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1. National consensus on the cardiological treatment and follow-up of Kawasaki disease

Author

Ana Barrios Tascón, Fernando Centeno Malfaz, Henar Rojo Sombrero, Elisa Fernández-Cooke, Judith Sánchez-Manubens, Javier Pérez-Lescure Picarzo, Leticia Albert de la Torre, Carlos Alcalde Martín, María Álvarez-Fuente, Carolina Blanco Rodríguez, Gemma Giralt García, Federico Gutiérrez-Larraya, Libertad Latorre Navarro, Antonio Sánchez Andrés, Belén Toral Vázquez, Paula de Vera McMullan, Georges Akel Pérez, Francisco Javier Alados Arboledas, Josune Alegría Echauri, Patricia Aparicio García, Paola Arévalo, August Armengol Rofes, María Arroyas Sánchez, Enrique José Balbacid Domingo, Antonio Baño Rodrigo, María Silvina Barcudi Abbona, Isabel Barranco Fernández, Clara María Bernáldez Torralva, Enrique Blanca Jover, Sonia Blázquez Trigo, María Jose Bravo Sayago, María Jesús Caldeiro Díaz, María Teresa Cantero Tejedor, José Ignacio Carrasco Moreno, Carmen Carreras Blesa, Juan Manuel Carretero Bellón, María Pia Cassanello, Adela Cristina Cis Spoturno, Rosa Collell Hernández, Juan Antonio Costa Orvay, David Crespo Marcos, Héctor Augusto Cuéllar Manotas, Victorio Cuenca Peiro, Adalgisa Patricia de Caro, María de la Parte Cancho, Lucas Alberto Degano Iglesias, Lucía Deiros Bronte, Beatriz del Pozo Menéndez, Laura del Rey Megías, Juan José Díez Tomás, Paola Dolader Colina, Olga Domínguez García, María Nieves Domínguez Garrido, Paula Domínguez Manzano, Jesús Duque Bedoya, Javier Echeverría Espinosa, Fidel Ernesto Echeverría Nava, Hemir David Escobar Pinela, María Esquivias Asenjo, Ana Patricia Fariña Ruiz, Javier Fernández Aracama, Javier Fernández Sarabia, María Teresa Fernández Soria, Natalia Fernández Suárez, Aina Ferré Belda, Sergio Flores Villar, Julio Fontenla García, Ángeles Fuertes Moure, Antonia Pastora Gallego García de Vinuesa, Marta Gambra Arzoz, Francisco García Angleu, Estefanía García Cerro, María Elvira Garrido-Lestache Rodríguez-Monte, Nuria Gil Villanueva, Maribel Giner Crespo, Gema Giralt García, María Ersilia González Carrasco, María Aránzazu González Marín, Cristina González Menchén, Fernando Gran Ipiña, Inmaculada Guillén Rodríguez, María Teresa Guixeres Esteve, Manuel Haro Gómez, Aida Hernández Blanco, Yolanda Herranz Sánchez, Carmen Herrera del Rey, Aleida Ibañez Fernández, Gema Iñigo Martín, Ignacio Izquierdo Fos, María Ángeles Izquierdo Riezu, María Soledad Jiménez Casso, Lorenzo Jiménez Montañés, Carlos Labrandero de Lera, Bernardo López Abel, María Lozano Balseiro, José Luaces González, Nazaret Macías Julián, Jesús Antonio Mairal Cazcarra, María José Maldonado Toral, Alejandra Manchola Linero, Begoña Manso García, MaríMaravall Llagaria, Sonia Marcos Alonso, Cristina Marimón Blanch, Ismael Martín de Lara, María Martínez del Villar, María Isabel Martínez Lorente, Patricia Martínez Olorón, María Isabel Martínez Soto, Laura Marzo Checa, Miguel Ángel Matamala Morillo, Constancio Medrano López, Paula Méndez Abad, Francisco Meza Ortiz, Ana Moriano Gutiérrez, Antonio Moruno Tirado, Ángeles Ortega Montes, Alfonso Ortigado Matamala, Almudena Ortiz Garrido, Ignacio Oulego Erroz, Jorge Roberto Palacios Argueta, Laura Parra Agüera, Esteban Peiró Molina, Julio Ernesto Peralta Salas, César Jorge Perera Carrillo, Dolores Pérez Campos, Verónica Pérez Herrera, María Ángeles Pérez Moneo Agapito, Alejandro Pérez Muñuzuri, Ana María Pérez Pardo, José María Pérez Roldán, Francisco Javier Pérez-Lescure Picarzo, María Rosa Pérez-Piaya Moreno, Francesca Perin, Isabel Pinto Fuentes, Beatriz Plata Izquierdo, María Portoles Morales, María Ángeles Puigdevall Dalmau, Erika Pulido Ovalle, María Teresa Raga Poveda, Sara Rellán Rodríguez, Susana María Rey García, Erika Rezola Arcelus, Bibiana Riaño Méndez, Andrés Rico Armada, Natalia Rivero Jiménez, Moisés Rodríguez González, María Dolores Rodríguez Mesa, Raúl Rodríguez Serrano, María Henar Rojo Sombrero, Violeta Román Barba, Carlos Romero Ibarra, Félix Romero Vivas, Fernando Rueda Núñez, Joaquín Rueda Soriano, Anna Sabaté Rotés, Francisco Javier Salas Salguero, Julio Federico Saldaña Capuñay, Carlos Salido Peracaula, Alberto Sánchez Calderón, Cristina Sánchez Vaquerizo, Elena Sanz Pascual, María Isabel Serrano Rob, Ana Siles Sánchez-Manjavacas, Adolfo Sobrino Baladrón, Ruth Solana García, Dolors Soriano Belmonte, Moisés Sorlí García, Pedro Suárez Cabrera, Amalia Tamariz-Martel Moreno, Rocío Tamariz-Martel Moreno, María Ángeles Tejero Hernández, María Torres Rico, Susana Uriel Prat, Ana Isabel Usano Carrasco, Estíbaliz Valdeolmillos Padrino, María Teresa Valero Adán, Sandra Villagrá Albert, Javier Villalba Nogales, Carin Cristina Walter, Marta Yagüe Martín, and María Dolores Zambrano Casajona

