Non-dilated left ventricular cardiomyopathy

Article written and reviewed by Dr Luca Moretti

Non-dilated left ventricular cardiomyopathy is a phenotypic category introduced by the 2023 ESC guidelines to describe disease of the left ventricular myocardium that has not produced an increase in ventricular volumes. The criterion may be met by non-ischemic scar or fatty replacement, with or without global or regional wall-motion abnormalities, or by isolated global hypokinesia in the absence of scar. In both pathways, the ventricle must be non-dilated according to measurements adjusted for body size, sex and age. The definition does not automatically assign a cause or establish a uniform level of risk.

The acronym NDLVC stands for non-dilated left ventricular cardiomyopathy and does not designate a single molecular disease. It encompasses configurations produced by genetic variants, inflammatory injury, systemic diseases and interactions between inherited vulnerability and the environment. The same imaging appearance can therefore have very different familial and therapeutic implications. The observed phenotype is the starting point for building a stratified etiologic diagnosis.

The category fills two historical gaps. The first involved patients with hypokinesia and normal volumes, previously described as having hypokinetic non-dilated cardiomyopathy; the second included individuals with left ventricular scar, arrhythmias and relatively preserved function who did not meet criteria for DCM or ARVC. The new framework recognizes that fibrosis and arrhythmias may precede dilatation or remain the dominant feature throughout life.

The diagnosis must not be trivialized as a simple LGE finding. A small equivocal area, motion artifact, an ischemic scar or epicardial fat mistaken for fatty replacement does not establish NDLVC. Likewise, a borderline ejection fraction in an athlete does not necessarily identify cardiomyopathy. Multimodality coherence among measurements, tissue findings, ECG, arrhythmias and clinical context is essential to avoid overdiagnosis.

The clinical importance stems from the possible dissociation between pump function and electrical risk. A normally sized ventricle with preserved ejection fraction may contain an extensive scar capable of sustaining ventricular tachycardia; in another patient, hypokinesia may gradually progress to heart failure and dilatation. Separate stratification of arrhythmic and hemodynamic risks guides monitoring, treatment and device therapy more accurately than ejection fraction alone.

Definition, nosologic boundaries and epidemiology

The first branch of the definition requires non-ischemic scar or fatty replacement of the left ventricle and allows normal global function, global hypokinesia or regional abnormalities. LGE documents focal expansion of the extracellular space and is the main noninvasive marker of scar. By itself, it does not establish the exact histologic mechanism and does not directly measure inflammatory activity. The qualifying scar must have an extent and distribution compatible with myocardial disease.

The second branch concerns isolated global hypokinesia without scar and without dilatation. In this setting, it is essential to exclude loading conditions, coronary artery disease, persistent tachycardia, negative inotropic drugs and physiologic variants capable of explaining the dysfunction. The reduction in ejection fraction must not be merely apparent because of contouring error or a poor acoustic window. Reproducible dysfunction is confirmed with quantitative measurements and, when necessary, with a second modality.

The absence of dilatation is not a visual impression. End-diastolic volumes are indexed to body surface area and compared with technique-specific reference ranges, taking sex and age into account. Appropriate z scores are required in children. A small ventricle with reduced ejection fraction and low stroke volume differs from a ventricle at the upper limit of normal that is enlarging compared with previous examinations. The dimensional measurement should therefore be reported numerically.

A retrospective cohort published by Aimo and colleagues in 2025 sought to make this boundary more reproducible by studying 388 patients with non-ischemic cardiomyopathy who underwent cardiac magnetic resonance. In the relationship between indexed end-diastolic volume and the composite outcome of death or ventricular arrhythmias, inflection points were around 96 mL/m² in women and 105 mL/m² in men; among patients classified as non-dilated, ejection fractions below 45% or 40% identified groups with a less favorable prognosis. These proposed thresholds, however, derive from a single selected observational population and do not replace the ESC definition, validated normal ranges for technique, age and sex, or assessment of the individual trajectory. Their value is to generate hypotheses and promote uniform measurement, not to turn a decimal value of volume or function into a universal biologic boundary.

