Mitral early-diastolic inflow peak velocity (E)-to-left atrial strain ratio as a novel index for predicting elevated left ventricular filling pressures in patients with preserved left ventricular ejection fraction.

OBJECTIVES: We sought to explore the relationship between an index of left ventricular diastolic function parameters combined with left atrial strain and the diastolic function of patients with preserved ejection fraction. METHODS: We prospectively enrolled 388 patients with left ventricular ejection fraction (LVEF) ≥ 50%, 49 of whom underwent left heart catherization. Transthoracic echocardiography was performed within 12 h before or after the procedure. Left atrial (LA) strain was obtained by speckle tracking echocardiography. These patients served as the test group. The remaining patients (n = 339) were used to validate the diagnostic performance of the mitral early-diastolic inflow peak velocity (E)-to-left atrial reservoir strain ratio (E/LASr) in left ventricular diastolic dysfunction. RESULTS: Invasive measurements of LV end-diastolic pressure (LVEDP) demonstrated that the E/LASr ratio was increased in patients with elevated LVEDP [ 2.0 (1.8-2.2) vs 3.0 (2.6-4.0), p < 0.001] in the test group (n = 49). After adjusting for age, mitral A, E/e' ratio and ß-blocker use, the E/LASr ratio was an independent predictor of elevated LVEDP and showed good diagnostic performance in determining elevated LVEDP [area under the curve (AUC) 0.903, cutoff value 2.7, sensitivity 74.2%, specificity 94.4%]. In the validation group (n = 339), the E/LASr ratio also performed well in diagnosing elevated left atrial pressure (LAP) (AUC 0.904, cutoff value 3.2, sensitivity 76.5%, specificity 89.0%), while with a cut-off value of 2.7, the E/LASr ratio showed high accuracy in discriminating elevated LAP. In addition, E/LASr was a good index of excellent diagnostic utility (AUC: 0.899 to 0.996) in the categorization of diastolic dysfunction grades. Regarding the clinical relevance of this index, the E/LASr ratio could accurately diagnose HF with preserved ejection fraction (HFpEF) (0.781), especially in patients with "indeterminate" status (AUC: 0.829). Furthermore, an elevated E/LASr ratio was significantly associated with the risk of rehospitalization due to major adverse cardiac events (MACEs) within one year (odds ratio: 1.183, 95% confidence interval: 1.067, 1.312). CONCLUSIONS: In patients with EF preservation, the E/LASr ratio is a novel index for assessing elevated left ventricular filling pressure with high accuracy.

Mutation of Arg723Gly in beta-myosin heavy chain gene in five Chinese families with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a form of cardiomyopathy with an autosomal dominant inherited disease, which is caused by mutations in at least one of the sarcomeric protein genes. Mutations in the beta-myosin heavy chain (beta-MHC) are the most common cause of HCM. This study was to reveal the disease-causing gene mutations in Chinese population with HCM, and to analyze the correlation between the genotype and phenotype. METHODS: The exons 3 to 26 of MYH7 were amplified by PCR, and the PCR products were sequenced in five non-kin HCM patients. A 17-year-old patient was detected to be an Arg723Gly mutation carrier. Then his family was gene-screened, and the correlation between genotype and phenotype was analyzed. RESULTS: The mutation of Arg723Gly in a Chinese family with HCM was detected for the first time. With a C-G transversion in nucleotide 13,619 of the MYH7 gene, located at the essential light chain interacting region in S1, the replacement of arginine by glycine took place at amino acid residue 723. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy with left atria enlargement. There was no obstruction in the left ventricular outflow tract. In his family, a total of 13 individuals were diagnosed HCM and 5 of them were dead of congestive heart failure at a mean age of 66-year-old. Eight living members were all detected to carry the mutation, in which 3 developed progressive heart failure. Moreover, the heart function of the people evidently deteriorates when their age are older than 50. The mutation and the disease show co-separated. CONCLUSION: The Arg723Gly mutation is a malignant type. In Chinese the mutation has the similar characters to the former report but has low degree malignant.

[Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene in a Chinese pedigree].

OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease and an Arg723Gly mutation in beta-myosin heavy chain (beta-MHC) gene was found in 3 Spanish families with malignant HCM. We detected this gene mutation in 5 Chinese pedigrees with hypertensive cardiomyopathy. METHODS: Five Chinese pedigrees with HCM and 80 age-matched normal control subjects were chosen for the study. The exons in the functional regions of the beta-MHC gene were amplified with PCR and the products were sequenced, genotype and phenotype analyzed. RESULTS: Arg723Gly mutation was identified in exon 20 in one pedigree. In this pedigree, 13 out of 25 family members were diagnosed as HCM, 5 died of heart failure, all HCM patients in this pedigree had Arg723Gly mutation and 3 of them had NYHA III and 2 of them were diagnosed as HCM before the age of 20. CONCLUSIONS: Arg723Gly mutation was also one of the main disease-causing genes in Chinese familial HCM. The mutation of Arg723Gly is a malignant phenotype as shown by early progressive heart failure development and poor prognosis in this pedigree with Arg723Gly mutation.