Cardiac Rhabdomyomas Presenting with Critical Cardiac Obstruction in Neonates and Infants: Treatment Strategies and Outcome, A Single-Center Experience.

Cardiac rhabdomyomas are the most common benign pediatric heart tumor in infancy, which are commonly associated with tuberous sclerosis complex (TSC). Most rhabdomyomas are asymptomatic and spontaneously regress over time. However, some cases especially in neonates or small infants can present with hemodynamic instability. Surgical resection of the tumor, which has been the gold standard in alleviating obstruction, is not always possible and may be associated with significant morbidity and mortality. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be safe and effective in the treatment of TSC. We present the outcomes of neonates and an infant who received treatment for symptomatic rhabdomyomas at a tertiary cardiology center. Medical records were reviewed to obtain clinical, demographic, and outcome data. Six patients received interventions for symptomatic rhabdomyomas, median age at presentation was 1 day old (range from 1 to 121 days old), and 67% of the patients had a pathogenic mutation in TSC gene. One patient underwent surgical resection of solitary tumor at right ventricular outflow tract (RVOT) successfully. In the four patients with left ventricular outflow tract (LVOT) obstruction, two patients received combined therapy of surgical debulking of LVOT tumor, Stage I palliation procedure, and mTORi and two patients received mTORi therapy. One patient with RVOT obstruction underwent ductal stenting and received synergistic mTORi. Four of the five patients had good response to mTORi demonstrated by the rapid regression of rhabdomyoma size. 83% of patients are still alive at their latest follow-up, at two to eight years of age. One patient died on day 17 post-LVOT tumor resection and Hybrid stage one due to failure of hemostasis, in the background of familial factor VII deficiency. Treatment of symptomatic rhabdomyoma requires individualized treatment strategy based on the underlying pathophysiology, with involvement of multidisciplinary teams. mTORi is effective and safe in inducing rapid regression of rhabdomyomas. A standardized mTORi prescription and monitoring guide will ensure medication safety in neonates and infants with symptomatic cardiac rhabdomyoma. Although the majority of tumors responded to mTORi, some prove to be resistant. Further studies are warranted, ideally involving multiple international centers with a larger number of patients.

Long-term use of everolimus for refractory arrhythmia in a child with tuberous sclerosis complex.

Tuberous sclerosis complex is associated with the occurrence of cardiac rhabdomyomas that may result in life-threatening arrhythmia unresponsive to standard antiarrhythmic therapy. We report the case of an infant with multiple cardiac rhabdomyomas who developed severe refractory supraventricular tachycardia (SVT) that was successfully treated with everolimus. Pharmacological mTOR inhibition rapidly improved arrhythmia within few weeks after treatment initiation and correlated with a reduction in tumor size. Intermediate attempts to discontinue everolimus resulted in rhabdomyoma size rebound and recurrence of arrhythmic episodes, which resolved on resumption of therapy. While everolimus treatment led to successful control of arrhythmia in the first years of life, episodes of SVT reoccurred at the age of 6 years. Electrophysiologic testing confirmed an accessory pathway that was successfully ablated, resulting in freedom of arrhythmic events. In summary we present an in-depth evaluation of the long-term use of everolimus in a child with TSC-associated SVT, including the correlation between drug use and arrhythmia outcome. This case report provides important information on the safety and efficacy of an mTOR inhibitor for the treatment of a potentially life-threatening cardiac disease manifestation in TSC for which the optimal treatment strategy is still not well established.

