TY - JOUR
T1 - Pathophysiological processes and novel biomarkers associated with congestion in heart failure
AU - Pandhi, Paloma
AU - ter Maaten, Jozine M.
AU - Anker, Stefan D.
AU - Ng, Leong L.
AU - Metra, Marco
AU - Samani, Nilesh J.
AU - Lang, Chim C.
AU - Dickstein, Kenneth
AU - de Boer, Rudolf A.
AU - van Veldhuisen, Dirk J.
AU - Voors, Adriaan A.
AU - Sama, Iziah E.
N1 - Funding Information:
Dr. de Boer is supported by a grant from the European Research Council (ERC CoG 818715, SECRETE-HF).
Copyright Information:
© 2022 by the American College of Cardiology Foundation. Published by Elsevier.
PY - 2022/9
Y1 - 2022/9
N2 - Background: Congestion is the main driver behind symptoms of heart failure (HF), but pathophysiology related to congestion remains poorly understood.Objectives: Using pathway and differential expression analyses, the authors aim to identify biological processes and biomarkers associated with congestion in HF.Methods: A congestion score (sum of jugular venous pressure, orthopnea, and peripheral edema) was calculated in 1,245 BIOSTAT-CHF patients with acute or worsening HF. Patients with a score ranking in the bottom or top categories of congestion were deemed noncongested (n = 408) and severely congested (n = 142), respectively. Plasma concentrations of 363 unique proteins (Olink Proteomics Multiplex CVD-II, CVD-III, Immune Response and Oncology II panels) were compared between noncongested and severely congested patients. Results were validated in an independent validation cohort of 1,342 HF patients (436 noncongested and 232 severely congested).Results: Differential protein expression analysis showed 107/363 up-regulated and 6/363 down-regulated proteins in patients with congestion compared with those without. FGF-23, FGF-21, CA-125, soluble ST2, GDF-15, FABP4, IL-6, and BNP were the strongest up-regulated proteins (fold change [FC] >1.30, false discovery rate [FDR], P < 0.05). KITLG, EGF, and PON3 were the strongest down-regulated proteins (FC <−1.30, FDR P < 0.05). Pathways most prominently involved in congestion were related to inflammation, endothelial activation, and response to mechanical stimulus. The validation cohort yielded similar findings.Conclusions: Severe congestion in HF is mainly associated with inflammation, endothelial activation, and mechanical stress. Whether these pathways play a causal role in the onset or progression of congestion remains to be established. The identified biomarkers may become useful for diagnosing and monitoring congestion status.
AB - Background: Congestion is the main driver behind symptoms of heart failure (HF), but pathophysiology related to congestion remains poorly understood.Objectives: Using pathway and differential expression analyses, the authors aim to identify biological processes and biomarkers associated with congestion in HF.Methods: A congestion score (sum of jugular venous pressure, orthopnea, and peripheral edema) was calculated in 1,245 BIOSTAT-CHF patients with acute or worsening HF. Patients with a score ranking in the bottom or top categories of congestion were deemed noncongested (n = 408) and severely congested (n = 142), respectively. Plasma concentrations of 363 unique proteins (Olink Proteomics Multiplex CVD-II, CVD-III, Immune Response and Oncology II panels) were compared between noncongested and severely congested patients. Results were validated in an independent validation cohort of 1,342 HF patients (436 noncongested and 232 severely congested).Results: Differential protein expression analysis showed 107/363 up-regulated and 6/363 down-regulated proteins in patients with congestion compared with those without. FGF-23, FGF-21, CA-125, soluble ST2, GDF-15, FABP4, IL-6, and BNP were the strongest up-regulated proteins (fold change [FC] >1.30, false discovery rate [FDR], P < 0.05). KITLG, EGF, and PON3 were the strongest down-regulated proteins (FC <−1.30, FDR P < 0.05). Pathways most prominently involved in congestion were related to inflammation, endothelial activation, and response to mechanical stimulus. The validation cohort yielded similar findings.Conclusions: Severe congestion in HF is mainly associated with inflammation, endothelial activation, and mechanical stress. Whether these pathways play a causal role in the onset or progression of congestion remains to be established. The identified biomarkers may become useful for diagnosing and monitoring congestion status.
KW - biomarkers
KW - congestion
KW - heart failure
KW - pathway analysis
UR - http://www.scopus.com/inward/record.url?scp=85136092547&partnerID=8YFLogxK
U2 - 10.1016/j.jchf.2022.05.013
DO - 10.1016/j.jchf.2022.05.013
M3 - Article
C2 - 36049813
SN - 2213-1779
VL - 10
SP - 623
EP - 632
JO - JACC: Heart Failure
JF - JACC: Heart Failure
IS - 9
ER -