Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy

for the HCMNet Investigators

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: Sarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH-) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to investigate if circulating biomarkers of cardiovascular stress and collagen metabolism among G+/LVH- individuals, measured at rest and following exercise provocation, yield further insights into the underlying biology of HCM. Methods: We studied 76 individuals with overt HCM, 50 G+/LVH- individuals and 41 genotype-negative related controls enrolled in a cross-sectional, multicentre observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2) and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal telopeptide of type I collagen; galectin-3; periostin) were measured. Results: Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH- subjects and controls at rest, along with an exaggerated increase in NT-proBNP and hsTnI in response to exercise. We found no detectable differences in resting or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with healthy controls despite subtle echocardiographic differences in cardiac structure and function. Conclusion: Dynamic exercise testing exaggerated resting differences in natriuretic peptides and troponin elevations among individuals with overt HCM. In contrast, we found no differences in biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with controls even after maximal exercise provocation. Our findings highlight the need for continued investigation into early phenotypes of sarcomeric gene mutations and the evolution of HCM.

Original languageEnglish (US)
Article numbere000615
JournalOpen Heart
Volume4
Issue number2
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

Fingerprint

Hypertrophic Cardiomyopathy
Fibrosis
Biomarkers
Galectin 3
Natriuretic Peptides
Mutation
Troponin
Troponin I
Brain Natriuretic Peptide
Left Ventricular Hypertrophy
Collagen Type I
Genes
Multicenter Studies
Observational Studies
Collagen
Genotype
Phenotype
pro-brain natriuretic peptide (1-76)

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy. / for the HCMNet Investigators.

In: Open Heart, Vol. 4, No. 2, e000615, 01.11.2017.

Research output: Contribution to journalArticle

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title = "Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy",
abstract = "Objective: Sarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH-) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to investigate if circulating biomarkers of cardiovascular stress and collagen metabolism among G+/LVH- individuals, measured at rest and following exercise provocation, yield further insights into the underlying biology of HCM. Methods: We studied 76 individuals with overt HCM, 50 G+/LVH- individuals and 41 genotype-negative related controls enrolled in a cross-sectional, multicentre observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2) and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal telopeptide of type I collagen; galectin-3; periostin) were measured. Results: Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH- subjects and controls at rest, along with an exaggerated increase in NT-proBNP and hsTnI in response to exercise. We found no detectable differences in resting or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with healthy controls despite subtle echocardiographic differences in cardiac structure and function. Conclusion: Dynamic exercise testing exaggerated resting differences in natriuretic peptides and troponin elevations among individuals with overt HCM. In contrast, we found no differences in biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with controls even after maximal exercise provocation. Our findings highlight the need for continued investigation into early phenotypes of sarcomeric gene mutations and the evolution of HCM.",
author = "{for the HCMNet Investigators} and Ho, {Jennifer E.} and Ling Shi and Day, {Sharlene M.} and Colan, {Steven D.} and Russell, {Mark W.} and Jeffrey Towbin and Sherrid, {Mark V.} and Canter, {Charles E.} and John Jefferies and Anne Murphy and Matthew Taylor and Luisa Mestroni and Cirino, {Allison L.} and Sleeper, {Lynn A.} and Peter Jarolim and Bego{\~n}a Lopez and Arantxa Gonzalez and Javier Diez and Orav, {E. John} and Ho, {Carolyn Y.}",
year = "2017",
month = "11",
day = "1",
doi = "10.1136/openhrt-2017-000615",
language = "English (US)",
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T1 - Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy

AU - for the HCMNet Investigators

AU - Ho, Jennifer E.

AU - Shi, Ling

AU - Day, Sharlene M.

AU - Colan, Steven D.

AU - Russell, Mark W.

AU - Towbin, Jeffrey

AU - Sherrid, Mark V.

AU - Canter, Charles E.

AU - Jefferies, John

AU - Murphy, Anne

AU - Taylor, Matthew

AU - Mestroni, Luisa

AU - Cirino, Allison L.

AU - Sleeper, Lynn A.

AU - Jarolim, Peter

AU - Lopez, Begoña

AU - Gonzalez, Arantxa

AU - Diez, Javier

AU - Orav, E. John

AU - Ho, Carolyn Y.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Objective: Sarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH-) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to investigate if circulating biomarkers of cardiovascular stress and collagen metabolism among G+/LVH- individuals, measured at rest and following exercise provocation, yield further insights into the underlying biology of HCM. Methods: We studied 76 individuals with overt HCM, 50 G+/LVH- individuals and 41 genotype-negative related controls enrolled in a cross-sectional, multicentre observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2) and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal telopeptide of type I collagen; galectin-3; periostin) were measured. Results: Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH- subjects and controls at rest, along with an exaggerated increase in NT-proBNP and hsTnI in response to exercise. We found no detectable differences in resting or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with healthy controls despite subtle echocardiographic differences in cardiac structure and function. Conclusion: Dynamic exercise testing exaggerated resting differences in natriuretic peptides and troponin elevations among individuals with overt HCM. In contrast, we found no differences in biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with controls even after maximal exercise provocation. Our findings highlight the need for continued investigation into early phenotypes of sarcomeric gene mutations and the evolution of HCM.

AB - Objective: Sarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH-) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to investigate if circulating biomarkers of cardiovascular stress and collagen metabolism among G+/LVH- individuals, measured at rest and following exercise provocation, yield further insights into the underlying biology of HCM. Methods: We studied 76 individuals with overt HCM, 50 G+/LVH- individuals and 41 genotype-negative related controls enrolled in a cross-sectional, multicentre observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2) and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal telopeptide of type I collagen; galectin-3; periostin) were measured. Results: Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH- subjects and controls at rest, along with an exaggerated increase in NT-proBNP and hsTnI in response to exercise. We found no detectable differences in resting or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with healthy controls despite subtle echocardiographic differences in cardiac structure and function. Conclusion: Dynamic exercise testing exaggerated resting differences in natriuretic peptides and troponin elevations among individuals with overt HCM. In contrast, we found no differences in biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with controls even after maximal exercise provocation. Our findings highlight the need for continued investigation into early phenotypes of sarcomeric gene mutations and the evolution of HCM.

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DO - 10.1136/openhrt-2017-000615

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