Spongy cardiomyopathy, more correctly defined as left ventricular non-compaction (LVNC) or, according to the more recent approach of the European Society of Cardiology (ESC) guidelines, left ventricular hypertrabeculation when the finding is isolated, transient or acquired in adulthood, is a condition characterized by prominent endocardial trabeculae, deep intertrabecular recesses communicating with the ventricular cavity and variable thinning of the compact myocardial layer. The traditional definition evokes the “spongy” appearance of the myocardium, but this morphological image does not automatically coincide with a clinically significant cardiomyopathy. The central difficulty of the disease is precisely this: distinguishing a simple accentuation of trabeculae, which is also frequent in healthy individuals, athletes, pregnant women and patients with haemodynamic overload, from a true pathological myocardial condition associated with ventricular dysfunction, arrhythmias, thromboembolism, familial aggregation or genetic disease.
The true prevalence is uncertain because it depends on the imaging method, the criteria applied and the population studied. The increasing use of high-resolution echocardiography, cardiac magnetic resonance (CMR) and family screening has led to an increase in diagnoses, but also to a concrete risk of overdiagnosis. In children, non-compaction is described among the main forms of paediatric cardiomyopathy, often associated with genetic diseases, congenital defects, metabolic syndromes or neuromuscular disorders. In adults, it may present as an isolated finding, as a phenotype associated with dilated, hypertrophic, arrhythmogenic or restrictive cardiomyopathy, or as a secondary adaptation to conditions of increased volume load. Prognosis is therefore extremely variable: an individual with isolated hypertrabeculation, normal ejection fraction, no fibrosis and no arrhythmias does not have the same risk as a patient with a dilated ventricle, systolic dysfunction, late gadolinium enhancement (LGE), ventricular tachycardia, atrial fibrillation, intracavitary thrombus or a high-risk genetic variant.
Spongy cardiomyopathy should not be interpreted as a single disease with a single cause, but as a morphological phenotype that may result from congenital, genetic, syndromic, neuromuscular, metabolic or acquired mechanisms. The older embryological explanation attributed the condition to an arrest of myocardial compaction during fetal development. In the early stages of cardiogenesis, the ventricular myocardium has a broad trabecular network, useful for increasing the exchange surface before full coronary maturation; subsequently, the myocardium progressively compacts, especially from the epicardium towards the endocardium, from the base towards the apex and from the septum towards the free wall. If this process remains incomplete, prominent trabeculae and deep recesses may persist. This theory remains important, but today it is considered insufficient to explain all cases, because hypertrabeculation may appear or increase even after birth, in adulthood and in reversible conditions.
Genetic causes include variants in sarcomeric, cytoskeletal, nuclear, mitochondrial and ion-channel genes, as well as genes involved in cardiac development. Among the most frequently reported genes are MYH7, MYBPC3, TTN, ACTC1, TNNT2, TNNI3, TPM1, LMNA, DES, LDB3, MIB1, NKX2-5, TBX20, PRDM16, RBM20 and TAZ. Some variants produce a predominantly non-compaction phenotype, whereas others determine overlap with dilated cardiomyopathy, hypertrophic cardiomyopathy, septal defects, arrhythmias, conduction disorders or neuromuscular disease. This heterogeneity explains why two patients with the same ratio between non-compact and compact layers may have completely different prognoses. The anatomical ratio measures shape, but clinical risk depends on function, fibrosis, genotype, arrhythmias, family history and comorbidities.
In neonates and children, non-compaction may be isolated or associated with congenital heart disease, genetic syndromes, neuromuscular disorders and metabolic diseases. Barth syndrome, linked to variants in the TAZ gene and to defective mitochondrial cardiolipin metabolism, is a classic example because it may associate non-compaction, dilated or hypertrophic cardiomyopathy, neutropenia, skeletal myopathy and growth delay. Mitochondrial diseases, dystrophinopathies, muscular dystrophies, congenital myopathies and oxidative phosphorylation defects may also present with marked ventricular trabeculation. In these cases, spongy myocardium is a manifestation of a systemic disease, not a purely anatomical abnormality of the ventricle.
