Arrhythmogenic Left Ventricular Cardiomyopathy (ALVC)

Details

ALVC is the dominant-left phenotypic variant of arrhythmogenic cardiomyopathy: non-ischaemic subepicardial or mid-myocardial LV scar, most often inferolateral, with ventricular arrhythmias of LV origin and no or minor RV involvement. It has been recognised with desmosomal variants producing predominantly LV disease and with non-desmosomal variants (LMNA, PLN, FLNC, SCN5A, RBM20, DES). Diagnostic criteria now exist — the 2020 Padua criteria introduced LV-specific structural, ECG and arrhythmic findings, and the 2023 European Task Force criteria revised them — but neither has been prospectively validated. (sources/acm-padua-criteria-ijc-2020, rating: high; sources/acm-european-tf-criteria-rcm-2024, rating: high)

Key Facts

Epidemiology

• ALVC is significantly under-studied relative to ARVC. Diagnostic criteria now exist (Padua 2020; European Task Force 2023) but are not prospectively validated, so prevalence estimates are not comparable across centres. (sources/acm-padua-criteria-ijc-2020; sources/acm-european-tf-criteria-rcm-2024)
• Biventricular forms are common: 50% of ARVC index patients and 17% of family members show LV dysfunction; left-dominant and biventricular phenotypes are increasingly recognized with CMR. (sources/acm-hrs-2019)

Pathophysiology

• Gene-specific mechanisms: ALVC is produced by both desmosomal and non-desmosomal variants, each with distinct pathophysiology:
  • DSP — desmosomal disruption → LV-predominant fibrosis and arrhythmia
  • LMNA — nuclear envelope instability → conduction disease + AF → VT → DCM/ALVC
  • PLN — calcium handling dysregulation → inferolateral LGE + VT
  • FLNC — sarcomeric structural protein disruption → ring-like LGE + VT
  • SCN5A — sodium channel dysfunction → conduction disease + VT
  • RBM20, DES — additional non-desmosomal mechanisms
    Each gene produces a distinct phenotypic profile including or excluding conduction disease, skeletal myopathy, lipodystrophy, or low-voltage ECG. (sources/acm-hrs-2019)

Clinical Presentation

• ECG abnormalities vary by gene:
  • TWI in I, aVL, V4–V6
  • Generalized low voltage (PLN, DSP)
  • Progressive AV block (LMNA)
  • Minor repolarization changes only (FLNC and DES, where ECG is not an early marker)
    (sources/acm-hrs-2019)
• LGE on CMR is often subepicardial or mid-wall in the LV and may be the sole imaging abnormality in DSP-related disease — present even with normal LVEF and absent ECG changes. (sources/acm-hrs-2019)
• Overlap with DCM: The key distinction from DCM is arrhythmia as the early/dominant clinical presentation; LV dilatation and impaired function may be absent in early ALVC. As disease advances, the phenotype can become indistinguishable from DCM with HF. (sources/acm-hrs-2019)

Diagnosis

Padua Criteria (2020)

• ALVC is diagnosed when there is LV structural (with or without morpho-functional) abnormality plus a pathogenic ACM-causing variant, in the absence of RV involvement. Genetic confirmation is required because LV findings alone overlap with DCM, myocarditis and sarcoidosis. (sources/acm-padua-criteria-ijc-2020, rating: high)
• LV structural criterion — major: LGE in a stria pattern in ≥1 Bull's Eye segment of the free wall (subepicardial or mid-myocardial), septum or both, in two orthogonal views. Septal junctional LGE is excluded.
• LV morpho-functional — minor: global LV systolic dysfunction (reduced EF or global longitudinal strain) with or without dilatation; regional LV hypokinesia or akinesia of the free wall, septum or both.
• LV repolarisation — minor: inverted T waves in V4–V6 without complete LBBB.
• LV depolarisation — minor: low QRS voltages (<0.5 mV peak-to-peak) in limb leads, after excluding obesity, emphysema and pericardial effusion.
• LV arrhythmia — minor: >500 PVCs/24 h or non-sustained/sustained VT with RBBB morphology, excluding the fascicular pattern.

2023 European Task Force Criteria

• The genetic requirement is removed. ALVC can be diagnosed on clinical criteria regardless of genotype or aetiology, by analogy with DCM and HCM being primary or secondary. Post-myocarditis scar and genotype-negative idiopathic cases now qualify. (sources/acm-european-tf-criteria-rcm-2024, rating: high)
• LV structural criteria were re-tiered: major = "ring-like" LGE of ≥3 segments; minor = LGE of 1–2 Bull's Eye segments. Patchy/focal LGE is non-diagnostic.
• LV depolarisation was upgraded: low limb-lead voltages (<0.5 mV in all limb leads, other causes excluded) are major rather than minor.
• LV morpho-functional was tightened: the regional LV hypokinesia/akinesia criterion was removed, leaving global LV systolic dysfunction as the only minor morpho-functional criterion.
• LV arrhythmia criteria expanded: frequent or exercise-induced RBBB-morphology PVCs, RBBB NSVT/SVT, and cardiac arrest from VF/VT of unknown morphology are minor criteria.
• A morpho-functional or structural criterion remains mandatory, and the standard definite/borderline/possible thresholds apply (2 major, 1 major + 2 minor, or 4 minor; 1 major + 1 minor or 3 minor; 1 major or 2 minor).

