Endomyocardial diseases

Article written and reviewed by Dr Luca Moretti

Endomyocardial diseases are a heterogeneous group of conditions in which injury involves the ventricular endocardium and, to a variable extent, the underlying myocardium and atrioventricular apparatus. The location of the lesion explains some common features: alteration of the antithrombotic properties of the chamber surface, deposition of thrombotic material, fibrous thickening, reduction of the effective cavity, and impaired filling. The designation is anatomic and does not identify a single cause. In particular, the term endocarditis, when referring to eosinophilic disease, does not imply infection and does not necessarily describe a valvular vegetation.

This group includes Loeffler endocarditis and hypereosinophilic endomyocardial disease, endomyocardial fibrosis described mainly in tropical areas, and endocardial fibroelastosis, which is particularly relevant in fetal and pediatric age groups. The first two terms may describe different aspects of the same eosinophilic process, respectively the cardiac phenotype and its place within a systemic disease. Tropical endomyocardial fibrosis, however, has not been demonstrated to be an eosinophilic outcome in every case; fibroelastosis represents a different pattern of endocardial response, characterized by abundant elastic tissue as well as collagen.

The frequency of the group cannot be summarized by a single epidemiologic estimate. Eosinophilic diseases are rare, but their recognition depends on access to hematologic diagnostics and imaging; endomyocardial fibrosis has a markedly uneven geographic distribution and may be underdiagnosed; fibroelastosis is often detected in the context of congenital heart disease or infantile cardiomyopathy rather than recorded as an independent disease. Observed severity is also affected by selection: a surgical series collects advanced lesions, whereas echocardiographic screening may identify abnormalities that are still minimally symptomatic. Clinically, the common problem is to recognize how much dysfunction depends on an active process and how much on an anatomic change that has already become organized.

Etiology, pathogenesis, and pathophysiology

The normal endocardium is a biologically active interface between blood and the cardiac wall. Endothelial integrity limits platelet adhesion and coagulation; the underlying matrix contributes to the mechanical properties of the ventricular surface. An inflammatory insult may make this surface thrombogenic before an obvious change in geometry appears. Subsequent repair deposits extracellular matrix and may incorporate thrombi adherent to the wall, transforming an initially cellular and potentially reversible lesion into a structural limitation. Distribution of the process is critical: apical thickening reduces available volume, whereas a lesion extending to the subvalvular apparatus also alters mitral or tricuspid function.

In eosinophilic injury, degranulation releases cationic proteins, peroxidase, and other mediators capable of damaging cardiomyocytes and endothelium and promoting thrombosis. Eosinophilia may result from clonal myeloid proliferation, a response to cytokines produced by other cells, drugs, parasitic infection, or immune-mediated disease. The classic sequence of necrosis, thrombosis, and fibrosis describes one possible evolution, but does not impose three sharply separated periods: inflammatory, thrombotic, and scar components may coexist. In addition, the circulating count captures only one compartment of the disease and does not directly measure degranulation that has already occurred in the heart.

In endomyocardial fibrosis from endemic regions, etiologic hypotheses include environmental, nutritional, immune, and individual susceptibility interactions. Epidemiologic associations have not identified an explanation that is both necessary and sufficient for every case. The established lesion preferentially involves the apices and ventricular inflow regions, may retract the subvalvular apparatus, and can leave the outflow tracts relatively spared. This pattern differs from the diffuse fibrosis of many cardiomyopathies and helps explain why a ventricle with apparently good contraction may contain and mobilize only a very small amount of blood.

Endocardial fibroelastosis develops mainly in the immature heart, in which abnormalities of flow, loading, and growth interact with remodeling processes. It may accompany left ventricular outflow obstruction, genetic or metabolic cardiomyopathy and, in selected cases, injury associated with maternal autoantibodies. Fibroelastic thickening increases wall stiffness and may hinder functional recovery even after correction of the hemodynamic cause. Forms with a dilated left ventricle and those with a small or hypoplastic ventricle do not pose the same surgical problem: in the latter, it also matters whether the chamber can grow and sustain systemic work.

