Flow disturbances and the development of endocardial fibroelastosis.

OBJECTIVES: Endothelial-to-mesenchymal transition (EndMT) has been identified as the underlying mechanism of endocardial fibroelastosis (EFE) formation. The purpose of this study was to determine whether hemodynamic alterations due to valvar defects promote EndMT and whether age-specific structural changes affect ventricular diastolic compliance despite extensive surgical resection of EFE tissue. MATERIAL AND METHODS: We analyzed EFE tissue from 24 patients with hypoplastic left heart syndrome (HLHS) who underwent left ventricular (LV) rehabilitation surgery at Boston Children's Hospital between December 2011 and March 2018. Six patients with flow disturbances across the aortic valve and/or mitral valve but no HLHS diagnosis and macroscopic appearance of "EFE-like tissue" in the LV were included for comparison. All samples were examined for amount of collagen/elastin production and degradation, and presence of active EndMT by histologic analysis. RESULTS: EFE tissue from patients with and without HLHS consisted predominantly of elastin and collagen fibers. There was no alteration in degradation activity for collagen or elastin as shown by in situ zymography. Active EndMT was found in all patients with and without HLHS with flow disturbances ("EFE-like"). In patients with HLHS, EFE infiltrated into the underlying myocardium with increasing age. CONCLUSIONS: Patients with and without HLHS with flow disturbances due to stenotic or incompetent valves develop EndMT-derived fibrotic tissue covering the LV. When EFE recurs, it is directly associated with flow disturbances and switches to an infiltrative growth pattern with increasing age, leading to increased diastolic stiffness of the LV.

Cardiac mass in Behçet's disease.

Cardiac mass is a rare manifestation of Behçet's disease (BD). Intracardiac thrombosis, endomyocardiofibrosis, endocardial fibroelastosis, inflammatory mass and cystic change have been reported as different entities of cardiac mass in BD. Here we presented 6 cases of this rare manifestation of BD. The clinical and pathological features were reviewed.

Unusual aortic valve anomaly in the fetus: a case report.

Aortic valve anomalies in fetal life usually concern aortic valve stenosis, in severe forms associated to left ventricular impairment - endocardial fibroelastosis and mitral valve insufficiency. Isolated aortic regurgitation in utero is infrequent and is usually considered to be due to a rare anomaly: aorto-left ventricular tunnel. We describe an unusual case of fetal aortic valve anomaly with severe dysplasia, with a marked regurgitant flow through the aortic valve, passing in a retrograde way from the duct, associated with a marked left ventricular endocardial fibroelastosis and dysfunction, resulting in the fatal outcome of the case.

[Advance in research on endocardial fiborelastosis].

Endocardial fiborelastosis (EFE) is a common infantile myocardiosis. The pathogenesis of EFE may be associated with viral infection, genetic factors, immune factors and endocardial dysplasia. The fundamental pathological changes of EFE include hyperplasia of endocardium elastic fibers and collagen fibers. Acute EFE is a frequent type. Clinical manifestations of EFE are non-specific and children with EFE mainly present with congestive heart failure. Echocardiography is very helpful to the diagnosis of EFE. It is necessary to differentiate EFE from pneumonia complicated by acute congestive heart failure, viral myocarditis and anomalous origin of the left coronary artery. Treatment is meant to control symptoms of congestive heart failure. Patients who respond well to digitalis and have good medication compliance have a favorable prognosis.

Refractory dilated cardiomyopathy associated with metastatic neuroblastoma.

A 2-year-old African American male presented with heart failure and an abdominal mass. Computerized tomography (CT) scan revealed a 7 cm adrenal lesion, confirmed as poorly differentiated neuroblastoma (NB). CT and meta-iodobenzoguanidine (MIBG) scans identified multiple metastases, but cardiac MIBG imaging was absent. Cardiac ejection fraction (EF) was 8% with 7% shortening fraction. The patient underwent six cycles of chemotherapy and investigational immunotherapy. Cardiac function improved to 26% EF. However, the tumor proved unresponsive to treatment. The patient died from stage IV congestive heart failure (CHF) and progressive NB. Autopsy confirmed dilated cardiomyopathy with endocardial fibroelastosis.

Left heart growth, function, and reintervention after balloon aortic valvuloplasty for neonatal aortic stenosis.

