Physicians' Academy for Cardiovascular Education

AF associated with different CV risk marker profiles in HFpEF and HFrEF

Comparing biomarker profiles of patients with heart failure: atrial fibrillation vs. sinus rhythm and reduced vs. preserved ejection fraction

Literature - Santema BT, Kloosterman M, Van Gelder IC et al. - Eur Heart J 2018; published online ahead of print

Introduction and methods

Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are known to have different pathophysiological backgrounds, and therefore, atrial fibrillation (AF) may have different effects on these two HF phenotypes [1-3]. Biomarkers may contribute to the understanding of these differences. Therefore, this post hoc analysis of the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) [4,5] evaluated the biomarker profiles of patients with HFrEF and HFpEF, with and without AF.

BIOSTAT-CHF is an observational study that included patients with new-onset or worsening signs and/or symptoms of HF, documented either by left ventricular ejection fraction (LVEF) of ≤40%, or plasma concentrations of NTproBNP >2000 pg/mL, who were categorized into two groups based on transthoracic echocardiography: HFrEF (LVEF <40%) and HFpEF (LVEF ≥50%). Patients with unknown LVEF and those with LVEF of 40%-49% were excluded from this analysis. Biomarker profiles were created based on the Olink Cardiovascular III panel, which includes 92 CVD-related biomarkers. The primary outcome was time to all-cause mortality.

Main results


In this observational study AF was associated with a homogeneously elevated CV risk marker profile in HFrEF patients, whereas in HFpEF, the presence of AF was associated with a more scattered risk marker profile. These findings suggest that there might be differences in underlying pathophysiological mechanisms of AF in these two HF phenotypes.

Editorial comment

In their editorial article, Nishimura and Maisel [6] note that in the study of Santema et al., risk markers were not increased in patients with AF and HFpEF, a finding that is not in accordance with existing data, and emphasize that despite that, the mortality was higher in the total cohort of HF with AF, which leaves a question open in regard to the clinical implications of the various biomarker profiles. Moreover, they point at a weakness in the inclusion criteria, which allow the inclusion of only those HFpEF patients who had increased NT-proBNP levels, who probably represent the ‘sickest’ HFpEF patients. Next, the authors discuss the importance of clinical context in interpretation of biomarkers. Current national guidelines rely heavily on cardiac biomarkers for the diagnosis and management of conditions such as HF. However, while these biomarkers can be extremely valuable, various underlying conditions, such as the presence of HFpEF vs. HFrEF and AF vs. normal SR, can drastically change the expressed biomarkers as seen in this study. They conclude: ‘Elevation of biomarkers can be reflective of a number of competing mechanisms, and interpretation must be done with caution. The ability to use and interpret these biomarkers appropriately is integral to the care of cardiac patients.’


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Find this article online at Eur Heart J

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