Non-Dilated Left Ventricular Cardiomyopathy (NDLVC)

Non-dilated left ventricular cardiomyopathy is the newest phenotype in this whole section — formally introduced by the 2023 ESC cardiomyopathy guideline — and it exists specifically to fix a real, recurring diagnostic problem: patients whose hearts show genuine myocardial disease without ever meeting the dilation, hypertrophy, or RV-focused criteria the other phenotypes require. See Introduction to Diseases of the Myocardium for how NDLVC fits into the broader five-phenotype framework this page builds on.

Why This Category Exists

Before 2023, a patient with genuine LV myocardial disease — scarring or hypokinesia on imaging — but without dilation, hypertrophy, or RV-predominant findings had no consistent diagnostic home. Depending on which clinician or center evaluated them, the same patient might be called DCM without dilation, arrhythmogenic left ventricular cardiomyopathy (ALVC), left-dominant ARVC, or arrhythmogenic DCM without actually meeting formal diagnostic criteria for any of those labels. An earlier ESC statement had proposed the term “hypokinetic non-dilated cardiomyopathy” to capture this gap; the current guideline replaces that term with NDLVC.

Formal Definition

NDLVC is defined as the presence of non-ischemic LV scarring or fatty replacement — regardless of whether regional or global wall motion abnormality is present — or isolated global LV hypokinesia without scarring, in a ventricle that is neither dilated nor hypertrophied. It can be further characterized by the presence or absence of systolic dysfunction (regional or global).

Two points worth stating precisely: isolated LV dysfunction without scarring is itself sufficient to meet this category, and the definition deliberately doesn’t require a specific degree of dysfunction — a structurally normal-looking heart with genuine non-ischemic scar on tissue characterization, and a completely preserved ejection fraction, can still carry this diagnosis.

A Complete Worked Example, From the Guideline Itself

The 2023 guideline includes an illustrative case worth reproducing in full, since it demonstrates exactly how the phenotype-first, then-etiology diagnostic philosophy (see the Introduction page) plays out in practice:

A 17-year-old male presents with palpitations and a family history of sudden cardiac death; physical examination is normal. Echocardiography shows a non-dilated LV with EF 55% and a subepicardial scar. ECG shows sinus rhythm with minor intraventricular conduction delay and 200 ventricular ectopics with a few couplets over 24 hours. Genetic testing identifies a DSP truncating variant (specifically DSP Trp180*).

Under the older framework, this patient might variably have been labeled DCM (despite no actual dilation), ALVC, or arrhythmogenic cardiomyopathy — three different names for essentially the same uncertainty. Under the current phenotype-based approach, the diagnosis becomes specific and actionable: autosomal dominant DSP-related non-dilated LV cardiomyopathy phenotype with subepicardial scar and low-normal EF — a description that directly informs genetic counseling, family screening, and device decisions, rather than leaving the patient with an ambiguous label.

Genetics

The genes most commonly implicated in NDLVC are DSP, FLNC (truncating variants), DES, LMNA, and PLN — with substantial genetic overlap with both DCM and ARVC, reflecting how closely related these three phenotypes genuinely are at the molecular level. Desmoplakin (DSP) variants cause a particularly distinctive form of disease: a high prevalence of LV fibrosis paired with recurrent, myocarditis-like inflammatory episodes — a pattern worth specifically recognizing, since a patient presenting with repeated “myocarditis” flares and a family history of cardiomyopathy or sudden death should prompt consideration of underlying DSP-related NDLVC rather than assuming each episode is an isolated, unrelated event.

Genetic testing is recommended in every patient with NDLVC. Identifying a pathogenic or likely pathogenic variant improves prediction of disease course and progression, can directly inform device implantation decisions (below), supports genetic counseling, and enables structured family screening. Conduction disease and arrhythmia evaluation carry particular importance in NDLVC specifically, since these are often early phenotypic features — sometimes preceding any detectable structural abnormality.

