By Van Selby, MD

Assistant Professor of Medicine, University of California, San Francisco, Cardiology Division, Advanced Heart Failure Section

Dr. Selby reports no financial relationships relevant to this field of study.

SYNOPSIS: Among patients hospitalized for acute heart failure, hemoconcentration was associated with reduced 90-day mortality and may be a useful marker for guiding therapy.

SOURCE: Breidthardt T, Weidmann ZM, Twerenbold R, et al. Impact of haemoconcentration during acute heart failure therapy on mortality and its relationship with worsening renal function. Eur J Heart Fail 2017;19:226-236.

Decongestion is a primary goal in the management of acute heart failure (AHF), and hemoconcentration has been identified as a potential marker of decongestion. Breidthardt et al sought to evaluate the association between hemoconcentration, worsening renal function (WRF), and mortality in patients hospitalized for AHF. In a prospective cohort of 1,019 patients hospitalized for AHF at a single academic center in Switzerland, serial measurements of hematocrit, hemoglobin, total protein, creatinine, and albumin levels were made. Hemoconcentration was defined as a simultaneous increase in at least three of the four markers above admission values at any point during hospitalization. Patients with hemoconcentration were further subdivided into those achieving early (day 1-4) vs. late (day 5 or beyond) hemoconcentration. Worsening renal function (WRF) was defined as any increase of at least 0.3 mg/dL in serum creatinine at any time during hospitalization. The primary outcome was 90-day mortality.

Overall, 38.5% of patients met criteria for hemoconcentration during their hospitalization, and the median time until the occurrence of hemoconcentration was 6.3 days. There were no significant baseline clinical or demographic differences between those with and without hemoconcentration. Patients with hemoconcentration had greater evidence of successful decongestion during their hospitalization as measured by change in B-type natiuretic peptide level and weight loss. After adjusting for other predictors of death, hemoconcentration was associated with reduced 90-day mortality (hazard ratio [HR], 0.59; P = 0.01). However, the mortality reduction was only observed in patients with late hemoconcentration (late vs. early hemoconcentration HR, 0.41; P = 0.03). Patients with hemoconcentration were more likely to develop WRF (37.1 vs. 30.8%; P = 0.04). However, patients with hemoconcentration and WRF still had lower 90-day mortality than patients without hemoconcentration. The authors concluded that hemoconcentration is an inexpensive and easily accessible measure of adequate decongestion in AHF and is associated with lower mortality.

COMMENTARY

Correction of hypervolemia is a mainstay of treatment for AHF. However, accurate assessment of volume status can be challenging, and often is made based on a combination of physical exam, symptoms, imaging studies, and laboratory results. Studies have found that many AHF patients ultimately leave the hospital without adequate fluid removal, contributing to high observed rates of readmission and adverse outcomes after hospital discharge. Accurate, reliable assessment of congestion has been referred to as the Holy Grail of heart failure management, and additional tools to guide treatment of AHF are needed. The concept of hemoconcentration as a clinical marker is based on the idea that successfully reducing intravascular volume must lead to an increased concentration of large intravascular molecules such as hemoglobin and albumin. Several prior studies have identified a correlation between hemoconcentration and improved outcomes after hospitalization for AHF. However, these studies often were performed in highly selected populations, without rigorous definitions for hemoconcentration. This study is among the largest to date, evaluating hemoconcentration prospectively in a real-world AHF cohort. The findings strengthen the association between hemoconcentration and reduced mortality following hospitalization for AHF. In this study, there was a clear distinction between patients who achieved early vs. late hemoconcentration. Survival among patients who achieved hemoconcentration within the first four days of hospitalization was no better than among those who did not achieve hemoconcentration. The authors suggested that patients achieving later hemoconcentration may be more likely to experience persistent hemoconcentration, and, therefore, a slow and steady approach to diuretics may be preferable.

The finding that patients with hemoconcentration are more likely to develop worsening renal failure during hospitalization has been reported previously. WRF often prompts clinicians to de-escalate diuretic therapy, and may explain why many of the “early hemoconcentrators” in this study regressed to “no hemoconcentration” by the time of discharge, and, therefore, had higher mortality compared to those with a late, sustained hemoconcentration. The authors showed the benefits of decongestion (and hemoconcentration) outweigh the risks associated with WRF, suggesting clinicians should not let a small rise in creatinine prevent them from achieving adequate diuresis in patients admitted for AHF.

The primary limitation of this study is its observational design. Although there is a clear association between hemoconcentration and improved outcomes, we cannot conclude that incorporating hemoconcentration as a therapeutic target in AHF management protocols will improve mortality. Hopefully, future studies will address this. This study adds to a growing body of literature demonstrating the prognostic value of hemoconcentration in AHF. No measurement of volume status is perfect, and hemoconcentration cannot replace other measures completely. Rather, it should be viewed as another tool to complement the current options for assessing congestion. It is a low-cost, practical, noninvasive test, and given the clear association with outcomes, clinicians should strongly consider incorporating hemoconcentration into the management of AHF.