The characteristic mechanical consequence of fibrosing forms is restrictive physiology. The diastolic pressure-volume curve becomes steeper: a modest increase in volume requires a substantial increase in filling pressure. Blood accumulates upstream and the atria dilate, while preload reserve during exercise falls. Apical obliteration adds a loss of effective cavity volume. A preserved ejection fraction can therefore coexist with low stroke output because it expresses a proportion of ventricular volume rather than the absolute volume ejected. When the myocardium is also involved, reduced contractility is added to diastolic dysfunction.

Involvement of the atrioventricular apparatus alters coaptation through adhesion, retraction, or incorporation of chordae and papillary muscles. The resulting regurgitation further increases atrial pressures and upstream overload; part of stroke volume is ejected toward the atrium, reducing forward output. Right-sided forms are dominated by systemic venous congestion and reduced effective pulmonary flow; left-sided forms increase pulmonary venous pressure and right ventricular workload. The combination of restriction and regurgitation explains why systolic-function quantification alone does not adequately represent hemodynamic severity.

Thrombosis arises from the interaction among an injured surface, local flow conditions, and the blood state. In active eosinophilia, cellular and coagulation activation may favor it even without a major reduction in ejection fraction; stasis contributes in hypokinetic or deformed chambers. With organization, the boundary between adherent thrombus and fibrous tissue can become less distinct. Imaging must therefore reconstruct not only the presence of a mass but also its relationship with the wall, vascularity, motion, and evolution over time: these elements have different implications for anticoagulation, causal treatment, and surgery.

Clinical manifestations

Onset depends on the predominant mechanism. Eosinophilic myocarditis may present with chest pain, elevated troponin, arrhythmias, or rapid hemodynamic deterioration before endocardial thickening and apical obliteration develop. In chronic forms, exertional dyspnea, fatigue, and reduced exercise capacity reflect the inability to increase output adequately without raising filling pressures. Progression from symptoms only during activity to orthopnea or resting congestion indicates reduced reserve, but may also be precipitated by intercurrent infection, anemia, arrhythmias, or interruption of therapy.

Right-sided congestion may dominate the picture with ascites, hepatomegaly, jugular venous distention, and edema, sometimes with relatively mild respiratory symptoms. An apparently hepatic presentation therefore does not exclude a cardiac cause, particularly when right atrial dilation and apical deformation are marked. In left-sided forms, dyspnea and signs of pulmonary congestion predominate. Auscultation may reveal murmurs of mitral or tricuspid insufficiency; murmur intensity and duration depend on loading conditions and do not replace echocardiographic assessment of severity.

An embolic event may precede recognizable heart failure. Stroke, limb ischemia, and visceral infarctions suggest a left-sided source, whereas thrombi in right-sided chambers may contribute to pulmonary thromboembolism. Palpitations, presyncope, and syncope require distinction among supraventricular arrhythmias, ventricular arrhythmias, and conduction disturbances. Loss of atrial contraction or marked heart-rate acceleration may be poorly tolerated by a stiff ventricle, in which filling time and atrial contribution have particular hemodynamic importance.

The history should connect the cardiac phenotype with the clinical context. Recently introduced drugs, skin eruptions, asthma, neuropathy, gastrointestinal symptoms, travel, and previous parasitic exposures guide the study of eosinophilia; splenomegaly, hematologic abnormalities, and constitutional symptoms may suggest clonal disease. In infants, feeding difficulty, sweating, tachypnea, and poor growth may be the first signs of heart disease with fibroelastosis. Reconstruction of pregnancy, fetal ultrasound findings, and family history then has a different value from the tropical or hematologic history of an adult.

Investigations and diagnosis

Assessment proceeds on three connected planes: anatomic distribution, functional consequences, and cause. ECG, troponin, natriuretic peptides, complete blood count with differential, and renal and hepatic function provide an initial assessment, but none alone identifies an endomyocardial disease. Troponin supports the presence of myocardial injury, natriuretic peptides reflect hemodynamic stress, and eosinophilia directs an etiologic pathway; normal values do not exclude a scarred lesion. Priorities change in the presence of shock, life-threatening arrhythmias, or embolization: stabilization and urgent investigations must proceed together.