Practical Points

• CMR with LGE is the diagnostic linchpin. LGE may be the only abnormality — global systolic dysfunction and wall-motion abnormality can both be absent — so a normal echo or cine-CMR does not exclude ALVC. (sources/acm-evolving-criteria-jaha-2021, rating: high)
• The LGE pattern is characteristic: subepicardial or mid-myocardial stria in the inferolateral free wall, often with septal involvement and a circumferential "ring-like" distribution.
• LVEF and LGE are linearly related in ALVC but unrelated in DCM, which helps separate the two; in ALVC the dysfunction reflects loss of contractile mass, in DCM it reflects impaired myocyte force generation. (sources/acm-evolving-criteria-jaha-2021)
• RBBB-morphology VT is a weak localising sign: two-thirds arise from the apical/inferior septum of a dilated RV, and only 17% from the LV. (sources/acm-evolving-criteria-jaha-2021)
• T-wave inversion extending from V2 to V6 may reflect severe RV dilatation rather than LV disease, because the displaced RV sits under the lateral leads.

Historical HRS 2019 Definition

• HRS 2019 defined ALVC by arrhythmia of predominantly LV origin plus cardiomyopathy not explained by ischaemic, valvular or hypertensive disease, with a separate requirement for documentation of LV-origin arrhythmia. That construct is broader and less anatomically specific than the Padua/European TF criteria. (sources/acm-hrs-2019, rating: very high)

Genetics

• Key causative genes: DSP, LMNA, PLN, FLNC, SCN5A, RBM20, DES — each producing a distinct phenotypic profile including or excluding conduction disease, skeletal myopathy, lipodystrophy, or low-voltage ECG. (sources/acm-hrs-2019)
• Both desmosomal (DSP) and non-desmosomal (LMNA, PLN, FLNC, SCN5A) variants are implicated, distinguishing ALVC from ARVC which is predominantly desmosomal. (sources/acm-hrs-2019)

Contradictions / Open Questions

• ALVC vs. NDLVC — classification conflict: Padua and the 2023 European TF criteria define ALVC as a distinct diagnosis; ESC 2023 does not recognise it, classifying these patients under NDLVC (or DCM if the LV is dilated). The definitions do not map cleanly because the European TF relies on tissue characterisation while ESC relies on end-diastolic volume. (sources/acm-padua-criteria-ijc-2020; sources/acm-european-tf-criteria-rcm-2024; sources/esc-cmp-2023, rating: very high)
• The 2023 criteria removed the genetic requirement — on no accuracy data. Padua required a pathogenic variant to separate ALVC from DCM, myocarditis and sarcoidosis; the 2023 European TF criteria accept any aetiology. Sensitivity rises and specificity is unmeasured, so the number of phenocopies now labelled ALVC is unknown. (sources/acm-padua-criteria-ijc-2020; sources/acm-european-tf-criteria-rcm-2024)
• No prospective validation of any ALVC criteria set. Padua was derived and tested in the same Padua cohort; the 2023 revision has no diagnostic-accuracy study. Case ascertainment therefore still varies by centre, and prevalence estimates are not comparable across publications. (sources/acm-evolving-criteria-jaha-2021; sources/acm-european-tf-criteria-rcm-2024)
• The LV morpho-functional criteria moved in opposite directions in 2023: the regional hypokinesia/akinesia criterion was removed while low limb-lead voltages were promoted to major. One change reduces sensitivity, the other increases it, and neither is supported by prospective data. (sources/acm-european-tf-criteria-rcm-2024)
• ALVC risk is disproportionate to LVEF. The 2023 authors argue SCD risk is substantial even with preserved ejection fraction, which is why they no longer require a genetic result or a depressed LVEF to diagnose — but the risk data supporting this are observational and mostly from desmosomal and FLNC cohorts. (sources/acm-european-tf-criteria-rcm-2024)

Connections

• Related to concepts/Arrhythmogenic-Cardiomyopathy
• Related to concepts/ACM-Diagnostic-Criteria — the criteria in full
• Related to concepts/ARVC-Task-Force-Criteria
• Related to entities/ARVC
• Related to entities/NDLVC
• Related to entities/DSP
• Related to entities/LMNA
• Related to entities/PLN
• Related to entities/FLNC
• Related to entities/SCN5A
• Related to concepts/Late-Gadolinium-Enhancement

Sources

• sources/acm-hrs-2019
• sources/acm-padua-criteria-ijc-2020
• sources/acm-evolving-criteria-jaha-2021
• sources/acm-european-tf-criteria-rcm-2024
• sources/esc-cmp-2023