Subjects
Enfermedad de Kawasaki, Síndrome linfomucocutáneo, Vasculitis, Arteritis, Aneurisma coronario, Arterias coronarias, Pediatrics, RJ1-570
Abstract

Kawasaki disease is a self-limiting acute vasculitis that affects small and medium-sized vessels, and is the most common cause of acquired heart disease in children in our environment. Up to 25% of untreated patients develop coronary aneurysms. It is suspected that an infectious agent may be the trigger of the disease, but the causative agent is still unknown. Based on the previous evidence, recommendations are proposed for the diagnosis, treatment of acute disease, and the long-term management of these patients, in order to unify criteria. The diagnosis must be quick, based on easy-to-use algorithms and with the support of complementary tests. This document includes the indication of available imaging techniques, as well as the planning of cardiological examinations based on the initial involvement. Intravenous immunoglobulin is the basis of the initial treatment. The role of corticosteroids is still controversial, but there are studies that support its use as adjuvant treatment. A multidisciplinary working group has developed a scheme with different treatment guidelines depending on the risk factors at diagnosis, the patient's clinical situation, and response to previous treatment, including indications for thromboprophylaxis in patients with coronary involvement. The stratification of risk for long-term treatment is essential, as well as the recommendations on the procedures based on the initial cardiological involvement and its progression. Patients with coronary aneurysms require continuous and uninterrupted cardiological monitoring for life. Resumen: La enfermedad de Kawasaki es una vasculitis aguda autolimitada que afecta a vasos de pequeño y mediano calibre y es la causa más común de enfermedad cardiaca adquirida en niños en nuestro medio. Hasta un 25% de pacientes no tratados desarrollan aneurismas coronarios. Se sospecha que un agente infeccioso puede ser el desencadenante de la enfermedad, pero aún se desconoce el agente causal. En base a la evidencia previa, se proponen recomendaciones para el diagnóstico, tratamiento de la enfermedad aguda y manejo a largo plazo de estos pacientes, con el fin de unificar criterios. El diagnóstico debe ser rápido, basado en algoritmos de fácil manejo y con el apoyo de pruebas complementarias. Este documento recoge la indicación de las técnicas de imagen disponibles, así como la planificación de las revisiones cardiológicas en función de la afectación inicial. La inmunoglobulina intravenosa es la base del tratamiento inicial. El papel de los corticoides aún es controvertido, pero cada vez hay más estudios que avalan su uso como tratamiento adyuvante. Un equipo multidisciplinar ha elaborado un esquema con diferentes pautas de tratamiento en función de los factores de riesgo al diagnóstico, situación clínica del paciente y respuesta al tratamiento previo, incluyendo indicaciones sobre tromboprofilaxis en pacientes con afectación coronaria. La estratificación del riesgo para el tratamiento a largo plazo es esencial, así como las recomendaciones acerca del proceder en función de la afectación cardiológica inicial y su evolución. Los pacientes con aneurismas coronarios requieren un seguimiento cardiológico continuo e ininterrumpido de por vida.

