Elsevier

American Heart Journal

Volume 164, Issue 5, November 2012, Pages 763-770.e3
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Biomarkers in acutely decompensated heart failure with preserved or reduced ejection fraction

https://doi.org/10.1016/j.ahj.2012.08.014Get rights and content

Background

Acute decompensated heart failure (ADHF) occurs with preserved (heart failure with preserved ejection fraction [HFpEF] ≥50%) or reduced (heart failure with reduced ejection fraction [HFrEF] <50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers, specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, and a biomarker that reflects collagen synthesis.

Methods

In this prespecified ancillary analysis of patients with ADHF enrolled in the Diuretic Optimization Strategies Evaluation study, clinical features and N-terminal pro–B-type NP, cystatin C, plasma renin activity, aldosterone, oxidative stress (uric acid), and procollagen type III N-terminal peptide were compared in HFpEF and HFrEF at enrollment and 60-day follow-up.

Results

Compared with HFrEF (n = 219), HFpEF (n = 81) patients were older, heavier, more commonly female, less treated with RAAS antagonists, but with similar New York Heart Association class, jugular venous pressure, and edema severity. N-terminal pro–B-type NP was lower, and systolic blood pressure and cystatin C were higher in HFpEF. Despite higher systolic blood pressure and less RAAS antagonist use in HFpEF, plasma renin activity and aldosterone levels were similar in HFpEF and HFrEF as were uric acid and procollagen type III N-terminal peptide levels. Changes in biomarker levels from enrollment to 60 days were similar between HFrEF (n = 149) and HFpEF (n = 50).

Conclusion

Lower NP levels in decompensated HFpEF occur in association with similar ADHF severity, more impaired vascular and renal function but similar elevation of biomarkers that reflect RAAS activation, oxidative stress, and collagen synthesis as in HFrEF.

Section snippets

Methods

The DOSE study was a prospective, randomized, double-blind, controlled trial conducted by the Heart Failure Clinical Research Network (HFCRN) examining responses to different diuretic intensification (1.0 and 2.5 times outpatient dose) and administration (intravenous bolus or continuous infusion) strategies. The data coordinating center (Duke Clinical Research Institute) was responsible for data management and statistical analysis. The study was approved by the institutional review board at

Clinical characteristics in HFrEF and HFpEF with ADHF

A total of 308 patients were enrolled in the DOSE trial. Left ventricular ejection fraction (LVEF) assessment within 1 year (median of 1.3 months, IQR of 0 to 5.9 months) was available in 300 patients (echocardiogram [n = 287], radionuclide [n = 3] or contrast ventriculogram [n = 6], or other [n = 4]) (Table I). There were 219 patients (73%) with HFrEF (median LVEF 24%, IQR 20%-32%) and 81 patients (27%) with HFpEF (median LVEF 57%, IQR 55%-64%). Consistent with previous reports, HFpEF patients

Discussion

In this well-characterized, prospectively enrolled cohort of patients with ADHF, NT-proBNP levels were lower in HFpEF than HFrEF despite similar severity of ADHF. Heart failure with preserved ejection fraction was characterized by higher systolic blood pressure, more severe renal dysfunction but similar biomarkers of RAAS activation, and oxidative stress as well as the serum peptide, PIIINP, which reflects collagen synthesis. Furthermore, changes in all biomarkers at follow-up were

Limitations

Assessment of biomarkers was carried out at enrollment and administration of diuretics before enrollment may have influenced our findings. The DOSE trial did not mandate EF measurement during the hospitalization. However, the median time since EF evaluation was 1.3 months, and the characteristics of HFpEF patients were similar to those described in other studies. The smaller number of subjects with paired data at 60 days limited power to detect differences and patients who were sicker may not

Conclusion

In this contemporary, prospectively enrolled cohort of patients with ADHF, patients with HFpEF had similar HF severity as patients with HFrEF. However, as compared with HFrEF, HFpEF patients had lower NT-proBNP; higher systolic blood pressure; and more severe renal dysfunction with similar levels of RAAS activation, oxidative stress, and a marker that reflects collagen synthesis. These findings underscore the importance of similarly altered biomarkers of neurohumoral activation, oxidative

Disclosures

The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents.

References (36)

  • V.R. Dharnidharka et al.

    Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis

    Am J Kidney Dis

    (2002)
  • M.G. Shlipak et al.

    Cystatin-C and mortality in elderly persons with heart failure

    J Am Coll Cardiol

    (2005)
  • R.V. Shah et al.

    The effect of renin-angiotensin system inhibitors on mortality and heart failure hospitalization in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis

    J Card Fail

    (2010)
  • C.R. Benedict et al.

    Comparative neurohormonal responses in patients with preserved and impaired left ventricular ejection fraction: results of the Studies of Left Ventricular Dysfunction (SOLVD) Registry. The SOLVD Investigators

    J Am Coll Cardiol

    (1993)
  • G. Guder et al.

    Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure

    Circulation

    (2007)
  • D.W. Kitzman et al.

    Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure

    J Am Med Assoc

    (2002)
  • M. Nagase et al.

    Role of natriuretic peptide receptor type C in Dahl salt-sensitive hypertensive rats

    Hypertension

    (1997)
  • T.J. Wang et al.

    Impact of obesity on plasma natriuretic peptide levels

    Circulation

    (2004)
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    Jerome L. Fleg, MD, Clin. Inv., CHF served as guest editor for this article.

    Funding sources: The HFCRN is supported by grants HL084861, HL084875, HL084877, HL084889, HL084890, HL084891, HL084899, HL084904, HL084907, and HL084931. K.B. is supported by HL07111-83, whereas support for mentoring K.B. as a HFCRN Skills Development fellow is provided by HL084907 and UL1 RR024150.

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