Chronic Pulmonary Aspergillosis with Pleuroparenchymal Fibroelastosis-like Features.

A 64-year-old man who presented with repeated bouts of pneumothorax was admitted to our hospital because of gradually progressive dyspnea and repeated episodes of a fever. The physiological, radiological and pathological findings were consistent with pleuroparenchymal fibroelastosis (PPFE). In addition, the serum-specific precipitating antibody for Aspergillus was positive. After the administration of voriconazole, a marked improvement was observed in the imaging and physiological findings. Given this clinical course, we diagnosed the patient with PPFE secondary to aspergillosis. The present case suggests that a therapeutic approach based on the cause of secondary PPFE may improve the prognosis of PPFE.

Serial echocardiography for immune-mediated heart disease in the fetus: results of a risk-based prospective surveillance strategy.

OBJECTIVE: Mothers carrying anti-Ro antibodies are frequently referred for weekly echocardiograms to early detect and treat antibody-mediated fetal heart disease. We tested a surveillance strategy based on anti-Ro antibody titers. METHODS: From 2009 to 2014, 232 pregnancies were referred for maternal anti-Ro antibodies. At the baseline echocardiogram, anti-Ro titers were measured by enzyme-linked immunosorbent essay and results categorized as negative (<8 U/mL; n = 43; excluded), low-moderate positive (8-49 U/mL; n = 62; group 1) or high positive (50 - >100 U/mL; n = 127; group 2). Serial echocardiograms to ≥24 weeks were only recommended for group 2 mothers. RESULTS: Group 1 patients underwent significantly less fetal echocardiograms when compared with group 2 mothers (median 2 vs. 4; p < 0.001). Isolated endocardial fibroelastosis (n = 1) and incomplete (n = 4) or complete (n = 4) heart block were diagnosed in 9 (8%) pregnancies with anti-Ro titers >100 U/mL but none with lower titers (odds ratio 17.78; p = 0.004). Incomplete block and endocardial fibroelastosis regressed with transplacental corticosteroid and immune globulin therapy. CONCLUSIONS: Limiting serial fetal echocardiograms to women with high anti-Ro antibody levels is safe and more cost effective. While numbers of echocardiograms were significantly reduced in referrals with anti-Ro titers <50 U/mL, reversible abnormalities with prenatal treatment were detected by serial echocardiography in group 2 patients. © 2017 John Wiley & Sons, Ltd.

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.

Use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody-mediated cardiomyopathy.

OBJECTIVES: This study sought to evaluate the outcome of maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis following intravenous gamma globulin (IVIG) and corticosteroid therapy. BACKGROUND: We have previously shown that 85% of fetuses and infants with maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis suffer demise or need for transplant. In an attempt to improve this outcome, in 1998, we began to empirically treat affected patients with IVIG and corticosteroids. METHODS: We reviewed the clinical records and echocardiograms of 20 affected patients encountered in our institutions and treated with IVIG and corticosteroids from 1998 to 2009. RESULTS: All 20 were initially referred at a median gestational age of 23 weeks (range 18 to 38 weeks). Nineteen mothers were anti-Ro antibody positive, 8 anti-La antibody positive, and 7 had clinical autoimmune disease. Endocardial fibroelastosis was seen in 16 and was not obvious in 4 others with reduced ventricular function, and 16 (80%) had reduced or borderline ventricular shortening fraction (≤30%) before or after birth. Eighteen had atrioventricular block at referral (16 in 3°). During pregnancy, maternal IVIG was given in 9 and dexamethasone in 17. After birth, 17 infants received IVIG (n = 14) and/or corticosteroids (n = 15). Twelve underwent pacemaker implantation. Four with hydrops at presentation died perinatally, despite initial improvement in function in 3. At a median follow-up of 2.9 years (1.1 to 9.8 years), 16 (80%) patients are currently alive with normal systolic ventricular function and 6 are not paced. CONCLUSIONS: Treatment of maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis with IVIG and corticosteroids potentially improves the outcome of affected fetuses. Further studies are needed to determine the optimal dose and timing of IVIG administration.

[Preliminary study on the effect of carvedilol on children with primary endocardial fibroelastosis].

