Plasmatic and myocardial microRNA profiles in patients with Hypertrophic Cardiomyopathy.
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ABSTRACT:
SUBMITTER: Lombardi M
PROVIDER: S-EPMC8287979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-DIXA-D-1124 | biostudies-other
Project description:The myocardial contraction fraction (MCF: stroke volume to myocardial volume) is a novel volumetric measure of left ventricular myocardial shortening. The purpose of the present study was to assess whether MCF could predict adverse outcomes for HCM patients. A retrospective cohort study of 438 HCM patients was conducted. The primary and secondary endpoints were all-cause mortality and HCM-related mortality. The association between MCF and endpoints was analysed. During a follow-up period of 1738.2 person-year, 76 patients (17.2%) reached primary endpoint and 50 patients (65.8%) reached secondary endpoint. Both all-cause mortality rate and HCM-related mortality rate decreased across MCF tertiles (24.7% vs. 17.9% vs. 9.5%, P trend = 0.003 for all-cause mortality; 16.4% vs. 9.7% vs. 6.1%, P trend = 0.021 for HCM-related mortality). Patients in the third tertile had a significantly lower risk of developing adverse outcomes than patients in the first tertile: all-cause mortality (adjusted HR: 0.26, 95% CI: 0.12-0.56, P = 0.001), HCM-related mortality (adjusted HR: 0.17, 95% CI: 0.07-0.42, P < 0.001). At 1-, 3-, and 5-year of follow-up, areas under curve were 0.699, 0.643, 0.618 for all-cause mortality and 0.749, 0.661, 0.613 for HCM-related mortality (all P value < 0.001), respectively. In HCM patients, MCF could independently predict all-cause mortality and HCM-related mortality, which should be considered for overall risk assessment in clinical practice.
| S-EPMC7552384 | biostudies-literature
Project description:Circulating microRNA expression has become a biomarker of cardiovascular disease; however, the association of microRNA expression between circulation and myocardium in hypertrophic cardiomyopathy remains unclear. The present study aimed to find a circulating biomarker correlated not only to myocardial expression, but also to cardiac hypertrophy and fibrosis. Forty-two cases of hypertrophic obstructive cardiomyopathy (HOCM) diagnosed by echocardiography and magnetic resonance were analysed for microRNA expression in plasma and myocardial tissue. The results showed that myocardial miR-221 was significantly increased (z = -2.249, P = 0.024) and significantly correlated with collagen volume fraction (CVF) (r = 0.516, P < 0.001), late gadolinium enhancement (LGE) (r = 0.307, P = 0.048), and peripheral circulation (r = 0.434, P = 0.004). Moreover, circulating miR-221 expression was significantly correlated with CVF (r = 0.454, P = 0.002), LGE (r = 0.630, P = 0.004), maximum interventricular septal thickness (MIVST) of echocardiography (r = 0.318, P = 0.042), and MIVST of magnetic resonance (r = 0.342, P = 0.027). The area under the receiver operating characteristic curve of miR-221 was 0.764. Circulating miR-221 is consistent with that in myocardial tissue, and correlated with myocardial fibrosis and hypertrophy. It can be used as a biomarker for evaluating myocardial hypertrophy and fibrosis in HOCM.
| S-EPMC6954366 | biostudies-literature
Project description:BackgroundMyocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia.ObjectivesThis study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia.MethodsA total of 50 HCM patients (47 ± 15 years of age, 77% male) and 30 healthy control subjects (46 ± 16 years of age, 70% male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T.ResultsDiastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95% confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036).ConclusionsDT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor.
| S-EPMC6548973 | biostudies-literature
Project description:Accumulating evidence suggests that individuals with sarcomeric hypertrophic cardiomyopathy (HCM) carrying MYH7 mutations may have a worse prognosis than MYBPC3 mutation carriers. Myocardial deformation analysis is superior to standard echocardiography in detecting subtle myocardial dysfunction and scar formation, but studies evaluating the association with HCM genotype are scarce. We therefore aimed to compare myocardial strain parameters between MYBPC3 and MYH7 mutation carriers with proven HCM. Participants of the prospective Graz HCM Registry carrying at least one causative mutation in MYBPC3 (n = 39) or MYH7 (n = 18) were enrolled. MYBPC3 mutation carriers were older, predominantly male and more often treated with an implantable cardioverter-defibrillator (39% vs. 0%; p = 0.002). Using analyses of covariance, there were no significant differences between MYBPC3 and MYH7 mutation carriers with regard to left ventricular global longitudinal strain (estimated marginal means ± standard deviation: -16.9 ± 0.6% vs. -17.3 ± 0.9%; p = 0.807) and right ventricular 6-segments endocardial strain (-24.3 ± 1.0% vs. 26.3 ± 1.5%; p = 0.285). Our study suggests, that myocardial deformation analysis may not be helpful in concluding on the underlying HCM genotype, and vice versa.
