Non-dilated left ventricular cardiomyopathy: overview

Article written and reviewed by Dr Luca Moretti

Non-dilated left ventricular cardiomyopathy, abbreviated in the international literature as NDLVC, identifies a phenotype in which the left ventricle is not enlarged but shows significant structural or functional myocardial injury. The first branch of the definition includes non-ischemic scar or fatty replacement of the left ventricle regardless of whether global or regional wall-motion abnormalities are present; the second includes isolated global left ventricular hypokinesia without scar. The absence of dilatation therefore describes ventricular geometry, not the benign nature of the disease. This non-dilated phenotype may be electrically unstable even when pump function appears only mildly impaired.

The term was formalized by the 2023 ESC guidelines to bring together conditions that previous systems distributed among hypokinetic non-dilated cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, previous myocarditis and unclassified forms. The choice addresses a clinical need: to recognize myocardial disease before any dilative remodeling becomes evident. Phenotypic classification, however, does not claim to assign a cause, which must be sought through imaging, genetics, family history and assessment of acquired conditions.

Cardiac magnetic resonance has made visible a component of disease that conventional echocardiography could miss. A normal-sized heart may contain a subepicardial, mid-wall or circumferential scar capable of interrupting uniform impulse propagation and promoting ventricular reentry. A non-ischemic scar is meaningful only when its distribution, technical quality and clinical context are coherent, because not every area of late gadolinium enhancement is equivalent to cardiomyopathy.

The phenotype may result from pathogenic variants in genes such as DSP, FLNC, PLN, LMNA, DES and other genes validated for cardiomyopathy, but it may also follow inflammatory injury or represent the result of several concomitant factors. Within the same family, the same variant may produce NDLVC, dilated cardiomyopathy, conduction disorders or a predominantly arrhythmic form. This intrafamilial heterogeneity prevents the diagnosis from being reduced to a rigid gene-imaging correspondence.

Assessment of non-dilated left ventricular cardiomyopathy requires morphologic criteria, differential diagnosis, arrhythmic risk and pump function to be considered in the same patient. The cause remains decisive because a desmosomal variant, healed myocarditis and sarcoidosis may share part of the imaging appearance but not the same treatment. Integrated reasoning therefore links the finding to its mechanism and concrete clinical consequences.

A new phenotype for a previously recognized problem

Before the NDLVC definition, the 2016 ESC position statement had proposed hypokinetic non-dilated cardiomyopathy for global systolic dysfunction of the left ventricle or both ventricles, with an ejection fraction below 45%, in the absence of dilatation and without abnormal loading conditions or coronary artery disease sufficient to explain the findings. That proposal broadened the spectrum of dilated cardiomyopathy and allowed relatives to be recognized at a less advanced stage. The 2023 category takes a further step by also including isolated scar injury, even when global contractility is preserved.

The extension of the definition reflects the different value of morphologic markers. Dilatation is one possible late response, whereas scar may appear early and constitute the main substrate of disease. In genotypes associated with subepicardial injury, arrhythmias and myocarditis-like episodes, waiting for ventricular volume to increase would mean losing a diagnostic window. Early recognition allows rhythm, function and family members to be monitored before overt heart failure develops.

NDLVC is not synonymous with arrhythmogenic left ventricular cardiomyopathy, although an important proportion of left-dominant forms fall within the new phenotype. The term arrhythmogenic emphasizes a biologic and electrical presentation, whereas NDLVC describes what is observed in the left ventricle irrespective of etiology. The 2020 Padua criteria and their 2024 European Task Force refinement define ALVC through multiparametric evidence and certainty categories, whereas the 2023 ESC classification remains morphofunctional. The etiologic neutrality of NDLVC therefore allows both genetic and non-genetic causes to be included, while requiring the most plausible substrate to be specified subsequently.

Nor does the presence of hypokinesia without dilatation automatically prove an early phase of DCM. Some patients progress to increased volumes, others remain stable, while still others mainly develop arrhythmias or conduction disorders. The trajectory is influenced by gene, sex, age, exposures and response to treatment. A longitudinal diagnosis is more accurate than a prediction built from a single image.

Dimensional limits must be referenced to body surface area, sex and age and measured with a quantitative method. A ventricle that appears normal by eye may be small for body habitus or relatively enlarged compared with a previous examination without yet exceeding the population limit. Indexed volume reduces classification error, while serial comparison reveals biologically important changes even within the normal range.