BACKGROUND: Transcatheter balloon aortic valvuloplasty (BAVP) has become the first-line treatment for critical aortic stenosis (AS) in neonates. However, little is known about the growth and function of left heart structures or about patterns of reintervention on the left heart after neonatal BAVP. METHODS AND RESULTS: Between 1985 and 2002, 113 patients underwent neonatal BAVP at < or =60 days of age. There were 16 early deaths (14%), with a significant decrease from 1985 to 1993 (22%) to 1994 to 2002 (4%), and 6 patients had successful early conversion to a univentricular circulation. In the short term, the mean relative gradient reduction was 54+/-26%, and significant aortic regurgitation (AR) developed in 15% of patients. The 91 early survivors with a biventricular circulation were followed up for 6.3+/-5.3 years, during which time there was a steady increase in the frequency of significant AR. Freedom from moderate or severe AR was 65% at 5 years. In almost all patients with a baseline aortic annulus z score less than -1, the annulus diameter increased to within the normal range within 1 to 2 years. Similarly, left ventricular (LV) end-diastolic dimension z scores, which ranged from -5 to 7.5 before BAVP, normalized within 1 to 2 years in nearly all patients with a predilation z score less than -1. Among early survivors with a biventricular circulation, reintervention-free survival on the LV outflow tract was 65% at 1 year and 48% at 5 years, with younger age, higher pre- and post-BAVP gradients, and a larger balloon-annulus diameter ratio associated with decreased reintervention-free survival (P<0.01). Seventeen surgical interventions were performed on the aortic valve in 15 patients, including replacement in 7. Survival free from aortic valve replacement was 84% at 5 years. CONCLUSIONS: BAVP for AS during the first 60 days of life results in short-term relief of AS in the majority of patients. Among early survivors, initially small left heart structures may be associated with worse subacute outcomes but typically normalize within 1 year. Reintervention for residual/recurrent AS or iatrogenic AR is relatively common, particularly during the first year after BAVP, but aortic valve replacement during early childhood is seldom necessary.

Critical aortic stenosis in early infancy: surgical treatment for residual lesions after balloon dilation.

BACKGROUND: The optimal management for critical aortic stenosis in early infancy continues to challenge cardiologists and cardiac surgeons. We present a review of our experience with the surgical treatment of residual aortic valve disease after percutaneous balloon dilation for critical aortic stenosis in early infancy. METHODS: Since 1989, 11 of the 38 patients who survived aortic balloon dilation (28.9%) have undergone surgical treatment for residual aortic valve dysfunction. Median time from aortic balloon dilation to surgical intervention was 7 months (range 1 to 56 months). Residual aortic stenosis was the predominant problem in 8 patients and aortic regurgitation was predominant in 2 patients. RESULTS: Aortic valvuloplasty was possible in 5 children; pulmonary autograft replacement of the aortic valve was performed in 6 children. Two children underwent a Ross-Konno procedure because of annulus hypoplasia and severe left ventricular outflow tract obstruction. Two early deaths occurred after a Ross-Konno procedure, both with findings of severe left ventricular fibroelastosis at the pathologic examination. Median follow-up time was 5 years (range 1 month to 11.9 years). No late deaths occurred. One patient with moderate-severe aortic valve regurgitation after aortic valvuloplasty underwent a successful Ross operation. All 9 patients are asymptomatic and are in good clinical condition. CONCLUSIONS: We are convinced that the best aortic valve in the pediatric age group is the native one, provided it can function acceptably. However, in cases where conservative surgical treatment fails to yield a functional aortic valve, replacement of the valve is indicated, and the best aortic valve substitute in infants is the pulmonary autograft because of its potential for growth.

Estudo de 11 casos de fibroelastose endocárdica primária / Primary endocardial fibroelastosis: study of 11 cases

INTRODUÇÃO: A fibroelastose endocárdica (FEE) é definida como espessamento difuso do endocárdio ventricular em função da proliferação de fibras colágenas e elásticas. Pode ser classificada como primária ou secundária. A FEE primária apresenta-se na forma dilatada, mais comum, ou na forma restritiva. Geralmente manifesta-se como insuficiência cardíaca inexplicada, em crianças com menos de 12 meses de idade. OBJEIVOS: Avaliar aspectos epidemiológicos, clínicos e anatomopatológicos da FEE primária. MATERIAL E MÉTODO: Foram pesquisadas, entre 1960 e 2000, 6.211 necropsias perinatais e pediátricas do Hospital de Clínicas da Universidade Federal do Paraná (UFPR), tendo sido verificados 11 casos de FEE. RESULTADOS: Em nove casos (81,8%), o surgimento dos sintomas ocorreu antes de 1 ano de idade. Em oito (72,7%), o óbito ocorreu antes de 1 ano de idade. Dentre os sinais clínicos, destacaram-se taquipnéia (54,5%), hepatomegalia (45,5%), tosse (36,4%), cianose (36,4%) e febre (36,4%). Todas as radiografias (n = 6) apresentavam cardiomegalia. O espessamento endocárdico predominou no coração esquerdo (90,9%). A causa de óbito foi insuficiência respiratória aguda em cinco casos (45,5%) e choque cardiogênico em quatro (36,4%). DISCUSSÃO E CONCLUSÕES: Os resultados mostram acometimento predominante de crianças com menos de 1 ano de idade e rápida progressão para óbito. Sinais clínicos freqüentes, como taquipnéia, tosse e febre, sugeriram infecção respiratória, que foi confirmada por necropsia em três casos (27,3%). Os exames complementares mostraram apenas achados sugestivos de insuficiência cardíaca. Os dados analisados neste estudo mostram que, em nosso meio, a FEE primária não difere significativamente do que é apresentado na literatura internacional em relação a características epidemiológicas, clínicas e anatomopatológicas.

