detection methods at key stages of patient care: pre-admission, admission to the emergency department, in-hospital management, and lastly, discharge and continued monitoring in the community. The multidisciplinary working group, which consisted of cardiologists, emergency physicians, and a nephrologist with both clinical and research backgrounds, reviewed the current literature regarding the various scores, tools, and tests to detect and quantify congestion. This paper describes the role of each tool at key stages of patient care and discusses the advantages of telemedicine as a means of providing true integrated patient care.

View all citing articles on Scopus

: Funding: None.

: Conflict of Interest: MV and SJG: None. GCF receives research support from the Agency for Healthcare Research and Quality (significant) and is a consultant to Medtronic (modest), Gambro (significant), and Novartis (significant). AAV receives consultancy fees and research grants from Alere, AstraZeneca, Bayer, Boehringer Ingelheim, Cardio3 Biosciences, Celladon, Johnson & Johnson, Merck/MSD, Novartis, Servier, Torrent, Trevena, and Vifor. JB receives research support from the National Institutes of Health, European Union, Health Resources and Services Administration, and U.S. Food and Drug Administration; is a consultant to Amgen, Bayer, Celladon, Gambro, GE Healthcare, Janssen, Medtronic, Novartis, Ono, Relypsa, and Trevena; and has stock options in Stemedica. MG is a consultant to Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical, and Trevena Therapeutics.

: Authorship: All authors had access to the data and played a role in writing this manuscript.

View full text

ReviewHemoconcentration-guided Diuresis in Heart Failure

Abstract

Section snippets

Concentrating on the Problem: Optimizing Volume and Quality

Pitfalls of Traditional Approaches

Hemoconcentration: A Review of the Available Data

Hemoconcentration: Considerations and Qualifications

A Proposed Hemoconcentration-Guided Therapeutic Strategy

Conclusions

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

J Card Fail

J Am Coll Cardiol

J Am Coll Cardiol

Int J Cardiol

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

J Card Fail

Am J Gastroenterol

J Card Fail

J Card Fail

J Am Coll Cardiol

Int J Cardiol

J Am Coll Cardiol

Trends in length of stay and short-term outcomes among Medicare patients hospitalized for heart failure, 1993-2006

JAMA

Diagnoses and timing of 30-day readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia

JAMA

Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the PROTECT Study

Eur Heart J

Thirty-day readmissions: the clock is ticking

JAMA

Review
Hemoconcentration-guided Diuresis in Heart Failure