NDLVC is not synonymous with arrhythmogenic left ventricular cardiomyopathy. The latter reflects a biologic process that is often genetic, characterized by arrhythmic vulnerability and predominantly left-sided fibrous or fibrofatty replacement, whereas NDLVC includes any etiology that meets the phenotype. A patient with healed myocarditis may fall within the category without having desmosomal disease. The nosologic distinction prevents heredity from being assigned solely on the basis of LGE location.

The relationship with DCM is equally nuanced. Non-dilated hypokinesia may be an early phase of a dilating continuum, but arrhythmogenic scar may remain associated with normal volumes and follow a different natural history. The same family may include both phenotypes, especially in association with FLNC, DSP, LMNA or PLN. A partial continuum does not justify using the two terms as synonyms.

In the 2023 ESC classification, NDLVC is a general and etiologically neutral phenotype. The category is based on the two branches described above, both in the absence of dilatation, and does not require a genetic variant, ventricular arrhythmia or ring-like LGE to be assigned. Subsequent investigation of the cause may trace the phenotype to an inherited cardiomyopathy, an inflammatory process or a systemic disease, but does not change the originally descriptive nature of the category. This framework is not a diagnostic score for arrhythmogenic cardiomyopathy.

The 2020 Padua criteria instead pursued a specific objective: to diagnose and characterize right-dominant, biventricular or left-dominant arrhythmogenic cardiomyopathy using morphofunctional, tissue, electrocardiographic, arrhythmic and familial or genetic categories. The introduction of left ventricular LGE filled a gap in the 2010 Task Force criteria, which had been built around ARVC. Because a non-ischemic left ventricular scar can have many causes, the Padua version required, for a diagnosis of isolated ALVC without right ventricular criteria, demonstration of a causal variant in a gene associated with arrhythmogenic cardiomyopathy. The genetic requirement served to protect specificity and shows why ALVC and NDLVC were not interchangeable.

The European Task Force consensus, published online in 2023 and in the 2024 volume of the International Journal of Cardiology, subsequently proposed a refinement of the Padua criteria. It strengthened CMR characterization of scar, recognized a ring-like subepicardial or mid-wall LGE pattern as a distinctive sign of left ventricular involvement, and updated left ventricular electrocardiographic and arrhythmic criteria; most importantly, it allows the ALVC phenotype to be described from a combination of clinical criteria even when the cause is acquired or remains unidentified, separating phenotypic classification from subsequent etiologic attribution. Consequently, the same patient may meet both the ESC definition of NDLVC and the ETF criteria for ALVC, but the overlap does not make the two entities synonymous: non-dilated hypokinesia without scar, for example, belongs to NDLVC but does not by itself define a scar-based arrhythmogenic cardiomyopathy. This multiparametric framework is a proposed consensus and requires critical application and further external validation.

Prevalence cannot yet be measured reliably. Earlier cohorts used different definitions and often selected patients according to genetics, myocarditis, arrhythmias or CMR, producing non-comparable denominators. Unequal access to CMR also causes underdiagnosis of silent scar. The emerging epidemiology requires prospective registries using uniform criteria and separating etiologic subgroups.

The category includes adults and children, symptomatic probands and relatives identified through screening. Age at expression depends on the gene and modifiers, while penetrance and expressivity may differ between sexes. Apparent rarity at older ages may reflect selective survival or previous alternative diagnoses. The clinical distribution should not be inferred from referral-center series alone, which are enriched for complex phenotypes.

Etiology, genetics and mechanisms of injury

In genetic forms, injury may originate from intercellular junctions, the cytoskeleton, nuclear envelope, sarcomere or calcium regulation. These pathways converge on cardiomyocyte loss, inflammatory activation, matrix deposition and conduction disorganization. Dilatation is not required for a reentry circuit to form. The fibrous substrate explains why electrical disease may precede mechanical impairment.

DSP encodes desmoplakin, which links the desmosome to intermediate filaments. Pathogenic variants, especially truncating variants, can produce subepicardial left ventricular scar, episodes of injury with pain and troponin elevation, premature beats and major arrhythmias. The right ventricle may be normal and left ventricular ejection fraction only mildly reduced. The DSP phenotype demonstrates that a recurrent myocarditis-like presentation may be an expression of inherited cardiomyopathy.