Diagnóstico prenatal de rabdomioma fetal asociado a esclerosis tuberosa: a propósito de un caso / Prenatal diagnosis of fetal rhabdomyoma associated with tuberous sclerosis

Los rabdomiomas son los tumores benignos cardíacos más frecuentes encontrados en vida fetal y postnatal, asociándose frecuentemente a esclerosis tuberosa. A propósito de un caso manejado en nuestra maternidad el año 2014 se revisó la literatura existente sobre su diagnóstico, manejo, implicancias pronósticas. Se trata de una embarazada de 23 años que fue referida a las 25 semanas a nuestro servicio, el estudio ecográfico revela tres imágenes cardiacas concordantes con rabdomiomas en las paredes ventriculares y el septum. No se detectan otras anormalidades y se controla en forma seriada con ultrasonido. Se realiza a las 33 semanas resonancia nuclear magnética fetal con el objetivo de evidenciar signos de esclerosis tuberosa los cuales se evidencian en el examen y se confirman en exámenes postnatales. Se comenta el diagnóstico diferencial con otros neoplasias benignas cardiacas como teratomas, fibromas y hemangiomas. Las posibles complicaciones de los rabdomiomas dependerán de su ubicación y tamaño, produciendo alteraciones en flujo o bien menos frecuentemente arritmias. La asociación más importante de esta patología es con esclerosis tuberosa de manera que se debe realizar una cuidadosa anamnesis familiar, estudios de imágenes que deben abarcar el SNC, corazón y riñones. Finalmente en ese contexto realizar la mejor consejería a los padres.

Rhabdomyomas are the most common benign cardiac tumors found in fetal and postnatal life, frequently being associated with tuberous sclerosis. In relation to a case handled in our maternity unit in 2014, existing literature on cardiac rhabdomyomas diagnosis, management and prognostic implications, was revised. The case concerned a 25 week pregnant 23 year old patient, who was referred to our facility; ultrasound examination reveals three cardiac images consistent with rhabdomyomas in the ventricular walls and the septum. No other abnormalities are detected and the patient is monitored with a series of ultrasound. At 33 weeks a fetal magnetic resonance imaging is performed in order to show signs of tuberous sclerosis which are noted in the examination and confirmed in post natal tests. Differential diagnosis with other benign cardiac neoplasms such as teratomas, fibromas and hemangiomas is discussed. Possible complications of the rhabdomyomas will depend on its location and size, producing changes in flow or less frequent arrhythmias. The most important association of this pathology is with tuberous sclerosis, therefore the family medical history must be carefully evaluated, and imaging controls that should include the CNS, heart and kidneys. Finally in this context give the best counseling to the parents.

Arritmia cardíaca fetal como manifestação inicial de rabdomioma na esclerose tuberosa / Fetal cardiac arrhythmia as an initial indication of rhabdomyoma in tuberous sclerosis

Relata-se caso de esclerose tuberosa (ET) diagnosticada a partir de arritmia cardíaca fetal e múltiplos rabdomiomas cardíacos. A ET é doença autossômica dominante, multissistêmica, com incidência de 1:10000 nascimentos, caracterizada por múltiplos hamartomas em órgãos de origem mesodérmica e ectodérmica. O rabdomioma é o tumor primário do coração mais frequênte na infância, associando-se à ET em 50 por cento dos casos. Outras manifestações incluem epilepsia, retardo mental e alterações compressivas nos órgãos acometidos. A ET tem graves manifestações físicas e psicológicas, exigindo acompanhamento multidisciplinar. Objetiva-se propiciar o entendimento e o reconhecimento da doença, integrando os profissionais envolvidos no seu manejo.

Cambios electrocardiogáficos y arritmias en pacientes pediátricos con rabdomioma / Electrocardiographical changes and arrhythmias in pediatric patients with rabdomiome

