No abstract available.
Adolescent ; Adrenergic beta-Antagonists/therapeutic use ; Calcium Channel Blockers/therapeutic use ; Cardiomyopathy, Hypertrophic, Familial/complications/genetics/*pathology/physiopathology/therapy ; Electric Countershock ; Electrocardiography ; Female ; Genetic Predisposition to Disease ; Heart Failure/etiology/therapy ; Heart Septum/drug effects/*pathology/physiopathology/ultrasonography ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pedigree ; Phenotype ; Tachycardia, Ventricular/etiology/therapy ; Treatment Outcome ; Ventricular Outflow Obstruction/etiology

β-myosin heavy chain mutations are the most frequently identified basis for hypertrophic cardiomyopathy (HCM). A transgenic mouse model (αMHC(403)) has been extensively used to study various mechanistic aspects of HCM. There is general skepticism whether mouse and human disease features are similar. Herein we compare morphologic and functional characteristics, and disease evolution, in a transgenic mouse and a single family with a MHC mutation. Ten male αMHC(403) transgenic mice (at t-5 weeks, -12 weeks, and -24 weeks) and 10 HCM patients from the same family with a β-myosin heavy chain mutation were enrolled. Morphometric, conventional echocardiographic, tissue Doppler and strain analytic characteristics of transgenic mice and HCM patients were assessed. Ten male transgenic mice (αMHC(403)) were examined at ages -5 weeks, -12 weeks, and -24 weeks. In the transgenic mice, aging was associated with a significant increase in septal (0.59±0.06 vs. 0.64±0.05 vs. 0.69±0.11 mm, P<0.01) and anterior wall thickness (0.58±0.1 vs. 0.62±0.07 vs. 0.80±0.16 mm, P<0.001), which was coincident with a significant decrease in circumferential strain (-22%±4% vs. -20%±3% vs. -19%±3%, P=0.03), global longitudinal strain (-19%±3% vs. -17%±2% vs. -16%±3%, P=0.001) and E/A ratio (1.9±0.3 vs. 1.7±0.3 vs. 1.4±0.3, P=0.01). The HCM patients were classified into 1st generation (n=6; mean age 53±6 years), and 2nd generation (n=4; mean age 32±8 years). Septal thickness (2.2±0.9 vs. 1.4±0.1 cm, P<0.05), left atrial (LA) volume (62±16 vs. 41±5 mL, P=0.03), E/A ratio (0.77±0.21 vs. 1.1±0.1, P=0.01), E/e' ratio (25±10 vs. 12±2, P=0.03), global left ventricular (LV) strain (-14%±3% vs. -20%±3%, P=0.01) and global LV early diastolic strain rate (0.76±0.17 s(-1) vs. 1.3±0.2 s-1, P=0.01) were significantly worse in the older generation. In β-myosin heavy chain mutations, transgenic mice and humans have similar progression in morphologic and functional abnormalities. The αMHC(403) transgenic mouse model closely recapitulates human disease.
Adult ; Age Factors ; Aging ; Animals ; Cardiomyopathy, Hypertrophic, Familial ; genetics ; physiopathology ; Cross-Sectional Studies ; Disease Models, Animal ; Echocardiography, Doppler ; Female ; Heart ; physiopathology ; Humans ; Male ; Mice, Transgenic ; Middle Aged ; Myocardium ; metabolism ; pathology ; Myosin Heavy Chains ; genetics ; Phenotype ; Species Specificity ; Young Adult

Asymmetric septal hypertrophy with systolic anterior motion of the mitral valve is frequently a phenotypic, but not pathognomonic, expression of genetic hypertrophic cardiomyopathy (HCM) with or without obstruction. It can, however, be associated nonspecifically with other forms of increased left ventricular (LV) afterload. We herein report the case of a young man with obesity cardiomyopathy and heart failure who presented with asymmetric septal hypertrophy and marked LV hypertrophy, and endomyocardial biopsy ruled out genetic HCM.
Adult ; Cardiomyopathy, Hypertrophic, Familial ; Diagnosis, Differential ; Echocardiography ; Humans ; Hypertrophy, Left Ventricular ; complications ; diagnosis ; Male ; Obesity, Morbid ; complications

