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Comparative Study
. 2018 Nov;47(6):565-575.
doi: 10.1016/j.hrtlng.2018.09.002. Epub 2018 Oct 9.

Comparative symptom biochemistry between moderate and advanced heart failure

Christopher S Lee  1 , Quin E Denfeld  2 , Bradley E Aouizerat  3 , Corrine Y Jurgens  4 , Christopher V Chien  5 , Emily Aarons  6 , Jill M Gelow  7 , Shirin O Hiatt  8 , James O Mudd  9
Affiliations
Comparative Study

Comparative symptom biochemistry between moderate and advanced heart failure

Christopher S Lee et al. Heart Lung. 2018 Nov.

Abstract

Background: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF).

Objectives: The purpose of this paper was to compare relationships between peripheral biomarkers of HF pathogenesis and physical symptoms between patients with advanced versus moderate HF.

Methods: This was a two-stage phenotype sampling cohort study wherein we examined patients with advanced HF undergoing ventricular assist device implantation in the first stage, and then patients with moderate HF (matched adults with HF not requiring device implantation) in the second stage. Linear modeling was used to compare relationships among biomarkers and physical symptoms between cohorts.

Results: Worse myocardial stress, systemic inflammation and endothelial dysfunction were associated with worse physical symptoms in moderate HF (n=48), but less physical symptom burden in advanced HF (n=48).

Conclusions: Where patients are in the HF trajectory needs to be taken into consideration when exploring biological underpinnings of physical HF symptoms.

Keywords: Biomarkers; Heart failure; Symptoms.

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Figures

Figure 1:
Figure 1:
Multi-Marker Strategy to Capture Key Elements of Heart Failure Pathogenesis. The primary source and interpretation of each biomarkers is presented. Abbreviations: NTproBNP = amino terminal pro-B-type natriuretic peptide; sE-selectin = soluble E-selectin; sP-selectin = soluble P-selectin; sST2 = soluble interleukin-1 receptor precursor; sTNFαR1 = soluble tumor necrosis factor α receptor 1.
Figure 2:
Figure 2:. Relationships between NTproBNP and Symptoms Comparing Moderate to Advanced Heart Failure.
In each image, the symptoms are presented on the y-axis, the natural log of NTproBNP (a metric of myocardial stress) is presented on the x-axis (within the range observed in this study), results from the moderate heart failure cohort are represented by dashed lines with circles at the mean, and results from the advanced heart failure cohort are represented by solid gray lines with squares at the mean. Higher levels of NTproBNP were associated with worse early & subtle symptoms in moderate heart failure, but were associated with fewer early & subtle symptoms in advanced heart failure (interaction p=0.006). Similarly, higher levels of NTproBNP were associated with worse wake disturbances in moderate heart failure but fewer wake disturbances in advanced heart failure (interaction p=0.005). Higher levels of NTproBNP also were associated with worse pain interference in moderate heart failure but less pain interference in advanced heart failure (interaction p=0.025) – data not shown in graph for economy of presentation. CI = confidence interval; NTproBNP = amino terminal pro-B-type natriuretic peptide.
Figure 3:
Figure 3:. Relationships between sTNFαR1 and Symptoms Comparing Moderate to Advanced Heart Failure.
In each image, the symptoms are presented on the y-axis, the natural log of sTNFαR1 (a metric of systemic inflammation) is presented on the x-axis (within the range observed in this study), results from the moderate heart failure cohort are represented by dashed lines with circles at the mean, and results from the advanced heart failure cohort are represented by solid gray lines with squares at the mean. Higher levels of sTNFαR1 were associated with greater pain severity and interference in moderate heart failure, but were associated with less pain severity and interference in advanced heart failure (both interaction p<0.05). CI = confidence interval; sTNFαR1 = soluble tumor necrosis factor α receptor 1.
Figure 4:
Figure 4:. Relationships between sE-Selectin and Symptoms Comparing Moderate to Advanced Heart Failure.
In each image, the symptoms are presented on the y-axis, the natural log of sE-Selectin (a metric of endothelial dysfunction) is presented on the x-axis (within the range observed in this study), results from the moderate heart failure cohort are represented by dashed lines with circles at the mean, and results from the advanced heart failure cohort are represented by solid gray lines with squares at the mean. Higher levels of sE-Selectin were associated with worse dyspnea in moderate heart failure, but were associated with less dyspnea in advanced heart failure (interaction p=0.034). Similarly, higher levels of sE-Selectin were associated with worse early & subtle symptoms in moderate heart failure but less early & subtle symptoms in advanced heart failure (interaction p=0.007). CI = confidence interval; sE-Selectin = soluble E-Selectin.
See this image and copyright information in PMC

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