Introduction

Endocardial fibroelastosis (EFE) is a rare paediatric cardiac disorder characterised by diffuse thickening of the endocardium resulting from the proliferation of collagen and elastin fibres. It primarily affects infants under one year of age and may present as idiopathic (primary EFE) or as secondary to underlying structural heart disease.¹ Although the precise aetiology remains unclear, current evidence implicates immune-inflammatory mechanisms and disturbances in endothelial-to-mesenchymal transition pathways. 

Pathophysiology

EFE results in restrictive ventricular function, as the thickened endocardium hinders both myocardial contraction and relaxation. Histologically, it is characterised by dense, acellular connective tissue overlying the endocardial lining, frequently accompanied by myocytolysis and subendocardial fibrosis.² Secondary EFE can arise in response to chronic pressure overload conditions, such as congenital aortic stenosis or hypoplastic left heart syndrome.

Emerging evidence implicates abnormal endothelial-mesenchymal transition as a central pathogenic mechanism, with defects in cell signalling and receptor pathways driving pathological tissue remodelling. Viral infection and genetic predisposition have also been proposed as contributory factors in selected cases.

Clinical presentation

The majority of cases present within the first few months of life, with over 60% occurring before the age of 12 months. Symptoms often develop following respiratory infections, although some infants may present without any preceding triggers. The clinical picture is typically dominated by signs of congestive cardiac failure. Infants may exhibit respiratory distress, tachypnoea, poor feeding, gastrointestinal disturbances such as retching and vomiting, and features of systemic congestion, including hepatomegaly and peripheral oedema.³ Additional non-specific symptoms, including pallor, fatigue, and diaphoresis, are also frequently observed.

On physical examination, tachycardia and the presence of a gallop rhythm are common findings. Systolic murmurs, particularly those associated with mitral regurgitation, may also be detected. Radiological and echocardiographic investigations provide further diagnostic insight: chest radiographs often reveal an enlarged cardiac silhouette, while echocardiography demonstrates left ventricular dilatation, impaired contractility, and diffuse endocardial thickening. Electrocardiographic findings are variable but may include ST-T segment abnormalities, left ventricular hypertrophy, and arrhythmias.⁴ The appearance of an “infarct pattern” on the electrocardiogram is regarded as a marker of poor prognosis.

Diagnosis

The definitive diagnosis of EFE rests on histopathological confirmation obtained through endomyocardial biopsy, which typically reveals marked hyperplasia of collagen and elastin fibres within the endocardium. However, as a biopsy is invasive and results may be delayed, clinicians often rely on a combination of clinical features and imaging modalities to establish a working diagnosis and initiate early management.⁵

Chest radiography frequently demonstrates cardiomegaly accompanied by evidence of pulmonary venous congestion. Echocardiography remains the cornerstone of non-invasive assessment, characteristically showing uniform left ventricular enlargement, diffuse endocardial echo enhancement, and impaired contractility. Cardiac magnetic resonance imaging (MRI) provides further diagnostic precision, with findings of endocardial thickening, decreased global ventricular function, and tissue characterisation supportive of EFE. Laboratory investigations may reveal elevated NT-proBNP and other biochemical markers of heart failure, typically in the absence of signs of systemic infection, which helps distinguish EFE from infective or inflammatory cardiomyopathies. In selected cases, genetic and viral testing may be considered to explore potential aetiological factors.⁶

Management strategies

Management of EFE is multifaceted, requiring both acute stabilisation and long-term disease control.

Acute heart failure management

Infants presenting with acute decompensated heart failure require prompt and aggressive intervention. Supportive care includes oxygen supplementation, judicious sedation (for example, chlorpromazine or promethazine), and close haemodynamic monitoring. Decongestive therapy forms the mainstay of pharmacological management: cardiac glycosides such as digoxin (or cedilanid in some centres) are employed to improve myocardial contractility, while loop diuretics, most commonly furosemide, are administered to alleviate volume overload.⁷ Corticosteroids, including dexamethasone, may be considered in selected cases to reduce myocardial oedema, although their use remains controversial. Management of complications is equally important; oral iron supplementation is indicated in the presence of anaemia, and mechanical ventilation may be required in cases of severe respiratory compromise. Nutritional support plays a vital role, particularly in infants who often suffer from poor feeding and associated deficiencies.⁷

Long-term care

Chronic management focuses on maintaining cardiac function and delaying disease progression. Long-term therapy frequently involves low-dose digoxin and careful titration of diuretics to balance symptom control with the risk of electrolyte disturbances and renal dysfunction. Immunomodulatory therapies are an area of growing interest: emerging evidence suggests that biological immunotherapy, including steroids and other agents, may attenuate disease progression in selected patients, though their use is limited by contraindications and the need for careful patient selection.⁸

Heart transplantation remains the definitive therapy for refractory EFE. It is indicated in infants and children who fail to respond to maximal medical therapy or who exhibit progressive ventricular dysfunction with escalating mortality risk. Despite the challenges of donor availability and post-transplant complications, outcomes following transplantation in this population have improved significantly in recent years.

