Arrhythmogenic Cardiomyopathy (ACM)
Definition
Arrhythmogenic cardiomyopathy is a heart muscle disease affecting the right ventricle, the left ventricle or both, whose distinctive feature is non-ischaemic myocardial scar — fibrous or fibro-fatty replacement — that underlies global or regional ventricular dysfunction and predisposes to scar-related ventricular arrhythmias, regardless of the severity of systolic dysfunction. This is the Padua definition and the one used by the 2023 European Task Force, which proposes the broader label "scarring/arrhythmogenic cardiomyopathy" to make the point that the scar, not the aetiology, defines the disease. (sources/acm-padua-criteria-ijc-2020, rating: high; sources/acm-european-tf-criteria-rcm-2024, rating: high)
The competing HRS 2019 definition is broader still — "an arrhythmogenic heart muscle disorder not explained by ischemic, hypertensive, or valvular disease" — and incorporates sarcoidosis, amyloidosis, myocarditis, Chagas disease, lamin A/C, filamin C, phospholamban and ion-channel diseases. The Padua and European Task Force authors reject that construct because "arrhythmic clinical presentation" is not a pathobiological basis for grouping heterogeneous diseases. (sources/acm-hrs-2019, rating: very high)
Key Concepts
Spectrum and Classification
| Variant | Ventricular involvement | Detail |
|---|---|---|
| ARVC (dominant-right) | RV-predominant; no or minor LV abnormality | entities/ARVC |
| Biventricular ACM | Parallel RV and LV involvement | Criteria applied in both ventricular blocks |
| ALVC (dominant-left) | LV-predominant; no or minor RV abnormality | entities/ALVC |
- The variant is decided by morpho-functional and structural criteria, not by genotype. A PKP2 variant can produce ARVC, biventricular disease or ALVC, and the same family may span the spectrum. (sources/acm-padua-criteria-ijc-2020, rating: high)
- NDLVC is not an ACM variant. It is the ESC 2023 category that replaces ALVC and left-dominant ARVC for classificatory purposes; the 2023 European Task Force criteria reject that substitution. See entities/NDLVC. (sources/esc-cmp-2023, rating: very high; sources/acm-european-tf-criteria-rcm-2024)
- Under the HRS 2019 umbrella, ACM also encompasses acquired and systemic causes — cardiac amyloidosis, sarcoidosis, myocarditis, Chagas disease, LMNA, FLNC, PLN and ion-channel disease. The Padua/European Task Force construct is narrower and treats those as genocopies or phenocopies to be classified separately. (sources/acm-hrs-2019; sources/acm-european-tf-criteria-rcm-2024)
- Overlap with other cardiomyopathies: sarcomeric variants can produce an ACM-like phenotype (troponin T → SCD without significant hypertrophy; troponin I → RCM with AF), and ACM overlaps with RCM and LVNC. (sources/acm-hrs-2019)
Shared Genetic Architecture
- Causative genes span multiple protein classes: desmosomal (PKP2, DSP, DSG2, DSC2, JUP), nuclear envelope (LMNA), sodium channel (SCN5A), cytoskeletal (FLNC, DES, LDB3/ZASP), calcium handling (PLN), RNA splicing (RBM20), transmembrane (TMEM43) and chaperone (BAG3). Desmosomal detail and ClinGen validity for ARVC are on entities/ARVC; the ALVC gene set is on entities/ALVC. (sources/acm-hrs-2019, rating: very high)
- Autosomal dominant inheritance predominates; 3–6% carry multiple pathogenic variants, associated with earlier onset (<20 versus 35 years for single-variant patients) and higher lifetime arrhythmia/SCD risk. (sources/acm-hrs-2019)
- Penetrance is incomplete and age-related. Expression peaks between 20 and 50 years (40%); expression under 14 is almost exclusively seen in probands, not at-risk relatives. (sources/acm-hrs-2019)
Final Common Pathway
- The "final common pathway" hypothesis holds that ACM subtypes converge on dysfunction of protein complexes at the intercalated disc — primarily the desmosome in ARVC, with broader involvement of the area composita (desmosome plus adherens junction) across ACM. (sources/acm-hrs-2019)
- Full mechanism: concepts/Final-Common-Pathway · concepts/Desmosome.
Diagnostic Approach
- Four generations of criteria exist: 1994 Task Force, 2010 revised International Task Force, 2020 Padua, and 2023 European Task Force. The 2010 criteria remain the version cited by ESC 2023; Padua and the 2023 European TF are the specialist standard. Full comparison: concepts/ACM-Diagnostic-Criteria; 2010 detail: concepts/ARVC-Task-Force-Criteria.