Transthoracic echocardiography is the initial examination for defining the apices, cavity volumes, endocardial thickening, adherent masses, atria, and atrioventricular apparatus. Views should avoid apical foreshortening, which can simulate a small cavity or mask obliteration; echocardiographic contrast can clarify a poorly visible endocardial border or suspected thrombus. Quantification of regurgitation requires multiple parameters and should be interpreted together with forward stroke volume. The two ventricles should also be described separately, because a predominantly right-sided picture may be underestimated by an assessment focused on left ventricular ejection fraction.

Doppler assessment integrates atrioventricular flows, tissue velocities, atrial dimensions, estimated pulmonary pressures, and signs of congestion. Rapid early filling followed by abrupt deceleration is compatible with restriction, but varies with heart rate, rhythm, and loading; a single measurement neither identifies the cause nor proves irreversible impairment. In comparison with constrictive pericarditis, respiratory dependence of flows, ventricular interaction, and annular velocity behavior are important. Mixed conditions and significant valvular disease may make these signs less interpretable and require multimodality integration.

Cardiac magnetic resonance imaging completes the description of geometry and characterizes tissue. Cine sequences show obliteration and function; edema-sensitive sequences and mapping contribute to the search for inflammatory activity; late enhancement documents extracellular-space expansion and the distribution of injury. Subendocardial involvement not confined to a coronary territory may suggest endomyocardial disease. Thrombus generally lacks perfusion and behaves differently from fibrous tissue, although organization and age alter its signal. Persistent enhancement alone is not equivalent to inflammation that remains treatable.

When the picture suggests myocarditis, updated CMR criteria integrate a T2-based marker and a T1-based marker to support the presence of myocardial inflammation. Positivity does not establish eosinophilic etiology, and sensitivity depends on timing and phenotype. Likewise, MRI showing endocardial fibrosis does not automatically reconstruct its remote cause. In young children, the need for sedation and clinical stability affect feasibility: added value should be proportionate to the diagnostic question, without delaying management of critical heart disease already defined by echocardiography.

The etiologic work-up is guided by the phenotype. In hypereosinophilia, reactive causes, clonal proliferations, and still-unexplained forms are distinguished with selected hematologic and molecular investigations; finding a fusion responsive to a tyrosine kinase inhibitor directly changes treatment. In fibroelastosis, obstruction, coronary abnormalities, maternal immune context, and clues to genetic or metabolic cardiomyopathy should be sought. In endomyocardial fibrosis, geographic origin increases plausibility but does not replace morphologic demonstration. Investigations should resolve a concrete uncertainty, avoiding unselected panels that produce incidental results that are difficult to interpret.

Endomyocardial biopsy is particularly relevant when recognition of a specific myocarditis changes urgent therapy, especially in fulminant presentations or with major arrhythmias and conduction disturbances. Sampling may miss a focal lesion and previous treatment may attenuate the infiltrate; a negative result should therefore be interpreted in relation to sample quality and location. The presence of thrombi alters procedural risk and choice of access. In typical and stable fibrotic forms, biopsy requires a real diagnostic benefit, whereas surgical tissue, when available, can provide broader characterization.

The differential diagnosis includes infiltrative cardiomyopathies, apical hypertrophy, ischemic sequelae, thrombi due to ventricular dysfunction, constrictive pericarditis, and intracavitary masses. A territorial scar distribution favors ischemia; true hypertrophy preserves recognizable myocardial architecture; constriction primarily involves the pericardial restraint. In unresolved cases, catheterization and pressure assessment can clarify hemodynamics and operability. Rapid early filling with a diastolic plateau is not exclusive to a single disease: it should be interpreted together with respiratory variation, pressures in different chambers, and anatomy.

Treatment and prognosis

Etiologic treatment is integrated with management of thrombosis and residual mechanical damage. In eosinophilic forms, rapidly suppressing the responsible process may limit necrosis and subsequent fibrosis, but the appropriate drug depends on the cause: a proliferation with a molecular target, a vasculitis, and a drug reaction require different strategies. In established endomyocardial fibrosis, no pharmacologic therapy has been shown to remove the scar; in fibroelastosis, control of the underlying heart disease and assessment of ventricular function are central. An image of endocardial thickening alone is not an indication for immunosuppression.

