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.

Flow disturbances and progression of endocardial fibroelastosis - a case report.

Endocardial fibroelastosis (EFE) is described as thickening of the endocardium and is associated with hypoplastic left heart syndrome (HLHS). The stimulus for EFE and the mechanism for recurrence and/or progression need to be investigated. In this report, we describe the case of a 4-year-old HLHS patient who underwent several surgeries with EFE resections due to recurrence of EFE. EFE recurrence was associated with flow disturbances due to valvar defects. At her latest follow-up 7 months after the last surgery, competent valves and no EFE were identified on all imaging study.

A case of cardioembolic stroke due to intracardiac papillary fibroelastoma evaluated by using transesophageal echocardiography.

A 62-year-old woman had a prior ischemic stroke in the right temporal lobe with dysarthria and dysesthesia of the left hand. Embolic stroke of undetermined source (ESUS) was diagnosed and warfarin was administered. However, transient ischemic attack recurred upon admission to our hospital. Paroxysmal atrial fibrillation and cerebral arterial stenotic lesions were absent. Transesophageal echocardiography revealed a mobile hyperechoic structure on the aortic valve indicating papillary fibroelastoma. She was diagnosed with a brain embolism due to the intracardiac tumor which was surgically excised and pathologically confirmed as papillary fibroelastoma. This type of tumor is relatively rare but it is important as an embolic source especially in ESUS. Transesophageal echocardiography was indispensable for detecting the embolic source in this patient with ESUS.

Successful Biopsy and Removal of a Tricuspid Valve Papillary Fibroelastoma in Cardiac Catheterization Laboratory: A Case Report.

Papillary fibroelastomas are rare benign cardiac tumours with a predilection for cardiac valves. Because of the rarity of these tumours, management is individualized, but some recommend surgical removal of all papillary fibroelastomas due to the increased risk of embolization. We report a case of a 71-year-old man who presented with a sessile mass on the tricuspid valve. The mass, a papillary fibroelastoma, was successfully biopsied and removed in the cardiac catheterization laboratory. This report demonstrates a unique minimally invasive way of approaching a cardiac tumour wherein a major surgery was avoided.

Endocardial fibroelastosis is caused by aberrant endothelial to mesenchymal transition.

RATIONALE: Endocardial fibroelastosis (EFE) is a unique form of fibrosis, which forms a de novo subendocardial tissue layer encapsulating the myocardium and stunting its growth, and which is typically associated with congenital heart diseases of heterogeneous origin, such as hypoplastic left heart syndrome. Relevance of EFE was only recently highlighted through the establishment of staged biventricular repair surgery in infant patients with hypoplastic left heart syndrome, where surgical removal of EFE tissue has resulted in improvement in the restrictive physiology leading to the growth of the left ventricle in parallel with somatic growth. However, pathomechanisms underlying EFE formation are still scarce, and specific therapeutic targets are not yet known. OBJECTIVE: Here, we aimed to investigate the cellular origins of EFE tissue and to gain insights into the underlying molecular mechanisms to ultimately develop novel therapeutic strategies. METHODS AND RESULTS: By utilizing a novel EFE model of heterotopic transplantation of hearts from newborn reporter mice and by analyzing human EFE tissue, we demonstrate for the first time that fibrogenic cells within EFE tissue originate from endocardial endothelial cells via aberrant endothelial to mesenchymal transition. We further demonstrate that such aberrant endothelial to mesenchymal transition involving endocardial endothelial cells is caused by dysregulated transforming growth factor beta/bone morphogenetic proteins signaling and that this imbalance is at least in part caused by aberrant promoter methylation and subsequent transcriptional suppression of bone morphogenetic proteins 5 and 7. Finally, we provide evidence that supplementation of exogenous recombinant bone morphogenetic proteins 7 effectively ameliorates endothelial to mesenchymal transition and experimental EFE in rats. CONCLUSIONS: In summary, our data point to aberrant endothelial to mesenchymal transition as a common denominator of infant EFE development in heterogeneous, congenital heart diseases, and to bone morphogenetic proteins 7 as an effective treatment for EFE and its restriction of heart growth.

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.

Echocardiographic evaluation of fetal cardiac function: clinical and anatomical correlations in two cases of endocardial fibroelastosis.

BACKGROUND: Two fetuses with endocardial fibroelastosis, one with critical aortic stenosis and one with high-output cardiac failure due to chorioangiomatosis, are presented to evaluate the correlation between Doppler echocardiographic findings, the fetal clinical condition and the anatomical substrate found at postmortem. METHODS: Doppler measurements of cardiac function (systolic, diastolic and global) and a cardiovascular score incorporating five parameters of fetal well-being were recorded. RESULTS: In the fetus with critical aortic stenosis, the cardiovascular score was diminished, there was no hydrops, the systolic and global cardiac function indices were within normal limits but the diastolic function indices were abnormal. The fetus with high-output cardiac failure was hydropic, the cardiovascular score was diminished and abnormal Doppler indices of systolic, diastolic and global cardiac function were found. In both fetuses, abnormalities in the measured Doppler parameters were found consistent with clinical cardiac dysfunction and the postmortem findings. CONCLUSION: Recognition of abnormal diastolic function Doppler indices may assist in earlier identification of fetal cardiac compromise.