Published
2018
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2. Isolation and expansion of thymus‐derived regulatory T cells for use in pediatric heart transplant patients

Author

Giovanna Lombardi, Monica Sen, Rowa Y. Alhabbab, Marco Romano, Michael Burch, Cristiano Scottà, Robert I. Lechler, and Andres Rico-Armada

Subjects
Male, 0301 basic medicine, CD3, Immunology, Population, chemical and pharmacologic phenomena, Thymus Gland, Biology, T-Lymphocytes, Regulatory, Immune tolerance, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Humans, Immunology and Allergy, IL-2 receptor, Child, education, Interleukin-7 receptor, education.field_of_study, Infant, FOXP3, hemic and immune systems, Flow Cytometry, Thymic Tissue, 030104 developmental biology, Child, Preschool, biology.protein, Heart Transplantation, Female, 030215 immunology
Abstract

Regulatory T-cells (Tregs) are a subset of T-cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. In this study, we developed a GMP-compatible protocol for expanding sorted thymus derived CD3+ CD4+ CD25+ CD127- (Tregs) as well as CD3+ CD4+ CD25+ CD127- CD45RA+ (RA+ Tregs) cells. We aimed to understand whether thymic RA+ Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA+ Tregs. We show that both Tregs and RA+ Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN-γ producing cells. High levels of FOXP3, CTLA4 and CD25 expression, demethylation of the FOXP3 promoter and high suppressive ability were found with no differences between Tregs and RA+ Tregs. After freezing and thawing all Treg preparations maintained their suppressive ability, stability as well as CD25 and FOXP3 expression. The number of thymic Tregs that could be isolated with our protocol, their fold expansion and functional characteristics allow the clinical application of this cell population to promote tolerance in paediatric heart transplant patients. This article is protected by copyright. All rights reserved.

Published
2021
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3. Outcome for children following admission to hospital with a first episode of heart failure, due to heart muscle disease, in the ventricular assist device (VAD) era

Author

Neil Seller, Anthony Hermuzi, Andres Rico-Armada, Louise Coats, Asif Hasan, John O'Sullivan, David Crossland, and Zdenka Reinhardt

Subjects
Male, Pediatrics, medicine.medical_specialty, Adolescent, Referral, medicine.medical_treatment, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Hospital Mortality, 030212 general & internal medicine, Child, Retrospective Studies, Heart Failure, First episode, business.industry, Infant, Newborn, Infant, Dilated cardiomyopathy, General Medicine, medicine.disease, Hospitalization, Survival Rate, Transplantation, Treatment Outcome, Muscle disease, Child, Preschool, Ventricular assist device, Heart failure, Pediatrics, Perinatology and Child Health, Circulatory system, Heart Transplantation, Female, Heart-Assist Devices, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract

Aims:Most reports on the outcome of children who present with heart failure, due to heart muscle disease, are from an era when ventricular assist devices were not available. This study provides outcome data for the current era where prolonged circulatory support can be considered for most children.Methods & Results:Data was retrieved on 100 consecutive children, who presented between 2010 – 2016, with a first diagnosis of unexplained heart failure. Hospital outcome was classified as either death, transplantation, recovery of function or persistent heart failure. Median age at presentation was 24 months and 58% were < 5 years old. Hospital mortality was 12% and 59% received a heart transplant. Most, 79%, of the transplants were carried out on patients with a device. Recovery of function was observed in 18% and 10% stabilised on oral therapy. Eighty-four percent of the deaths occurred in the Conclusion:Heart failure in children who require referral to a transplant unit is a serious illness with a high chance of either transplantation or death. Modifications in assist devices will be required to improve safety, especially for children < 5 years old where the donor wait may be prolonged. The identification of children who may recover function requires further study.

Published
2019
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6. 35 The outcome for children following their first presentation with heart failure to a transplantation unit between 2010 – 2015

Author

A Rico-Armada, John O'Sullivan, Antony Hermuzi, MA Sajnach-Menke, David S. Crossland, and Zdenka Reinhardt

Subjects
Pediatrics, medicine.medical_specialty, Referral, Heart disease, business.industry, medicine.disease, Transplantation, Heart failure, Circulatory system, medicine, Outcome data, Presentation (obstetrics), business, Oral therapy
Abstract

Purpose Most reports on the outcome of children who present with heart failure are from an era when ventricular assist devices (VAD) were not available. This study provides outcome data for the modern era where prolonged circulatory support can be considered for children of all ages. Methods Data on children who presented from 2010–2015, with a first diagnosis of heart failure, excluding those with structural heart disease, was retrieved. Results The median age at presentation, in the 100 children, was 18 months. Overall, hospital mortality was 15%, 50% received a heart transplant, 25% recovered systolic function and 15% stabilised on oral therapy. Mean time from admission to death was 89 days. Most children (63%) were Conclusion Heart failure in children which requires referral to a transplant unit remains a very serious illness with a high chance of either transplantation or death. Modifications to the current VAD support will be required to enable this group to survive to either recovery or access to the inadequate heart donor pool.

Published
2018
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9. 35 The outcome for children following their first presentation with heart failure to a transplantation unit between 2010 – 2015

Author

Rico-Armada, A, Crossland, D, Hermuzi, A, Sajnach-Menke, M, Reinhardt, Z, and O’Sullivan, J

Abstract

PurposeMost reports on the outcome of children who present with heart failure are from an era when ventricular assist devices (VAD) were not available. This study provides outcome data for the modern era where prolonged circulatory support can be considered for children of all ages.MethodsData on children who presented from 2010–2015, with a first diagnosis of heart failure, excluding those with structural heart disease, was retrieved.ResultsThe median age at presentation, in the 100 children, was 18 months. Overall, hospital mortality was 15%, 50% received a heart transplant, 25% recovered systolic function and 15% stabilised on oral therapy. Mean time from admission to death was 89 days. Most children (63%) were <5 years old and most of the deaths (11/15) occurred in that group. Comparing age groups: mortality was higher (19% versus 8%); transplantation rate was lower (41% versus 65%); VAD use higher (62% versus 48%) and more recovered systolic function (29% versus 19%) in the <5 years versus those ≥5 years. The mean duration of VAD, in those who died in the <5 year group, was 106 days (compared to 61 days in those who survived).ConclusionHeart failure in children which requires referral to a transplant unit remains a very serious illness with a high chance of either transplantation or death. Modifications to the current VAD support will be required to enable this group to survive to either recovery or access to the inadequate heart donor pool.

Published
2018
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