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Prognostic impact of plasma volume estimated from hemoglobin and hematocrit in heart failure with preserved ejection fraction

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Abstract

Background

Plasma volume (PV) estimated from Duarte's formula (based on hemoglobin/hematocrit) has been associated with poor prognosis in patients with heart failure (HF). There are, however, limited data regarding the association of estimated PV status (ePVS) derived from hemoglobin/hematocrit with clinical profiles and study outcomes in patients with HF and preserved ejection fraction (HFpEF).

Methods and results

Patients from North and South America enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) with available hemoglobin/hematocrit data were studied. The association between ePVS (Duarte formula and Hakim formula) and the composite of cardiovascular mortality, HF hospitalization, or aborted cardiac arrest was assessed. Among 1747 patients (age 71.6 years; males 50.1%), mean ePVS derived from Duarte formula was 4.9 ± 1.0 mL/g. Higher Duarte-derived ePVS was associated with prior HF admission, diabetes, more severe congestion, poor renal function, higher natriuretic peptide level, and E/e'. After adjustment for potential covariates including natriuretic peptide, higher Duarte-derived ePVS was associated with an increased rate of the primary outcome [highest vs. lowest ePVS quartile: adjusted-HR (95%CI) = 1.79 (1.28–2.50), p < 0.001]. Duarte-derived ePVS improved prognostic performance on top of clinical and routine variables (including natriuretic peptides) (NRI = 11, p < 0.001), whereas Hakim-derived ePVS did not (p = 0.59). The prognostic value of Duarte-derived ePVS was not modified by renal function (P interaction > 0.10 for all outcomes).

Conclusion

ePVS from Duarte’s formula was associated with congestion status and improved risk stratification regardless of renal function. Our findings suggest that Duarte-derived ePVS is a useful congestion variable in patients with HFpEF.

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Acknowledgements

The TOPCAT trial was funded and sponsored by the NHLBI. The Nancy team is supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program (reference: ANR-15-RHUS-0004), by the French PIA project “Lorraine Université d’Excellence” (reference: ANR-15-IDEX-04-LUE), the ANR FOCUS-MR (reference: ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02), and Contrat de Plan Etat Lorraine IT2MP and FEDER Lorraine.

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Author notes

  1. Masatake Kobayashi and Nicolas Girerd contributed equally to this work.

Authors and Affiliations

  1. Centre d’Investigations Cliniques 1433, Université de Lorraine, INSERM, CHRU de Nancy, Inserm 1116 and INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network, Institut Lorrain du cœur Et des, Vaisseaux Louis Mathieu, 4, rue du Morvan, 54500, Vandoeuvre-Les-Nancy, Nancy, France

    Masatake Kobayashi, Nicolas Girerd, Kevin Duarte, Gregoire Preud’homme & Patrick Rossignol

  2. Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA

    Bertram Pitt

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  1. Masatake Kobayashi
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  2. Nicolas Girerd
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Correspondence to Patrick Rossignol.

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Conflict of interest

P.R. reports grants and personal fees from AstraZeneca, grants and personal fees from Bayer, grants and personal fees from CVRx, personal fees from Fresenius, grants and personal fees from Novartis, personal fees from Grunenthal, personal fees from Servier, personal fees from Stealth Peptides, personal fees from Vifor Fresenius Medical Care Renal Pharma, personal fees from Idorsia, personal fees from NovoNordisk, personal fees from Ablative Solutions, personal fees from G3P, personal fees from Corvidia, personal fees from Relypsa, outside the submitted work; and Cofounder: CardioRenal, a company developing a telemonitoring loop in heart failure (including potassium measurements). B.P. reports personal fees (consulting) from Bayer, KBP Pharmaceuticals, AstraZeneca, Relypsa/Vifor, Sanofi, sc Pharmaceuticals, Sarfez pharmaceuticals, Stealth Peptides, Cereno Scientific, SQinnovations, G3 pharmaceuticals, Ardelyx and Tricida; stock options from KBP Pharmaceuticals, sc Pharmaceuticals, Sarfez pharmaceuticals, Relypsa, Cereno scientific, SQinnovations, G3 pharmaceuticals, Ardelyx and Tricida; patent for site specific delivery of eplerenone to the myocardium US patent Number 9931412. N.G. reports honoraria from Novartis and Boehringer. All other authors have no conflicts to disclose.

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Kobayashi, M., Girerd, N., Duarte, K. et al. Prognostic impact of plasma volume estimated from hemoglobin and hematocrit in heart failure with preserved ejection fraction. Clin Res Cardiol 109, 1392–1401 (2020). https://doi.org/10.1007/s00392-020-01639-4

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