Nexilin in cardiomyopathy: unveiling its diverse roles with special focus on endocardial fibroelastosis.

Cardiac disorders exhibit considerable heterogeneity, and understanding their genetic foundations is crucial for their diagnosis and treatment. Recent genetic analyses involving a growing number of participants have uncovered novel mutations within both coding and non-coding regions of DNA, contributing to the onset of cardiac conditions. The NEXN gene, encoding the Nexilin protein, an actin filament-binding protein, is integral to normal cardiac function. Mutations in this gene have been linked to cardiomyopathies, cardiovascular disorders, and sudden deaths. Heterozygous or homozygous variants of the NEXN gene are associated with the development of endocardial fibroelastosis (EFE), a rare cardiac condition characterized by excessive collagen and elastin deposition in the left ventricular endocardium predominantly affecting infants and young children. EFE occurs both primary and secondary to other conditions and often leads to unfavorable prognoses and outcomes. This review explores the role of NEXN genetic variants in cardiovascular disorders, particularly EFE, revealing that functional mutations are not clustered in a specific domain of Nexilin based on the cardiac disorder phenotype. Our review underscores the importance of understanding genetic mutations for the diagnosis and treatment of cardiac conditions.

Endocardial fibroelastosis in infants and young children: a state-of-the-art review.

Endocardial fibroelastosis (EFE) is a rare cardiac condition characterized by excessive endocardial thickening secondary to fibroelastic tissues that commonly present in infants and young children. Most of endocardial fibroelastosis cases are secondary forms, which occur in conjunction with other cardiac diseases. Endocardial fibroelastosis has been associated with poor prognosis and outcomes. In light of recent advancements in understanding pathophysiology, several new data have revealed compelling evidence that abnormal endothelial-to-mesenchymal transition is the root cause of endocardial fibroelastosis. This article aims to review the recent development in pathophysiology, diagnostic workup, and management, and to discuss possible differential diagnoses.

Prolapse Volume to Prolapse Height Ratio for Differentiating Barlow's Disease From Fibroelastic Deficiency.

BACKGROUND: As mitral valve (MV) repair for Barlow's disease remains surgically challenging, it is important to distinguish Barlow's disease from fibroelastic deficiency (FED) preoperatively. We hypothesized that the prolapse volume to prolapse height ratio (PV-PH ratio) may be useful to differentiate Barlow's disease and FED.Methods and Results:In 76 patients with MV prolapse who underwent presurgical transesophageal echocardiography, the 3D MV morphology was quantified: 19 patients were diagnosed with Barlow's disease and 57 with FED. The patients with Barlow's disease had greater prolapse volume and height than the patients with FED, as well as greater PV-PH ratio (0.61±0.35 vs. 0.17±0.10, P<0.001). Receiver-operating characteristic analysis revealed that with a cutoff value of 0.27, the PV-PH ratio differentiated Barlow's disease from FED with 84.2% sensitivity and 84.2% specificity. Net reclassification improvement showed that the differentiating ability of the PV-PH ratio was significantly superior to prolapse volume (1.30, P<0.001). After being adjusted by each of prolapse volume and height, annular area and shape, and the number of prolapsed segments, the PV-PH ratio had an independent association with Barlow's disease. CONCLUSIONS: The PV-PH ratio was able to differentiate Barlow's disease from FED with high accuracy. 3D quantification including this value should be performed before MV repair.

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.

Primary endocardial fibroelastosis and nonimmune hydrops fetalis: case report with autopsy.

Endocardial fibroelastosis is an important cause of congestive heart failure and death in infancy and early childhood. When present, it is commonly associated with non immune hydrops fetalis. The aim of this study is to draw attention for possible cardiac abnormalities in cases of fetal hydrops, and report a case of premature death by primary endocardial fibroelastosis with autopsy.

Endocardial fibroelastosis causing sudden death in an infant: Autopsy case report of an unusual lesion.