Ejection fraction is load-dependent and may remain normal despite regional abnormalities or reduced longitudinal strain. Conversely, a mildly low fraction in an athlete, in the presence of increased volume and normal contractile reserve, does not automatically identify NDLVC. The hemodynamic context includes blood pressure, heart rate, valves, training and measurement quality, avoiding diagnoses based on an isolated threshold.

The usefulness of the new category therefore lies in its ability to organize signs that previously remained disconnected. An abnormal ECG, ectopy, family history and CMR scar can converge into a recognizable phenotype even without cardiomegaly. The definition becomes clinically productive when it opens an etiologic and prognostic pathway. A descriptive label without further investigation does not improve care.

Biologic pathways converging on the left ventricle

Desmosomal proteins connect cardiomyocytes and distribute mechanical forces through the tissue. DSP variants can weaken this architecture, promote cell death and activate inflammatory and fibrotic responses that often involve the left ventricle. The result may be extensive subepicardial scar with function still preserved. Desmoplakin cardiomyopathy is one of the most informative models of this dissociation between volume and risk.

Truncating FLNC variants alter a protein that connects the cytoskeleton and sarcolemma. In affected families they have been associated with subepicardial fibrosis, ventricular arrhythmias, sudden death and progression to heart failure, with overlap between dilated and arrhythmogenic phenotypes. Cardiac filaminopathy shows why genotype must be interpreted together with CMR rather than only with ejection fraction.

The PLN p.Arg14del deletion impairs regulation of calcium in the sarcoplasmic reticulum and may produce low voltages, ectopy, inferolateral fibrosis and progressive dysfunction. LMNA instead tends to associate conduction disorders, atrial fibrillation and ventricular arrhythmias with structural impairment that may initially be modest. These gene-specific phenotypes make surveillance based only on ventricular diameter inadequate.

Other genes may fall within the NDLVC spectrum, but the association must rest on robust gene-disease validity and rigorous variant classification. Indiscriminate panels increase the number of variants of uncertain significance without providing an explanation. A VUS does not establish etiology and must not be used to decide predictive testing in relatives. Interpretive quality matters more than the number of sequenced genes.

Inflammation may be a cause, modifier or manifestation of genetic cardiomyopathy. In DSP-related forms, episodes of chest pain and troponin elevation with an appearance similar to acute myocarditis, sometimes recurrent, have been described before scar or dysfunction develops. Attributing every episode to a virus without considering family history and CMR pattern may delay diagnosis. The myocarditis-like phenotype requires an interpretation that integrates the acute phase and family history.

Non-genetic myocarditis may leave a subepicardial scar in a non-dilated ventricle. In that situation, the question is not only whether inflammation occurred, but whether it is still active, whether the scar explains the arrhythmias and whether a treatable systemic disease exists. Inflammatory causality is not established by routine viral serology, and biopsy is reserved for situations in which the result can change treatment.

Sarcoidosis, autoimmune diseases, toxins and some neuromuscular conditions may produce scar or dysfunction without dilatation. The distribution of injury, extracardiac signs and pre-test probability guide targeted investigations, avoiding unstructured test batteries. A systemic diagnosis may radically change treatment and prognosis, but it must not be inferred from a single nonspecific imaging pattern.

The relationship with dilated cardiomyopathy is that of a partly shared spectrum. Some genes and acquired factors produce both phenotypes, even within the same family, and an initially non-dilated ventricle may increase in volume as disease progresses. The transition does not erase the previous diagnosis but documents phenotypic remodeling that must be recorded over time.

Clinical recognition and multimodality integration

Presentation may be incidental during CMR performed for premature beats or may occur with palpitations, syncope, chest pain or dyspnea. In younger individuals, ventricular tachycardia or cardiac arrest may precede symptoms of heart failure. In relatives, the first sign may be an abnormal ECG while conventional imaging is still within normal limits. This clinical variability requires reconstruction even of apparently non-cardiac events such as drownings or unexplained accidents.

The ECG looks for low voltages, T-wave inversion, QRS fragmentation, atrioventricular and intraventricular blocks, atrial arrhythmias and ventricular ectopy. No isolated finding is diagnostic, but the combination may guide genetic suspicion and the need for prolonged monitoring. The electrical signal may precede reduced function and should be compared with age, training and medications.

Echocardiography defines volumes, ejection fraction, regional wall motion, right ventricular function, valves and pressures. Strain may reveal subtle dysfunction, but it depends on image quality and software and does not replace diagnostic criteria. Confirmation of the absence of dilatation requires indexed measurements and, when margins are uncertain, the greater reproducibility of CMR. Consistent quantification is essential in serial follow-up.

