Non-Dilated Left Ventricular Cardiomyopathy

Monogenic (Mendelian): a substantial share carry DCM/ACM-overlap variants (DSP, FLNC, DES, LMNA, TTN)^[1]

Acquired: includes post-myocarditis scar^[1]

Complex (likely polygenic): an umbrella phenotype; the non-monogenic remainder is heterogeneous and likely polygenic^[1]

Inheritance: Autosomal dominant most common (penetrance 30–50%); X-linked (TAZ, nearly 100% penetrance in males); mitochondrial (variable). For autosomal dominant forms, first-degree relatives have a 50% risk of inheriting the pathogenic variant.^[1]

Familial proportion: Approximately 40–50% of NDLVC cases have an identifiable genetic cause; family history of cardiomyopathy is present in ~30–50% of cases. Genetic testing using the DCM panel (R132) is recommended for all cases.^[1]

Genetic yield: ~40-50% (overlaps extensively with DCM gene panel)

Genetic overlap with the DCM / ARVC spectrum:

• Arrhythmogenic / scar-associated: DSP, FLNC, DES, PLN, RBM20 (overlap with the ARVC spectrum; associated with LV fibrosis and arrhythmic risk, often disproportionate to LV impairment)
• Sarcomeric: MYH7 (~15%, penetrance 60-80%), MYBPC3 (~10%, penetrance 50-70%), ACTC1 (~5%), TNNT2 (~3-5%), TPM1 (rare)
• Cytoskeletal: TTN (~20-25%, penetrance 30-40%), LDB3/ZASP (~2-3%)
• Nuclear envelope: LMNA (~5%, high penetrance, arrhythmia risk)
• X-linked: TAZ (~1-2% overall, nearly 100% penetrance in males) - Barth syndrome (infantile CM, neutropenia, 3-methylglutaconic aciduria, growth delay)
• Other: DTNA, PRDM16, FKTN (rare)

Gene frequencies and penetrance figures derive largely from referral cohorts and vary with variant class and ascertainment; treat them as indicative rather than fixed.

Pathophysiology: Shares pathways with the DCM and arrhythmogenic cardiomyopathy spectrum (sarcomeric, cytoskeletal and desmosomal dysfunction) producing myocardial fibrosis/scar and LV systolic impairment without dilatation. Excessive trabeculation, if present, is now regarded as a phenotypic trait or epiphenomenon rather than the primary disease (the historical "arrested compaction" theory is disputed); 2023 ESC: trabeculations alone do NOT define the condition.

Genetic testing: Same gene panel as DCM (R132). Genetic diagnosis important for family screening, prognosis (LMNA, TAZ high-risk), and distinguishing from isolated trabeculations (common normal variant).

A category introduced by the 2023 ESC guidelines, so robust prevalence data are lacking and its true frequency is uncertain.^[1]

Separate issue: excessive LV trabeculation / "non-compaction" was historically over-diagnosed on non-specific echocardiographic criteria; the 2023 guideline reclassifies it as a phenotypic trait, not a distinct cardiomyopathy.^[1]

Can present at any age from infancy to late adulthood.

Confirmatory work-up: echocardiography establishes a non-dilated LV with systolic dysfunction; CMR with late gadolinium enhancement characterises fibrosis and helps exclude other phenotypes; and genetic testing (DCM/arrhythmogenic panel) is recommended, genotype drives arrhythmic risk and family screening.^[1]

2023 ESC Definition:

• Non-dilated LV with non-ischaemic LV scar / fibrofatty replacement (with or without systolic dysfunction), OR
• Isolated global LV hypokinesia without scar, in a non-dilated LV
• Does NOT meet criteria for HCM, DCM, ARVC or another specific cardiomyopathy
• Excessive trabeculation, if present, is not itself diagnostic

Key Change: NDLVC is defined by scar or dysfunction, not by trabeculation; excessive trabeculation alone is now a phenotypic trait, not a cardiomyopathy

Clinical Features:

• Heart failure symptoms
• Arrhythmias (AF, VT)
• Thromboembolic events
• Family history in ~40-50%

Echocardiography:^[1]

• Assess LV size and systolic function, dysfunction is required for diagnosis
• Trabeculations may be present but are NOT diagnostic in isolation
• Exclude other causes of LV dysfunction (HCM, DCM, infiltrative)

Cardiac MRI:^[1]

• Better characterisation of trabeculations and myocardial structure
• Late gadolinium enhancement for fibrosis, prognostic significance
• Do NOT diagnose based on trabeculation measurements alone

Genetic testing: R132 DCM panel^[1]

Treat as per standard heart failure guidelines:

• Guideline-directed medical therapy for HFrEF
• ACEi/ARB, beta-blockers, MRA, SGLT2i
• Anticoagulation if AF or LV thrombus
• Consider anticoagulation even in sinus rhythm if severe dysfunction

Device therapy: ICD/CRT as per standard HFrEF guidelines, but lower the ICD threshold for high-risk genotypes (LMNA, FLNC, PLN, DSP, RBM20), where arrhythmic risk exceeds that predicted by LVEF alone.^[1]

• Ventricular arrhythmia and sudden cardiac death: can precede systolic dysfunction, with risk driven by genotype (LMNA, FLNC, PLN, DSP, RBM20, DES)^[1]
• Progression to overt DCM and heart failure.
• Atrial fibrillation and conduction disease.

Risk stratification: Use standard DCM/HFrEF risk tools

Prognosis: Similar to dilated cardiomyopathy when matched for EF

ICD indications: Same as DCM (primary prevention if LVEF ≤35% despite OMT)

Based on ESC 2023 Cardiomyopathy guidelines^[1].

Advanced / complicated = falling LVEF, significant ventricular arrhythmia, high-risk genotype (LMNA, FLNC, PLN, DSP, RBM20), or a device in situ.

Genotype-positive / phenotype-negative (G+/P−) = a confirmed pathogenic-variant carrier with no overt disease expression yet.

	Genotype+ / Phenotype−	Uncomplicated / Stable	Advanced / Complicated
Frequency	Every 2–3 yrs (genotype-guided)	Every 1–2 years	Every 3–6 months
Clinical review	Symptoms	Symptoms, NYHA, arrhythmia history	As above + device check
ECG	Each screening visit	Annual 12-lead	Each visit
Echocardiography	Each screening visit	Every 1–2 years	6-monthly
Holter / ambulatory	If high-risk genotype	Annual (genotype-driven)	6-monthly
CMR	Consider (early fibrosis)	Baseline + if phenotype changes (LGE)	As indicated
Family screening	–	Cascade ECG + imaging (genotype-guided)	–

Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.

• Do NOT diagnose based on trabeculations alone - requires LV dysfunction^[1]
• Prominent trabeculations are common normal variants
• Manage as DCM/HFrEF - not a separate disease entity^[1]
• Screen family members as for DCM
• Genetic testing using DCM panel (R132)^[1]