BACKGROUND: The profile and clinical significance of the oral microbiome in patients with non-obstructive hypertrophic cardiomyopathy (noHCM) and obstructive hypertrophic cardiomyopathy (oHCM) remain unexplored. The objective of this study was to evaluate the difference of oral microbiome between noHCM and oHCM patients. METHODS: This cross-sectional study enrolled 18 noHCM patients and 26 oHCM patients from Fuwai Hospital, Chinese Academy of Medical Sciences between 2020 and 2021. Clinical and periodontal evaluations were conducted, and subgingival plaque samples were collected. Metagenomic sequencing and subsequent microbial composition and functional analyses were performed. RESULTS: Compared to oHCM patients, those with noHCM had higher systolic blood pressure (138.1 ± 18.8 mmHg vs . 124.2 ± 13.8 mmHg, P = 0.007), a larger body circumference (neck circumference: 39.2 ± 4.0 cm vs . 35.1 ± 3.7 cm, P = 0.001; waist circumference: 99.7 ± 10.5 cm vs . 92.2 ± 10.8 cm, P = 0.027; hip circumference: 102.5 ± 5.6 cm vs . 97.5 ± 9.1 cm, P = 0.030), a greater left ventricular end-diastolic diameter (46.6 ± 4.9 mm vs . 43.1 ± 4.9 mm, P = 0.026), and a lower left ventricular ejection fraction (64.1 ± 5.7 % vs . 68.5 ± 7.8%, P = 0.048). While overall biodiversity and general microbial composition were similar between the noHCM and oHCM groups, ten taxa displayed significant differences at the genus and species levels, with Porphyromonas gingivalis showing the highest abundance and greater enrichment in noHCM (relative abundance: 7.79535 vs . 4.87697, P = 0.043). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified ten distinct pathways, with pathways related to energy and amino acid metabolism being enriched in oHCM patients, and those associated with genetic information processing less abundant in the oHCM group. Metabolic potential analysis revealed ten significantly altered metabolites primarily associated with amino sugar and nucleotide sugar metabolism, porphyrin metabolism, pentose and glucuronate interconversion, and lysine degradation. CONCLUSIONS The higher abundance of Porphyromonas gingivalis , which is known to impact cardiovascular health, in noHCM patients may partially account for clinical differences between the groups. Pathway enrichment and metabolic potential analyses suggest microbial functional shifts between noHCM and oHCM patients, potentially reflecting inherent metabolic changes in HCM.
Humans ; Cardiomyopathy, Hypertrophic/microbiology* ; Female ; Male ; Microbiota/genetics* ; Middle Aged ; Cross-Sectional Studies ; Adult ; Mouth/microbiology* ; Aged

Hypertrophic cardiomyopathy (HCM) is a major contributor to cardiovascular diseases (CVD), the leading cause of death globally. HCM can precipitate heart failure (HF) by causing the cardiac tissue to weaken and stretch, thereby impairing its pumping efficiency. Moreover, HCM increases the risk of atrial fibrillation, which in turn elevates the likelihood of thrombus formation and stroke. Given these significant clinical ramifications, research into the etiology and pathogenesis of HCM is intensifying at multiple levels. In this review, we discuss and synthesize the latest findings on HCM pathogenesis, drawing on key experimental studies conducted both in vitro and in vivo. We also offer our insights and perspectives on these mechanisms, while highlighting the limitations of current research. Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.
Cardiomyopathy, Hypertrophic/physiopathology* ; Humans ; Animals

Humans ; Apical Hypertrophic Cardiomyopathy ; Heart Aneurysm/complications* ; Cardiomyopathy, Hypertrophic/complications* ; Ventricular Outflow Obstruction/etiology*

Humans ; Apical Hypertrophic Cardiomyopathy ; Heart Aneurysm/complications* ; Cardiomyopathy, Hypertrophic/complications* ; Ventricular Outflow Obstruction/etiology*