CMR establishes whether the ventricle is truly non-dilated and characterizes tissue through LGE, T1 and T2 mapping and extracellular volume. Inferolateral subepicardial, septal mid-wall or ring-like LGE may support different hypotheses, but no distribution is perfectly specific. Edema and elevated T2 suggest recent injury, whereas persistent LGE mainly reflects expansion of the extracellular space. The tissue pattern must be linked to coronary anatomy, troponin, rhythm and genotype.

The non-ischemic nature of the scar must be demonstrated rather than assumed. An infarction generally follows a coronary territory and involves the subendocardium, whereas many cardiomyopathies spare the subendocardial layer and have mid-wall or subepicardial distribution. Embolism, vasospasm and recanalization can nevertheless produce ischemic scars without current stenosis. Etiologic attribution arises from concordance between coronary anatomy and injury distribution.

Ambulatory ECG monitoring quantifies premature beats, couplets, nonsustained ventricular tachycardia, atrial arrhythmias and pauses. Twenty-four hours may underestimate intermittent phenomena, so duration is adapted to symptoms and event probability. Premature-beat morphology suggests the site of origin and may correlate with scar. A serial arrhythmic burden is more informative than a single random count.

Exercise testing assesses functional capacity, blood-pressure response and the occurrence of arrhythmias during adrenergic stimulation, but a negative result does not exclude risk at rest or in the following hours. Cardiopulmonary exercise testing is useful when dyspnea and limitation are not explained by global function. The response to exercise contributes to individualized prescription and should not become unnecessary maximal provocation in unstable phenotypes.

A three-generation history, physical examination and laboratory testing complete imaging. Troponin, natriuretic peptides, creatinine, electrolytes, thyroid function, blood count, iron and tests guided by systemic signs are chosen according to the clinical problem. Skin and hair may provide clues in desmosomal diseases, while weakness or elevated creatine kinase points toward neuromuscular involvement. Extracardiac red flags become useful when sought with a precise etiologic question.

Arrhythmic risk and risk of progression

The absence of dilatation does not protect against ventricular arrhythmias because reentry depends on electrical heterogeneity of scar more than chamber volume. Sustained ventricular tachycardia, ventricular fibrillation and probably arrhythmic syncope carry immediate clinical weight. Extensive LGE, nonsustained tachycardia and some genetic variants also increase concern. Electrical risk is therefore estimated separately from the degree of heart failure.

Ejection fraction retains value, but it cannot be the only filter for prevention of sudden death. Studies in non-ischemic cardiomyopathies show that CMR fibrosis adds prognostic information, especially when function is not severely depressed. In NDLVC this observation is conceptually central because scar may be the feature that defines the phenotype. Multiparametric stratification integrates genotype, arrhythmias, syncope, family history and imaging.

Variants in LMNA, FLNC, DSP, PLN and RBM20 may modify the threshold at which a defibrillator is considered, but gene and variant are not interchangeable. Variant type, validity of the association, familial penetrance and the individual phenotype must be verified. An asymptomatic carrier without findings does not automatically receive the same treatment as a patient with scar and tachycardia. Actionable genetics requires clinical evidence and informed consent.

Mechanical progression may present with reduced ejection fraction, increasing volumes, functional mitral regurgitation and heart failure symptoms. Transition to a dilated phenotype is not inevitable and the rate varies greatly. Standardized follow-up allows a true change to be distinguished from measurement error. The ventricular trajectory matters more than an immutable label assigned at the first examination.

Episodes of myocardial injury with pain and elevated troponin may add new scar and precede arrhythmic events or deterioration. In the presence of a DSP genotype, a myocarditis-like picture is not automatically regarded as a single resolved event. At the same time, not every troponin rise indicates genetic reactivation because ischemia, pulmonary embolism and other causes remain possible. Inflammatory recurrence requires complete reassessment.

Heart failure may remain absent for years despite extensive LGE, whereas in other patients dysfunction progresses rapidly. Natriuretic peptides, right ventricular function, functional class, cardiopulmonary exercise testing and hospitalizations define hemodynamic risk. Management should avoid both minimizing an asymptomatic patient with an arrhythmic substrate and overestimating a stable, limited scar. The prognostic balance distinguishes the probabilities of arrhythmia, heart failure and non-cardiac death.