OBJECTIVE: Endocardial fibroelastosis (EFE), a common pediatric cardiovascular disease, often results in chronic heart failure (CHF) and death. Clinical trials have shown that the regimen of combining beta-adrenoreceptor blocker with traditional medicines against CHF can improve left ventricular function and prevent the ventricle from remodeling in patients with CHF. The present study aimed to observe the effect of carvedilol on concentration of plasma brain-type natriuretic peptide (BNP), and safety in children with EFE. METHODS: Twenty-one children with EFE were randomly divided into two groups: (1) treated with traditional regimen (digoxin, prednisone and/or diuretics) (n = 10); (2) treated with carvedilol plus traditional regimen (n = 11). Measurement of plasma concentration of BNP by ELISA, cardiac function by ultrasound were performed before and after 6 months of treatment. The changes in clinical symptom, heart rate, heart function, side effect and maximal tolerance dose after treatment with carvedilol were observed. RESULTS: Plasma concentration of BNP was much higher in the group of patients with EFE [(865 +/- 702) ng/L] than that of control group [(154 +/- 78) ng/L] (P < 0.01), and there was a positive correlation between plasma concentration of BNP and cardiac function classification, and cardiac function grades II, III, and IV corresponded to plasma concentration of BNP (286 +/- 125) ng/L, (437 +/- 386) ng/L, (1673 +/- 859) ng/L respectively in children with EFE. Compared with the group treated with traditional medicines, plasma concentration of BNP [(403 +/- 216) ng/L vs. (219 +/- 87) ng/L] significantly decreased, the clinical symptom was significantly improved, cardio-thoracic ratio (CTR) (0.60 +/- 0.05 vs. 0.54 +/- 0.06) (P < 0.05) and heart rate [(115 +/- 20) bpm vs. (90 +/- 14) bpm] (P < 0.01) decreased, ejection fraction (EF) (46.6% +/- 13.4% vs. 54.5% +/- 12.9%), fractional shortening (21.6% +/- 8.1% vs. 24.1% +/- 7.5%), mean velocity of circumferential fiber shortening [(0.8 +/- 0.5) cir/s vs. (0.9 +/- 0.4) cir/s] were significantly increased (P < 0.01), left ventricular end-systolic dimension [(34.0 +/- 8.6) mm vs. (32.2 +/- 9.1) mm] (P < 0.05), left ventricular mass [(65.9 +/- 34.1) g vs. (65.9 +/- 34.1) g], interventricular septal thickness at end-systole [(6.0 +/- 1.0) mm vs (5.5 +/- 1.1) mm] were notably decreased (P < 0.01) after treatment with carvedilol. CONCLUSION: These data indicated that plasma concentration of BNP significantly increased in children with EFE, carvedilol can decrease plasma concentration of BNP, inhibit the remodeling of ventricle, significantly improve the cardiac function in children with EFE. Carvedilol is effective and safe in treatment of children with EFE.

[Restrictive cardiomyopathy in childhood]. / Restriktive Kardiomyopathie. Ein seltenes Krankheitsbild im Kindesalter.

Restrictive cardiomyopathy is a rare heart muscle disease in childhood. By presenting a case report of a 15 year old adolescent, the aim of this article is to describe diagnosis, pathogenesis and therapy of restrictive cardiomyopathy. A review of the literature comprising pediatric studies on restrictive cardiomyopathy serves as a basis to discuss recommendations for therapeutic strategies in pediatric patients with this rare disease.

Combination of fatal digoxin poisoning with endocardial fibroelastosis.

This is the first report in the forensic literature of a combination of fatal digoxin poisoning with endocardial fibroelastosis (EFE). Typical morphological features of EFE as the cause of clinically diagnosed cardiomyopathy were present in the autopsy of a 3-year-old girl, including cardiac hypertrophy and marked thickening of the left-sided endocardium, consisting of numerous elastic and collagenic fibres. After exclusion of cardiac and cerebral causes of death, accidental digoxin intoxication was proved. Postmortem toxicological analyses by fluorescence polarization immunoassay (FPIA) disclosed digoxin levels of 71 micrograms/kg (femoral vein blood), 77 micrograms/kg (cardiac blood), 255 and 221 micrograms/kg (cardiac muscle of the right and left chamber), 163 micrograms/kg (psoas muscle), 91 micrograms/kg (lung), 222 micrograms/kg (liver) and 520 micrograms/kg (kidney). The results are compared with the antemortem digoxin concentration of 39 ng/ml serum. The case is discussed from its unusual morphological and toxicological aspects, with special consideration of possible medical malpractice.

[Diagnosis and treatment of infantile endocardial fibroelastosis].

The diagnosis, treatment and etiology of primary infantile endocardial fibroelastosis were studied in 33 patients from 1989 to 1992. Two dimensional echocardiography with Doppler examination showed that the thickness of the endocardium obviously increased and systolic and diastolic functions of the left ventricles were abnormal. Endomyocardial biopsy proved that the endocardium and myocardium under went pathological changes. The virus probe examination of biopsy tissue showed negative results and the effectiveness of immunosuppressive therapy (total effective rate 96%) indicated that this disease is probably of autoimmune etiology. The facts led us to nominate this disease as infantile endomyocardial disease. Besides, the classification, diagnostic criteria, principles of treatment and prognosis of this disease were discussed.

