van der Meer P, Postmus D, Ponikowski P, et al.
J Am Coll Cardiol. 2013 May 14;61(19):1973-81. doi: 10.1016/j.jacc.2012.12.050

Background

Anemia is frequently seen in patients with chronic heart failure (HF) and is associated with a two-fold increased mortality rate [1,2]. Anaemia in HF can be the consequence of various conditions. In acute decompensated HF (AHF) attention is drawn to haemodilution as a cause of anaemia. An increase in haematocrit in AHF was associated with impaired renal function (3,4). In one study it was related to improved survival (3), while it was not in another study (4). Only baseline and discharge haemoglobin levels were studied.
The current study aimed to evaluate the effect of changes in haemoglobin levels on clinical outcome, in 1969 patients with AHF. Haemoglobin was measured at multiple time points in the first week after admission for AHF. This is a non-prespecified post-hoc analysis of the PROTECT (Placebo-Controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) study (5,6).

Main results

• Haemoconcentration was seen in 69.1% of the patients and  associated with a better renal function at baseline. Decline in renal function during the first week was more pronounced in patients with as compared to without haemoconcentration (% change in creatinine: +6.4 + 26 vs. +3.1 +26, P=0.01).
• Decline in renal function was seen in 46% of patients, and was associated with older age, lower haemoglobin levels at baseline, and a higher increase in haemoglobin levels during the first week as compared to patients with improved renal function (+0.38 +1.2 vs. +0.16 + 1.1, P<0.01).
• Haemoglobin levels increased on average with 0.3 + 0.7 g/dl over the first week of hospitalisation. Interaction analysis revealed that a steeper increase of the haemoglobin curve over time was associated with better baseline renal function. Also, greater weight reduction in the first 4 days after admission was associated with a steeper increase in haemoglobin levels.
• The primary outcome of all-cause mortality by day 180 was lower in patients with no anaemia at baseline and haemoconcentration. In a multivariate model, the absolute change in haemoglobin predicted 180-day mortality (HR: 0.66, 95%CI: 0.51-0.86, P=0.002). Baseline haemoglobin concentration lost its predictive value after correction for renal function and age.

Conclusion

In patients with AHF and renal dysfunction, a large increase in haemoglobin during hospitalisation is associated with better survival at 180 day. Statistical analysis suggests that renal function and age are more important in determining clinical outcome than baseline haemoglobin levels. This study suggests that patients with AHF and preserved renal function are decongested better, as indicated by the increased haemoglobin levels. A rapid increase in haemoglobin levels in the first week is associated with a favourable prognosis, despite a small decrease in renal function.

Editorial comment [7]

Although almost half of the patients who present with AHF are anaemic, until now the prognostic value of haemoglobin was unclear in this situation. The current study addresses this issue.
Patients with haemoconcentration seemed to experience more effective reduction in intravascular plasmavolume. The findings suggest that resolution of congestion may be important even when some decline in renal function is the result.
This study concerns a non-prespecified post-hoc analysis, so the results may not be easily generalised to a broader AHF population. Nevertheless, the data indicate an important contributing role for  haemodilution to the development of anaemia in AHF patients. Anaemia in AHF may reflect the severity of overload and haemoconcentration may follow on effective relief of congestion.

References

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2. Groenveld HF, Januzzi JL, Damman K, et al. Anemia and mortality in heart failure patients a systematic review and meta-analysis. J Am Coll Cardiol 2008;52:818 –27.
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4. Davila C, Reyentovich A, Katz SD. Clinical correlates of haemoconcentration during hospitalization for acute decompensated heart failure. J Card Fail 2011;17:1018 –22.
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6. Weatherley BD, Cotter G, Dittrich HC, et al. Design and rationale of the PROTECT study: a placebo-controlled randomized study of the selective A1 adenosine receptor antagonist rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function. J Card Fail 2010;16:25–35.
7. Desai AS. Hemoglobin concentration in acute decompensated heart failure: a marker of volume status?
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