Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy

• Published in: Open heart Vol. 4; no. 2; p. e000615
• Main Authors: Ho, Jennifer E, Shi, Ling, Day, Sharlene M, Colan, Steven D, Russell, Mark W, Towbin, Jeffrey A, Sherrid, Mark V, Canter, Charles E, Jefferies, John Lynn, Murphy, Anne, Taylor, Matthew, Mestroni, Luisa, Cirino, Allison L, Sleeper, Lynn A, Jarolim, Peter, Lopez, Begoña, Gonzalez, Arantxa, Diez, Javier, Orav, E John, Ho, Carolyn Y
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.11.2017; BMJ Publishing Group
• Series: Original research article
• Subjects: Biomarkers; Cardiomyopathy; Collagen; Genotype & phenotype; Heart Failure and Cardiomyopathies; Mutation; Studies; biomarker; hypertrophic cardiomyopathy; echocardiography
• ISSN: 2053-3624; 2398-595X; 2053-3624
• DOI: 10.1136/openhrt-2017-000615

ObjectiveSarcomeric 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.MethodsWe 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.ResultsIndividuals 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.ConclusionDynamic 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.