Truncating FLNC variants impair filamin C and are associated with a cardiac phenotype often dominated by fibrosis, ventricular arrhythmias and risk of heart failure. Subepicardial or mid-wall LGE, sometimes ring-like, may precede a severe reduction in ejection fraction. FLNC missense variants are also associated with hypertrophic or myopathic phenotypes and cannot be interpreted as equivalent to truncating variants. Allele specificity is essential in risk estimation.

PLN regulates SERCA2a and therefore calcium reuptake into the sarcoplasmic reticulum. The p.Arg14del variant, particularly well studied in Dutch populations, may cause low voltages, ectopy, inferolateral fibrosis and progression from early electrical phases to heart failure. Risk varies among carriers and families, making deterministic prediction inappropriate. The PLN phenotype requires attention to rhythm even before dilatation develops.

LMNA is frequently associated with atrioventricular conduction disease, atrial arrhythmias and ventricular tachycardia in a cardiomyopathy that may initially have only modest structural abnormalities. Male sex, non-missense variants and specific clinical parameters have contributed to dedicated risk models. The need for pacing may arise before severe dysfunction. Laminopathy-related risk requires planning the type of device while considering both bradycardia and prevention of sudden death.

Variants in RBM20, DES, TMEM43 and other validated genes may produce overlapping arrhythmic and dilated phenotypes. TTN and sarcomeric genes may present with non-dilated hypokinesia, but their significance depends on variant class and context. DMD and other neuromuscular diseases may show subepicardial scar before cardiac symptoms. Gene-phenotype associations guide further investigation without becoming exclusive criteria.

Genetic testing has a higher yield in the presence of family history, young onset, conduction block, ventricular tachycardia, a suggestive scar pattern, or cutaneous and neuromuscular signs. It should use genes with at least moderate evidence and methods capable of detecting the relevant variant classes. A pathogenic variant demonstrates predisposition but does not exclude concomitant factors. The genetic result is always compared with segregation and phenotype.

Variants of uncertain significance are not actionable findings. They do not justify an ICD, prenatal diagnosis or discharge from follow-up of relatives who do not carry them. Segregation in affected relatives and periodic reassessment may add evidence, but decisions remain anchored to clinical data. VUS management is a component of quality and protects the family from irreversible interpretations.

Myocarditis may leave a non-ischemic scar without dilatation or act as a second hit in a genetically predisposed carrier. Autoimmunity, infection and toxic mechanisms cannot be distinguished by scar geometry alone. A remote episode with viral symptoms does not establish etiology, and routine viral serology has little value for identifying myocardial infection. The inflammatory hypothesis requires coherent timing, biomarkers, CMR findings and biopsy indications.

Cardiac sarcoidosis, eosinophilic diseases, giant-cell myocarditis and immune-therapy cardiotoxicity are time-dependent diagnoses in appropriate presentations. They may produce scar, block, tachycardia and dysfunction while volumes are still normal. Systemic signs, PET, laboratory testing and targeted biopsy help distinguish them. A treatable cause must be sought urgently when therapeutic benefit depends on the active phase.

Clinical presentation and electrical phenotype

Many patients are identified after palpitations or incidentally observed ectopy. Perception of heartbeats does not quantify burden, because frequent premature beats may be asymptomatic and only a few events may be strongly perceived. The morphology of the ectopic QRS may suggest an epicardial or scar-related origin without localizing the substrate with certainty. Objective monitoring separates symptoms, frequency and complexity of the arrhythmia.

Syncope requires detailed reconstruction. A sudden event during exertion or without prodrome, with trauma and rapid recovery, increases suspicion of an arrhythmic cause, whereas orthostatic circumstances and neurovegetative symptoms point elsewhere but do not exclude coexistence. Intermittent block and ventricular tachycardia are both possible in conduction-related genotypes. Unexplained syncope modifies risk stratification only after plausible alternatives have been considered.