ABSTRACT: Endocardial fibroelastosis is characterized by proliferation of both elastic and collagenous fibers within the endocardium, causing diffuse or localized thickening. A four-and-a-half-month-old baby was admitted to a local hospital, with a history of seizures for one day. Baby developed features of heart failure and died within one week after admission. At the post-mortem examination, heart was found to be enlarged with dilated ventricles. The endocardium of left ventricle was markedly thickened with a whitish appearance. Histopathology showed a thick layer of collagenous fibrous tissue in the endocardium, which was confirmed by Masson trichrome stain. The cause of death was offered as dilated cardiomyopathy due to endocardial fibroelastosis. The underlying mechanisms of myocardial fibrosis remain unclear. It is hypothesized that genetic, infectious, inflammatory, and nutritional processes are involved in this condition. This case highlights the importance of gross specimen examination and special staining methods to support histopathology after postmortem examination, for ascertaining the cause of death.

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.

Faciocardiorenal syndrome: a wide clinical spectrum?

Faciocardiorenal syndrome (FCRS), also named Eastman-Bixler syndrome, is an apparent autosomal recessive entity, characterized by endocardial fibroelastosis, unusual facial appearance, renal defects and mental retardation. We report a 7 months male patient, with the diagnosis of endocardial fibroelastosis, an abnormal facial appearance (arched eyebrows, broad nasal root, long philtrum and microretrognathia) and psychomotor delay. Associated anomalies were: plagiocephaly, broad halluces, nail hypoplasia, cryptorchidism, diastasis recti, and adducted thumbs. Focal seizures in the mouth were also observed. The radiographs revealed advanced bone age and metaphyseal widening of femur and tibia. FCRS has an unknown etiology with only three reported cases so far (since 1977). We report a patient with the main features of FCRS but without the renal component, suggesting that this entity can present a wide clinical spectrum. Based on these findings and on the few previously reported cases with a highly variable phenotype when compared with the original report, we suggest that FCRS should be further clinical delineated according to the following leading anomalies: endocardial fibroelastosis, unusual facial appearance and mental retardation, in order to find more cases that allow a wider clinical description and the identification of the genetic defect(s).

[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.

Fetal echocardiographic assessment of endocardial fibroelastosis in maternal anti-SSA antibody-associated complete heart block.

BACKGROUND: There are few reports describing the features of maternal anti-SSA antibody-associated congenital complete heart block (CCHB) patients developing endocardial fibroelastosis (EFE). The aim of this study was to describe the clinical features and the outcome of patients with CCHB, with or without EFE. METHODS AND RESULTS: Over a 20-year period, 12 consecutive patients diagnosed with maternal anti-SSA antibody-associated CCHB were identified. The maternal anti-SSA antibody levels were measured and fetal echocardiographic findings were reviewed. The ratios of the thickness of the endocardium to that of the whole wall of the left ventricle (LE/W) and right ventricle (RE/W) were measured to investigate the degree of endocardial thickening. A total of 7 patients survived (living group) and were not diagnosed as having EFE. The remaining 5 patients died and were diagnosed with EFE during autopsy (dead group). Fetal echocardiography of the patients showed differences in the thickening and hyperintensity of the endocardium. The RE/W value was significantly higher in the dead group than in the living group. The titers of both maternal anti-52-kDa and anti-60-kDa SSA antibodies were high, but showed no significant differences between the 2 patient groups. CONCLUSIONS: EFE was the major negative prognostic factor for CCHB. Myocardial damage, predominantly in the right ventricle, was related to the outcome of CCHB associated with EFE.

Ross-Konno and endocardial fibroelastosis resection after hybrid stage I palliation in infancy: successful staged left-ventricular rehabilitation and conversion to biventricular circulation after fetal diagnosis of aortic stenosis.

We report a patient who presented during fetal life with severe aortic stenosis, left-ventricular dysfunction, and endocardial fibroelastosis (evolving hypoplastic left heart syndrome). Management involved in utero and postnatal balloon aortic valvuloplasty for partial relief of obstruction and early postnatal hybrid stage I palliation until recovery of left-ventricular systolic function had occurred. The infant subsequently had successful conversion to a biventricular circulation by combining resection of endocardial fibroelastosis with single-stage Ross-Konno, aortic arch reconstruction, hybrid takedown, and pulmonary artery reconstruction.

Combined Aortic and Mitral Annular Enlargement With Fibrous Skeleton Reconstruction.