In adults, persistent congenital forms must be distinguished from acquired hypertrabeculation. Increased trabeculation has been described in pregnancy, in athletes, in chronic anaemias, in haemoglobinopathies, in conditions of high preload and in some cardiomyopathies with ventricular dilatation. During pregnancy, the increase in plasma volume, cardiac output and volume load may make trabeculation more evident, sometimes with regression after delivery. In athletes, exercise-induced physiological remodelling may be associated with more prominent trabeculae, especially when large ventricular cavities and increased diastolic filling coexist. These conditions should not be automatically labelled as disease if there are no symptoms, family history, significant electrocardiographic abnormalities, ventricular dysfunction, fibrosis, arrhythmias or embolic events.
The pathogenesis of genetically determined forms involves several levels of cardiomyocyte biology. Sarcomeric variants alter force generation, calcium sensitivity and contractile efficiency. TTN variants may impair passive elasticity, sarcomere structure and the response to mechanical stress, generating a continuum with dilated cardiomyopathy. LMNA variants alter the nuclear lamina, mechanotransduction, nuclear stability and transcriptional regulation, with a higher risk of conduction disorders and malignant arrhythmias. RBM20 variants modify the splicing of titin and other cardiac transcripts, favouring ventricular dysfunction and arrhythmic phenotypes. Mitochondrial abnormalities reduce adenosine triphosphate (ATP) production, increase oxidative stress and make the myocardium more vulnerable to chronic load.
The structural damage does not consist only in the presence of trabeculae. The clinical problem arises when the compact layer is thin or functionally insufficient, when the ventricular wall does not develop adequate systolic force, when the endocardial architecture favours blood stasis or when the tissue shows fibrosis and electrical instability. Deep recesses communicate with the ventricular cavity and may slow local flow. If contractility is reduced, blood stagnates between the trabeculae, especially at the apex and along the lateral walls, increasing the risk of thrombus. If atrial fibrillation, ventricular dilatation or reduced ejection fraction coexist, embolic risk increases further.
Systolic dysfunction may derive from three integrated mechanisms. The first is reduced effective compact mass, which limits the ability of the ventricle to generate pressure and output. The second is the underlying myocyte disease, especially when the spongy phenotype is part of a genetic, metabolic or neuromuscular cardiomyopathy. The third is secondary remodelling, in which dilatation, wall stress, fibrosis and neurohormonal activation progressively worsen function. From this perspective, non-compaction is not only a morphological abnormality, but a possible amplifier of heart failure when it combines with contractile weakness, increased volume and maladaptive remodelling.
Diastolic dysfunction may appear even when left ventricular ejection fraction (LVEF) is preserved. Prominent trabeculae, altered endocardial architecture, stiffness of the compact myocardium, associated hypertrophy or interstitial fibrosis may impair ventricular filling and increase diastolic pressures. The patient may therefore present with exertional dyspnoea, exercise intolerance or congestion even without marked reduction in LVEF. This aspect is particularly important in phenotypes overlapping with hypertrophic or restrictive cardiomyopathy, in which trabeculation is only one part of the haemodynamic problem.
The arrhythmic substrate arises from the combination of structural disorganization, fibrosis, dilatation, myocyte dysfunction, ion-channel abnormalities and conduction instability. The trabeculae themselves are not necessarily arrhythmogenic, but a ventricle with scar tissue, LGE, high-risk mutations, systolic dysfunction or conduction disorders may generate re-entry circuits and ventricular tachycardia. Atrial fibrillation may be secondary to atrial dilatation, increased filling pressures, heart failure or genetic predisposition. Atrioventricular blocks and conduction abnormalities require particular attention to genes such as LMNA, DES and SCN5A, or to neuromuscular or infiltrative diseases to be considered in the differential diagnosis.
Thromboembolic pathophysiology is traditionally considered one of the pillars of the disease. The triad that favours thrombosis includes stasis within the intertrabecular recesses, ventricular dysfunction with reduced flow velocity and atrial arrhythmias. However, risk is not uniform: a patient with isolated hypertrabeculation and normal LVEF does not have the same profile as a patient with advanced heart failure, atrial fibrillation, apical thrombus or previous embolic stroke. For this reason, the decision to use anticoagulation should not be based on the “spongy” image alone, but on the entire clinical context.
