14 research outputs found
Machine Learning Identifies Clinical and Genetic Factors Associated With Anthracycline Cardiotoxicity in Pediatric Cancer Survivors
BACKGROUND Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging. OBJECTIVES This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. METHODS We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (\u3c= 250 mg/m(2)), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin \u3e250 mg/m(2) were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in human induced pluripotent stem cell-derived cardiomyocytes, and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. RESULTS Thirty-one genes were differentially enriched for variants between case patients and control patients (p \u3c 0.001). Only 42.6% case patients harbored a variant in these genes compared to 89.6% control patients (odds ratio: 0.09; 95% confidence interval: 0.04 to 0.17; p = 3.98 x 10(-15)). A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical-only model. In vitro inhibition of gene-associated pathways (PI3KR2, ZNF827) provided protection from cardiotoxicity in cardiomyocytes. CONCLUSIONS Our study identified variants in cardiac injury pathway genes that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and it also provided new targets in autophagy genes for the development of cardio-protective drugs
Fetal supraventricular tachyarrhythmias. experience of a fetal cardiology reference center
Objetivo - Avaliar a forma de apresentação, diagnóstico e tratamento das taquiarritmias supraventriculares fetais, através do relato de uma série de casos acompanhados em um centro terciário de cardiologia fetal. Métodos - São descritos 25 casos de taquiarritmia supraventricular diagnosticados intra-útero, no período de janeiro/89 a outubro/97, em uma população compreendendo 3117 gestantes. Resultados - Foram diagnosticados 17 casos de taquiarritmia supraventricular e 8 casos de flutter atrial fetal. As idades gestacionais variaram de 26 a 40 semanas. Doze fetos apresentavam hidropisia no momento do diagnóstico (6 com taquicardia supraventricular (TSV) e 6 com flutter atrial). Quatro fetos com TSV apresentavam cardiopatias estruturais (dois casos de anomalia de Ebstein e dois com comunicação interventricular). Todos os fetos foram internados na Unidade de Cardiologia Fetal para monitorização e tratamento. Entre os 17 fetos com TSV, 12 apresentaram reversão da arritmia após administração de digoxina, mas esta medida não foi eficaz em nenhum paciente com flutter. Dois pacientes com TSV e seis com flutter necessitaram interrupção da gestação para cardioversão elétrica pós-natal. A mortalidade foi de 3/17 no grupo da TSV (incluindo dois pacientes com anomalia de Ebstein) e de 0/8 no grupo com flutter. Conclusão - As taquiarritmias supraventriculares fetais são eventos raros na população geral. Entretanto, podem provocar insuficiência cardíaca e óbito intrauterino. Como a resposta ao tratamento é satisfatória, tornam- se de extrema importância o diagnóstico precoce e o tratamento adequado.Purpose - To describe the presentation, diagnosis and treatment of fetal supraventricular tachyarrhythmias in a series of fetuses followed in a tertiary Fetal Cardiology Center. Methods - Twenty-five fetuses with diagnosis of supraventricular tachyarrhytmia were reported from January 1989 to October 1997, among 3117 pregnant women referred for fetal cardiac evaluation. Results - There were 17 fetuses with the diagnosis of supraventricular tachycardia (SVT) and 8 patients with atrial flutter (AF). Gestational age ranged from 26 to 40 weeks. Twelve patients were hydropic at presentation (6 with SVT and 6 AF). Four fetuses with SVT showed structural abnormalities (two with Ebsten’s anomaly and two with VSD). All patients were admitted to the Fetal Cardiology Unit for monitoring and treatment. Among 17 fetuses with SVT, twelve showed good response to digoxin administration, but this drug was not useful in any of the patients with flutter. In two patients with SVT and in six with AF, the pregnancy was interrupted to perform post-natal cardioversion. The mortality rate was 3/17 in the SVT group (including 2 patients with ebstein's anomaly and 0/ 8 in the flutter group) Conclusion - Fetal supraventricular tachyarrithmias are rare in the general population. Nevertheless, the fetus may present with severe heart failure and death. Considering the satisfactory therapeutic response, accurate diagnosis and early treatment of these conditions are extremely important
Fetal supraventricular tachyarrhythmias. experience of a fetal cardiology reference center
Objetivo - Avaliar a forma de apresentação, diagnóstico e tratamento das taquiarritmias supraventriculares fetais, através do relato de uma série de casos acompanhados em um centro terciário de cardiologia fetal. Métodos - São descritos 25 casos de taquiarritmia supraventricular diagnosticados intra-útero, no período de janeiro/89 a outubro/97, em uma população compreendendo 3117 gestantes. Resultados - Foram diagnosticados 17 casos de taquiarritmia supraventricular e 8 casos de flutter atrial fetal. As idades gestacionais variaram de 26 a 40 semanas. Doze fetos apresentavam hidropisia no momento do diagnóstico (6 com taquicardia supraventricular (TSV) e 6 com flutter atrial). Quatro fetos com TSV apresentavam cardiopatias estruturais (dois casos de anomalia de Ebstein e dois com comunicação interventricular). Todos os fetos foram internados na Unidade de Cardiologia Fetal para monitorização e tratamento. Entre os 17 fetos com TSV, 12 apresentaram reversão da arritmia após administração de digoxina, mas esta medida não foi eficaz em nenhum paciente com flutter. Dois pacientes com TSV e seis com flutter necessitaram interrupção da gestação para cardioversão elétrica pós-natal. A mortalidade foi de 3/17 no grupo da TSV (incluindo dois pacientes com anomalia de Ebstein) e de 0/8 no grupo com flutter. Conclusão - As taquiarritmias supraventriculares fetais são eventos raros na população geral. Entretanto, podem provocar insuficiência cardíaca e óbito intrauterino. Como a resposta ao tratamento é satisfatória, tornam- se de extrema importância o diagnóstico precoce e o tratamento adequado.Purpose - To describe the presentation, diagnosis and treatment of fetal supraventricular tachyarrhythmias in a series of fetuses followed in a tertiary Fetal Cardiology Center. Methods - Twenty-five fetuses with diagnosis of supraventricular tachyarrhytmia were reported from January 1989 to October 1997, among 3117 pregnant women referred for fetal cardiac evaluation. Results - There were 17 fetuses with the diagnosis of supraventricular tachycardia (SVT) and 8 patients with atrial flutter (AF). Gestational age ranged from 26 to 40 weeks. Twelve patients were hydropic at presentation (6 with SVT and 6 AF). Four fetuses with SVT showed structural abnormalities (two with Ebsten’s anomaly and two with VSD). All patients were admitted to the Fetal Cardiology Unit for monitoring and treatment. Among 17 fetuses with SVT, twelve showed good response to digoxin administration, but this drug was not useful in any of the patients with flutter. In two patients with SVT and in six with AF, the pregnancy was interrupted to perform post-natal cardioversion. The mortality rate was 3/17 in the SVT group (including 2 patients with ebstein's anomaly and 0/ 8 in the flutter group) Conclusion - Fetal supraventricular tachyarrithmias are rare in the general population. Nevertheless, the fetus may present with severe heart failure and death. Considering the satisfactory therapeutic response, accurate diagnosis and early treatment of these conditions are extremely important
Taquiarritmias supraventriculares no feto. Experiência de uma unidade de referência em cardiologia fetal Fetal supraventricular tachyarrhythmias. Experience of a fetal cardiology reference center
OBJETIVO: Avaliar a forma de apresentação, diagnóstico e tratamento das taquiarritmias supraventriculares fetais, através do relato de uma série de casos acompanhados em um centro terciário de cardiologia fetal. MÉTODOS: São descritos 25 casos de taquiarritmia supraventricular diagnosticados intra-útero, no período de janeiro/89 a outubro/97, em uma população compreendendo 3117 gestantes. RESULTADOS: Foram diagnosticados 17 casos de taquiarritmia supraventricular e 8 casos de flutter atrial fetal. As idades gestacionais variaram de 26 a 40 semanas. Doze fetos apresentavam hidropisia no momento do diagnóstico (6 com taquicardia supraventricular (TSV) e 6 com flutter atrial). Quatro fetos com TSV apresentavam cardiopatias estruturais (dois casos de anomalia de Ebstein e dois com comunicação interventricular). Todos os fetos foram internados na Unidade de Cardiologia Fetal para monitorização e tratamento. Entre os 17 fetos com TSV, 12 apresentaram reversão da arritmia após administração de digoxina, mas esta medida não foi eficaz em nenhum paciente com flutter. Dois pacientes com TSV e seis com flutter necessitaram interrupção da gestação para cardioversão elétrica pós-natal. A mortalidade foi de 3/17 no grupo da TSV (incluindo dois pacientes com anomalia de Ebstein) e de 0/8 no grupo com flutter. CONCLUSÃO: As taquiarritmias supraventriculares fetais são eventos raros na população geral. Entretanto, podem provocar insuficiência cardíaca e óbito intra-uterino. Como a resposta ao tratamento é satisfatória, tornam-se de extrema importância o diagnóstico precoce e o tratamento adequado.<br>PURPOSE: To describe the presentation, diagnosis and treatment of fetal supraventricular tachyarrhythmias in a series of fetuses followed in a tertiary Fetal Cardiology Center. METHODS: Twenty-five fetuses with diagnosis of supraventricular tachyarrhytmia were reported from January 1989 to October 1997, among 3117 pregnant women referred for fetal cardiac evaluation. RESULTS: There were 17 fetuses with the diagnosis of supraventricular tachycardia (SVT) and 8 patients with atrial flutter (AF). Gestational age ranged from 26 to 40 weeks. Twelve patients were hydropic at presentation (6 with SVT and 6 AF). Four fetuses with SVT showed structural abnormalities (two with Ebsten's anomaly and two with VSD). All patients were admitted to the Fetal Cardiology Unit for monitoring and treatment. Among 17 fetuses with SVT, twelve showed good response to digoxin administration, but this drug was not useful in any of the patients with flutter. In two patients with SVT and in six with AF, the pregnancy was interrupted to perform post-natal cardioversion. The mortality rate was 3/17 in the SVT group (including 2 patients with ebstein's anomaly and 0/8 in the flutter group) CONCLUSION: Fetal supraventricular tachyarrithmias are rare in the general population. Nevertheless, the fetus may present with severe heart failure and death. Considering the satisfactory therapeutic response, accurate diagnosis and early treatment of these conditions are extremely important
Fetal tachyarrhythmia with 1:1 atrioventricular conduction. Adenosine infusion in the umbilical vein as a diagnostic test
This is the report of a case of fetal tachyarrhythmia with 1:1 atrioventricular conduction detected by pre-natal echocardiography in a fetus at 25-weeks gestation. Adenosine infusion via cordocentesis was performed as a diagnostic test to differentiate between atrioventricular nodal reentrant supraventricular tachyarrhythmia and atrial flutter. After infusion, transient 2:1 atrioventricular dissociation was obtained and the diagnosis of atrial flutter was made. Transplacental therapy with digoxin and amiodarone was then successfully used