In a pediatric population, congenital or acquired disease of the aortic and mitral valves may coexist and sometimes require replacement of both valves. Enlargement of aortic and mitral annuli may also be required. We demonstrate a challenging case that required upsizing of both prosthetic valves by redo anterior aortoventriculoplasty and patch enlargement of the aortic-mitral fibrous body. This case highlights the complexity and feasibility of enlarging both annuli in a reoperative setting, to implant larger prostheses.

An uncommon cause of coronary artery ostial obstruction: papillary fibroelastoma.

Cardiac papillary fibroelastoma is a benign tumor that mainly affects cardiac valves. The tumor has the potential to cause angina and myocardial infarction due to embolization of tumor fragments. We describe a rare case of right coronary artery ostial obstruction by a 12 x 19 mm sized papillary fibroelastoma located in the sinus of Valsalva. The report underlies the importance of echocardiography in diagnosis and intraoperative treatment of this type of cardiac mass.

Early detection of anomalous origin of left coronary artery from the right pulmonary artery after successful repair of critical coarctation of the aorta.

Left ventricular (LV) function is impaired by increased afterload in neonates with severe coarctation of the aorta, which may result in endocardial fibroelastosis. Repair of the coarctation usually solves the problem, with LV function normalizing after a few weeks. This report describes a patient who underwent successful repair of critical coarctation with normalization of LV function despite signs of endocardial fibroelastosis but with persisting elevation of cardiac troponin T. Cardiac catheterization showed the rare coincidence of anomalous origin of left coronary artery from the right pulmonary artery (ALCAPA) and coronary sinus orifice atresia with left superior vena cava.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) presenting as a complete heart block.

A 51-year-old previously asymptomatic man presented with complete heart block (CHB). During pacemaker implantation, fluoroscopy showed a peculiar pattern of cardiac calcification. Coronary angiography, performed to determine the origin of calcification, demonstrated an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). A left ventriculogram showed normal ventricular contraction. Echocardiography demonstrated normal systolic function without any regional wall motion abnormality. The endocardium of the mid and basal portions of the anteroseptal, anterior and anterolateral walls as well as both of the papillary muscles were calcified. Specifically noted was a calcific bar extending across the base of the interventricular septum (IVS) on both the echocardiogram and the left ventricle angiogram. The development of CHB in the absence of transmural myocardial infarction is intriguing. It is likely that endocardial fibroelastosis during infancy led to endocardial fibrosis and scarring subsequent calcium deposition. Extension of this calcification into the conduction system may have led to CHB. This is the first report of an adult patient with ALCAPA presenting with CHB.

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.

Endocardial fibroelastosis in a dog with congestive heart failure.

In a 6-month-old, intact female, Japanese spitz presenting with severe dyspnea, lung ultrasonography revealed confluent B lines associated with severe echocardiographic left sided volume overload and systolic dysfunction. A congenital shunt or valvular dysplasia was not demonstrable. On electrocardiogram, there was a constant sinus rhythm, respectively sinus tachycardia. Cardiac troponin I was normal. Within 2 days of admission, the dog died of heart failure. On macroscopic postmortem examination, the left ventricle and atrium were markedly dilated, and the left ventricular endocardium had a mild diffuse whitish appearance. Histopathology revealed moderate to severe thickening of the left ventricular endocardium, composed mostly of abundant elastic fibers and fewer collagen fibers, diagnostic for endocardial fibroelastosis. In addition, there were mild degenerative changes of the atrioventricular valves. Endocardial fibroelastosis is a rare congenital disease and should be considered in a young dog if more common causes of echocardiographic dilated cardiomyopathy phenotype are ruled out.

Cardiac tumors: optimal cardiac MR sequences and spectrum of imaging appearances.

OBJECTIVE: This article reviews the optimal cardiac MRI sequences for and the spectrum of imaging appearances of cardiac tumors. CONCLUSION: Recent technologic advances in cardiac MRI have resulted in the rapid acquisition of images of the heart with high spatial and temporal resolution and excellent myocardial tissue characterization. Cardiac MRI provides optimal assessment of the location, functional characteristics, and soft-tissue features of cardiac tumors, allowing accurate differentiation of benign and malignant lesions.