The pathophysiological sequence can be described progressively: a genetic, syndromic or acquired predisposition generates excessive trabeculation or persistence of a non-compact layer; if the compact myocardium is adequate and there is no fibrosis, arrhythmia or dysfunction, the finding may remain clinically silent; if, however, the same architecture is associated with a sarcomeric, energetic, cytoskeletal or nuclear defect, the ventricle loses contractile efficiency, wall stress increases, neurohormonal systems are activated, dilatation and fibrosis develop, rhythm becomes unstable and the recesses may favour thrombosis. Clinically relevant disease therefore does not arise from the isolated trabecula, but from the interaction between morphology, myocardial biology and haemodynamic consequences.
Clinical presentation is highly variable and must be reconstructed starting from the patient’s history. Some patients reach diagnosis after an echocardiogram performed for a murmur, palpitations, family history, sports eligibility, pregnancy, oncological monitoring, electrocardiographic abnormalities or assessment of congenital heart disease. Others present with heart failure, syncope, arrhythmias, stroke, systemic embolism or cardiac arrest. The same ventricular image may therefore have different meanings depending on the context: an incidental finding in an asymptomatic individual, a sign of inherited cardiomyopathy, a manifestation of neuromuscular disease, physiological adaptation or an advanced phenotype with high risk.
During history-taking, the clinician should ask about exertional dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, dependent oedema, reduced exercise tolerance, fatigue, chest pain, palpitations, syncope, presyncope, focal neurological episodes, previous stroke, peripheral embolism, history of intracardiac thrombosis, seizures, muscle weakness, exercise intolerance, deafness, visual disturbances, developmental delay, short stature, recurrent infections, myoglobinuria, family history of cardiomyopathy, sudden death, heart transplantation, pacemaker or defibrillator implantation at a young age. The search for extracardiac symptoms is essential because non-compaction may be the cardiac tip of a systemic genetic or metabolic disease.
In paediatric patients, the picture may include feeding difficulty, poor growth, sweating during feeding, tachypnoea, irritability, hepatomegaly, recurrent infections, motor delay or prenatal diagnosis of heart disease. In older children, reduced physical performance, syncope, palpitations, chest pain or incidental detection of a murmur and electrocardiographic abnormalities may occur. Paediatric age requires specific attention to genetic syndromes, congenital defects, mitochondrial diseases, dystrophinopathies and Barth syndrome, because the cardiac diagnosis may precede recognition of the systemic disease.
In adults, the most common symptom, when the disease is clinically expressed, is exertional dyspnoea. It may be due to reduced contractility, diastolic dysfunction, functional mitral regurgitation, increased filling pressures or arrhythmias. Fatigue and reduced functional capacity may precede overt heart failure. In patients with reduced LVEF, the clinical picture tends to overlap with that of dilated cardiomyopathy: progressive dyspnoea, orthopnoea, oedema, weight gain from salt and water retention, asthenia, reduced peripheral perfusion and, in advanced cases, hypotension, oliguria and cardiac cachexia.
Palpitations are frequent but non-specific. They may reflect ventricular ectopy, supraventricular tachycardia, atrial fibrillation, atrial flutter, non-sustained ventricular tachycardia or sustained ventricular tachycardia. Syncope is a symptom of greater severity, because it may depend on ventricular arrhythmias, conduction blocks, vasovagal response, hypotension due to heart failure or, more rarely, pulmonary embolism. Unexplained syncope in a patient with a spongy phenotype, LGE, reduced LVEF, family history of sudden death or a high-risk genetic variant requires rapid specialist assessment.
Embolic events may be the first manifestation. A cryptogenic ischaemic stroke, transient ischaemic attack, peripheral embolism or splenic or renal infarction may lead to the discovery of a hypertrabeculated ventricle with apical thrombus or systolic dysfunction. The likelihood that hypertrabeculation is causally relevant increases if there is reduced LVEF, atrial fibrillation, documented thrombus, very deep recesses, previous embolism or absence of other embolic sources. Here too, morphology alone is not enough: a plausible thromboembolic context must be demonstrated.
Chest pain may occur, but it is not the most characteristic symptom. It may depend on microvascular ischaemia, increased wall stress, concomitant coronary artery disease, tachyarrhythmias, hypertension, myocarditis or extracardiac causes. In patients with acute pain, elevated troponin or ischaemic changes on the electrocardiogram (ECG), the presence of trabeculation must not distract from excluding acute coronary syndrome or myocarditis. The diagnosis of spongy cardiomyopathy must not become an automatic explanation for every cardiac symptom.
