RESUMO
BACKGROUND: Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and ß-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM). METHODS: Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: α2cdel322-325, ß1Arg389, and ß2Arg16. Data were analyzed by genotype and ß-blocker use. Mean age at enrollment was 8.5 y. RESULTS: One-year event-free survival was 51% in advanced and 80% in stable DCM. High-risk genotypes were associated with higher left ventricular (LV) filling pressures, higher systemic and pulmonary vascular resistance, greater decline in LV ejection fraction (P < 0.05), and a higher frequency of mechanical circulatory support while awaiting transplant (P = 0.05). While ß-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving ß-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving ß-blockers (interaction P < 0.05). CONCLUSION: Our study identifies genetic risk markers that may help in the identification of patients at risk for developing decompensated HF and who may benefit from early institution of ß-blocker therapy before progression to decompensated HF.
Assuntos
Antagonistas Adrenérgicos beta/metabolismo , Cardiomiopatia Dilatada/complicações , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Hemodinâmica/fisiologia , Receptores Adrenérgicos/genética , Adolescente , Sequência de Bases , Criança , Primers do DNA/genética , Ecocardiografia , Frequência do Gene , Genótipo , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Hemodinâmica/genética , Humanos , Estimativa de Kaplan-Meier , Dados de Sequência Molecular , Mutação de Sentido Incorreto/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Análise de Sequência de DNA , Deleção de Sequência/genética , Volume Sistólico , Taxa de Sobrevida , Resistência Vascular , Pressão VentricularRESUMO
BACKGROUND: The healthcare burden related to congenital heart disease (CHD) is increasing with improving survival. We assessed changing trends in prenatal risk factors for CHD in the current era in a Canadian cohort. METHODS AND RESULTS: CHD patients <18 years old (n=2339) and controls without structural heart disease (n=199) were prospectively enrolled in an Ontario province-wide biobank registry from 2008-2011. Family history, frequency of extra-cardiac anomalies (ECAs), and antenatal risk factors were assessed. Temporal trends were analyzed and associations with CHD were measured using linear and logistic regression. Family history of CHD and frequency of major ECAs was higher in cases versus controls (P<0.001). Despite an increase in genetic testing in the recent era, only 9.5% of cases with CHD had a confirmed genetic diagnosis. Yield of genetic testing (ie, frequency of abnormal results) was higher in familial and syndromic cases. There was an increase in parental age at conception, maternal prepregnancy body mass index, maternal urinary tract infections, type 1 diabetes, and exposure to nonfertility medications during pregnancy from 1990-2011. Later year of birth, family history of CHD, presence of major ECAs, maternal smoking during pregnancy, and maternal medication exposure were associated with increased odds of CHD (P<0.05 for all). Advanced parental age was associated with increased odds of CHD caused by genetic abnormalities. CONCLUSIONS: The increase in prenatal risk factors for CHD highlights the need for more rigorous ascertainment of genetic and environmental factors including gene-environment interactions that contribute to CHD.
Assuntos
Cardiopatias Congênitas/epidemiologia , Diagnóstico Pré-Natal , Feminino , Testes Genéticos , Cardiopatias Congênitas/genética , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Several changes occur during the transformation of normal tissue to neoplastic tissue. Such changes in molecular composition can be detected by Raman spectroscopy. Raman spectroscopy is a nondestructive method of measuring these changes, which suggests the possibility of real-time diagnosis during medical procedures. METHODS: This study seeks to evaluate the ability of Raman spectra to distinguish tissues. The Raman signatures of normal kidney, lung, and liver tissue samples from pigs and rats were characterized in vitro. Further, a human neuroblastoma and a hepatoblastoma, obtained at resection were also studied. RESULTS: The Raman spectra of the animal samples of kidney, liver, and lung are distinctly different in the intensity distribution of the Raman peaks. Further, the spectra of a given organ from pigs and rats, although similar, were different enough to distinguish between the 2 animals. In the patient tissues, the Raman spectra of normal liver, viable tumor, and fibrotic hepatoblastoma were very different. Fibrotic tissue showed a greater concentration of carotenoids, whereas viable tissue was rich in proteins and nucleic acids. The normal tissue showed both components. Similar differences were also seen in the neuroblastoma tissue. CONCLUSIONS: The results of this study show the potential use of Raman spectroscopy in clinical diagnosis.
