Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis.
BACKGROUND
Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics.


METHODS
Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n = 26); (2) transthyretin (ATTR) cardiac amyloidosis (n = 7); (3) left ventricular hypertrophy (LVH) (n = 45); (4) systolic heart failure (n = 42); and (5) non-cardiac systemic amyloidosis (n = 7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients.


RESULTS
HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median = 622, interquartile range (IQR): 299-1228 pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median = 134, IQR: 94-163 pg/mL, p < 0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p = 0.13 and 0.057, respectively).


CONCLUSIONS
HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.
a Department of Medicine, Division of Cardiovascular Medicine , Vanderbilt University School of Medicine , Nashville , TN , USA.
Kristopher J
KJ
Swiger
a Department of Medicine, Division of Cardiovascular Medicine , Vanderbilt University School of Medicine , Nashville , TN , USA.
Eitan A
EA
Friedman
a Department of Medicine, Division of Cardiovascular Medicine , Vanderbilt University School of Medicine , Nashville , TN , USA.
Evan L
EL
Brittain
a Department of Medicine, Division of Cardiovascular Medicine , Vanderbilt University School of Medicine , Nashville , TN , USA.
Kelsey A
KA
Tomasek
b Department of Biostatistics , Vanderbilt University School of Medicine , Nashville , TN , USA , and.
Shi
S
Huang
a Department of Medicine, Division of Cardiovascular Medicine , Vanderbilt University School of Medicine , Nashville , TN , USA.
Yan R
YR
Su
c Department of Medicine , Cardiovascular Institute, Maine Medical Center , Portland , ME , USA.
Douglas B
DB
Sawyer
a Department of Medicine, Division of Cardiovascular Medicine , Vanderbilt University School of Medicine , Nashville , TN , USA.
Daniel J
DJ
Lenihan
D000368:Aged; D000686:Amyloidosis / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins; D009202:Cardiomyopathies / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D037502:Galectin 3 / Q000097:blood; D037161:Galectins; D054143:Heart Failure, Systolic / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D007147:Immunoglobulin Light Chains / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000378:metabolism; D012042:Registries; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D015415:Biomarkers; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C066855:HGF protein, human; C508600:IL6 protein, human; D007147:Immunoglobulin Light Chains; D015850:Interleukin-6; C428445:LGALS3 protein, human; D011228:Prealbumin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor
Cardiac amyloidosis; biomarkers; cardiomyopathy; hepatocyte growth factor