Endocardial fibroelastosis of the right ventricle and tricuspid valve in a young adult with Behcet's disease.

Endocardial fibroelastosis is characterized by massive proliferation of collagenous and elastic tissue, in which the pathological process is restricted to the endocardium. In this report, we present the case of a 20-year-old man with Behcet's disease and endocardial fibroelastosis of the right ventricle involving tricuspid valve resulting in a tumor mass that was resected along with tricuspid valve replacement. The clinical and pathological features of this rare entity are reviewed.

Miocárdio não compactado de ventrículo esquerdo: relato de caso com estudo de necropsia / Noncompaction of ventricular myocardium: case report with autopsy

O miocárdio não compactado de ventrículo esquerdo é cardiomiopatia genética em decorrência de uma anormalidade da morfogênese endomiocárdica. Quando presente, geralmente está associado a outras anomalias cardíacas congênitas, sendo raro seu achado isolado sem outras alterações estruturais cardíacas associadas. Desde seu primeiro relato em 1990, a não compactação do miocárdio vem sendo amplamente estudada a fim de se estabelecerem caráter genético, história natural, métodos de diagnóstico, repercussões hemodinâmicas e prognóstico. O objetivo deste estudo foi relatar um caso de miocárdio não compactado isolado de ventrículo esquerdo com estudo de necrópsia.

Noncompaction of the ventricular myocardium is a genetic cardiomyopathy due to an alteration in endomyocardial morphogenesis. When present, it is commonly associated with other congenital cardiac diseases, whereas it is rare as an isolated finding without other associated cardiac structural alterations. Since its first report in 1990, the noncompaction of the ventricular myocardium has been widely studied in order to establish its genetic character, natural history, diagnostic methods, hemodynamic repercussions and prognosis. This study aims to report the case of an isolated noncompaction of the left ventricular myocardium with autopsy.

Cardiac papillary fibroelastoma as a cause of embolic stroke: ultrasound and histopathological characteristics.

Although a cardiac papillary fibroelastoma is a benign cardiac tumor, it can cause severe embolic complications. A 51-year-old man presented with an ischemic stroke in the right middle cerebral artery territory. Transesophageal echocardiography revealed a small mobile tumor on the mitral valve as the only detectable source of emboli to the brain. On histology, the tumor was diagnosed as a papillary fibroelastoma. In this paper, the detailed characteristics of the tumor on ultrasound and histopathology are documented. In patients with cryptogenic stroke, transesophageal echocardiography should be done to rule out such an unusual emboligenic heart disease.

Myocardial tumor necrosis factor-alpha expression in a sudden death due to dilated cardiomyopathy with endomyoelastofibrosis.

During the clinical course of dilated cardiomyopathy, arrhythmias, thromboembolism and sudden death are common and may occur at any stage. In patients with dilated cardiomyopathy, elevated plasma levels of tumor necrosis factor-alpha are associated with poor prognosis. In animal experiments and clinical trials, myocardial tumor necrosis factor-alpha expression correlates with increased mortality rates. A case of sudden death of a previously asymptomatic young man, having a definitive autoptic diagnosis of dilated cardiomyopathy with endomyoelastofibrosis, is presented. We investigated the cardiac morphology and the expression of tumor necrosis factor-alpha in cardiac tissue specimens to elucidate the role of tumor necrosis factor-alpha expression in this fatal case. Our results demonstrate a strong positive myocytes reaction for tumor necrosis factor-alpha in the heart specimens. The pathogenesis of the fatal event is discussed with particular reference to the histological findings and myocytes expression of tumor necrosis factor-alpha.

Papillary fibroelastoma of the aortic valve and coronary artery disease visualized by 64-slice CT.

BACKGROUND: A 75-year-old male with a history of myocardial infarction and recent transient ischemic attack was referred to a cardiology clinic for preoperative evaluation before a cystectomy. Transthoracic and transesophageal echocardiography revealed a mobile mass on the right coronary cusp of the aortic valve. Multislice CT demonstrated a significant narrowing in the proximal left anterior descending coronary artery. INVESTIGATIONS: Physical examination, chest radiography, laboratory testing, electrocardiography, transthoracic and transesophageal echocardiography, multislice-CT coronary angiography, pathological and histological examination of the surgically excised tissue. DIAGNOSIS: Papillary fibroelastoma of the aortic valve in conjunction with coronary artery disease. MANAGEMENT: Surgical excision of the mobile lesion and an end-to-side anastomosis of the left internal mammary artery to the left anterior descending coronary artery.