Anillo vascular. Diagnóstico por ecocardiografía en periodo fetal

Congenital anomalies of the aortic arch and its branches may cause compression of the esophagus and trachea and be responsible of secondary compressive symptoms but frequently have an asymptomatic course. Advances in fetal echocardiography and the three vessel and trachea view (3VT) with a proper visualization of upper mediastinumallows accurate diagnosis of vascular rings. Detection of these abnormalities requires to rule out further congenital malformations and to detect genetic anomalies. Prenatal diagnosis contributes to detect postnatal asymptomatic cases and its systematic prenatal detection would allow estimating a real prevalence of vascular rings in the general population.Las alteraciones congénitas del arco aórtico, especialmente los anillos vasculares, pueden producir compresión de la tráquea y del esófago y originar síntomas secundarios aunque en muchas ocasiones son asintomáticos. El avance de la ecocardiografía prenatal, y especialmente la visualización del mediastino superior fetal con el plano tres vasos-tráquea (3VT), permite un diagnóstico preciso de los anillos vasculares en la vida fetal. La detección de estas anomalías obliga a descartar otras malformaciones fetales y anomalías genéticas. Su detección prenatal contribuye a detectar casos asintomáticos y su búsqueda sistemática permitiría una estimación de la prevalencia real en la población

Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer.

OBJECTIVES: Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients. PATIENTS AND METHODS: We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC. RESULTS: Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C>T, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses. CONCLUSION: Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.This work was supported by the Spanish Association against Cancer (AECC: Asociación Española contra el Cáncer). Human Genotyping lab is a member of CeGen, PRB2-ISCIII and is supported by grant PT13/0001, of the PE I+D+i 2013-2016, funded by ISCIII and FEDER (Fondo Europeo de Desarrollo Regional). Sara Ruiz-Pinto is a predoctoral fellow supported by the Severo Ochoa Excellence Programme (Project SEV-2011-0191)

Exome array analysis identifies ETFB as a novel susceptibility gene for anthracycline-induced cardiotoxicity in cancer patients.

PURPOSE: Anthracyclines are widely used chemotherapeutic drugs that can cause progressive and irreversible cardiac damage and fatal heart failure. Several genetic variants associated with anthracycline-induced cardiotoxicity (AIC) have been identified, but they explain only a small proportion of the interindividual differences in AIC susceptibility. METHODS: In this study, we evaluated the association of low-frequency variants with risk of chronic AIC using the Illumina HumanExome BeadChip array in a discovery cohort of 61 anthracycline-treated breast cancer patients with replication in a second independent cohort of 83 anthracycline-treated pediatric cancer patients, using gene-based tests (SKAT-O). RESULTS: The most significant associated gene in the discovery cohort was ETFB (electron transfer flavoprotein beta subunit) involved in mitochondrial β-oxidation and ATP production (P = 4.16 × 10-4) and this association was replicated in an independent set of anthracycline-treated cancer patients (P = 2.81 × 10-3). Within ETFB, we found that the missense variant rs79338777 (p.Pro52Leu; c.155C > T) made the greatest contribution to the observed gene association and it was associated with increased risk of chronic AIC in the two cohorts separately and when combined (OR 9.00, P = 1.95 × 10-4, 95% CI 2.83-28.6). CONCLUSIONS: We identified and replicated a novel gene, ETFB, strongly associated with chronic AIC independently of age at tumor onset and related to anthracycline-mediated mitochondrial dysfunction. Although experimental verification and further studies in larger patient cohorts are required to confirm our finding, we demonstrated that exome array data analysis represents a valuable strategy to identify novel genes contributing to the susceptibility to chronic AIC

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.J.P.L.’s lab is sponsored by Grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/ 501100011039; Grant PDC2021-121735-I00 funded by MCIN/AEI/10.13039/501100011039 and by the “European Union Next Generation EU/PRTR”, the Regional Government of Castile and León (CSI144P20). J.P.L. and P.L.S. are supported by the Carlos III Health Institute (PIE14/00066). AGN laboratory and human patients’ studies are supported by an ISCIII project grant (PI18/01242). The Human Genotyping unit is a member of CeGen, PRB3, and is supported by grant PT17/0019 of the PE I + D + i 2013–2016, funded by ISCIII and ERDF. SCLl is supported by MINECO/FEDER research grants (RTI2018-094130-B-100). CH was supported by the Department of Defense (DoD) BCRP, No. BC190820; and the National Cancer Institute (NCI) at the National Institutes of Health (NIH), No. R01CA184476. Lawrence Berkeley National Laboratory (LBNL) is a multi-program national laboratory operated by the University of California for the DOE under contract DE AC02-05CH11231. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D +i, 2017–2020, funded by ISCIII and FEDER. RCC is funded by fellowships from the Spanish Regional Government of Castile and León. NGS is a recipient of an FPU fellowship (MINECO/FEDER). hiPSC-CM studies were funded in part by the “la Caixa” Banking Foundation under the project code HR18-00304 and a Severo Ochoa CNIC Intramural Project (Exp. 12-2016 IGP) to J.J.S

The need for a Spanish registry of interventional procedures to treat congenital heart disease and standards for center accreditation

Over the last 3 decades, the percutaneous treatment of congenital heart diseases has made significant progress. Currently, it is the therapy of choice to treat many of these diseases like atrioventricular septal defects, pulmonary valve stenosis or coarctation of the aorta. Multiple procedures throughout the life of a patient are required to treat complex heart disease like stenting and, more recently, percutaneous valves, which have become additional alternatives to surgery. Since 1990, cath lab activity is regulated in the registries published by the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC).1 In the annual publications of these registries there is a small section dedicated to congenital heart disease in the adult population with details on the activity performed, but without an in-depth analysis of the outcomes, complications or mortality. The ACI-SEC and the Spanish Society of Pediatric Cardiology and Congenital Heart Disease Working Group on Hemodynamics have joined forces—for the first time in our country—to conduct a registry of the procedures performed in patients of all ages with congenital heart disease since the fetal stage until the adult age with the collaboration of pediatric and adult cardiologists.2 The Spanish Society of Cardiovascular and Endovascular Surgery has recently published a registry..

