Genetic Determinants and Genotype-Phenotype Correlations in Vietnamese Patients With Dilated Cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is an important cause of heart failure and cardiac transplantation. This study determined the prevalence of DCM-associated genes and evaluated the genotype-phenotype correlation in Vietnamese patients.Methods and Results:This study analyzed 58 genes from 230 patients. The study cohort consisted of 64.3% men; age at diagnosis 47.9±13.7 years; familial (10.9%) and sporadic DCM (82.2%). The diagnostic yield was 23.5%, 44.0% in familial and 19.6% in sporadic DCM.TTNtruncating variants (TTNtv) were predominant (46.4%), followed byTPM1,DSP,LMNA,MYBPC3,MYH6,MYH7,DES,TNNT2,ACTC1,ACTN2,BAG3,DMD,FKTN,PLN,TBX5,RBM20,TCAP(2-6%). Familial DCM, genotype-positive andTTNtv-positive patients were younger than those with genotype-negative and sporadic DCM. Genotype-positive patients displayed a decreased systolic blood pressure and left ventricular wall thickness compared to genotype-negative patients. Genotype-positive patients, particularly those withTTNtv, had a family history of DCM, higher left atrial volume index and body mass index, and lower right ventricle-fractional area change than genotype-negative patients. Genotype-positive patients reached the combined outcomes more frequently and at a younger age than genotype-negative patients. Major cardiac events occurred more frequently in patients positive with genes other thanTTNtv. CONCLUSIONS: The study findings provided an overview of Vietnamese DCM patients' genetic profile and suggested that management of environmental factors may be beneficial for DCM patients.

Presence of Hypertrophic Cardiomyopathy Related Gene Mutations and Clinical Manifestations in Vietnamese Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated primarily with pathogenic mutations in sarcomeric genes. The aim of this study was to identify the prevalence and distribution of disease-causing mutations in HCM-associated genes and the genotype-phenotype relationship in Vietnamese patients with HCM.Methods and Results:Genetic testing was performed by next-generation sequencing in 104 unrelated probands for 23 HCM-related genes and in 57 family members for the mutation(s) detected. Clinical manifestations were recorded for genotype-phenotype correlation analysis. Mutation detection rate was 43.4%. Mutations inMYBPC3accounted for 38.6%, followed byTPM1(20.5%),MYH7(18.2%),TNNT2(9.1%),TNNI3(4.5%) andMYL2(2.3%). A mutation inGLAassociated with Fabry disease was found in 1 patient. A mutation inTPM1(c.842T>C, p.Met281Thr) was identified in 8 unrelated probands (18.2%) and 8 family members from 5 probands. Genotype-positive status related toMYH7,TPM1, andTNNT2mutations was associated with severe clinical manifestations.MYH7-positive patients displayed worse prognosis compared withMYBPC3-positive patients. Interestingly,TPM1c.842T>C mutation was associated with high penetrance and severe HCM phenotype. CONCLUSIONS: We report for the first time the prevalence of HCM-related gene variants in Vietnamese patients with HCM.MYH7,TPM1, andTNNT2mutations were associated with unfavorable prognosis.

Hypertension treatment in the Asia-Pacific: the role of and treatment strategies with nebivolol.

Hypertension is a common disease, and hypertensive patients are at increased risk of cardiovascular events. The prevalence and socioeconomic burden of hypertension in the Asia-Pacific region are predicted to increase in the coming decades. Effective blood pressure lowering reduces overall cardiovascular morbidity and mortality in patients, yet doubt has been raised regarding the use of (mainly older generation) ß-blockers as initial therapy in hypertension. Consequently, several international treatment guidelines do not recommend ß-blockers for the treatment of hypertension. However, in contrast to first-generation and second-generation ß-blockers, the third-generation, vasodilating ß-blocker nebivolol has a considerably better metabolic, haemodynamic and side effect profile. In addition to providing effective blood pressure control similar to other ß-blockers and drugs from other antihypertensive classes, nebivolol exerts a dual mechanism for increasing the bioavailability of the naturally occurring vasodilator nitric oxide. The clinical benefits and significance of enhancing nitric oxide levels in hypertensive patients have been shown in direct comparisons of nebivolol with other ß-blockers. While ß-blockers generally provide comparable blood pressure reductions, only nebivolol demonstrated enhanced vasodilation and blood flow by increasing the expression of endothelial nitric oxide synthase and therefore increasing nitric oxide release from the endothelium. In contrast to other ß-blockers, therefore, it has been suggested that nebivolol has beneficial effects in several hypertensive subgroups due to its vasodilating properties. Considering the existing data, it may be timely for treatment guidelines to recommend third-generation vasodilating ß-blockers as a first-line option for the pharmacotherapy of hypertension.

Mitral valve repair with aortic valve replacement in rheumatic heart disease.

From 1992 to 2001, 609 patients with rheumatic heart disease underwent aortic valve replacement with either mitral valve repair (n = 201) or mitral valve replacement (n = 408). Follow-up extended to 10 years. Thirty-day mortality was 1.4% for mitral valve repair and 0.7% for mitral valve replacement (p = 0.4). Survival at 9 years was 96.5 +/- 1.4% after mitral valve repair and 89.7 +/- 7.8% after mitral valve replacement (p = 0.73). Freedom from major bleeding at 9 years was 94.8 +/- 2.4% after mitral valve repair and 81 +/- 7.2% after mitral valve replacement (p = 0.03). Freedom from other valve-related complications and from mitral valve re-operation was similar for the two groups. This study showed that in patients with rheumatic heart disease the results of mitral valve repair with aortic valve replacement were comparable to those of double valve replacement. Major bleeding was less frequent after mitral valve repair with aortic valve replacement. Therefore, whenever feasible, mitral valve repair should be attempted in patients with rheumatic heart disease who need concomitant aortic valve replacement.

Mitral valve repair in children using Carpentier's techniques.

Controversy remains regarding whether valve repair is preferable to valve replacement in children suffering from rheumatic mitral valve disease. To answer this question, 130 children aged 3 to 15 years (mean age, 11.8 +/- 2.8 years) undergoing surgery between January 1992 and December 1997 using Carpentier's techniques were reviewed. There were 111 cases of rheumatic valve diseases (85%), 17 cases of congenital mitral valve malformations (13%), one case of Barlow's syndrome (1%), and one case of bacterial endocarditis (1%). Valve dysfunction was classified into three types according to Carpentier's classification. There were 14 type II (leaflet prolapse), 78 type III (restricted leaflet motion), and 38 associated type II (anterior leaflet) and III (posterior leaflet) cases. There was one early (in-hospital) death (0.7%); the remaining 129 children were examined every 6 months. At the last examination, 99.2% of the patients were still alive, 96.8% were free of reoperation, and 89% showed no sign of significant residual stenosis or insufficiency on echocardiography. There have been no thromboembolisms. We conclude that mitral valve repair using Carpentier's techniques is the preferred procedure in the surgical treatment of mitral valve incompetence in children, even in those with rheumatic valvular disease. Copyright 1999 by W.B. Saunders Company