OBJECTIVE: To determine the associated mutations in myosin-binding protein C3 (MYBPC3) in Chinese patients with family hypertrophic cardiomyopathy (FHCM) and to analyze the genotype and phenotype correlation. METHODS: One family with 27 family members affected with FHCM was chosen for the study. The full encoding exons of MYBPC3 were amplified with PCR and the products were sequenced. The clinical data and echocardiography were collected. RESULTS: Two missense mutations in the family were identified: one was C.2526C>G mutation which caused a tyrosine (Tyr) to terminator exchange at amino acid residue 842 and the other was C.2971G>A mutation which resulted in a valine (Val) to methionine (Met) exchange at amino acid residue 991. Four patients in the family suffered from HCM with asymmetric interventricular septal hypertrophy. The left ventricular diastolic function was significantly reduced. Signs of regional diastolic abnormalities occurred in some mutation carriers. CONCLUSION Severe hypertrophy and diastolic dysfunction of the disease are compatible with the presence of double mutations in MYBPC3. Signs of regional diastolic abnormalities suggest a primary response to the mutations of MYBPC3 expression.
Adolescent ; Adult ; Aged ; Base Sequence ; Cardiomyopathy, Hypertrophic, Familial ; diagnostic imaging ; genetics ; Carrier Proteins ; genetics ; China ; ethnology ; Echocardiography, Doppler ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Young Adult

BACKGROUND: As the patients who undergo heart transplantation have achieved better survival in recent years, a growing number of recipients are at a risk for experiencing surgical complications in addition to rejection and infection. In this paper, we report on our experience with the surgical complications that occurred in heart transplant recipients. MATERIAL AND METHOD: From April 1994 to September 2003, 37 heart transplantations were performed at our center by a single surgeon. The indications for transplantation were dilated cardiomyopathy, ischemic cardiomyopathy, valvular cardiomyopathy and familial hypertrophic cardiomyopathy. RESULT: Twenty postoperative complications required surgeries in 15 patients (41%). The types of operations required were; redo-sternotomy for bleeding (5), pericardiostomy for effusion (4), implantation of a permanent pacemaker (1), right lower lobe lobectomy for aspergilloma (1), removal of urinary stone (1), cholecystectomy for gall bladder stone (1), drainage of a perianal abscess (1), paranasal sinus drainage (1), total hip replacement (1), partial gingivectomy due to gingival hypertrophy (1), urethrostomy (1), herniated intervertebral disc operation (1) and total hysterectomy for myoma uteri (1). The locations of the complications were mediastinal in 10 (27%) cases and extramediastinal in 10 (27%) cases. CONCLUSION: The relatively high incidence of extrathoracic complications associated with heart transplantation emphasizes the importance of a multidisciplinary approach to the improve long-term survival when managing those complex patients.
Abscess ; Arthroplasty, Replacement, Hip ; Cardiomyopathies ; Cardiomyopathy, Dilated ; Cardiomyopathy, Hypertrophic, Familial ; Cholecystectomy ; Drainage ; Gingival Hypertrophy ; Gingivectomy ; Heart ; Heart Transplantation ; Hemorrhage ; Humans ; Hysterectomy ; Incidence ; Intervertebral Disc ; Myoma ; Pericardial Window Techniques ; Postoperative Complications ; Rejection (Psychology) ; Transplants ; Urinary Bladder Calculi ; Urinary Calculi ; Uterus

BACKGROUNDHypertrophic 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.

METHODSThe 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.

RESULTSThe 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.

CONCLUSIONThe Arg723Gly mutation is a malignant type. In Chinese the mutation has the similar characters to the former report but has low degree malignant.

Adolescent ; Adult ; Cardiomyopathy, Hypertrophic, Familial ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Myosin Heavy Chains ; genetics ; Ventricular Myosins ; genetics

OBJECTIVEHypertrophic 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.

METHODSFive 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.