La incidencia de tumores cardíacos en pediatría es menor de 0,1%, en su mayoría son de carácter benigno y másde la mitad rabdomiomas. La historia natural de estos tumores es de regresión y la mayoría no produce síntomas. No es infrecuente la asociación con cambios electrocardiográficos, dependiendo de la localización tumoral, y ocasionalmente su presentación concomitante con taquicardias ventriculares, bloqueos aurículo-ventriculares y supraventriculares por vías anómalas.Revisamos nuestra experiencia en pacientes diagnosticados con rabdomioma asociados a arritmias y suevolución. 18 pacientes, nueve de ellos varones diagnosticados con tumoración cardíaca y etiquetados como rabdomioma por imagenología, a una edad media de 7,7 meses (uno prenatalmente). 22% (4) presentaban esclerosis tuberosa asociada. La media de seguimiento es de 17 años. De los 18 pacientes, siete presentaban bloqueo de rama derecha (dos aislado, tres con bloqueo aurículo-ventricular de primer grado, dos con bloqueo aurículo-ventricular de segundo grado y extrasístoles ventriculares), tres debutaron con taquicardia o fibrilación ventricular, uno con bradicardia neonatal y siete con preexcitación intermitente (cuatro con taquicardia supraventricular), cinco fallecieron durante meses posteriores al diagnóstico, dos de ellos tempranamente en relación con arritmias ventriculares incontrolables, uno por problemas hemodinámicos obstructivos previo a cirugía y dos en el postoperatorio inmediato (ninguno de ellos tenía el diagnóstico de esclerosis tuberosa). De los 13 pacientes restantes, seis requirieron ser intervenidos por obstrucción tumoral. En uno se implantó un marcapasos AAI por disfunción sinusal evolutiva postoperatoria y en un paciente persiste preexcitación electrocardiográfica, sin taquicardia y en tratamiento con betabloqueantes, y en dos bloqueo de rama derecha, uno de ellos asociado a bloqueo aurículo ventricular de primer grado...

The incidence of cardiac tumors in children is < 0,1%; most of them are benign and more than half of them arerhabdomyosarcoma. The majority regresses without symptoms. Frequently, depending on the tumors location, electrocardiographic changes can be seen, occasionally with ventricular tachyarrhythmia, auricular-ventricular blockage and supraventricular tachyarrhythmia due to accessory pathways. Our experience with patients who had rhabdomyosarcoma with arrhythmias and their evolution is described in thispaper. 18 patients were included, nine boys with the diagnosis of rhabdomyosarcoma through image with an age average of 7,7 months old (one was done prenatal). Four patients (22%) had tuberous sclerosis associated. Follow–up was done for an average of 17 years. Of the 18 patients, seven had sinoatrial block (two isolated, three with first degree AV block, two with second degree block and ventricular extrasystoles), three started with VT/VF, one had neonatal bradyarrhythmia and seven with intermitent preexcitement (four with SVT), five died months after the diagnosis, two died prematurelydue to uncontrollable ventricular arrhythmias, one had preoperative hemodynamic problems and two diedinmedialtely after surgery (none had tuberous sclerosis). Of the 13 patients left, six needed surgery due to tumoralobstruction. One patient needed a cardiac pacing and another patient persist with electrocardiographicpreexcitation, without tachyarrhythmia who is treated with â-blockers. Two have sinoatrial block, one of them firstdegree block. Of the rest three were operated and 16 had tumoral regression.Electrocardiographic alterations and arrythmias associated to tumors are frequent, malignant arrythmias can befatal but most of them dissapear when surgery of the tumor is practiced.

Giant aortic aneurysm and rhabdomyomas in infant with tuberous sclerosis (Case report) / Aneurisma gigante de la aorta abdominal y rabdomiomas en un lactante con esclerosis tuberosa

We present the case of a giant aneurysm and dissection of the abdominal aorta in an eight month old infant. Imaging studies especially a helicoid computerized axial tomography with 3D reconstruction, showed a lesion which extended from the diaphragm to the iliac arteries. The clinical findings and the above mentioned studies revealed non-obstructive heart rhabdomyomas, tubers in the brain and the abdominal aortic aneurysm, all of which were consistent with the diagnosis of tuberous sclerosis.

Presentamos el caso, de un niño de 8 meses con un aneurisma gigante de la aorta abdominal. La imagen de la tomografía axial computarizada helicoidal con reconstrucción tridimensional, mostró que dicha lesión iniciaba a nivel del diafragma y llegaba hasta las arterias ilíacas con disección de su pared. El cuadro clínico y los estudios apoyaron el diagnóstico de esclerosis tuberosa con rabdomiomas cardíacos, no obstructivos. Por la gravedad de dicha lesión, el desenlace fue fatal.