BACKGROUND: Endocardial fibroelastosis (EFE) is a diffuse thickening of the ventricular endocardium resulting from proliferation of fibrous and elastic tissue. Primary and secondary forms have been described. Primary EFE occurs in the dilated and contracted forms. EFE usually manifests as unexplained congestive heart failure in infants younger than 1 year old. OBJECTIVES: To analyze the epidemiologic, clinical and anatomopathological aspects of primary EFE. METHODS: Eleven cases of histologically confirmed EFE were found in 6211 necropsies performed between 1960 and 2000 in the Hospital of the University of Paraná. Results: In nine cases (81.8%) the initial clinical presentation occurred before the age of 1 year. In eight cases (72.7%) patients died before the age of 1 year. The most common clinical findings were tachypnea (54.5%), hepatomegaly (45.5%), cough (36.4%) and fever (36.4%). Cardiomegaly was the main radiographic finding, present in all cases (n = 6). The endocardial thickening was more frequent at the left heart (90.9%). The death cause was acute respiratory failure in five cases (45.5%) and cardiogenic chock in four cases (36.4%). DISCUSSION AND CONCLUSIONS: The results showed that EFE affects usually infants younger than 1 year old that rapidly progress to death. Some common clinical findings like tachypnea, cough and fever suggested respiratory infection which was confirmed by necropsy in three cases (27.3%). The complementary tests showed only non-specific findings of congestive heart failure. The information analyzed here demonstrated no significant difference of the epidemiological, clinical and anatomopathological characteristics of primary EFE between Brazil and the international literature.

Heart transplantation in a patient with isolated noncompaction of the left ventricular myocardium.

We describe a patient with isolated noncompaction of the left ventricle who presented with worsening congestive heart failure and was successfully treated with heart transplantation. The prognosis for these patients is poor because of accelerated event rates of fatal arrhythmias, thromboemboli, and profound left ventricular decompensation. Only 7 patients with isolated noncompaction of the left ventricle have been reported to have undergone heart transplantation. Herein we describe a patient with isolated noncompaction of the left ventricle who underwent successful heart transplantation.

Secondary endocardial fibroelastosis associated with Pompe disease and multicystic dysplastic kidney.

An infant with secondary endocardial fibroelastosis (EFE) associated with glycogen storage disease II (Pompe disease) and multicystic dysplastic kidney (MCDK) is described. She had had refractory heart and renal failure from the early neonatal period. In spite of administration of cathecholamines and diuretics, ventilator support, and peritoneal dialysis, her heart failure due to reduction of left ventricular contractility progressively worsened. She died on the 40th day after admission. Histological examination of a left ventricular autopsy specimen showed prominent thickening of the endocardium due to fibroelastosis, and a lacework-like structure due to accumulation of glycogen in the cardiomyocytes. The EFE was derived from degeneration of the smooth muscle in the endocardium and cardiomyocytes due to glycogen storage. In addition, we supposed that the renal failure due to MCDK made the preload for the ventricles increase and accelerated her heart failure.

Establecimiento del virus de la parotiditis epidémica como agente etiológico de la fibroelastosis endocárdica / Establishment of the epidemic mumps virus as etiologic agent endocardial fibroelastosis