Chest pain, fever and elevated troponin may mimic viral myocarditis or an acute coronary syndrome. In DSP-related cardiomyopathy, these episodes may precede dysfunction by years and leave new scar. Coronary artery disease must nevertheless be excluded according to age and risk, especially if LGE involves the subendocardium. Episodic injury acquires genetic significance when it recurs or is associated with family history and a characteristic pattern.

Dyspnea, fatigue and reduced exercise tolerance occur with dysfunction, inadequate chronotropic response, arrhythmias or elevated filling pressures. Mild symptoms do not always correlate with ejection fraction and may also depend on anemia, lung disease and deconditioning. Cardiopulmonary exercise testing helps define the mechanism in selected cases. Functional limitation is measured rather than inferred solely from the reported functional class.

Cardiac arrest may be the first manifestation in a previously healthy individual. In this setting, assessment includes exclusion of reversible causes, coronary disease, toxins, channelopathies and cardiomyopathies, using CMR and genetics appropriately. A non-ischemic scar provides a possible substrate but does not eliminate other diagnoses. Secondary prevention proceeds in parallel with etiologic investigation.

The ECG may show low voltages in peripheral leads, inferolateral T-wave inversion, fragmented QRS, terminal delay, bundle branch block or atrioventricular block. No pattern is obligatory and a normal tracing does not exclude scar. Serial evolution may be more informative than the initial snapshot. The ECG phenotype guides gene selection and the duration of monitoring.

Atrial fibrillation and other supraventricular tachyarrhythmias may precede dysfunction, particularly in laminopathies and some TTN carriers. They should be treated for symptoms and thromboembolic risk according to general criteria, but they are also a clue to myocardial disease when they occur early. Persistent tachycardia can also cause hypokinesia without dilatation. The arrhythmia-myocardium relationship is reassessed after rhythm or rate control.

Multimodality diagnosis and differential diagnosis

The diagnostic pathway begins with personal and family history, physical examination, ECG, laboratory testing, echocardiography and ambulatory monitoring. Medications, alcohol, stimulants, chemotherapy, infections, autoimmune diseases, sports activity and symptom chronology are reconstructed. The pedigree covers at least three generations and includes early pacemakers, transplantation and sudden deaths. Pre-test probability determines which subsequent investigations have real yield.

Echocardiography quantifies volumes and function with biplane or three-dimensional methods, describes regional abnormalities and assesses the right ventricle, atria, valves and pressures. Global longitudinal strain can detect subclinical impairment and regional distributions, but it has no universal diagnostic threshold for NDLVC. Loading conditions, image quality and vendor influence the value. The echocardiographic measurement must be reproducible and compared with previous studies.

CMR is the central modality because it provides accurate volumes and tissue characterization. Cine sequences confirm geometry and wall motion, while LGE identifies focal fibrosis; native T1 and extracellular volume may suggest diffuse abnormalities and T2 supports active edema. Normal mapping does not exclude a focal scar and absent LGE does not exclude genetic disease. Integrated CMR interpretation avoids turning each sequence into a binary test.

An inferolateral subepicardial pattern is seen in myocarditis and several genetic cardiomyopathies, including DSP, FLNC and muscular dystrophies. Mid-wall septal LGE is common in the dilated spectrum, whereas a circumferential subepicardial or ring-like distribution suggests arrhythmogenic phenotypes without being pathognomonic. Extent and multifocality add information. The language of LGE should report location, layer, percentage and technical quality.

Myocardial fatty replacement is difficult to assess reliably. A thin wall, adjacent epicardial fat, partial-volume effects and artifacts may mimic intramyocardial infiltration, while fat-water techniques and dedicated sequences are not available everywhere. Non-ischemic left ventricular fatty replacement, if reliably documented in the absence of dilatation, may meet the NDLVC phenotypic criterion even without further structural, electrical or genetic abnormalities. Confirmation of fat requires specific expertise and multimodality correlation.

Ischemic scar involves the subendocardium and generally follows a coronary territory, with transmural extension proportional to necrosis. Mid-wall and subepicardial patterns favor a non-ischemic cause, but embolism, spasm, dissection or recanalization may leave infarcts without persistent stenosis. CT coronary angiography or invasive angiography is selected according to risk and presentation. Exclusion of ischemia requires concordance among anatomy, distribution and history.