RESULTSArg723Gly 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.

CONCLUSIONSArg723Gly 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.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Cardiomyopathy, Hypertrophic, Familial ; genetics ; China ; epidemiology ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Mutation ; Myosin Heavy Chains ; genetics ; Pedigree ; Phenotype ; Young Adult

OBJECTIVEThe aim of this study was to screen the disease-causing gene mutations and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy (HCM).

METHODSThere are 91 family members from these 10 pedigrees and 5 members were normal mutated carriers, 23 members were HCM patients (14 male) aged from 1.5 to 73 years old. The functional regions of myosin heavy chain gene (MYH7), cardiac myosin-binding protein C (MYBPC3) and cardiac troponin T gene (TNNT2) were screened with PCR and direct sequencing technique. Clinical information from all patients was also evaluated in regard to the genotype.

RESULTSMutations were found in 5 out of 10 pedigrees. Mutations in MYH7 (Arg663His, Glu924Lys and Ile736Thr) were found in 3 pedigrees and 3 patients from these pedigrees suffered sudden death at age 20-48 years old during sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation (Arg502Trp and splicing mutation IVS27 + 12C > T) and 1 with novel frame shift mutation (Gly347fs) and the latter pedigree has sudden death history. No mutation was identified in TNNT2.

CONCLUSIONSAlthough the Han Chinese is a relatively homogeneous ethnic group, different HCM gene mutations were responsible for familiar HCM suggesting the heterogeneity nature of the disease-causing genes and HCM MYH7 mutations are associated with a higher risk of sudden death in this cohort. Furthermore, identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of familiar HCM.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Cardiac Myosins ; genetics ; Cardiomyopathy, Hypertrophic, Familial ; ethnology ; genetics ; Carrier Proteins ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Middle Aged ; Mutation ; Myosin Heavy Chains ; genetics ; Pedigree ; Phenotype ; Troponin T ; genetics ; Young Adult

OBJECTIVETo detect the disease-causing gene mutation of hypertrophic cardiomyopathy (HCM) in a Chinese family and to analyze the correlation of the genotype and the phenotype.

METHODSOne family affected with HCM was studied. The clinical data including symptom, physical examination, echocardiography and electrocardiography were collected. The full encoding exons and flanking sequences of beta-myosin heavy chain gene (MYH7) and cardiac myosin-binding protein C gene (MYBPC3) were amplified with PCR and the products were sequenced.

RESULTSA G8887A mutation, which is an acceptor splicing site of intron 15 (IVS15-1G > A) in MYBPC3 (gi: Y10129) was identified in 6 out of 11 family members. Three mutation carriers developed HCM at 48 - 75 years old with mild chest pain, chest distress and asymmetric septal hypertrophy (13 - 14 mm) and remaining mutation carriers are free of HCM. No mutation was identified in MYH7 gene.

CONCLUSIONHCM caused by the IVS15-1G > A mutation is a benign phenotype. It is helpful to screen MYBPC3 gene mutation in late-onset HCM patients with mild symptoms.

Adult ; Aged ; Cardiac Myosins ; genetics ; Cardiomyopathy, Hypertrophic, Familial ; genetics ; Carrier Proteins ; genetics ; Case-Control Studies ; Genotype ; Humans ; Middle Aged ; Mutation ; Myosin Heavy Chains ; genetics ; Pedigree ; Phenotype ; Polymerase Chain Reaction

Although hypertrophic cardiomyopathy (HCM) may cause heart failure, HCM and dilated cardiomyopathy (DCM) are generally recognized as separate diseases. This report describes two cases of maternally inherited familial HCM, which, after pregnancy, rapidly deteriorated to heart failure and cardiac chamber dilatation, resembling DCM. Some members of this family also suffered sudden cardiac death (SCD).
Cardiomyopathy, Dilated ; Cardiomyopathy, Hypertrophic ; Cardiomyopathy, Hypertrophic, Familial* ; Death, Sudden, Cardiac* ; Dilatation ; Heart Failure ; Humans ; Pregnancy*