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) frequently leads to myocardial ischemia and cardiac dysfunction. Even genotype-positive/phenotype-negative (G⁺/P^-) individuals, carriers of pathogenic sarcomere gene mutations without left ventricular hypertrophy, remain at risk of progression to clinical HCM. This study aims to evaluate myocardial perfusion and contractile function in familial HCM patients and their first-degree relatives using myocardial contrast echocardiography (MCE) and velocity vector imaging (VVI), in order to identify early myocardial dysfunction and at-risk individuals within families. METHODS: Thirty-five genetically confirmed HCM patients with left ventricular hypertrophy were assigned to a G⁺/P⁺ group. A total of 30 first-degree relatives carrying sarcomere mutations but without echocardiographic evidence of left ventricular hypertrophy were assigned to a G⁺/P^- group. A total of 38 age- and sex-matched gene-negative healthy family members served as controls. All participants underwent MCE and VVI assessments. Myocardial perfusion parameters, including peak intensity (PI), time to peak concentration (TP), and the ratio of declining intensity and declining time (dI/dT), as well as strain parameters including global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) were recorded and analyzed for differences and correlations. RESULTS: Compared to both the G⁺/P^- and normal control groups, the G⁺/P⁺ group had significantly lower PI, dI/dT, GLS, and GRS, along with significantly increased TP (all P<0.05). GLS and GRS were positively correlated with PI (r=0.629 and r=0.613, respectively; both P<0.01) and negatively correlated with TP (r=-0.597 and r=-0.571, respectively; both P<0.01). Compared to the normal control group, the G⁺/P^- group showed a significant reduction in GLS (P<0.05), but no significant differences in GRS, GCS, PI, TP, or dI/dT (all P>0.05). CONCLUSIONS Myocardial contractile dysfunction in HCM patients is closely related to impaired perfusion. Even in the absence of wall hypertrophy, sarcomere mutation carriers show early signs of subclinical left ventricular dysfunction. MCE and VVI can quantitatively assess myocardial perfusion and function, offering valuable tools for early detection and risk stratification in HCM patients and their relatives.
Humans ; Male ; Female ; Myocardial Contraction/physiology* ; Echocardiography/methods* ; Adult ; Cardiomyopathy, Hypertrophic/genetics* ; Middle Aged ; Cardiomyopathy, Hypertrophic, Familial/genetics* ; Family ; Mutation

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome, and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors, including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high-precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening in the fetal gene reprogramming in HCM.
Cardiomyopathy, Hypertrophic/metabolism* ; Humans ; Animals ; DNA Methylation ; Mice ; Transcriptome ; Chromatin/genetics* ; Early Growth Response Protein 1/metabolism* ; Male ; Epigenome ; Nucleosomes/genetics* ; Female ; Middle Aged ; Disease Models, Animal ; Adult

OBJECTIVE: To explore the clinical and genetic characteristics of eight children with Primary hypertrophic cardiomyopathy (HCM). METHODS: Eight children with HCM admitted to the Department of Cardiology of Henan Children's Hospital from January 2018 to December 2021 were selected as the study subjects. Clinical data of the children were collected. Whole exome sequencing was carried out on two children, and trio whole exome sequencing was carried out on the remainder 6 children. Sanger sequencing was used to verify the candidate variants in the children and their parents, and the pathogenicity of the variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The patients had included 5 males and 3 females, with their ages ranging from 5 to 13 years old. The average age of diagnosis was (7.87 ± 4.8) years old, and the cardiac phenotype showed non-obstructive HCM in all of the patients. WES has identified variants of the MYH7 gene in 4 children, including c.2155C>T (p.Arg719Trp), c.1208G>A (p.Arg403Gln), c.1358G>A (p.Arg453His), and c.1498G>A (p.Glu500Lys). Based on the guidelines from the ACMG, the first 3 variants were classified as pathogenic, while c.1498G>A (p.Glu500Lys) was classified as likely pathogenic (PM1+PM2_Supporting+PM6+PP3), which was also unreported previously. The remaining four children had all harbored maternal variants, including MYL2: c.173G>A (p.Arg58Gln; classified as pathogenic), TPM1: c.574G>A (p.Glu192Lys) and ACTC1: c.301G>A (p.Glu101Lys)(both were classified as likely pathogenic), and MYBPC3: c.146T>G (p.Ile49Ser; classified as variant of uncertain significance). Seven children were treated with 0.5 ~ 3 mg/(kg·d) propranolol, and their symptoms had improved significantly. They were followed up until September 30, 2022 without further cardiac event. CONCLUSION Genetic testing can clarify the molecular basis for unexplained cardiomyopathy and provide a basis for clinical diagnosis and genetic counseling. Discovery of the c.1498G>A (p.Glu500Lys) variant has also expanded the spectrum of MYH7 gene mutations underlying HCM.
Female ; Male ; Humans ; Child ; Child, Preschool ; Adolescent ; Cytoskeletal Proteins ; Family ; Genetic Counseling ; Genetic Testing ; Cardiomyopathy, Hypertrophic/genetics*