Acute myocarditis is assessed using updated clinical and CMR criteria, seeking edema, non-ischemic injury and dysfunction in the appropriate temporal context. Residual LGE after resolution does not demonstrate active inflammation and does not justify immunosuppression. Recurrent episodes, family history and cutaneous involvement may suggest an underlying genetic cardiomyopathy. The distinction between activity and scar is decisive for avoiding unnecessary treatment.

Sarcoidosis may produce block, ventricular tachycardia, dysfunction and multifocal LGE, often basal or septal, but no isolated pattern is diagnostic. Fluorodeoxyglucose PET assesses metabolic activity after adequate preparation and guides biopsy toward more accessible extracardiac sites. Diagnosis follows specific clinical and histologic criteria. Suspicion of sarcoidosis increases with early conduction disease and compatible systemic disease.

Classic ARVC requires assessment of the right ventricle using dedicated criteria, but many arrhythmogenic cardiomyopathies are biventricular or left-dominant. The presence of minor right ventricular abnormalities does not negate NDLVC, whereas a definite right ventricular phenotype is classified separately. ECG, CMR, arrhythmias and genetics establish dominance. Ventricular classification describes what is present without forcing every desmosomal variant into the ARVC model.

Hypertrophic cardiomyopathy, noncompaction and the athlete's heart may show LGE or borderline function, but they are recognized from geometry, history and response to exercise. Prominent trabeculations alone do not constitute cardiomyopathy and may be physiologic. In athletes, contractile reserve, strain and selective detraining may help, although no single test is definitive. Adaptive physiology must be distinguished from disease before restrictions are imposed.

A high burden of premature beats or persistent tachycardia can cause hypokinesia and sometimes precede dilatation. Diffuse distribution of dysfunction, absence of LGE and recovery after arrhythmia control support causality, but scar may be the substrate generating ectopy. Cause and consequence can coexist. Documented reversibility is part of the diagnosis of arrhythmia-induced cardiomyopathy.

Basic laboratory testing includes complete blood count, electrolytes, renal and liver function, thyroid testing, iron, troponin and natriuretic peptides. Creatine kinase, autoantibodies, immunofixation, metabolic or infectious tests are requested in the presence of specific clues, not as indiscriminate screening. Viral serology does not demonstrate myocardial infection. A targeted panel reduces false positives while preserving the ability to recognize treatable causes.

Endomyocardial biopsy is reserved for presentations in which histology, immunohistochemistry or molecular testing can change treatment promptly. Shock, refractory arrhythmias, advanced block with suspected specific myocarditis or infiltration are relevant examples. Sampling may miss focal lesions and the site may be guided by imaging or mapping. Biopsy yield depends on patient selection and center expertise.

Prognostic stratification and prevention of sudden death

Prognosis includes at least three domains: ventricular arrhythmias, progression of heart failure and recurrence of myocardial injury. These outcomes do not necessarily share the same predictors. Extensive scar may dominate electrical risk, whereas biventricular function, symptoms and exercise capacity better describe hemodynamic risk. Domain-based assessment prevents complex conditions from being reduced to a single opaque percentage.

The retrospective study by Eda and colleagues compared 80 patients with NDLVC and ejection fraction below 50% with 283 patients with DCM, all with newly diagnosed non-ischemic cardiomyopathy. Over a median follow-up of almost six years, no significant difference emerged for the combined outcome of sudden death and rehospitalization for heart failure, whereas subsequent development of dilatation in the subgroup initially non-dilated was associated with a worse prognosis. The finding supports the need for serial monitoring of geometry and function, but applies exclusively to selected hypokinetic NDLVC defined by reduced ejection fraction and echocardiographic measurements: it does not quantify the risk of scar-based forms with preserved function and does not demonstrate universal prognostic equivalence between NDLVC and DCM.

