Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Eur Heart J ; 42(32): 3063-3073, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34263907

RESUMO

AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.


Assuntos
Cardiomiopatia Hipertrófica , Proteínas Musculares/genética , Proteínas Quinases/genética , Cardiomiopatia Hipertrófica/genética , Heterozigoto , Humanos , Mutação , Sarcômeros
2.
Front Cardiovasc Med ; 8: 748003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869653

RESUMO

Background: Arrhythmogenic cardiomyopathy (AC) is a life-threatening disease which predispose to malignant arrhythmias and sudden cardiac death (SCD) in the early stages of the disease. Risk stratification relies on the electrical, genetic, and imaging data. Our study aimed to investigate how myocardial deformation parameters may identify the subjects at risk of known predictors of major ventricular arrhythmias. Methods: A cohort of 45 subjects with definite or borderline diagnosis of AC was characterized using the advanced transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) and divided into the groups according to the potential arrhythmic risk markers, such as non-sustained ventricular tachycardia (NSVT), late gadolinium enhancement (LGE), and genetic status. Layer-specific global longitudinal strain (GLS) by TTE 2D speckle tracking was compared in patients with and without these arrhythmic risk markers. Results: In this study, 23 (51.1%) patients were men with mean age of 43 ± 16 years. Next-generation sequencing identified a potential pathogenic mutation in 39 (86.7%) patients. Thirty-nine patients presented LGE (73.3%), mostly located at the subepicardial-to-mesocardial layers. A layer-specific-GLS analysis showed worse GLS values at the epicardial and mesocardial layers in the subjects with NSVT and LGE. The epicardial GLS values of -15.4 and -16.1% were the best cut-off values for identifying the individuals with NSVT and LGE, respectively, regardless of left ventricular ejection fraction (LVEF). Conclusions: The layer-specific GLS assessment identified the subjects with high-risk arrhythmic features in AC, such as NSVT and LGE. An epicardial GLS may emerge as a potential instrument for detecting the subjects at risk of SCD in AC.

3.
Case Rep Cardiol ; 2018: 5757081, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29662705

RESUMO

Aortitis is an infrequent cause of aortic root dilatation and aortic valve regurgitation. Valve-sparing procedures have been proposed, but there is not clear evidence of which is the treatment of choice. We report the case of a 38-year-old pregnant lady with a diagnosis of idiopathic aortitis associated with aortic root aneurysm and severe aortic valve regurgitation.

4.
J Am Coll Cardiol ; 72(20): 2457-2467, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30442288

RESUMO

BACKGROUND: The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy. OBJECTIVES: This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy. METHODS: FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes. RESULTS: The authors identified 94 candidate variants in 132 probands. The variants' frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 [2.32%]) than in disease control subjects (18 of 2,777 [0.65%]; p < 0.001) or in the gnomAD database (1,049 of 138,606 [0.76%]; p < 0.001). FHOD3 mutations cosegregated with hypertrophic cardiomyopathy in 17 families, with a combined logarithm of the odds score of 7.92, indicative of very strong segregation. One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects (95% confidence interval: 1.3 to 37.9; p < 0.001) and 14.1 against gnomAD (95% confidence interval: 6.9 to 28.7; p < 0.001). Hypertrophic cardiomyopathy patients carrying (likely) pathogenic mutations in FHOD3 (n = 70) were diagnosed after age 30 years (mean 46.1 ± 18.7 years), and two-thirds (66%) were males. Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 ± 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up. CONCLUSIONS: FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/genética , Variação Genética/genética , Proteínas dos Microfilamentos/genética , Mutação/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Seguimentos , Forminas , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto Jovem
5.
Int J Cardiol ; 225: 289-295, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27744205

RESUMO

BACKGROUND: Clopidogrel has provided beneficial effects in acute coronary syndrome and percutaneous coronary intervention. Different polymorphisms have been associated with differences in clopidogrel response. The aim of this study was to check if CYP2C19/ABCB1-genotype-guided strategy reduces the rates of cardiovascular events and bleeding. METHODS: This experimental study included patients undergoing percutaneous coronary intervention with stent. The prospective genotype-guided strategy (intervention group) was compared against a retrospective non-tailored strategy (control group). Primary efficacy endpoint was the composite of cardiovascular death, acute coronary syndrome or stroke during 12months after intervention. Secondary endpoint was to compare the efficacy of the different antiplatelet therapies used in genotyping conditions. RESULTS: The study included 719 patients undergone stent, more than 86% with acute coronary syndrome. The primary endpoint occurred in 32 patients (10.1%) in the genotyping group and in 59 patients (14.1%) in the control group (HR 0.63, 95% CI (0.41-0.97), p =0.037). There was no difference in The Thrombolysis in Myocardial Infarction major and minor bleeding criteria between the two groups (4.1% vs. 4.7%, HR=0.80, 95% CI (0.39-1.63), p=0.55). In intervention group, there was no difference in the rate of events in patients treated with clopidogrel versus patients treated with other antiplatelet treatments (9.1% vs 11.5% p=0.44), or bleeding (3.7% vs 4.6%, p=0.69). CONCLUSIONS: The genotype-guided strategy could reduce the rates of composite of cardiovascular events and bleeding during 12months after percutaneous coronary intervention compared to a non-genotype-guide strategy.


Assuntos
Citocromo P-450 CYP2C19/genética , Genótipo , Intervenção Coronária Percutânea/tendências , Inibidores da Agregação Plaquetária/uso terapêutico , Stents , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Morte , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA