Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is one of the commonest inheritable cardiac disorders. Being a global disease with diffuse myocardial fibrosis, it has a wide range of adverse outcomes ending with sudden cardiac death. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) has become a reference standard for visualization of focal myocardial fibrosis. In the setting of less severe or more diffuse fibrosis, LGE is unlikely to reveal the presence of abnormal tissue given the lack of normal myocardium as a reference. Direct measurement of myocardial T1 time (T1 mapping) may improve these methodologic problems of LGE CMR in the setting of diffuse retention of gadolinium-based contrast material. So, we aim at this study to evaluate the clinical application of CMRI native and post-contrast T1 relaxation in assessing diffuse myocardial fibrosis non-invasively in hypertrophic cardiomyopathy. Results There was a significant difference between the percent of fibrosis detected by measuring the extracellular volume percent compared to that detected by LGE, with the former detecting fibrosis in 45.1% of the examined cardiac segments while the latter showed fibrosis in 20.9% of the cardiac segments. Also, measuring the native T1 values showed evidence of fibrosis in about 32.2% of the cardiac segments superseding the percent of fibrosis detected using the LGE alone. The ejection fraction percent showed a negative correlation with the left ventricular mass with a correlation coefficient value of − 0.139 where both interstitial and replacement fibrosis play an important role in the pathophysiology of diastolic dysfunction as well as impairing the myocardial contractility. Also, in cases of obstruction, the extracellular volume (ECV) is more likely to increase in the basal anterior and antero-septal segments as well as the basal inferior segment with P values 0.015, 0.013, and 0.045, respectively. Conclusion Diffuse fibrosis was found to be difficult to be distinguished using LGE. The unique ability of CMR to use proton relaxation times provides a quantitative measurement to detect increased interstitial volume in diffuse myocardial fibrosis. Moreover, it showed that in cases of obstruction, the segments exposed to the highest pressure are more vulnerable to the fibrotic process denoting a relationship between the pressure gradient and the adverse myocardial remodeling.

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Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/1532-429x-14-76 ◽

2012 ◽

Vol 14 (1) ◽

pp. 76 ◽

Cited By ~ 85

Author(s):

Andris H Ellims ◽

Leah M Iles ◽

Liang-han Ling ◽

James L Hare ◽

David M Kaye ◽

...

Keyword(s):

Cardiovascular Magnetic Resonance ◽

Hypertrophic Cardiomyopathy ◽

Magnetic Resonance ◽

Diastolic Dysfunction ◽

Myocardial Fibrosis ◽

Left Ventricular Diastolic Dysfunction ◽

Left Ventricular ◽

Diffuse Myocardial Fibrosis ◽

Ventricular Diastolic Dysfunction

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Abstract 15137: Detection of Diffuse Myocardial Fibrosis using Multi-slice T1 Mapping by Slice Interleaved T1 (STONE) Sequence in Patients With Hypertrophic Cardiomyopathy

Circulation ◽

10.1161/circ.132.suppl_3.15137 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Shingo Kato ◽

Sébastien Roujol ◽

Jihye Jang ◽

Tamer Basha ◽

Sophie Berg ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Myocardial Fibrosis ◽

Wall Thickness ◽

T1 Mapping ◽

Free Breathing ◽

Left Ventricular ◽

Diffuse Myocardial Fibrosis ◽

Mapping Technique ◽

Native T1 ◽

Native T1 Time

Introduction: In hypertrophic cardiomyopathy (HCM), there are significant variations in left ventricular (LV) wall thickness and fibrosis, which necessitates a volumetric coverage. Slice-interleaved T1 (STONE) mapping sequence allows for the assessment of native T1 time with complete coverage of LV myocardium. Hypothesis: We hypothesized that STONE sequence is useful for the assessment of regional native T1 time abnormality in HCM patients. Methods: Twenty-four septal HCM patients (56±16 years) and 10 healthy adult control subjects (57±15 years) were studied. Native T1 mapping was performed using STONE sequence which enables acquisition of 5 slices in the short-axis plane within a 90 sec free-breathing scan. We measured LV native T1 time and maximum LV wall thickness in each 16 segments from 3 slices (basal-, mid- and apical-slice) and evaluated the relationship between LV native T1 time and wall thickness. Late gadolinium enhanced (LGE) MRI was acquired to assess presence of myocardial enhancement. Results: In HCM patients, LV native T1 time was significantly elevated compared to healthy controls, regardless of presence or absence of LGE (mean native T1 time; LGE (+) segments (n=27), 1139±55 msec; LGE (-) segments (n=351), 1118±55 msec; healthy control (n=160),1065±35 msec; p<0.001 by one-way ANOVA, 6 segments were excluded from analysis due to artifacts). Among 351 segments without LGE, native LV T1 time was diffusely elevated over the 16 segments (Figure). Significant positive correlation was found between LV wall thickness and native LV T1 time (y=1013+8.7x, p<0.001). Conclusions: In HCM, substantial number of segments without LGE showed elevated native T1 time, and native T1 time was correlated with LV wall thickness. Multi-slice T1 mapping by using STONE sequence could be advantageous to overcome limited cardiac coverage of conventional single-slice T1 mapping technique and to accurately detect the diffuse myocardial fibrosis in HCM patients.

