Arrhythmogenic Left Ventricular Cardiomyopathy (ALVC)
Details
ALVC is an arrhythmogenic cardiomyopathy (ACM) with predominantly left ventricular origin of arrhythmia and structural abnormalities, distinct from ARVC's right-dominant phenotype. It has been recognized with the identification of desmosomal disease-causing variants producing predominantly LV arrhythmia and structural disease, and with non-desmosomal arrhythmia-associated variants (LMNA, PLN, FLNC, SCN5A). ALVC is significantly under-studied relative to ARVC, with no internationally validated diagnostic criteria yet established.
Epidemiology
- ALVC is significantly under-studied relative to ARVC, with no internationally validated diagnostic criteria yet established. (sources/acm-hrs-2019)
- 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
- Definition: ACM of LV origin diagnosed by: arrhythmia of isolated or predominantly LV origin in a proband or family member with cardiomyopathy not caused by ischemic, valvular, or hypertensive disease. Impaired LV function and/or structural abnormalities can be absent, mild, or severe. (sources/acm-hrs-2019)
- LV origin arrhythmia requirement: Documentation of ventricular arrhythmia of predominantly LV origin is required for diagnosis; precise VT definitions and VPC frequency thresholds for ALVC remain to be established. (sources/acm-hrs-2019)
- No validated international diagnostic criteria exist — unlike ARVC (Task Force Criteria), ALVC lacks standardized diagnostic thresholds, creating heterogeneous case ascertainment across centers. (sources/acm-hrs-2019)
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: HRS 2019 defines ALVC as a distinct subtype of ACM (arrhythmia of predominantly LV origin + cardiomyopathy not explained by other causes). ESC 2023 does not recognize ALVC as a category, instead classifying these patients under NDLVC (or DCM if dilatation is present). There are no validated international diagnostic criteria for ALVC, and the terminology is used inconsistently across publications. (sources/acm-hrs-2019, sources/esc-cmp-2023)
- Absence of validated diagnostic criteria: The HRS 2019 definition requires documentation of ventricular arrhythmia of predominantly LV origin as a key criterion, but precise VT definitions, VPC frequency thresholds, and minimum structural change requirements for ALVC remain undefined — creating heterogeneous case ascertainment across centers. (sources/acm-hrs-2019)
Connections
- Related to concepts/Arrhythmogenic-Cardiomyopathy
- Related to entities/ARVC
- Related to entities/DSP
- Related to entities/LMNA
- Related to entities/PLN
- Related to entities/FLNC
- Related to entities/SCN5A
- Related to concepts/ARVC-Task-Force-Criteria