| S-EPMC8535960 | biostudies-literature
Project description:One of the main causes of heart failure is cardiomyopathies. Among them, the most common is hypertrophic cardiomyopathy (HCM), characterized by thickening of the left ventricular muscle. This article focuses on HCM and other cardiomyopathies with myocardial hypertrophy, including Fabry disease, Pompe disease, and Danon disease. The genetics and pathogenesis of these diseases are described, as well as current and experimental treatment options, such as pharmacological intervention and the potential of gene therapies. Although genetic approaches are promising and have the potential to become the best treatments for these diseases, further research is needed to evaluate their efficacy and safety. This article describes current knowledge and advances in the treatment of the aforementioned cardiomyopathies.
| S-EPMC10488064 | biostudies-literature
Project description:Background Impaired myocardial blood flow (MBF) in the absence of epicardial coronary disease is a feature of hypertrophic cardiomyopathy (HCM). Although most evident in hypertrophied or scarred segments, reduced MBF can occur in apparently normal segments. We hypothesized that impaired MBF and myocardial perfusion reserve, quantified using perfusion mapping cardiac magnetic resonance, might occur in the absence of overt left ventricular hypertrophy (LVH) and late gadolinium enhancement, in mutation carriers without LVH criteria for HCM (genotype-positive, left ventricular hypertrophy-negative). Methods and Results A single center, case-control study investigated MBF and myocardial perfusion reserve (the ratio of MBF at stress:rest), along with other pre-phenotypic features of HCM. Individuals with genotype-positive, left ventricular hypertrophy-negative (n=50) with likely pathogenic/pathogenic variants and no evidence of LVH, and matched controls (n=28) underwent cardiac magnetic resonance. Cardiac magnetic resonance identified LVH-fulfilling criteria for HCM in 5 patients who were excluded. Individuals with genotype-positive, left ventricular hypertrophy-negative had longer indexed anterior mitral valve leaflet length (12.52±2.1 versus 11.55±1.6 mm/m2, P=0.03), lower left ventricular end-systolic volume (21.0±6.9 versus 26.7±6.2 mm/m2, P≤0.005) and higher left ventricular ejection fraction (71.9±5.5 versus 65.8±4.4%, P≤0.005). Maximum wall thickness was not significantly different (9.03±1.95 versus 8.37±1.2 mm, P=0.075), and no subject had significant late gadolinium enhancement (minor right ventricle‒insertion point late gadolinium enhancement only). Perfusion mapping demonstrated visual perfusion defects in 9 (20%) carriers versus 0 controls (P=0.011). These were almost all septal or near right ventricle insertion points. Globally, myocardial perfusion reserve was lower in carriers (2.77±0.83 versus 3.24±0.63, P=0.009), with a subendocardial:subepicardial myocardial perfusion reserve gradient (2.55±0.75 versus 3.2±0.65, P=<0.005; 3.01±0.96 versus 3.47±0.75, P=0.026) but equivalent MBF (2.75±0.82 versus 2.65±0.69 mL/g per min, P=0.826). Conclusions Regional and global impaired myocardial perfusion can occur in HCM mutation carriers, in the absence of significant hypertrophy or scarring.
| S-EPMC8475659 | biostudies-literature
Project description:Using a high-throughput gene expression profiling technology, we have illuminated novel potential microRNA (miRNA) components of the molecular disease process underlying human hypertrophic cardiomyopathy (HCM). It is hoped that this will fuel future research endeavors that will eventually uncover the role miRNAs may play in the phenotypic heterogeneity of the disease, and thus, provide potential tools for identifying patients with benign versus malignant forms of the disease. Case (n = 107)-Control (n=20) study comparing the microRNA transcriptome of cardiac tissues from patients with hypertrophic cardiomyopathy to the microRNA transcriptome of control donor cardiac tissues.
2012-09-01 | E-GEOD-36946 | biostudies-arrayexpress
Project description:Using a high-throughput gene expression profiling technology, we have illuminated novel potential microRNA (miRNA) components of the molecular disease process underlying human hypertrophic cardiomyopathy (HCM). It is hoped that this will fuel future research endeavors that will eventually uncover the role miRNAs may play in the phenotypic heterogeneity of the disease, and thus, provide potential tools for identifying patients with benign versus malignant forms of the disease.
2012-09-01 | GSE36946 | GEO
Project description: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.)
| S-EPMC3049917 | biostudies-literature