Physical examination may be normal in asymptomatic individuals with preserved LVEF. In patients with heart failure, tachycardia, hypotension, jugular venous distension, basal crackles, third heart sound, murmur due to mitral or tricuspid regurgitation, hepatomegaly, dependent oedema and signs of hypoperfusion may be detected. In children, tachypnoea, retractions, hepatomegaly, poor growth and sweating may appear. In syndromic or neuromuscular patients, the clinician should look for proximal weakness, hypotonia, winged scapulae, calf pseudohypertrophy, contractures, ptosis, ophthalmoplegia, deafness, short stature, skin abnormalities, dysmorphic features, cognitive impairment or signs of metabolic disease.
The real clinical sequence should therefore proceed from the symptom to the phenotype and from the phenotype to the cause. A patient with dyspnoea and a dilated ventricle requires assessment of heart failure, systolic function, ischaemia, arrhythmias and genetics. An asymptomatic athlete with prominent trabeculae requires analysis of ECG, family history, ventricular function, CMR and arrhythmias before defining disease. A pregnant woman with new hypertrabeculation requires postpartum follow-up before a permanent diagnosis is established, unless dysfunction, fibrosis or family history are present. A child with non-compaction and extracardiac signs requires a genetic-metabolic pathway. The clinical manifestation is therefore not a list of symptoms, but the expression of a diagnostic probability that changes with age, context and risk.
Diagnosis must begin with a methodological premise: there are no universally shared official diagnostic criteria capable of perfectly distinguishing physiological hypertrabeculation, pathological non-compaction and trabeculation secondary to another cardiomyopathy. According to the approach of the 2023 ESC guidelines on cardiomyopathies, left ventricular non-compaction should not automatically be treated as an autonomous cardiomyopathy in the general sense, but as a phenotypic trait that may be isolated or associated with hypertrophy, dilatation, systolic dysfunction, congenital heart disease, genetic syndromes or acquired conditions. To establish a clinically significant diagnosis, morphology, function, family history, ECG, arrhythmias, CMR, genetics, any extracardiac signs and follow-up must therefore be integrated.
The first level includes personal and family history, cardiological examination, 12-lead ECG, transthoracic echocardiography, Holter ECG, basic blood tests and assessment of natriuretic peptides if symptoms or dysfunction are present. Family history should reconstruct at least three generations, looking for cardiomyopathies, heart failure at a young age, sudden death, arrhythmias, pacemakers, implantable defibrillators, transplantation, congenital defects and neuromuscular diseases. The ECG may be normal, but it often shows non-specific repolarization abnormalities, ventricular hypertrophy, bundle branch blocks, pre-excitation, conduction disorders, ectopy or indirect signs of cardiomyopathy. A pathological ECG in an individual with marked trabeculation increases the probability that the finding is not a simple anatomical variant.
Echocardiography is the most accessible initial examination. It should describe the distribution of trabeculae, thickness of the compact layer, ratio between non-compact and compact layers, presence of recesses communicating with the ventricular cavity by colour Doppler, LVEF, ventricular dimensions, diastolic function, right ventricular function, valvular regurgitation, pulmonary pressures, intracavitary thrombi and global longitudinal strain (GLS) when available. The most frequently involved segments are often apical, lateral and mid-apical inferior segments; the basal septum is less typical. Isolated basal trabeculation or an inconsistent pattern should prompt consideration of alternative diagnoses or artefacts.
The historical echocardiographic criteria are useful as descriptive language, but they should not be used automatically. Chin criteria consider the ratio between the epicardium-to-recess distance and the epicardium-to-trabecular apex distance in end-diastole. Jenni criteria require a two-layer myocardium, a non-compact/compact ratio greater than 2 in end-systole, deep recesses perfused from the ventricular cavity and absence of other cardiac abnormalities that explain the picture. Stöllberger criteria consider numerous prominent trabeculae distal to the papillary muscles, moving synchronously with the myocardium and with perfused recesses. The problem is that these criteria have different sensitivity, different specificity and are not equivalent to one another; applied without context, they may diagnose LVNC in an excessive proportion of patients with heart failure and even in healthy controls.
CMR is the most important second-level examination because it offers better definition of the apex, quantification of volumes, assessment of trabeculated mass, measurement of the compact layer, tissue characterization and search for fibrosis. Petersen criteria define a ratio between non-compact and compact myocardium greater than 2.3 in end-diastole as suggestive of non-compaction. Jacquier criteria consider trabeculated mass greater than 20% of the global left ventricular mass. Other criteria, such as those of Grothoff and Captur, attempt to improve specificity by including non-compact mass, segmental distribution, compact layer thickness and trabecular fractal complexity. None of these criteria, in isolation, replaces clinical judgement.
