[Analysis on related factors of myocardial fibrosis in patients with hypertrophic cardiomyopathy].

Objective: To investigate the related factors of myocardial fibrosis in patients with hypertrophic cardiomyopathy. Methods: Patients with hypertrophic cardiomyopathy, hospitalized in the First People's Hospital of Yunnan Province from January 2016 to May 2020, were included in this cross-sectional study. Patients were divided into delayed enhancement positive group (fibrosis group) and non-delayed enhancement group (non-fibrosis group). According to the maximum left ventricular end diastolic wall thickness (LVMWT), patients in the fibrosis group was further divided into mild hypertrophy group, moderate hypertrophy group and severe hypertrophy group. The baseline clinical data of patients were collected by medical record management system. All enrolled patients underwent cardiac magnetic resonance imaging (CMR). The presence and location of myocardial fibrosis were identified by CMR gadolinium contrast delayed enhancement (LGE). The range of LGE (LGE%) was calculated by visual analysis. The levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in peripheral blood were measured. Results: A total of 48 patients ( age (46.4±14.3) years, 42 (87.5%) males) were enrolled. There were 34 LGE positive cases (fibrosis group) and 14 LGE negative cases (non-fibrosis group). Compared with non-fibrosis group, patients in fibrosis group were younger (P=0.038) and prevalence of NYHA grade Ⅲ/Ⅳ was higher (P=0.00). Compared with non-fibrosis group, patients in fibrosis group had thicker LVMWT (P= 0.008), higher left ventricular mass index(LVMI) (P=0.001), higher left ventricular end diastolic volume (LVEDV) (P=0.043), lower left ventricular ejection fraction (LVEF) and cardiac index (CI) (all P <0.05). The levels of NT-proBNP and cTnI were significantly higher in fibrosis group than in non-fibrosis group (2 760.5 (1 503.4, 3 783.6) ng / L vs. 861.3 (552.2, 1 092.8) ng / L, P=0.002; 0.970 (0.448, 1.684)µg / L vs. 0.147 (0.033, 0.251)µg / L, P=0.041).In fibrosis group, there were 15 cases of mild hypertrophy (mild hypertrophy group), 10 cases of moderate hypertrophy (moderate hypertrophy group), and 9 cases of severe hypertrophy (severe hypertrophy group). The LGE% and NT-proBNP and cTnI increased in proportion with increasing myocardial hypertrophy (P<0.05). LGE% was negatively correlated with age (r=-0.618, P=0.011), and positively correlated with NT-proBNP and cTnI levels (r=0.271, P=0.010; r=0.111,P=0.013, respectively), and positively correlated with LVEDV, LVMWT and LVMI (r=0.438, P=0.09; r=0.735, P=0.001; r=0.532, P=0.034, respectively). Conclusions: In patients with hypertrophic cardiomyopathy, the extent of myocardial fibrosis increases with the increase of myocardial hypertrophy. Myocardial fibrosis is negatively correlated with age, and positively correlated with NT-proBNP and cTnI, as well as LVEDV, LVMWT and LVMI in this patient cohort.

[Gene screening and phenotype analysis in a pedigree with familial hypertrophic cardiomyopathy from Yunnan Province].

Objective: To identify the disease-causing mutations in a pedigree with familial hypertrophic cardiomyopathy (HCM) from Yunnan province, and analyze the relationship between the genotype and the phenotype. Methods: The blood samples and the clinical data of the HCM family members were collected.The coding exons and their flanking intronic regions of 28 previously reported genes related to HCM were screened in the proband by high-throughput sequencing. The mutations in proband were confirmed and detected in all family members as well as in 159 healthy controls by Sanger sequencing.The relationship between the genotype and the phenotype was analyzed in this pedigree. Results: Two missense mutations of Arg1045His and Ala26Val in ß myosin heavy chain gene(MYH7) were identified. Genetic screening showed that the mother and brother of the proband carried Arg1045His mutation.Both mutations were absent in other family members and in 159 healthy controls.Disease onset age was less than 50 years old in this pedigree, chest pain, exertional dyspnea and syncope were the major symptoms, and all accompanied by severe left ventricular hypertrophy and left ventricular outflow tract stenosis.The grandma of the proband suffered sudden cardiac death. The proband had the worst symptoms and the earliest disease onset in this pedigree. Conclusions: We find a pedigree with familial HCM from Yunnan province carrying MYH7 Arg1045His and Ala26Val mutations. The study suggests that Arg1045His mutation in MYH7 gene caused HCM is malignant with early onset, severe ventricular hypertrophy and poor prognosis. Arg1045His and Ala26Val double-mutant might have dosage effects and aggravate the clinical phenotype of the patient.