Monitoring and follow-up

Ongoing monitoring is essential to assess both treatment response and disease progression. This involves regular clinical review, repeat imaging (particularly echocardiography and, where available, cardiac MRI), and laboratory assessment of cardiac biomarkers. Markers of clinical improvement include reduction in cardiac size, improved ventricular function, normalisation of electrocardiographic abnormalities, and stabilisation of biochemical indices of heart failure. Long-term follow-up should also address growth, nutritional status, and developmental milestones, as chronic cardiac illness in infancy carries significant implications for overall health and quality of life.⁹

Prognosis

The prognosis of endocardial fibroelastosis in infants remains guarded, despite advances in diagnostic and therapeutic strategies. Reported survival rates at four years are approximately 77% for confirmed cases. Outcomes are notably poorer in infants who present with acute heart failure, many of whom require cardiac transplantation in order to achieve long-term survival. Several clinical and investigative findings have been identified as markers of adverse prognosis. These include the persistence of an abnormal electrocardiogram, particularly the so-called “infarct pattern”; severely reduced left ventricular function, with an ejection fraction of less than 33% or a cardiac index below 3.5 L/min/m²; and a cardiothoracic ratio exceeding 55% following treatment. A poor or absent response to initial therapy also strongly predicts unfavourable outcomes.¹⁰

Even among survivors, chronic morbidity is common. Many children experience persistent symptoms of heart failure, require long-term pharmacological management, and are at risk of progressive ventricular dysfunction.¹¹ Nevertheless, early diagnosis combined with aggressive intervention may improve outcomes in selected cases, underscoring the importance of prompt recognition and timely initiation of therapy.

Complications

Infants with EFE and associated heart failure are vulnerable to a range of severe complications, which contribute significantly to the overall morbidity and mortality of the disease. Intracardiac thrombus formation is a recognised risk, arising from low-flow haemodynamics and arrhythmogenic states. Thromboembolic events, including stroke and systemic embolisation, can result from these thrombi, while severe mitral regurgitation may develop secondary to valvular involvement. Progressive heart failure may culminate in cardiogenic shock, and malignant arrhythmias can precipitate sudden cardiac death. Myocardial infarction may occur as a consequence of either embolic phenomena or ischaemia related to impaired myocardial perfusion ¹²

In prenatal presentations, hydrops fetalis has been documented, reflecting the profound haemodynamic compromise associated with the disease. Secondary EFE, which develops in association with structural congenital heart lesions, carries a variable prognosis. Outcomes in these cases depend largely on the nature of the underlying defect and the success of surgical interventions, such as valvuloplasty in infants with congenital aortic stenosis.¹³

Differential diagnosis

The diagnosis of EFE can be challenging, as its clinical and imaging features overlap with several other paediatric cardiac disorders. Dilated cardiomyopathy (DCM) is the most important differential, given the similarities in ventricular dilatation and impaired systolic function. However, unlike DCM, EFE has the potential for partial or complete reversal of cardiac dilatation with timely and effective treatment, a distinction that can influence both prognosis and management. Viral myocarditis also presents with acute heart failure and ventricular dysfunction, but is generally characterised by inflammatory changes on biopsy and often a preceding viral illness.¹⁴ Structural congenital heart diseases, such as atrioventricular septal defects or congenital aortic stenosis, may mimic or coexist with secondary EFE, complicating the diagnostic picture. Infiltrative cardiomyopathies, although rare in infancy, should also be considered in the broader differential, particularly in cases with atypical presentations or where there is multi-organ involvement.

