scholarly journals A Novel miRNA Screen Identifies miRNA-4454 as a Candidate Biomarker for Ventricular Fibrosis in Patients with Hypertrophic Cardiomyopathy

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1718
Author(s):  
Tilo Thottakara ◽  
Natalie Lund ◽  
Elisabeth Krämer ◽  
Paulus Kirchhof ◽  
Lucie Carrier ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ventricular Hypertrophy ◽  
Cardiac Fibrosis ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Healthy Controls ◽  
Novel Mirna ◽  
Potential Biomarker ◽  
Differentially Expressed Mirnas ◽  
Ventricular Fibrosis

(1) Background: Left ventricular hypertrophy, myocardial disarray and interstitial fibrosis are the hallmarks of hypertrophic cardiomyopathy (HCM). Access to the myocardium for diagnostic purposes is limited. Circulating biomolecules reflecting the myocardial disease processes could improve the early detection of HCM. Circulating miRNAs have been found to reflect disease processes in several cardiovascular diseases. (2) Methods: We quantified circulating miRNA molecules in the plasma of 24 HCM and 11 healthy controls using the Human v3 miRNA Expression Assay Kit Code set (Nanostring Tech., Seattle, WA, USA) and validated differentially expressed miRNAs using RT-PCR. (3) Results: In comparison to healthy controls, the levels of six miRNAs (miR-1, miR-3144, miR-4454, miR-495-3p, miR-499a-5p and miR-627-3p) were higher in the plasma of HCM patients than healthy individuals (p < 0.05). Of these, higher levels of miR-1, miR-495 and miR-4454 could be validated by real-time PCR. In addition, elevated miR-4454 levels were significantly correlated with cardiac fibrosis, detected by magnetic resonance imaging in HCM patients. (4) Conclusions: Circulating miR-1, miR-495-3p and miR-4454 levels are elevated in the plasma of HCM patients. To the best of our knowledge, this is the first report showing a correlation between miR-4454 levels and cardiac fibrosis in HCM. This suggests miR-4454 as a potential biomarker for fibrosis in these patients.

scholarly journals Clinical presentations of hypertrophic cardiomyopathy and implications for therapy

2018 ◽  
Vol 2018 (3) ◽  
Author(s):  
Carles Díez-López ◽  
Joel Salazar-Mendiguchía
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ventricular Hypertrophy ◽  
Small Vessel Disease ◽  
Interstitial Fibrosis ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Pathological Findings ◽  
Vessel Disease ◽  
Clinical Presentations ◽  
Index Cases

[first paragraph of article]Hypertrophic cardiomyopathy (HCM) is diagnosed in the presence of left ventricular hypertrophy of ≥15 mm in adult index cases, or ≥13 mm in relatives of known affected patients, that is not solely explained by abnormal loading conditions. In children, the left ventricle (LV) wall thickness should be more than two standard deviations above the predicted population mean. The typical anatomo-pathological findings include myocyte hypertrophy, disarray, interstitial fibrosis and small-vessel disease. Although all the myocytes are supposed to be affected, pathological alterations are not uniformly distributed throughout the myocardium. Asymmetrical hypertrophy of the interventricular septum is the most commonly observed phenotype, but any pattern of hypertrophy is consistent with the diagnosis.

scholarly journals Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kristina Sonnenschein ◽  
Jan Fiedler ◽  
David de Gonzalo-Calvo ◽  
Ke Xiao ◽  
Angelika Pfanne ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Serum Protein ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Heart Diseases ◽  
Left Ventricular ◽  
Protein Profiling ◽  
Healthy Population ◽  
Healthy Controls ◽  
Protein Levels

AbstractHypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.

scholarly journals Effects of candesartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Maqsood ◽  
H.A Shakeel ◽  
H.F Shoukat ◽  
M.D Khan ◽  
S.A.Y Shah ◽  
...  
Keyword(s):  
Late Gadolinium Enhancement ◽  
Hypertrophic Cardiomyopathy ◽  
Interstitial Fibrosis ◽  
Angiotensin Receptor Blockers ◽  
Left Ventricular ◽  
Funding Source ◽  
Gadolinium Enhancement ◽  
Percent Change ◽  
Lv Mass ◽  
Significant Difference

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) hypertrophy in the absence of pressure overload. Manifestations of the disease include heart failure associated with diastolic dysfunction and atrial and ventricular tachyarrhythmias. Pathological features of HCM include myocyte hypertrophy, interstitial fibrosis, and myocyte disarray and are mediated by angiotensin II. Purpose This study aimed to evaluate the effects of candesartan on left ventricular (LV) hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy (HCM). Methods In double-blind fashion, 30 patients (6 women, 24 men; age: 55±11 years) with HCM were randomly assigned to receive placebo (n=13) or candesartan 50 mg twice a day (n=17) for 1 year. To measure LV mass and extent of fibrosis, cardiac magnetic resonance imaging was performed at baseline and 1 year as assessed by late gadolinium enhancement. Results There was a trend toward a significant difference in the percent change in LV mass (median: +5% with placebo vs. −5% with candesartan; p=0.06). There was a significant difference in the percent change in the extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+30±27% with placebo vs. −22±44% with candesartan; p=0.03). Conclusion Our study concludes reduction of the progression of myocardial hypertrophy and fibrosis with candesartan in patients with hypertrophic cardiomyopathy. Our study population was limited so we warrant larger trials to confirm a place for angiotensin receptor blockers in the management of patients with hypertrophic cardiomyopathy. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): Self funding

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumin Li ◽  
Jia Liu ◽  
Yukun Cao ◽  
Xiaoyu Han ◽  
Guozhu Shao ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ejection Fraction ◽  
Myocardial Fibrosis ◽  
Troponin I ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Predictive Values ◽  
Non Invasive ◽  
Potential Biomarker

AbstractMyocardial 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.

Sign in / Sign up

Export Citation Format

Share Document