Proteomic Analysis of Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) Clinical Trial
Circulation: Heart Failure, 2025
Topriceanu C., Vissing C., Axelsson Raja A., Day S., Russell M., Zahka K., Pereira A., Colan S., Murphy A., Canter C., Bach R., Wheeler M., Rossano J., Owens A., Mestroni L., Taylor M., Moon J., Captur G., Patel A., Wilmot I., Soslow J., Becker J., Seidman C., Lakdawala N., Bundgaard H., Tahir U., Ho C.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Pathophysiology Patient Stratification | Blood |  Olink Explore 3072/384 |
Abstract
BACKGROUND:
In hypertrophic cardiomyopathy (HCM), the mechanisms through which pathogenic sarcomere variants (G+) lead to left ventricular hypertrophy (LVH) are not understood.
METHODS:
VANISH (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) was a multicenter, double-blind, placebo-controlled randomized trial testing valsartan’s ability to attenuate phenotypic progression in early sarcomeric (G+LVH+) and subclinical HCM (G+LVH-). The outcome was a composite Z score reflecting cardiac remodeling from baseline to year 2 (end of study). Baseline and year 2 blood samples were used to quantify 276 proteins using a proximity extension assay (Olink, Sweden). We explored relative differences in protein abundance between early and subclinical HCM at baseline. In addition, we compared proteomic changes between baseline and year 2 in subclinical HCM participants who experienced phenotypic conversion to early HCM (converters) versus nonconverters; early HCM participants receiving valsartan versus placebo; and in association with changes in Z score. Comparisons were made using t test/Mann-Whitney U test, linear mixed models, and generalized linear models, correcting for multiple testing.
RESULTS:
Circulating proteins were analyzed in 192 participants (32 subclinical and 160 early HCM [81 allocated to valsartan]). NT-proBNP (N-terminal pro-B-type natriuretic peptide) differentiated early from subclinical HCM and tracked with phenotypic progression in early HCM (1-unit worsening in Z score associated with a 27% increase in NT-proBNP [95% CI, 17–37%]). Some extracellular matrix remodeling proteins showed higher abundance (tissue-type plasminogen activator) in early compared with subclinical HCM or tracked with disease progression (decorin) in early HCM. Growth factors had higher relative abundance in early HCM (fibroblast growth factor-21). While no individual protein was able to distinguish converters from nonconverters, multiprotein the panels lipocalin 2, lectin-like oxidized low-density lipoprotein receptor 1, and either NT-proBNP or interleukin-17 receptor A, could distinguish these groups.
CONCLUSIONS:
NT-proBNP was the most robust protein to track progression. Studying pathways involving growth factors and extracellular matrix remodeling may yield additional insights into mechanisms behind disease progression.
REGISTRATION:
URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01912534.