Rabdomioma cardíaco y esclerosis tuberosa: diagnóstico prenatal / Rhabdomyoma cardiac and tuberous sclerosis: prenatal diagnosis

Se presenta un caso de diagnóstico y manejo prenatal de tumor intracardíaco catalogado por clínica y ultrasonografía como rabdomioma cardíaco. Se estudió una paciente embarazada de 37 semanas con un tumor cardíaco ecogénico, multifocal, que evolucionó in útero sin arritmia ni falla cardíaca. El parto se resolvió por vía vaginal a las 39 semanas y en la evolución del recién nacido se confirmó por tomografía computada (TC) y fondo de ojo el diagnóstico de esclerosis tuberosa. Se realiza revisión del tema destacando la conducta frente al parto según las condiciones de la función cardíaca fetal y el riesgo de esclerosis tuberosa en su evolución post natal.

Tumores cardíacos y pericárdicos en el niño: revisión de 15 años / Cardiac and pericardial tumors in children: review of 15 years

Rvisión de 14 casos de tumores cardiacos y pericárdicos en niños diagnosticados desde 1985 hasta 1999, en el Servicio de Cardiovascular del Hospital Luis Calvo Mackenna. Objetivo: evaluar el tipo de tumor, forma de presentación y pronóstico. El diagnóstico es mediante la ecocardiografía. Los tumores fueron rabdomiomas en 71 por ciento, mixoma, lipoma, teratoma quístico y sarcoma de Ewing. Edad de presentación: período antenatal en 3 pacientes y hasta 15 años; 50 por ciento en menores de 3 meses. Los síntomas má frecuentes fueron soplos cardiacos y arritmias. La mayoría de los rabdomiomas eran múltiples, ubicados en las distintas cavidades cardiacas. Un tercio de ellos se asoció con esclerosis tuberosa. El pronóstico dependió del tipo de tumor y de su ubicación. Fallecieron dos pacientes, un niño con sarcoma de Ewing y otro con rabdomioma intramural con foco arritmogénico ventricular

Tumores cardíacos / Cardiac tumors

A incidência dos tumores primários do coraçäo e pericárdio varia de 0,02 a 0,28%. Os mais freqüentes na infância säo os rabdomiomas, que, com os teratomas, säo responsáveis por mais de 75% das neoplasias em crianças com menos com menos de 1 ano. Suas manifestaçöes clínicas estäo relacionadas à sua localizaçäo no coraçäo. Sua forma, fixaçäo e crescimento determinam sua classificaçäo. A ecocardiografia está indicada na avaliaçäo do crescimento de rabdomiomas cardíacas, a longo prazo. A esclerose tuberosa destaca-se entre anomalias congênitas associadas ao rabdomioma. Clones cromossomicamente anormais e associaçöes teloméricas säo identificadas em mixomas cardiácos. Os aspectos genético e molecular dos tumores cardíacos necessitam ainda de ser melhor explorados

Esclerose tuberosa com rabdomioma de ventrículo esquerdo / Tuberous sclerosis associated with a left ventricle rabdomioma

Lactente do sexo feminino com espasmos em flexäo, manchas hipocrômicas na pele e sopro sistólico de ejeçäo. O diagnóstico clínico, apoiado por tomografia de crânio e neurossonografia, foi de esclerose tuberosa. Ecocardiograma e cineangiocardiografia revelaram tumor em via de saída do ventrículo esquerdo associado. Após a ressecçäo do rabdomioma a paciente evoluiu assintomática, controlado o quadro neurológico com ácido valpróico

Female infant, presenting with flexion spasms, skin hypochromatic spots and systolic ejection murmur. A clinical diagnosis of tuberous sclerosis, supported by computerized brain tomography and neurossonographic data, was made. Echocardiographic and cineangiocardiographic studies disclosed an associated tumor in left ventricle outlet. After ressection of the rhabdomyoma, the patient is assymptomatic with neural manifestations controlled under valproic acid.