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with rare type heart disease. METHODS: A pedigree identified at Shenzhen Maternity and Child Health Care Hospital Affiliated to Southern Medical University on July 9, 2021 was selected as the study subject. Clinical data were collected. Trio-whole exome sequencing (WES) was carried out for the proband and his parents. Candidate variants were validated by Sanger sequencing of his family members and bioinformatic analysis. RESULTS: The proband, a 5-month-old male, was found to have Barth syndrome (dilated myocardiopathy and left ventricular non-compaction). Trio-WES revealed that he has harbored a hemizygous c.542G>A (p.G181A) variant of the TAZ gene, which was inherited from his mother. In addition, his mother, aunt and maternal grandmother were also found to harbor a c.557G>A (p.R186Q) variant of the TNNI3 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.542G>A (p.G181A) variant of the TAZ gene was classified as likely pathogenic (PS2_Strong+PM2_Supporting+PP3), whilst the c.557G>A (p.R186Q) variant of the TNNI3 gene was classified as pathogenic (PP1_Strong+PS4_Strong+PP3+PP4+PM2_Supporting). CONCLUSION The c.542G>A (p.G181A) variant of the TAZ gene probably underlay the Barth syndrome in the proband, and the c.557G>A (p.R186Q) variant of the TNNI3 gene may be responsible for the hypertrophic cardiomyopathy in his mother, aunt and maternal grandmother. Above finding has expanded the mutational spectrum of the TAZ gene and facilitated the diagnosis of this pedigree.
Female ; Humans ; Infant ; Male ; Pregnancy ; Barth Syndrome ; Cardiomyopathy, Hypertrophic ; East Asian People ; Heart Diseases ; Pedigree

OBJECTIVES: To investigate the clinical phenotype and genotype characteristics of children withcardiomyopathy (CM) associated with MYH7 gene mutation. METHODS: A retrospective analysis was conducted on the medical data of five children with CM caused by MYH7 gene mutation who were diagnosed and treated in the Department of Cardiology, Hebei Children's Hospital. RESULTS: Among the five children with CM, there were three girls and two boys, all of whom carried MYH7 gene mutation. Seven mutation sites were identified, among which five were not reported before. Among the five children, there were three children with hypertrophic cardiomyopathy, one child with dilated cardiomyopathy, and one child with noncompaction cardiomyopathy. The age ranged from 6 to 156 months at the initial diagnosis. At the initial diagnosis, two children had the manifestations of heart failure such as cough, shortness of breath, poor feeding, and cyanosis of lips, as well as delayed development; one child had palpitation, blackness, and syncope; one child had fever, runny nose, and abnormal liver function; all five children had a reduction in activity endurance. All five children received pharmacotherapy for improving cardiac function and survived after follow-up for 7-24 months. CONCLUSIONS The age of onset varies in children with CM caused by MYH7 gene mutation, and most children lack specific clinical manifestations at the initial diagnosis and may have the phenotype of hypertrophic cardiomyopathy, dilated cardiomyopathy or noncompaction cardiomyopathy. The children receiving early genetic diagnosis and pharmacological intervention result in a favorable short-term prognosis.
Male ; Female ; Child ; Humans ; Retrospective Studies ; Cardiomyopathy, Dilated/genetics* ; Pedigree ; Phenotype ; Genotype ; Mutation ; Cardiomyopathy, Hypertrophic/diagnosis* ; Myosin Heavy Chains/genetics* ; Cardiac Myosins/genetics*

OBJECTIVE: To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A (MPS Ⅲ A). METHODS: A female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site. RESULTS: The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range. CONCLUSION The compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.
Female ; Humans ; Cardiomyopathy, Hypertrophic ; Contrast Media ; East Asian People ; Gadolinium ; Mucopolysaccharidosis III ; Mutation ; Pedigree ; Male ; Middle Aged