La necesidad de un registro español de intervencionismo en cardiopatías congénitas y de estándares para la capacitación de centros

Durante las tres últimas décadas, el tratamiento percutáneo de las cardiopatías congénitas ha evolucionado de una forma encomiable y, actualmente, es la terapia de elección en muchas de ellas, como los defectos septales auriculoventriculares, la estenosis valvular pulmonar y la coartación de aorta. En cardiopatías complejas, que requieren múltiples intervenciones a lo largo de la vida del paciente, el implante de stents, y más recientemente de válvulas percutáneas, se han convertido en alternativas a la cirugía. Desde 1990, la actividad de las salas de hemodinámica se recoge en los registros de la Asociación de Cardiología Intervencionista de la Sociedad Española de Cardiología (ACI-SEC)1. En las publicaciones anuales de estos registros existe un pequeño apartado dedicado a las cardiopatías congénitas del adulto, en el que se menciona la actividad realizada, pero sin un análisis pormenorizado de resultados, complicaciones y mortalidad. La colaboración de la ACI-SEC y el Grupo de Trabajo de Hemodinámica de la Sociedad Española de Cardiología Pediátrica y Cardiopatías Congénitas ha permitido realizar por primera vez en nuestro país un registro de procedimientos realizados en pacientes con cardiopatías congénitas de cualquier edad, desde la etapa fetal hasta la edad adulta, con la colaboración de cardiólogos pediatras y de adultos2. La Sociedad..

Sudden cardiac arrest as first symptom of a benign cardiac tumor growth

Primary cardiac tumors are rare, especially in the pediatric age. Most of them are benign in the sense they are not invasive. However, benign tumors maintain the potential for serious illness related to significant hemodynamic compromise or life-threatening dysrhythmias. We present the case of an infant with an initial diagnosis of cardiac rhabdomyoma who suffered ventricular arrhythmia and cardiac arrest. He suffered irreversible severe neurologic sequelae, due to his prolonged cardiopulmonary arrest and was finally diagnosed of cardiac fibroma. Good arrhythmia control was obtained after an extensive partial surgical resection of the tumor. This case highlights the importance of arrhythmia burden in this condition. A correct diagnosis based essentially in different imaging modalities and closer clinical and rhythm follow up could have avoided this ominous event

Herida cardiaca por arma de fuego. Presentación clínica y conducta terapéutica

ResumenLas heridas cardiacas por armas de fuego son poco frecuentes, pero constituyen una afección potencialmente grave por la gran morbimortalidad que acarrean. Se describe el caso de un paciente de 14 años que ingresa en nuestro centro en situación crítica, intubado y con compromiso hemodinámico tras haber recibido un disparo por arma de fuego en el hemitórax izquierdo. El ECG realizado mostraba elevación difusa del segmento ST. La radiografía de tórax informó de la presencia de cuerpo extraño de densidad metálica en el hemitórax izquierdo. El ecocardiograma transtorácico confirmó la presencia de taponamiento cardiaco, y una imagen redondeada hiperrefringente a nivel de la pared postero-lateral del ventrículo izquierdo (VI). Signos de repercusión hemodinámica como colapso diastólico de aurícula derecha y de ventrículo derecho, y variaciones respiratorias significativas en los flujos de llenado mitral y tricuspídeo. Una vez confirmado el taponamiento cardiaco y la presencia del proyectil alojado en el VI, y ante la situación de extrema gravedad, se trasladó de manera urgente a quirófano, evacuando el taponamiento y extrayendo el proyectil. El paciente evolucionó favorablemente. Como conclusión, el reconocimiento temprano de la lesión penetrante cardiaca, y la rápida intervención es crucial, sobre todo en sujetos sintomáticos y con compromiso hemodinámico.AbstractThe heart wounds from firearms are rare but are a potentially serious condition for the high morbidity and mortality they entail. For a 14 year old patient admitted to our hospital in critical condition, intubation and hemodynamic compromise after being shot by a firearm described in left chest. An ECG showed diffuse ST-segment elevation. Chest radiography reported the presence of metallic foreign body left chest density. Transthoracic echocardiography confirmed the presence of cardiac tamponade and a rounded image hyperdense level posterolateral wall of left ventricle (LV). Signs of hemodynamic and diastolic collapse of the right atrium and right ventricle and significant respiratory changes in mitral and tricuspid flows filling. A view confirmed cardiac tamponade and the presence of the projectile housed in VI and to the situation of extreme gravity moved to the operating room urgently evacuating plugging and removing the shell. The patient improved. In conclusion, early recognition of cardiac penetrating injury and early intervention is crucial, especially in symptomatic and hemodynamic compromise subjects