Echocardiographic Assessment

Comprehensive transthoracic echocardiography is recommended for every NDLVC patient, covering the same broad territory as a standard structural and functional study: global and regional LV anatomy, function, and hemodynamics; valvular heart disease; right heart function; pulmonary pressure; and atrial geometry. See LV Systolic Function for the general assessment framework this builds on.

Deformation imaging — tissue Doppler and speckle-tracking strain — has a specifically important role: it can detect subclinical myocardial dysfunction in genetic NDLVC carriers before conventional structural or functional measures become abnormal. This matters practically for family screening, where a genotype-positive relative may show strain abnormality years before meeting any conventional diagnostic threshold.

Echocardiography’s genuine, honest limitation here is worth stating directly: unlike several other phenotypes in this section, echo alone usually can’t confirm the diagnosis, since the defining feature — non-ischemic myocardial scarring — isn’t something echocardiography visualizes directly. Its role is comprehensive functional and structural characterization, early detection in at-risk relatives, and excluding alternative explanations — not tissue diagnosis.

Cardiac MRI: The Foremost Diagnostic Modality

This is a genuine departure from most of this section, where echocardiography does the heaviest diagnostic lifting: cardiac MRI with late gadolinium enhancement is the foremost imaging modality in NDLVC, because confirming the presence of non-ischemic myocardial fibrosis is essential to the diagnosis in most cases — a confirmation echo cannot provide on its own.

The LGE pattern itself correlates with genotype, offering real diagnostic and prognostic information beyond simply confirming scar is present:

Genetic/etiologic group	Typical LGE pattern
DSP, FLNC (truncating), PLN variants	Subepicardial, ring-like distribution
TTN, BAG3, LMNA, DMD, RBM20 variants, and post-myocarditis disease	More heterogeneous pattern, generally less scar (sometimes none), lower EF

CMR can also detect myocardial edema — suggesting an active inflammatory or myocarditic process — and describe the extent and pattern of fibrosis in more detail, which carries additional prognostic value for both arrhythmic risk and heart failure severity.

Laboratory and ECG Findings Worth Knowing

Specific ECG red flags correlate with particular genotypes in NDLVC: extremely low QRS voltage is associated with PLN variants, while AV block is associated with laminopathies and desminopathies — worth recognizing as genotype-suggestive findings on a routine ECG, not just nonspecific abnormalities.

Elevated C-reactive protein can be seen in NDLVC (and in ARVC), particularly in the context of recurrent myocarditis-like episodes — directly relevant to the DSP-specific pattern described above.

First-line laboratory testing in suspected NDLVC includes calcium, creatine kinase, C-reactive protein, full blood count, liver function, NT-proBNP (or BNP), phosphate, proteinuria, renal function, and troponin — with second-line testing (organ- and non-organ-specific autoantibodies, viral serology) reserved for patients where a specific inflammatory or autoimmune etiology is being actively pursued.

Endomyocardial Biopsy

Reserved for specific situations where the result would genuinely affect diagnosis or treatment, given the real procedural risk involved. Electroanatomic voltage mapping-guided biopsy, performed at experienced centers, can improve diagnostic yield in NDLVC specifically — directing the biopsy toward electrically abnormal myocardium rather than sampling blindly. The same patchy, non-coronary distribution of disease that makes biopsy genuinely useful in cardiac sarcoidosis applies here — a blind sample from an unaffected region can be falsely reassuring.

Sudden Cardiac Death Risk: The Central Clinical Challenge

This is arguably the single most important thing to understand about managing NDLVC, and it’s worth stating plainly: SCD risk here does not track reliably with ejection fraction.