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Diffuse myocardial fibrosis in pediatric hypertrophic cardiomyopathy

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/1532-429x-15-s1-o72 ◽

2013 ◽

Vol 15 (S1) ◽

Author(s):

Tarique Hussain ◽

Andrea Dragulescu ◽

Lee Benson ◽

Derek Wong ◽

Mark Friedberg ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Myocardial Fibrosis ◽

Diffuse Myocardial Fibrosis

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The link between left ventricular extracellular volume determined by T1 myocardial mapping and gut microbiota composition in individuals with heart failure and preserved ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0864 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A.N Kaburova ◽

O.M Drapkina ◽

S.M Uydin ◽

M.V Vishnyakova ◽

M.S Pokrovskaya ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Gut Microbiota ◽

Myocardial Fibrosis ◽

Volume Fraction ◽

Extracellular Volume ◽

Left Ventricular ◽

Diffuse Myocardial Fibrosis ◽

Rrna Gene ◽

Preserved Ejection Fraction

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) represents a major challenge in modern cardiology. As described previously, in HFpEF comorbidities promote a systemic inflammatory state, leading to diffuse myocardial fibrosis resulting in myocardial stiffening. Gut dysbiosis which is considered as the novel source of chronic systemic inflammation has been actively investigated as the risk factor for the development and aggravation of cardiovascular diseases including heart failure. Cardiac magnetic resonance T1-mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. Moreover, the extracellular volume (ECV) fraction can be calculated, providing information on the relative expansion of the extracellular matrix, thus being a noninvasive alternative to myocardial biopsy studies. Purpose The research was aimed at investigating the correlation between the left ventricular ECV and gut microbial genera in patients with HFpEF. Methods 42 patients with confirmed HF-pEF (mediana and interquartile range of age 67 [64; 72] years, 47% men, body mass index <35 kg/m2 with no history of myocardial infarction or diabetes mellitus) were enrolled in the study. The patients underwent transthoracic echocardiography with Doppler study, HF-pEF was confirmed according to the recent ESC guidelines (based on E/e' ratio, N-terminal pro-B type natriuretic peptide >125 pg/ml and symptoms of heart failure). The intestinal microbiome was investigated using high-throughput sequencing of bacterial 16S rRNA gene. As the last step of research T1-myocardial mapping with the modified look-locker inversion-recovery protocol (MOLLI) sequence at 1.5 Tesla was performed to assess left ventricular extracellular volume fraction. Results The mean±std in ECV was 31.02±4.4%. The relative abundance (%) of the most prevalent phyla in gut microbiota was 48±22.5 for Firmicutes, 47.4±22.8 for Bacteroidetes and 1.5 [1.5; 2.5] for Proteobacteria. The analysis showed significant negative correlations between ECV and the following bacterial genera: Faecalibacterium (r=−0.35), Blautia (r=−0.43), Lachnoclostridium (r=−0.32). Moreover ECV positively correlated with Holdemania (r=0.4), Victivallis (r=0.38), Dehalobacterium (r=0.38), Enterococcus (r=0.33) and Catabacter (r=0.32). All correlation values with p<0.05. Conclusion We discovered both negative and positive significant correlations between ECV – the non-invasive marker of myocardial fibrosis and several bacterial genera, which may have negative impact on myocardial remodeling in HF-pEF. Funding Acknowledgement Type of funding source: None

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

Scientific Reports ◽

10.1038/s41598-021-83678-z ◽

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.

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