The role of CMR is not only to measure trabeculae, but to establish whether cardiomyopathy exists. The presence of LGE indicates fibrosis or myocardial damage and modifies prognostic stratification. The LGE pattern may point towards dilated cardiomyopathy, previous myocarditis, arrhythmogenic cardiomyopathy, infiltrative disease or another overlapping phenotype. CMR also allows identification of apical thrombi, right ventricular involvement, hypertrophy, dilatation, regional abnormalities and reduced strain. A patient with marked trabeculation but CMR without fibrosis, with normal LVEF, normal volumes, normal Holter monitoring and negative family history has a very different clinical meaning from a patient with LGE, dilatation and non-sustained ventricular tachycardia.
Cardiac computed tomography may be useful when echocardiography and CMR cannot be performed or are non-diagnostic, but it is not the reference examination in most cases. It can define ventricular morphology and, if necessary, assess the coronary arteries, but it exposes the patient to radiation and does not offer the same tissue characterization as CMR. Contrast echocardiography may improve visualization of the apex and recesses when the acoustic window is poor, reducing the risk of confusing trabeculae, false tendons, thrombi or artefacts.
In the absence of universally shared official diagnostic criteria, according to the 2023 ESC guidelines, to establish a clinically relevant diagnosis of spongy phenotype or pathological hypertrabeculation it is necessary to:
elements required for a clinically significant diagnosis
The differential diagnosis is broad. Physiological hypertrabeculation in athletes is distinguished by absence of symptoms, negative family history, ECG compatible with athletic adaptation, normal or supranormal LVEF, absence of fibrosis, absence of significant arrhythmias and stability over time. Pregnancy may produce transient trabeculation; follow-up after delivery is essential. Dilated cardiomyopathy may show evident trabeculae due to remodelling and dilatation: in this case it is necessary to establish whether trabeculation is the primary cause, an epiphenomenon or part of the same genetic process. Apical hypertrophic cardiomyopathy may simulate apical trabeculation, but it shows true hypertrophy, reduced cavity size and a different pattern of myocardial mass. Myocarditis may cause dysfunction, pain, elevated troponin and LGE, but the inflammatory pattern and clinical history guide the diagnosis. Apical thrombi, false tendons and muscular bands may mimic trabeculae if imaging is incomplete.
Genetic assessment must be preceded by genetic counselling, because the result may have familial, insurance-related, reproductive and psychological implications. Testing is most useful when pre-test probability is high: paediatric age, family history, sudden death, non-ischaemic heart failure, reduced LVEF, ventricular arrhythmias, conduction disorders, extracardiac phenotype, suspected syndrome or overlap with dilated or hypertrophic cardiomyopathy. Interpretation must distinguish pathogenic variants, likely pathogenic variants, variants of uncertain significance and inconsistent findings. A variant of uncertain significance must not be used to diagnose disease or to decide invasive interventions in family members.
Family screening is indicated when the picture is compatible with inherited cardiomyopathy or when a pathogenic variant is identified. In first-degree relatives, history, ECG, echocardiography and, if necessary, CMR and Holter monitoring are used. If the familial variant is known, cascade genetic testing makes it possible to separate carrier relatives, who should be followed over time, from non-carriers, who can be reassured more robustly. If genetic testing is negative but family history is strong, clinical screening remains necessary because not all causal genes are known and not all variants are detectable or interpretable.
The final diagnosis must be formulated precisely. “Low-risk isolated hypertrabeculation” is not equivalent to “spongy cardiomyopathy with systolic dysfunction”. “Spongy phenotype associated with dilated cardiomyopathy” is not equivalent to “isolated non-compaction”. “Increased trabeculation in pregnancy” is not equivalent to “genetic cardiomyopathy”. Terminology must avoid both underestimation and excessive medicalization. The ideal report describes morphology, function, fibrosis, arrhythmias, thromboembolic risk, family history, suspected aetiology and follow-up plan.
