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      Predictive values of multiple non-invasive markers for myocardial fibrosis in hypertrophic cardiomyopathy patients with preserved ejection fraction

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          Abstract

          Myocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiac-specific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. The LGE-positive patients had significant higher serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels and lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group. The LGE% was independently associated with the Nt-proBNP levels, GCS, LV end-diastolic maximum wall thickness (MWT) and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP ≥ 108.00 pg/mL and MWT ≥ 17.30 mm had good diagnostic performance for LGE, with a specificity of 81.25% and sensitivity of 70.00%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.

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          Most cited references42

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          Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy.

          Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by left ventricular hypertrophy unexplained by secondary causes and a nondilated left ventricle with preserved or increased ejection fraction. It is commonly asymmetrical with the most severe hypertrophy involving the basal interventricular septum. Left ventricular outflow tract obstruction is present at rest in about one third of the patients and can be provoked in another third. The histological features of HCM include myocyte hypertrophy and disarray, as well as interstitial fibrosis. The hypertrophy is also frequently associated with left ventricular diastolic dysfunction. In the majority of patients, HCM has a relatively benign course. However, HCM is also an important cause of sudden cardiac death, particularly in adolescents and young adults. Nonsustained ventricular tachycardia, syncope, a family history of sudden cardiac death, and severe cardiac hypertrophy are major risk factors for sudden cardiac death. This complication can usually be averted by implantation of a cardioverter-defibrillator in appropriate high-risk patients. Atrial fibrillation is also a common complication and is not well tolerated. Mutations in over a dozen genes encoding sarcomere-associated proteins cause HCM. MYH7 and MYBPC3, encoding β-myosin heavy chain and myosin-binding protein C, respectively, are the 2 most common genes involved, together accounting for ≈50% of the HCM families. In ≈40% of HCM patients, the causal genes remain to be identified. Mutations in genes responsible for storage diseases also cause a phenotype resembling HCM (genocopy or phenocopy). The routine applications of genetic testing and preclinical identification of family members represents an important advance. The genetic discoveries have enhanced understanding of the molecular pathogenesis of HCM and have stimulated efforts designed to identify new therapeutic agents.
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            Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy.

            Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy and a proposed substrate for arrhythmias and heart failure. In animal models, profibrotic genetic pathways are activated early, before hypertrophic remodeling. Data showing early profibrotic responses to sarcomere-gene mutations in patients with hypertrophic cardiomyopathy are lacking. We used echocardiography, cardiac magnetic resonance imaging (MRI), and serum biomarkers of collagen metabolism, hemodynamic stress, and myocardial injury to evaluate subjects with hypertrophic cardiomyopathy and a confirmed genotype. The study involved 38 subjects with pathogenic sarcomere mutations and overt hypertrophic cardiomyopathy, 39 subjects with mutations but no left ventricular hypertrophy, and 30 controls who did not have mutations. Levels of serum C-terminal propeptide of type I procollagen (PICP) were significantly higher in mutation carriers without left ventricular hypertrophy and in subjects with overt hypertrophic cardiomyopathy than in controls (31% and 69% higher, respectively; P<0.001). The ratio of PICP to C-terminal telopeptide of type I collagen was increased only in subjects with overt hypertrophic cardiomyopathy, suggesting that collagen synthesis exceeds degradation. Cardiac MRI studies showed late gadolinium enhancement, indicating myocardial fibrosis, in 71% of subjects with overt hypertrophic cardiomyopathy but in none of the mutation carriers without left ventricular hypertrophy. Elevated levels of serum PICP indicated increased myocardial collagen synthesis in sarcomere-mutation carriers without overt disease. This profibrotic state preceded the development of left ventricular hypertrophy or fibrosis visible on MRI. (Funded by the National Institutes of Health and others.)
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              Tissue Tracking Technology for Assessing Cardiac Mechanics: Principles, Normal Values, and Clinical Applications.

              Tissue tracking technologies such as speckle tracking echocardiography and feature tracking cardiac magnetic resonance have enhanced the noninvasive assessment of myocardial deformation in clinical research and clinical practice. The widespread enthusiasm for using tissue tracking techniques in research and clinical practice stems from the ready applicability of these technologies to routine echocardiographic or cardiac magnetic resonance images. The technology is common to both modalities, and derived parameters to describe myocardial mechanics are the similar, albeit with different accuracies. We provide an overview of the normal values and reproducibility of the clinically applicable parameters, together with their clinical validation. The use of these technologies in different clinical scenarios, and the additive value to current imaging diagnostics are discussed.
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                Author and article information

                Contributors
                yuecui2020@163.com
                heshuishi@hust.edu.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                22 February 2021
                22 February 2021
                2021
                : 11
                : 4297
                Affiliations
                [1 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Radiology, Union Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; 1277 JieFang Avenue, Wuhan, 430022 China
                [2 ]GRID grid.412839.5, ISNI 0000 0004 1771 3250, Hubei Province Key Laboratory of Molecular Imaging, ; Wuhan, 430022 China
                [3 ]MR Collaboration, Siemens Healthineers Ltd, Shanghai, 201318 China
                Article
                83678
                10.1038/s41598-021-83678-z
                7900233
                33619345
                8b489721-1003-45ca-86ed-123b18babb3b
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 December 2020
                : 2 February 2021
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                © The Author(s) 2021

                Uncategorized
                cardiology,biomarkers,diagnostic markers
                Uncategorized
                cardiology, biomarkers, diagnostic markers

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