Treatment of congestion uses diuretics with clinical titration and monitoring of renal function and electrolytes. The restrictive ventricle poorly tolerates both overload and excessive reduction in preload: achieving a rapid decrease in edema at the cost of hypotension and hypoperfusion is not a good result. Drugs used in heart failure with reduced ejection fraction are considered when that phenotype is actually present, with attention to cause and tolerance. It is inappropriate to transfer the entire adult regimen automatically to a child or to restriction with a small cavity and preserved systolic function.

Anticoagulation has a specific rationale in intracardiac thrombus, embolism attributable to a cardiac source, and other established indications such as certain conditions associated with atrial fibrillation or prostheses. In eosinophilic disease, control of the cause complements antithrombotic protection because persistent activation and endocardial injury may maintain risk. Choice, duration, and monitoring take into account thrombus location, evolution on imaging, renal function, bleeding, and planned procedures. The mere presence of a scar or fibroelastosis does not justify universal anticoagulant treatment.

Rhythm control should be adapted to the physiology. Sustained tachycardia can impair filling, whereas marked heart-rate reduction may reduce output in a patient whose stroke volume cannot increase substantially. Atrial fibrillation therefore requires hemodynamic as well as electrocardiographic assessment. In severe inflammatory conditions, arrhythmia treatment and circulatory support proceed together with etiologic therapy; in scarred forms, risk stratification considers arrhythmic history, function, and underlying disease, without inferring an indication for a defibrillator from the label of endomyocardial disease alone.

Surgery may include endocardiectomy and valve treatment in advanced endomyocardial fibrosis. Benefit depends on the ability to recover a useful cavity and functioning valve apparatus, not merely on removal of visible tissue. In fibroelastosis associated with a borderline left ventricle, resection may form part of specialized ventricular recruitment programs that also address inflow, outflow, and flow distribution. These strategies are not interchangeable. In patients with refractory heart failure, assessment for advanced support or transplantation also considers extracardiac disease, cavity dimensions, and reversibility of the causative process.

Prognosis results from the interaction among cause, timeliness of treatment, and the proportion of irreversible damage. Normalization of eosinophilia does not demonstrate disappearance of a scar; reduction of a thrombus does not guarantee normalization of filling; correction of a congenital stenosis does not ensure adequate ventricular function. Follow-up should therefore measure disease activity, congestion, output, rhythm, valvular function, and anatomy separately. Frequency of testing and goals are adapted to the clinical phase, with earlier reassessment in the event of functional deterioration, new embolic symptoms, or rhythm abnormalities.

Complications

Refractory heart failure can lead to persistent congestion, renal and hepatic dysfunction, and progressive nutritional deterioration. Elevated venous pressure impairs organ function even when arterial pressure appears acceptable; low output further reduces perfusion and limits treatment tolerance. This combination may narrow the opportunity for a useful intervention. In children, harm is also expressed as growth failure and developmental difficulties, making it necessary to integrate cardiologic goals with nutrition and neurodevelopmental assessment.

Thromboembolic complications may leave permanent neurologic sequelae or cause visceral and peripheral ischemia; the source location and any shunt determine the territory involved. After an event, the risk of hemorrhagic transformation and organ injury interferes with antithrombotic therapy and the timing of procedures. Identification of an endocardial mass should not, however, lead to neglect of other embolic sources or local thrombosis, particularly in systemic diseases that diffusely alter coagulation.

Ventricular arrhythmias, conduction blocks, and loss of sinus rhythm may precipitate an already fragile hemodynamic balance. After surgery, residual regurgitation, diastolic dysfunction, thrombosis, and recurrence of the endocardial process remain possible, with mechanisms differing according to the disease. Added to these risks are bleeding from antithrombotic therapy and toxicity of causal treatments. Control of a single component therefore does not exhaust surveillance: a patient in hematologic remission or with corrected anatomy may retain a cardiac risk requiring a specific care pathway.