There is no specific therapy capable of “compacting” the myocardium or directly reducing trabeculae. Treatment depends on the clinical phenotype: observation in low-risk individuals, heart failure therapy if ventricular dysfunction is present, arrhythmic prevention if electrical risk is increased, anticoagulation if thromboembolic risk is documented, treatment of the genetic or systemic cause when identifiable and family follow-up when the disease is hereditary. Correct management does not start from the image, but from the clinical question: does the patient have a cardiomyopathy, an anatomical variant or a secondary phenotype?
In asymptomatic individuals with normal LVEF, normal volumes, absence of LGE, absence of significant arrhythmias, non-suspicious ECG and negative family history, the strategy is conservative. Periodic follow-up with clinical assessment, ECG, echocardiography, risk-modulated Holter monitoring and CMR is appropriate if the initial picture is uncertain or if symptoms appear. There is no indication for chronic pharmacological therapy, anticoagulation or defibrillator implantation on the sole basis of trabeculation. The patient must be informed about the meaning of the finding and the symptoms to report, while avoiding turning a low-risk finding into a disabling diagnosis.
When left ventricular systolic dysfunction or heart failure is present, treatment follows the guidelines for heart failure with reduced ejection fraction. Therapy includes inhibition of the renin-angiotensin-aldosterone system with an angiotensin receptor neprilysin inhibitor (ARNI), angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) according to tolerance, beta-blocker, mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter 2 inhibitor (SGLT2 inhibitor). Loop diuretics, intravenous iron in the case of iron deficiency, rate control, management of hypertension, treatment of comorbidities and cardiac rehabilitation complete therapy according to the clinical profile.
Cardiac resynchronization therapy (CRT) follows the general indications for heart failure: reduced LVEF, QRS complex duration and morphology, left bundle branch block, persistent symptoms despite optimized therapy and expected benefit. In patients with a spongy phenotype and left bundle branch block, CRT may improve synchronization, ventricular function and symptoms, but response depends on the amount of viable myocardium, degree of fibrosis and underlying cause. The presence of trabeculae is not a contraindication, but it may make anatomical assessment and optimal lead positioning more complex in some situations.
The implantable defibrillator (implantable cardioverter-defibrillator, ICD) is not indicated for the morphological diagnosis alone. It is indicated for secondary prevention after cardiac arrest, ventricular fibrillation or haemodynamically significant sustained ventricular tachycardia not attributable to a reversible cause. For primary prevention, the criteria for non-ischaemic cardiomyopathies are followed, integrating LVEF, symptoms, optimized therapy, LGE, syncope, non-sustained ventricular tachycardia, family history of sudden death and genotype. Variants in LMNA, FLNC, RBM20, PLN and other high-risk genes may lower the decision threshold when clinical or instrumental risk markers coexist. The decision must be individualized, because implanting an ICD in a patient with isolated hypertrabeculation alone exposes the patient to complications without demonstrated benefit.
Anticoagulation must be guided by real risk. It is indicated in patients with atrial fibrillation according to thromboembolic assessment, in patients with documented ventricular thrombus, in the case of a previous plausibly cardioembolic event and in patients with severe ventricular dysfunction when the risk of intracavitary stasis is high. Routine anticoagulation in all patients with trabeculation is not supported. In the presence of ventricular thrombus, treatment requires imaging follow-up until resolution; in cases without thrombus but with intermediate risk, the decision must consider LVEF, extent of akinesia, atrial fibrillation, apical recesses, embolic history and bleeding risk.
Supraventricular and ventricular arrhythmias must be treated according to mechanism and risk. Atrial fibrillation requires rate or rhythm control, anticoagulation when indicated and treatment of heart failure. Frequent ventricular ectopic beats require quantification of burden, correlation with symptoms and ventricular function, exclusion of tachycardiomyopathy and assessment for ablation if they are very frequent, symptomatic or responsible for dysfunction. Sustained ventricular tachycardia requires electrophysiological assessment, antiarrhythmic therapy, ablation in expert centres and ICD according to indication. Trabeculated anatomy may complicate substrate mapping, so complex cases should be managed in centres with experience in cardiomyopathies and advanced arrhythmology.
Treatment of syndromic or metabolic forms must be directed at the cause. Neuromuscular diseases require coordination with neurology, respiratory assessment, physiotherapy, conduction monitoring and heart failure prevention. In mitochondrial diseases, management includes multisystem assessment, avoiding mitochondrial toxins when possible and treating organ complications. In Barth syndrome, infection control, management of neutropenia, nutrition, paediatric cardiology and genetics are relevant. In associated congenital defects, treatment depends on haemodynamic anatomy. The cardiology page must not isolate the ventricle from the rest of the organism, because many spongy forms have systemic significance.