The prognosis of historical cohorts cannot be transferred uncritically to the new category because NDLVC aggregates phenotypes previously named in different ways. Studies published between 2024 and 2026 have begun to compare NDLVC and DCM, link CMR and genotype to outcomes and derive a specific five-year arrhythmic score; however, these remain retrospective cohorts from specialist centers with definitions and populations that are not perfectly uniform. This evolving evidence justifies neither inertia nor automatic rules, but requires shared decisions, external validation and reassessment over time.

Family, physical activity and continuity of care

Family history includes cardiomyopathy, heart failure, arrhythmias, pacemakers, ICDs, transplantation and sudden death, recording age and available documentation. A small family or one composed of young relatives may appear negative despite autosomal dominant transmission. De novo variants and incomplete penetrance also mask clustering. The clinical pedigree is updated when new diagnoses or autopsy reports emerge.

First-degree relatives undergo assessment with history, ECG and imaging, adapting Holter monitoring and CMR to the family phenotype. In genes associated with early scar, a normal echocardiogram does not always conclude screening. The aim is not to assign disease to every minimal abnormality but to identify a reproducible combination of signs. Family screening is more effective when the same criteria are used and images are retained for comparison.

If a pathogenic or likely pathogenic variant is identified in the proband, cascade testing can distinguish carrier relatives. An uncertain variant must not be used to discharge those who do not carry it or to diagnose those who do. The genetic result is accompanied by pre-test and post-test counseling because it concerns risk, reproduction and intrafamilial communication. Cascade testing targets the already documented causal variant.

Physical activity is not prohibited uniformly. Moderate aerobic exercise offers general benefits, whereas intense and prolonged loads may accelerate expression or arrhythmias in some desmosomal and arrhythmogenic cardiomyopathies. Genotype, LGE, function, symptoms, arrhythmias and type of sport determine the prescription. A shared assessment avoids both unrecognized exposure and deconditioning caused by generic restrictions.

Pregnancy, fever, proarrhythmic drugs, electrolyte disturbances and new exposures may modify stability. Preconception counseling reviews function, arrhythmias, treatment and mode of inheritance without confusing the probability of inheriting a variant with disease severity. During pregnancy some drugs are contraindicated and surveillance is planned before conception. Reproductive risk is individual and is not exhausted by the Mendelian percentage.

Follow-up combines symptoms, ECG, rhythm monitoring and imaging at intervals determined by risk. New syncope, persistent palpitations, chest pain with fever or increasing dyspnea require reassessment earlier than scheduled. CMR is repeated when it may change diagnosis or treatment, not according to an automatic frequency that is the same for everyone. Dynamic surveillance seeks clinically actionable changes.

Care involves cardiomyopathy specialists, imaging, electrophysiology, genetics and, when necessary, immunology or disciplines dedicated to systemic disease. Coordination is particularly important when scar, inflammation and a genetic variant coexist and no single finding explains everything. The final report should distinguish phenotype, probable etiology and level of certainty. This stratified diagnosis remains understandable even as the clinical picture evolves.

From assessment to clinical decision

The pathway begins by confirming that a true myocardial abnormality exists and that the ventricle is non-dilated according to corrected measurements. It continues by excluding ischemic scar and sufficient loading conditions, then integrates CMR, rhythm and history. Only after this phase does the term NDLVC acquire precision. The diagnostic sequence prevents an isolated finding from becoming a premature diagnosis.

The second question concerns the cause because a genetic disease, sarcoidosis and the sequela of myocarditis require different pathways. Genetic testing is particularly informative with family history, early arrhythmias, conduction disorders, ring-like LGE or extracardiac signs. Immunologic, metabolic and biopsy investigations are selected according to red flags. An etiologic approach avoids both underdiagnosis and indiscriminate screening.

The third question separates arrhythmic risk from hemodynamic impairment. A patient with preserved function and sustained ventricular tachycardia may require different protection from someone with mild hypokinesia without scar or arrhythmias. Likewise, heart failure therapy follows function and symptoms, not the label alone. Separation of risks makes decisions about drugs and devices proportionate.

The fourth question concerns what can change: exposures, exercise, active inflammation, treatable arrhythmias and concomitant medications. Even in the presence of a genetic variant, modifying factors may accelerate or slow expression. Treatment does not necessarily erase scar but may limit heart failure and recurrences. The persistent substrate explains why functional improvement does not automatically justify stopping surveillance.

Finally, the diagnosis must be translated into a plan for the patient and family. The plan specifies follow-up, warning signs that should bring the visit forward, exercise recommendations, pregnancy management and how to communicate with relatives. Uncertainties are made explicit and reassessed with new data. Documented continuity turns a recent category into a useful and verifiable clinical tool.