Future directions

Ongoing research aims to elucidate the pathogenic mechanisms underlying EFE, with particular focus on the role of endothelial-to-mesenchymal transition, immune-inflammatory pathways, and genetic predisposition. Improved understanding of these mechanisms may allow earlier identification of at-risk populations through genetic screening and biomarker discovery. Advances in imaging, including high-resolution echocardiography and cardiac MRI with tissue characterisation, are expected to refine early diagnosis and disease monitoring. In parallel, the development of targeted immunomodulatory therapies and other disease-modifying strategies may offer alternatives to conventional pharmacological treatment, with the potential to improve long-term outcomes. Ultimately, the establishment of evidence-based diagnostic and management guidelines, informed by multicentre studies and registries, will be essential to standardise care and optimise prognoses for affected infants.

Summary

Endocardial fibroelastosis (EFE) is a rare cardiac disorder of infancy, characterised by diffuse thickening of the heart’s endocardium due to abnormal proliferation of collagen and elastin fibres. This results in restrictive ventricular function and symptomatic heart failure. Most commonly affecting infants under one year of age, EFE may occur as an idiopathic condition or develop secondary to other structural heart diseases. Immune-inflammatory mechanisms and disturbances in endothelial-to-mesenchymal transition are thought to play central roles in its pathogenesis.

Clinically, EFE typically presents with severe features of cardiac failure, including respiratory distress, poor feeding, and systemic congestion. Early diagnostic imaging is essential, with echocardiography and cardiac MRI providing key insights into ventricular structure and function.

Management requires prompt stabilisation with supportive respiratory care, cardiac glycosides, diuretics, and, in selected cases, corticosteroids. Long-term treatment may involve maintenance pharmacotherapy, immunomodulatory approaches, and, in refractory cases, heart transplantation.

The prognosis remains guarded, with a high risk of mortality, chronic complications, and progressive functional decline. Favourable outcomes depend heavily on early recognition and timely intervention. Complications such as thromboembolism, arrhythmias, and worsening heart failure are frequent and pose significant clinical challenges. Current research is focused on improving diagnostic modalities, further defining pathogenic mechanisms, and developing targeted therapeutic strategies aimed at enhancing outcomes for affected infants.

FAQs

What is endocardial fibroelastosis (EFE)?

EFE is a rare paediatric cardiac disorder characterised by diffuse thickening of the endocardium due to excessive proliferation of collagen and elastin fibres. It most commonly affects infants under one year of age and can be either idiopathic (primary EFE) or secondary to congenital structural heart disease.

What causes EFE?

The exact cause remains unclear. Current evidence suggests contributions from immune-inflammatory processes, disturbances in endothelial-to-mesenchymal transition, viral infections, and genetic predisposition. Secondary EFE often develops in response to chronic pressure overload from congenital defects such as aortic stenosis or hypoplastic left heart syndrome.

How does EFE affect the heart?

EFE causes restrictive ventricular function by thickening the endocardium, which limits myocardial contraction and relaxation. This leads to impaired cardiac output and progressive heart failure in infants.

What symptoms do infants with EFE present with?

Most infants develop symptoms within the first year of life. Common signs include respiratory distress, tachypnoea, poor feeding, retching or vomiting, hepatomegaly, peripheral oedema, pallor, fatigue, and excessive sweating.

How is EFE diagnosed?

Definitive diagnosis requires histopathological confirmation through endomyocardial biopsy, showing collagen and elastin hyperplasia. However, diagnosis is usually guided by imaging and clinical findings. Key investigations include echocardiography, cardiac MRI, chest X-ray, and laboratory biomarkers such as NT-proBNP.

What treatments are available for EFE?

Management involves both acute and long-term strategies. Acute therapy includes supportive care (oxygen, sedation), cardiac glycosides (digoxin), diuretics (furosemide), and, in some cases, corticosteroids. Long-term care often requires maintenance of digoxin, careful diuretic use, and occasionally immunomodulatory therapies. In refractory cases, heart transplantation may be necessary.

What is the prognosis for infants with EFE?

The prognosis is guarded. The four-year survival rate is around 77%, but outcomes are significantly worse in infants presenting with acute heart failure. Poor prognostic markers include persistent ECG abnormalities (“infarct pattern”), low ejection fraction, enlarged cardiothoracic ratio, and lack of response to therapy. Survivors often require lifelong medical care.

What are the complications associated with EFE?

Infants with EFE are at risk of severe complications, including intracardiac thrombus formation, thromboembolism (leading to stroke), severe mitral regurgitation, arrhythmias with risk of sudden death, myocardial infarction, cardiogenic shock, and hydrops foetalis in prenatal cases.