Inheritance of familial primary endocardial fibroelastosis.

Two related families with 15 children, seven of whom developed endocardial fibroelastosis (EFE) are described. Three of the children died during infancy, and the disease was confirmed in one of them at autopsy. The survivors, two sisters age 5 years and 15 months (Family A) and two sisters age 17 and 14 years (Family B), are now symptomless and show a decrease in left ventricular hypertrophy. The mode of inheritance of EFE in our two families appears to be either autosomal or X-linked dominant with reduced penetrance.

Chronic afterload reduction in infants and children with primary myocardial disease.

The purpose of this study was to determine the long-term effects of chronic afterload reduction with oral hydralazine therapy in patients with primary myocardial disease (PMD). Twenty-six children aged 3 to 48 months with the diagnosis confirmed by M-mode and two-dimensional echocardiograms and angiograms were given digitalis and diuretics. Fourteen of these patients also received hydralazine orally in doses up to 4.0 mg/kg/day in four divided doses. Echocardiograms were initially repeated at 1- to 3-month intervals and subsequently at 6-month intervals. Long-term follow-up data were available in 10 patients given hydralazine and eight control patients; the follow-up interval ranged from 3 to 48 months. In the hydralazine group the shortening fraction rose from 14.5 +/- 4.9 to 23.2 +/- 7.5 (P less than 0.01), and the ratio of pre-ejection period to ejection time (0.52 +/- 0.05 to 0.35 +/- 0.06, P less than 0.001) and left ventricular size, normalized to body surface area (116 +/- 7 to 87 +/- 21, P less than 0.01), decreased. Significant improvement was demonstrated by echocardiography after 12 months of hydralazine therapy. There was no significant change in any of these values in the control group. We conclude that hydralazine therapy is a useful adjunct in the management of primary myocardial disease in infancy and childhood.

Prognostic value of the electrocardiogram in endocardial fibroelastosis.

Nine children with endocardial fibroelastosis were followed from the time of admission with congestive heart failure until either death or discharge. Review of multiple clinical features showed that only the electrocardiographic pattern could be correlated with death or survival. The presence of a delayed transition zone with anterior force loss on the initial electrocardiogram ('infarct pattern') was noted in all the children who died. Progression of these changes with a pattern of anterolateral 'infarct' in two and inferior wall 'infarct' in two occurred before death. Necropsy on three of the four children confirmed the diagnosis of endocardial fibroelastosis. There was extensive fibrosis and thinning of the left ventricular myocardium as well as involvement of the mitral valve structures. Review of published cases supports the view that an 'infarct' pattern in a child with endocardial fibroelastosis is usually associated with death and that this pattern is a negative prognostic sign for survival.

[Endocardial fibroelastosis (E.F.) and its differential diagnosis]. / Die Fibroelastosis Endocardica (F.E.) und ihre Differentialdiagnose

The endocardial fibroelastosis (EFE) is the most frequent cardiomyopathy. This disease is characterised by endocardial hyperplasia due to proliferation of elastic and collagenous fibres. There are primary and secondary forms. Within the primary form, the infantile form is the most frequent and of greatest importance to the pediatrician. This form is more a syndrom than a distinct disease. It is a reaction of the endocard due to several noxes. Lately a possible viral etiology is being discussed e.g. Parotitis, Coxsackie or other viruses. Clinical criteria for diagnosis are: cardiomegaly, left ventricular hypertrophy seen in 97% in the ECG, the absence of a murmur (or a soft apical mumur) absence of cyanosis and absence of systemic disease. Differential diagnosis is mainly between fibroplastic parietal endocarditis (FPE), cardiovascular collagenosis (CC) and endomyocard fibrosis (EMF). In FPE thrombosis is frequent and typically there is eosinophilia. CC is found in South Africa and is characterised by edema and fibrinoid necrosis. MEF is present mainly in Uganda, Nigeria and South India, characterised by endocardial fibrosis, valve involvement and eosinophilia. The obstructive hypertrophic cardiomyopathy is characterised by a pronounced cardiomegaly, insufficient weight gain as well as dyspnea and cyanosis. Catheterization shows a gradient across one or both of the outflow tracts due to hypertrophic subaortic or subpulmonic stenosis. Therapy of EFE consists in treating the cardiac decompensation and according to the severity of the disease, in steroids.