In a retrospective multicenter cohort of 462 patients studied with CMR and genetic testing, Castrichini and colleagues compared 235 patients with NDLVC and 227 with DCM. Compared with DCM, the NDLVC group had, on average, more preserved systolic function, a higher frequency of pathogenic or likely pathogenic variants in genes defined as arrhythmogenic and more frequent free-wall LGE; in the overall cohort, however, septal LGE, dilatation, age, advanced functional class, frequent ectopy and nonsustained tachycardia contributed to identifying the risk of sudden death or major arrhythmias. These results support an integrated interpretation of tissue, geometry, rhythm and genotype, but average differences between selected referral-center groups do not allow the fate of an individual patient to be inferred from the phenotypic label alone.

Documented ventricular tachycardia or fibrillation defines high risk and establishes indications for secondary prevention unless the cause is completely reversible. Probably arrhythmic syncope, nonsustained tachycardia, complex ectopy and increasing burden during follow-up are additional signals. Monitoring must be long enough for the frequency of events. The arrhythmic history retains greater weight than an occasional negative Holter recording.

Ejection fraction remains a predictor and guides established ICD indications in heart failure with severe persistent dysfunction despite therapy. In NDLVC, however, waiting for a very low threshold may be inappropriate when scar and an arrhythmogenic genotype are present. Guidelines allow a broader assessment in DCM and NDLVC by integrating clinical, CMR and genetic factors. Ejection fraction not considered in isolation is the operative principle of modern primary prevention.

The presence and extent of LGE are associated with arrhythmias and mortality in non-ischemic cardiomyopathies even when function is not severely reduced. Ring-like subepicardial distributions are common in DSP and FLNC disease and may signal a diffuse substrate. However, there is no universal threshold in grams or percentage that applies to every etiology and software package. Scar burden informs the decision without becoming an automatic switch for ICD implantation.

Gueli and colleagues applied the 2024 ETF criteria to 225 patients with NDLVC who underwent CMR and genetic testing. During a median follow-up of 3.3 years, 12 patients, equal to 5% of the cohort, experienced sudden death, ventricular fibrillation or sustained ventricular tachycardia; risk was higher in those who met borderline or definite criteria for ALVC or biventricular arrhythmogenic cardiomyopathy. In that specific population, LGE extent greater than 9% of ventricular mass was the strongest predictor and, beyond that value, fatty replacement added prognostic information. The cohort signal is consistent with the biologic importance of scar, but 9% is not a normative threshold: it depends on selection, technique and quantification and does not, by itself, constitute a universal criterion for diagnosis or ICD implantation.

Genotype modifies risk in a gene-specific manner. LMNA has models combining variant type, sex, conduction abnormalities, tachycardia and function; truncating FLNC variants, PLN p.Arg14del, RBM20 and DSP require specialist consideration because of the high arrhythmic component observed in cohorts. Variant classification and gene evidence must be robust. A high-risk gene does not replace characterization of the individual carrier.

In 2026, the first model dedicated to predicting a first major arrhythmia over five years in NDLVC was published. Retrospectively derived in 337 patients from two centers and evaluated in 216 patients from eleven European centers, the NDLVC-5y score combines male sex, nonsustained ventricular tachycardia, ejection fraction below 45%, septal and ring-like LGE, pathogenic or likely pathogenic variants in genes defined as high risk, and myocardial inflammation documented by CMR or biopsy. The outcome included sustained tachycardia, ventricular fibrillation or appropriate ICD therapy. This emerging model provides a multiparametric estimate, but specialist selection of the cohorts, the observational design and its recent introduction require further validation: it does not yet establish a universal threshold for implanting or withholding a defibrillator.

Electrophysiologic testing has a selective role and noninducibility does not guarantee protection. Programmed stimulation may be useful in defined contexts, but it is not a universal screening tool capable of resolving uncertainty in primary prevention. Likewise, signal-averaged ECG and other markers should not be used outside a validated model as sole decision makers. An invasive test is requested when its result has a concrete management consequence.

The ICD decision weighs the probability of arrhythmia against device complications, inappropriate shocks, infection, lead problems and competing risk. Age, need for pacing, anatomy, treatable arrhythmias and preferences influence the choice between transvenous and subcutaneous systems. In young people, exposure to complications lasts for decades. A shared decision makes expected benefits and uncertainties explicit.