La fibroelastosis endocárdica primaria es una miocardiopatía primaria caracterizada por dilatación e hipertrofia del ventrículo izquierdo, debido a un engrosamiento difuso del endocardio producido por la proliferación del tejido fibroso y elástico, que disminuye la flexibilidad ventricular y conduce a una marcada disfunción diastólica y sistólica del ventrículo izquierdo. Es fundamentalmente, una enfermedad del lactante menor, junto con las miocarditis activas, la fibroelastosis endocárdica constituye la inmensa mayoría de las cardiopatías del lactente y el niño pequeño. El diagnóstico diferencial entre ambas entidades es importante, pues las miocarditis activas responden al tratamiento inmunosupresor, el cual no está indicado en la fibroelastosis endocárdica. El ecocardiograma permite reconocer el endocardio engrosado e hiperrefringente, característico de esta enfermedad. Su etiología ha sido motivo de controversia, Frühling, en 1962, describió casos de fibroelastosis endocárdica durante una epidemia causada por el virus Coxsackie B. En el intervalo de 1963 y 1964, Norem, Adams y Anderson, por un lado y Shone, Muñoz Armas, Manning y Keith, por el otro, sugirieron un papel preponderante del virus de la parotiditis epidémica en su etiología, al encontrar reacción positiva a la prueba intradérmica con el antígeno de ese virus en más del 90 por ciento de casos estudiados. Nuestro estudio, con el mayor número de casos demostrados (50 pacientes), encontró negatividad de la prueba en 180 de 202 casos del grupo control (89 por ciento). En cambio, Gersony y Col, en un estudio publicado simultáneamente con el nuestro en la revista Pediatrics, en un grupo de sólo 16 pacientes con fibroelastosis endocárdica, excluyeron el virus de la parotiditis epidémica como agente etiológico. Este criterio había prevalecido hasta 1997, cuando Jiyuan Ni y Col; en la revista Circulation de enero de 1997, mediante una de las más avanzadas técnicas de la virología molecular, la reacción...

[A rare cause of obstruction of mitral valve prosthesis: periannular fibrosis. Diagnostic by transesophageal echocardiography]. / Une cause rare d'obstruction de prothèse valvulaire mitrale: le pannus fibreux périannulaire. Diagnostic par échocardiographie transoesophagienne.

The authors report a case of dysfunction of a double hemi-disc mitral valve prosthesis due to peri-annular fibrous overgrowth on the atrial side of the prosthesis. Conventional transthoracic Doppler echocardiography showed signs of thrombosis of the prosthesis. Transoesophageal echocardiography allowed a precise diagnosis of the lesions, resulting in immediate surgical referral.

Fatal Lyme carditis and endodermal heterotopia of the atrioventricular node.

A fatal case of Lyme carditis occurring in a Suffolk farmworker is reported. Post-mortem examination of the heart showed pericarditis, focal myocarditis and prominent endocardial and interstitial fibrosis. The additional finding of endodermal heterotopia ('mesothelioma') of the atrioventricular node raises the possibility that this could also be related to Lyme infection and account for the relatively frequent occurrence of atrioventricular block in this condition. Lyme disease should always be considered in a case of atrioventricular block, particularly in a young patient from a rural area. The heart block tends to improve and therefore only temporary pacing may be required.

Fetal echocardiographic signs of congenital endocardial fibroelastosis.

Endocardial fibroelastosis is characterized by a porcelain-like thickening of the endocardium, resulting in a marked increase in echodensity of the endocardium, as well as ventricular dilatation and aortic atresia. With improvement in prenatal ultrasound, this condition can be suspected in utero on the basis of ventricular enlargement, poor ventricular contractility, and marked echodensity of the endocardial surface. We present two cases in which such conditions were found on prenatal M-mode echocardiography and two-dimensional directed pulsed Doppler. Ventriculomegaly and hypocontractility of the ventricle are, however, nonspecific for such conditions; the diagnosis can be made accurately only by pathology. When such findings appear on ultrasound, all efforts should be made to deliver the patient in a perinatal center for optimal neonatal surgery to improve the survival of the newborn.

[Endocardial fibroelastosis: prenatal manifestation of aortic valve stenosis]. / Fibroélastose de l'endocarde: manifestation anténatale du rétrécissement aortique orificiel. Diagnostic échographique.

A diagnosis of fibroelastosis was made in a 33-week-old fetus, based on the echocardiographic features of a marked impairment of left ventricular contractility and hyperechogenicity of the endocardium. Fibroelastosis was associated with an aortic stenosis. There was no evidence of hydrops fetalis. Prenatal detection of this severe congenital heart disease allowed its early management in an intensive care unit. Heart failure due to closure of the ductus required the use of prostaglandin, then a surgical aortic valvulotomy was performed. There was no postoperative problem, and one year after surgery the infant is doing well. His left ventricular contractility is normal, and echocardiographic features of fibroelastosis are no more present. Prenatal diagnosis, use of prostaglandin and increasing safety of neonatal cardiac surgery have improved the prognosis of this serious association.

Endocardial fibroelastosis and myocardial calcification secondary to an anomalous right coronary artery arising from the pulmonary trunk.

The case of an infant with endocardial fibroelastosis and a coexistent anomalous right coronary artery that originated from the pulmonary trunk is presented. The causal relation between the two conditions is discussed.