For physical activity and sport, the decision must be risk-based. Moderate recreational physical activity is generally compatible with low-risk phenotypes, normal LVEF, absence of LGE and absence of significant arrhythmias. Competitive or high-intensity sport requires specialist assessment, exercise testing, Holter monitoring, CMR and family analysis. The presence of reduced LVEF, fibrosis, complex ventricular arrhythmias, unexplained syncope or a high-risk genotype imposes restrictions. In athletes with incidental hypertrabeculation, a diagnosis of cardiomyopathy should not be made without additional elements of disease, because the risk of inappropriate exclusion from sport is real.
Pregnancy requires preconception counselling in known cases. Women with normal LVEF, absence of fibrosis, absence of arrhythmias and a stable phenotype often tolerate pregnancy, but require cardiological surveillance. Women with reduced LVEF, heart failure, significant arrhythmias, previous embolic events or a high-risk genotype require multidisciplinary assessment. If hypertrabeculation appears during pregnancy, it is important to reassess after delivery before formulating a definitive diagnosis, unless clear markers of cardiomyopathy are present. Pregnancy is also a situation in which volume load may reveal a previously silent predisposition.
Prognosis depends more on ventricular function, fibrosis, arrhythmias and genotype than on the amount of trabeculae measured in isolation. Patients with preserved LVEF, absence of LGE, normal Holter monitoring and negative family history generally have a favourable prognosis, although they require monitoring. Patients with reduced LVEF, ventricular dilatation, extensive LGE, ventricular tachycardia, atrial fibrillation, thrombus, embolic events, conduction disorders or high-risk genetic variants have a greater probability of progressive heart failure, hospitalizations, sudden death, transplantation or need for devices. Prognostic stratification must be repeated over time, because the phenotype may evolve.
In advanced cases with refractory heart failure, the options are those of end-stage heart failure: pharmacological optimization, devices, left ventricular assist device (LVAD) and heart transplantation. Outcome after transplantation is generally linked to the severity of heart failure and comorbidities, rather than to trabecular morphology itself. In paediatric or syndromic patients, prognosis also depends on extracardiac disease, respiratory function, nutritional status, infections and neuromuscular or metabolic evolution.
The complications of spongy cardiomyopathy are distributed across three major areas: heart failure, arrhythmias and thromboembolism. This triad is historically associated with non-compaction, but it should not be applied indiscriminately to all individuals with prominent trabeculae. Risk emerges when the spongy morphology is associated with ventricular dysfunction, fibrosis, dilatation, arrhythmias, thrombi, family history or genetic disease. The complication does not arise from the single visible trabecula, but from the loss of mechanical efficiency, electrical instability and intracavitary stasis.
Heart failure is the most frequent complication in clinically expressed phenotypes. It may be systolic, diastolic or mixed. In systolic heart failure, the ventricle cannot generate adequate output because the compact myocardium is functionally insufficient or because the underlying cardiomyopathy causes contractile weakness. In diastolic heart failure, increased stiffness, fibrosis, associated hypertrophy or altered endocardial architecture impair filling. Clinically, dyspnoea, reduced functional capacity, pulmonary congestion, oedema, hospitalizations and, in the most severe cases, systemic hypoperfusion appear.
Progression towards dilated cardiomyopathy represents one of the most relevant evolutions. The ventricle dilates, LVEF decreases, wall stress increases and neurohormonal remodelling similar to that of other non-ischaemic cardiomyopathies is activated. Trabeculation may be present from the beginning or become more evident with dilatation. At this stage, distinguishing cause and effect may be difficult, but it has genetic and familial importance. The patient should not be followed simply as “LVNC”, but as non-ischaemic cardiomyopathy with a spongy phenotype, because therapeutic decisions depend on the severity of heart failure.
Ventricular arrhythmias are a potentially lethal complication. Frequent ectopy, non-sustained ventricular tachycardia, sustained ventricular tachycardia and ventricular fibrillation may derive from fibrosis, myocardial disorganization, dilatation, arrhythmogenic mutations and conduction abnormalities. Risk increases with reduced LVEF, LGE, syncope, family history of sudden death and genetic variants such as LMNA or RBM20. Sudden death may be the first manifestation in rare cases, especially when the disease has not been recognized or when the arrhythmic phenotype is dominant.