Progression toward DCM is recognized by serial increases in volumes, worsening function, functional regurgitation and symptoms. LGE, genotype, nonsustained tachycardia and conduction disease may accompany more aggressive trajectories, but individual prediction remains imperfect. Measurements performed with the same modality reduce noise. Dynamic prognosis is updated after each change in phenotype and does not remain tied to the initial assessment.

Treatment of the phenotype and the cause

There are no randomized trials dedicated to the entire NDLVC category, which is too heterogeneous for a single therapy. Treatment is composed of management of dysfunction, arrhythmic prevention, symptom control and etiologic intervention when available. Stable scar cannot be removed pharmacologically, but processes that promote remodeling and events can be modified. A modular treatment strategy replaces the idea of one protocol for every patient.

Full guideline-directed therapy for heart failure with reduced ejection fraction is prescribed when the patient has the corresponding dysfunction and meets clinical indications. ARNI or renin-angiotensin system inhibition, beta-blocker, mineralocorticoid receptor antagonist and SGLT2 inhibitor are introduced according to blood pressure, renal function, potassium and volume status. The NDLVC label does not limit these benefits. Prognostic medications, however, are guided by the functional phenotype, not by the presence of LGE alone.

An isolated scar with normal ejection fraction does not automatically justify the four pillars of HFrEF therapy. In preclinical carriers or patients with mild abnormalities, evidence for specific preventive therapy is incomplete and the decision is individualized. Blood pressure, ischemia, diabetes and other cardiovascular factors are nevertheless treated. Therapeutic proportionality prevents biologic plausibility from being confused with demonstrated benefit.

Diuretics are reserved for congestion and titrated to volume status, with no preventive value in a euvolemic patient. Digoxin, ivabradine and other drugs follow their own indications in heart failure or rhythm management. Cardiac resynchronization depends on ejection fraction, QRS duration, block morphology and symptoms, not on the non-dilated scar itself. Hemodynamic therapy responds to measurable problems and is reassessed after remodeling.

Beta-blockers may be useful for dysfunction, adrenergic symptoms and some arrhythmias, but they do not eliminate the substrate. Antiarrhythmic drugs are selected considering function, scar, extracardiac toxicity and proarrhythmic risk. Amiodarone may reduce recurrences in selected settings but does not replace an ICD when one is indicated. Pharmacologic control aims to reduce events and shocks without promising abolition of risk.

Ventricular tachycardia ablation is considered for recurrent episodes, shocks or drug intolerance. In forms with subepicardial scar, the circuit may require epicardial mapping, with risks and expertise that differ from an endocardial approach. Recurrence remains possible because the substrate may be diffuse or progressive. Circuit ablation treats the clinical arrhythmia but does not cure the cardiomyopathy.

An ICD is recommended for secondary prevention after cardiac arrest or hemodynamically significant sustained ventricular arrhythmia unless the cause is clearly reversible. For primary prevention, the decision integrates function, LGE, syncope, arrhythmias, genotype and family history after appropriate therapy and observation of the trajectory. Absence of dilatation alone does not reduce the indication. Individual selection balances protection against long-term complications.

Anticoagulation and antiplatelet therapy are not prescribed for LGE alone. Atrial fibrillation, intracavitary thrombus, embolism or other indications are managed according to specific guidelines. The absence of dilatation does not eliminate thromboembolic risk when atrial arrhythmias and clinical risk factors coexist. Thrombotic prevention remains distinct from arrhythmic prevention.

Immunosuppression is not a treatment for chronic scar and is not started on the basis of a remote CMR pattern. It is appropriate only in defined inflammatory or systemic conditions, with assessment of the active phase and the risk-benefit balance. Giant-cell myocarditis, sarcoidosis and immune-mediated cardiotoxicity follow different protocols. Etiologic therapy requires a sufficiently certain diagnosis and monitorable targets.

During an acute episode with pain, troponin elevation and suspected inflammation, coronary syndrome, embolism and other emergencies are excluded, after which exercise is restricted and heart failure or arrhythmias are treated. Return to activity depends on clinical normalization, biomarkers, function and rhythm, not merely symptom relief. A new area of LGE may modify risk stratification. The post-acute phase includes genetic investigation when recurrence or family history makes it plausible.

