Shared Molecular Mechanisms of Hypertrophic Cardiomyopathy and Its Clinical Presentations: Automated Molecular Mechanisms Extraction Approach

Glavaški, Mila; Velicki, Lazar

doi:10.3390/life11080785

Cited by 7 publications

(7 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pathophysiological features of HCM are: cardiomyocyte hypertrophy [ 77 , 78 , 79 , 80 ] and disarray [ 78 , 79 , 80 , 81 ], myocardial remodeling [ 79 , 82 , 83 ] and fibrosis [ 1 , 24 , 79 , 84 , 85 , 86 ], coronary microvascular dysfunction [ 20 , 79 , 80 , 87 , 88 ], myocardial ischemia [ 20 , 79 , 88 , 89 , 90 ] and hypercontractility [ 8 , 79 , 91 , 92 , 93 ], impaired myocardial relaxation [ 8 , 79 , 84 , 94 ], myocardial stiffness [ 79 , 81 , 84 ], and diastolic dysfunction [ 79 , 81 , 95 , 96 ].…”

Section: Outcomes Of Hcmmentioning

confidence: 99%

Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers

2023

Self Cite

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations of HCM are very variable. Some mutation carriers remain asymptomatic, while others develop severe HCM, terminal heart failure, or sudden cardiac death. Heterogeneity regarding both genetic mutations and the clinical course of HCM hinders the establishment of universal genotype–phenotype correlations. However, some trends have been identified. The presence of a mutation in some genes encoding sarcomeric proteins is associated with earlier HCM onset, more severe left ventricular hypertrophy, and worse clinical outcomes. There is a diversity in the mechanisms implicated in the pathogenesis of HCM. They may be classified into groups, but they are interrelated. The lack of known supplementary elements that control the progression of HCM indicates that molecular mechanisms that exist between genotype and clinical presentations may be crucial. Secondary molecular changes in pathways implicated in HCM pathogenesis, post-translational protein modifications, and epigenetic factors affect HCM phenotypes. Cardiac loading conditions, exercise, hypertension, diet, alcohol consumption, microbial infection, obstructive sleep apnea, obesity, and environmental factors are non-molecular aspects that change the HCM phenotype. Many mechanisms are implicated in the course of HCM. They are mostly interconnected and contribute to some extent to final outcomes.

show abstract

Section: Outcomes Of Hcmmentioning

confidence: 99%

Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers

2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hypertrophic cardiomyopathy (HCM) is among the most common forms of cardiomyopathy [1,2], with a recorded prevalence of 1 in 500 people among the general population [3][4][5][6], and recent studies estimating a prevalence of up to 1 in 200 people [5,[7][8][9][10][11]. It is an important cause of disability and mortality across all ages [12], and one of the leading causes of sudden cardiac deaths among the young [13,14].…”

Section: Introductionmentioning

confidence: 99%

Gene-Specific Discriminative Echocardiogram Findings in Hypertrophic Cardiomyopathy Determined Using Artificial Intelligence: A Pilot Study

Glavaški,

Ilić,

Velicki

2023

Cardiogenetics

Self Cite

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) is among the most common forms of cardiomyopathies, with a prevalence of 1:200 to 1:500 people. HCM is caused by variants in genes encoding cardiac sarcomeric proteins, of which a majority reside in MYH7, MYBPC3, and TNNT2. Up to 40% of the HCM cases do not have any known HCM variant. Genotype–phenotype associations in HCM remain incompletely understood. This study involved two visits of 46 adult patients with a confirmed diagnosis of HCM. In total, 174 genes were analyzed on the Next-Generation Sequencing platform, and transthoracic echocardiography was performed. Gene-specific discriminative echocardiogram findings were identified using the computer vision library Fast AI. This was accomplished with the generation of deep learning models for the classification of ultrasonic images based on the underlying genotype and a later analysis of the most decisive image regions. Gene-specific echocardiogram findings were identified: for variants in the MYH7 gene (vs. variant not detected), the most discriminative structures were the septum, left ventricular outflow tract (LVOT) segment, anterior wall, apex, right ventricle, and mitral apparatus; for variants in MYBPC3 gene (vs. variant not detected) these were the septum, left ventricle, and left ventricle/chamber; while for variants in the TNNT2 gene (vs. variant not detected), the most discriminative structures were the septum and right ventricle.

show abstract

“…Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease that results in left ventricular hypertrophy [ 1 ]. HCM is relatively common [ 2 ], with an incidence of 1 in 500 and some studies suggesting an even higher incidence of 1 in 200 [ 1 , 2 , 3 , 4 ]. Symptoms, signs, clinical presentation, and prognosis of HCM are highly heterogeneous and complex [ 2 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Other adverse HCM scenarios are atrial fibrillation (AF) [ 7 ] and heart failure (HF) [ 5 , 7 ]. However, the definite subtypes of HCM are not yet identified, and the precise genotype–phenotype associations of HCM [ 4 ] and the mechanisms leading to a particular outcome are unknown.…”

Section: Introductionmentioning

confidence: 99%

Subtypes and Mechanisms of Hypertrophic Cardiomyopathy Proposed by Machine Learning Algorithms

Glavaški

Preveden

Jakovljević

et al. 2022

Life

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) is a relatively common inherited cardiac disease that results in left ventricular hypertrophy. Machine learning uses algorithms to study patterns in data and develop models able to make predictions. The aim of this study is to identify HCM subtypes and examine the mechanisms of HCM using machine learning algorithms. Clinical and laboratory findings of 143 adult patients with a confirmed diagnosis of nonobstructive HCM are analyzed; HCM subtypes are determined by clustering, while the presence of different HCM features is predicted in classification machine learning tasks. Four clusters are determined as the optimal number of clusters for this dataset. Models that can predict the presence of particular HCM features from other genotypic and phenotypic information are generated, and subsets of features sufficient to predict the presence of other features of HCM are determined. This research proposes four subtypes of HCM assessed by machine learning algorithms and based on the overall phenotypic expression of the participants of the study. The identified subsets of features sufficient to determine the presence of particular HCM aspects could provide deeper insights into the mechanisms of HCM.

show abstract

Shared Molecular Mechanisms of Hypertrophic Cardiomyopathy and Its Clinical Presentations: Automated Molecular Mechanisms Extraction Approach

Cited by 7 publications

References 111 publications

Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers

Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers

Gene-Specific Discriminative Echocardiogram Findings in Hypertrophic Cardiomyopathy Determined Using Artificial Intelligence: A Pilot Study

Subtypes and Mechanisms of Hypertrophic Cardiomyopathy Proposed by Machine Learning Algorithms

Contact Info

Product

Resources

About