• Carriers of PLN, TMEM43, DES, DSP, LMNA, FLNC (truncating variants), and RBM20 variants have substantially higher rates of major arrhythmic events than other causes of NDLVC — regardless of LVEF. Most patients with NDLVC have normal or only mildly impaired systolic function, which is exactly why relying on EF alone, the way standard DCM risk stratification does, can genuinely underestimate risk in these specific genotypes.
• Genotype-specific and variant-specific risk calculators exist and should be used when available: a dedicated calculator for LMNA-related disease, and a variant-specific calculator for the PLN p.Arg14del variant — reflecting how far risk prediction in this disease has moved beyond a one-size-fits-all EF cutoff.
• Secondary prevention: ICD implantation is recommended for survivors of cardiac arrest, and for patients who have experienced sustained ventricular arrhythmia with hemodynamic compromise — the same standard as other cardiomyopathy phenotypes.
• Primary prevention: the LVEF ≤35% threshold used in DCM also applies to NDLVC, but — given the genotype-risk data above — ICD implantation should also be considered in NDLVC patients with non-sustained VT, a family history of sudden death, or significant LGE on CMR, even with preserved or near-normal EF. The patient’s specific genotype should factor directly into this risk estimate, not just their ejection fraction.
• Ambulatory ECG monitoring is recommended annually, or with any change in clinical status, specifically to detect supraventricular and ventricular arrhythmia or AV conduction block — monitored more frequently in high-risk genotypes (laminopathies, neuromuscular disease, PLN, and FLNC-truncating variants).

Clinical Presentation

Most patients with NDLVC are actually asymptomatic. When symptoms do occur, they typically relate to arrhythmia or conduction disease (syncope, palpitations) or diastolic heart failure (dyspnea). A genuinely sobering point worth stating directly: sustained ventricular arrhythmia, cardiac arrest, or sudden death can be the initial presentation in a proportion of patients — reinforcing why structured family screening and genotype-informed risk stratification matter so much here, rather than waiting for symptoms to guide the workup.

Family Screening

Data on the natural history of phenotype-negative variant carriers, and on the clinical yield of family cascade screening specifically in NDLVC, remain genuinely limited given how recently this category was formalized — but cross-sectional data suggest age-related penetrance increases over time, which is why long-term, precautionary evaluation of first-degree relatives is recommended even when an initial screening study looks entirely normal.

How to Diagnose It: A Practical Sequence

1. Consider NDLVC when LV dysfunction or scarring is present without dilation or hypertrophy — including isolated global hypokinesia without scarring, and cases presenting as recurrent myocarditis-like episodes, particularly with a family history of cardiomyopathy or sudden death.
2. Perform comprehensive TTE, including deformation imaging, since strain can detect subclinical dysfunction before conventional measures become abnormal — particularly relevant in genotype-positive relatives.
3. Pursue cardiac MRI with LGE as the primary confirmatory test — this, not echo, is what actually establishes the diagnosis in most cases, and the LGE pattern itself offers genotype-suggestive information.
4. Send genetic testing in every confirmed or strongly suspected case, given its direct implications for prognosis, device decisions, and family screening.
5. Correlate ECG findings with genotype-suggestive patterns — extremely low QRS voltage (PLN) and AV block (laminopathy, desminopathy) are both worth recognizing specifically.
6. Assess sudden death risk by genotype, not just EF — use a gene-specific or variant-specific risk calculator when the patient’s genotype has one available, and consider primary prevention ICD even with preserved EF when NSVT, a family history of SCD, or significant LGE are present.
7. Establish annual ambulatory ECG monitoring, more frequently in high-risk genotypes, given how often arrhythmia and conduction disease are early — sometimes the presenting — features of this disease.
8. Initiate long-term, precautionary first-degree relative screening, even after a normal initial study, given the age-related penetrance this disease shows.

Clinical Importance

NDLVC is the clearest illustration in this entire section of why the phenotype-first, then-etiology framework from the Introduction page actually matters in practice — a category that didn’t formally exist until 2023, built specifically to stop a real population of patients from being inconsistently labeled DCM, ALVC, or arrhythmogenic cardiomyopathy depending on which clinician saw them first. Its defining clinical lesson is equally direct: ejection fraction, the parameter most heart failure risk stratification is built around, genuinely isn’t the right tool here — genotype is, and treating NDLVC as “mild DCM” rather than its own distinct entity risks missing exactly the arrhythmic risk this diagnosis exists to capture.