Moderate aerobic exercise is generally encouraged in stable patients, but intensity and competition are adapted. In desmosomal arrhythmogenic cardiomyopathies, intense exposure is associated with greater penetrance and risk, and a DSP phenotype or extensive scar requires particular caution. Light activity is not automatically prohibited. Exercise prescription considers genotype, arrhythmias, function, symptoms and preferences.

Advanced heart failure is treated according to the same principles as other cardiomyopathies, with early referral to a center for ventricular assist devices or transplantation when hospitalizations, hypoperfusion, treatment intolerance or multiorgan deterioration occur. Initial absence of dilatation does not prevent end-stage progression, so assessment should be planned before irreversible shock develops. Advanced therapy is guided by current severity, not by the category in which the disease began.

Family screening, follow-up and special situations

First-degree relatives are assessed with clinical history, ECG and imaging even when the proband appears sporadic, because incomplete penetrance, small families and de novo variants may conceal heredity. Holter monitoring and CMR are added according to the gene, scar and family arrhythmias. A normal echocardiogram does not exclude an early scar phase in specific genotypes. Baseline screening is personalized without losing documentary uniformity.

When a pathogenic or likely pathogenic variant explains the phenotype, targeted cascade testing identifies carriers and non-carriers. Relatives who test negative for the causal variant can generally be discharged from specific surveillance if there are no other clinical reasons. Carriers without a phenotype receive follow-up, not an automatic diagnosis of NDLVC. The pre-phenotypic phase distinguishes genetic susceptibility from manifest disease.

If the proband's test is negative or shows only a VUS, a genetic origin is not excluded and clinical family screening continues according to history and guidelines. New genes, structural variants and future reclassifications may change interpretation. A pathway is needed to update reports. An uninformative negative result is not equivalent to a negative targeted test in a family with a known causal variant.

Patient follow-up includes symptoms, physical examination, ECG, function, volumes and rhythm, with shorter intervals in the presence of extensive LGE, a high-risk genotype, arrhythmias or an unstable trajectory. CMR is repeated when the expected change may alter management rather than simply as an annual routine. The same modality and comparable protocols facilitate comparison. Serial surveillance looks for new scar, dysfunction and increasing arrhythmic burden.

In children, indexing, development and the genetic spectrum require dedicated expertise. Neuromuscular and metabolic diseases carry greater weight and extracardiac signs may precede cardiac injury. Predictive testing in minors is appropriate when it changes surveillance during childhood. Pediatric assessment integrates parental consent, the child's progressive assent and structured transition to adult care.

Pregnancy increases circulating volume and heart rate and may reveal myocardial vulnerability. Before conception, function, arrhythmias, genotype, teratogenic medications and family history are reviewed, distinguishing maternal risk from transmission risk. Contraindicated medications are replaced in a planned manner and monitoring continues through the postpartum period. Preconception counseling should occur before therapeutic options become restricted.

The presence of an ICD does not automatically make intense sport safe because the device does not prevent progression, syncope or repeated shocks. Conversely, an NDLVC diagnosis without arrhythmias does not mandate a sedentary lifestyle. The decision considers the type of activity, environment, availability of rescue and the psychological impact of restrictions. Return to sport is agreed upon and reassessed if the phenotype changes.

The final report should state the phenotype, demonstrated or suspected cause, risk features and family plan. Formulations such as “genetic NDLVC due to a pathogenic DSP variant” communicate more information than an isolated acronym; when the cause remains uncertain, the level of evidence is stated. Classification may change with dilatation, new scar or a systemic diagnosis. Evolving documentation keeps decisions coherent across imaging, electrophysiology, genetics and heart failure care.

NDLVC exemplifies why cardiomyopathy cannot be judged solely by chamber shape. Tissue, electrical activity, genetics and time reveal disease before the heart enlarges and allow more targeted prevention. At the same time, the novelty of the category demands rigor to avoid medicalizing equivocal findings. The final clinical principle is to recognize the actual substrate, attribute its cause cautiously and treat demonstrated risk.