Supraventricular arrhythmias, particularly atrial fibrillation and atrial flutter, may occur due to increased filling pressures, atrial dilatation, heart failure or genetic predisposition. Atrial fibrillation worsens haemodynamic tolerance, reduces coordinated diastolic filling, increases embolic risk and may accelerate ventricular deterioration if the rate remains elevated. In patients with a spongy phenotype and heart failure, even apparently “common” arrhythmias may have a greater clinical impact because they occur in an already vulnerable ventricle.
Conduction disorders include atrioventricular blocks, bundle branch blocks, intraventricular conduction slowing and, in some genetic contexts, progression towards the need for a pacemaker. Their presence should suggest a search for specific causes, especially LMNA, DES and SCN5A variants, neuromuscular diseases or overlapping phenotypes. Left bundle branch block may worsen ventricular synchronization and contribute to heart failure, making CRT assessment useful when clinical and instrumental criteria are met.
Ventricular thrombosis occurs when blood stagnates in the intertrabecular recesses or in akinetic regions, especially at the apex. Risk is higher with reduced LVEF, ventricular dilatation, atrial fibrillation, already documented thrombus or previous embolic event. A ventricular thrombus may embolize into the systemic circulation, causing ischaemic stroke, transient ischaemic attack, acute limb ischaemia, renal infarction, splenic infarction or mesenteric embolism. The search for thrombus must be accurate because apical trabeculae may conceal it; in case of doubt, contrast echocardiography or CMR is useful.
Cardioembolic stroke is a feared complication because it may be the first clinical sign of the disease. The causal relationship must be assessed rigorously, excluding occult atrial fibrillation, carotid atherosclerosis, patent foramen ovale, haematological disorders and other embolic sources. When a hypertrabeculated ventricle, reduced LVEF, thrombus or atrial fibrillation coexist, the probability of a cardioembolic origin increases. Prevention requires anticoagulation in indicated cases and control of the cardiac substrate.
Valvular complications are generally functional. Mitral regurgitation may derive from ventricular dilatation, remodelling of the subvalvular apparatus, dyssynchrony or papillary muscle dysfunction. Tricuspid regurgitation may occur in the presence of pulmonary hypertension, right ventricular dilatation or advanced heart failure. These regurgitations worsen volume overload, increase upstream pressures and accelerate symptoms. Their severity may decrease with heart failure therapy and reverse remodelling, but persistent cases require dedicated assessment.
Right ventricular involvement is less typical but clinically important. It may indicate more extensive disease, an overlapping phenotype or advanced remodelling. Right ventricular dysfunction worsens systemic congestion, exercise tolerance and prognosis, especially if pulmonary hypertension, tricuspid insufficiency or respiratory disease coexist. CMR is particularly useful for assessing the right ventricle, because echocardiography may underestimate volumes and function in complex anatomies.
Complications in pregnancy include worsening heart failure, arrhythmias, thromboembolism and difficulties in pharmacological management. Risk is low in stable phenotypes with normal function, but increases markedly with reduced LVEF, pre-existing symptoms, arrhythmias or embolic history. Pregnancy may also reveal transient trabeculation or unmask cardiomyopathy. For this reason, postpartum follow-up is essential to distinguish reversible adaptation, peripartum cardiomyopathy with secondary trabeculation and true pre-existing spongy cardiomyopathy.
Paediatric complications include early heart failure, arrhythmias, growth delay, need for intensive care, transplantation and sudden death in the most severe phenotypes. When non-compaction is syndromic, prognosis also depends on infections, neuromuscular disease, respiratory compromise, metabolic disorders and nutritional difficulties. Follow-up in children must therefore be multidisciplinary and must include planned transition to adult cardiology, because risk does not disappear with growth.
The most frequent conceptual complication is overdiagnosis. Labelling an individual with physiological hypertrabeculation alone as having cardiomyopathy may generate anxiety, inappropriate sports restrictions, insurance difficulties, unnecessary follow-up, unnecessary therapies and excessive family screening. Underdiagnosis, conversely, exposes patients to heart failure, arrhythmias, thromboembolism and failure to recognize at-risk relatives. The point of balance is a graded diagnosis: describe the phenotype, measure risk, search for the cause and update the assessment over time.