- Any diagnosis requires at least one morpho-functional or structural criterion. Genetics, ECG abnormality or arrhythmia alone is insufficient, because ACM is a structural heart disease. (sources/acm-padua-criteria-ijc-2020)
- CMR with LGE is mandatory in practice to characterise the phenotype and exclude mimics; LV LGE may be the only abnormality, so a normal echo or cine-CMR does not exclude left-sided disease. (sources/acm-evolving-criteria-jaha-2021, rating: high)
- ALVC was redefined: Padua required a pathogenic ACM variant; the 2023 European TF criteria allow diagnosis on clinical criteria regardless of genotype or aetiology. (sources/acm-padua-criteria-ijc-2020; sources/acm-european-tf-criteria-rcm-2024)
Management Principles
- Management is phenotype- and genotype-specific, so no single class-wide regimen exists. ARVC exercise restriction, antiarrhythmics, ICD thresholds, ablation and heart-failure care are on entities/ARVC; ALVC and NDLVC management on their entity pages.
- Secondary-prevention ICD after cardiac arrest or haemodynamically unstable sustained VT applies across phenotypes. Primary prevention depends on genotype, LVEF, scar burden and additional risk factors. (sources/acm-hrs-2019)
- Exercise restriction is the major modifiable risk factor in ARVC — competitive and high-intensity endurance exercise is contraindicated (COR III: Harm). It is not established to the same degree in ALVC or in PLN p.Arg14del. See concepts/Exercise-Restriction-in-ARVC. (sources/acm-hrs-2019)
Nomenclature
- Three incompatible frameworks are in use. HRS 2019 treats ACM as a broad umbrella; Padua and the 2023 European TF retain a narrower scar-defined ACM that includes ALVC; ESC 2023 rejects ACM as a diagnostic category and classifies LV-dominant disease as NDLVC or DCM. (sources/acm-hrs-2019; sources/esc-cmp-2023; sources/acm-european-tf-criteria-rcm-2024)
- The 2023 European Task Force proposes "scarring/arrhythmogenic cardiomyopathy" to name the scar rather than the aetiology, and explicitly rejects ESC's "2010 ARVC plus NDLVC" construct. The rename is a proposal, not an adopted classification. (sources/acm-european-tf-criteria-rcm-2024)
Contradictions / Open Questions
- Nomenclature conflict — ACM versus phenotype-based classification: the same patient can be ALVC in Padua, ALVC in the European Task Force and NDLVC in ESC — three labels, two incompatible logics. (sources/acm-hrs-2019; sources/acm-padua-criteria-ijc-2020; sources/esc-cmp-2023; sources/acm-european-tf-criteria-rcm-2024)
- The HRS "arrhythmia-first" criterion excludes late presentations. Late-stage DCM-phenotype disease from a PKP2 or DSP variant may present with heart failure before arrhythmia is recognised, and be mis-categorised as DCM, missing exercise counselling and gene-specific ICD thresholds. (sources/acm-hrs-2019)
- Padua and the 2023 criteria disagree on whether genetics is required for ALVC. Padua required a pathogenic variant to separate ALVC from DCM, myocarditis and sarcoidosis; the 2023 criteria accept any aetiology. The change increases sensitivity but has no published specificity data, so the proportion of phenocopies now labelled ALVC is unknown. (sources/acm-padua-criteria-ijc-2020; sources/acm-european-tf-criteria-rcm-2024)
- "Scarring/arrhythmogenic cardiomyopathy" would make aetiology irrelevant. The proposal defines the disease by non-ischaemic scar plus arrhythmic risk, which could include sarcoidosis, myocarditis and idiopathic scar — the entities Padua excluded. Whether this is a useful category or a loss of specificity is unresolved. (sources/acm-european-tf-criteria-rcm-2024)
- All criteria sets lack external prospective validation. Padua was derived from one institution's practice and tested post hoc in its own cohort; the 2023 revision has no accuracy data. The field is treating consensus as evidence. (sources/acm-evolving-criteria-jaha-2021; sources/acm-european-tf-criteria-rcm-2024)
Connections
- Phenotypes: entities/ARVC · entities/ALVC · entities/NDLVC
- Criteria: concepts/ACM-Diagnostic-Criteria · concepts/ARVC-Task-Force-Criteria
- Mechanism and imaging: concepts/Final-Common-Pathway · concepts/Desmosome · concepts/Late-Gadolinium-Enhancement
- Genetics: entities/PKP2 · entities/DSP · entities/DSG2 · entities/DSC2 · entities/JUP · entities/TMEM43 · entities/DES · entities/PLN · concepts/ClinGen-Gene-Disease-Validity · concepts/Genetic-Testing-in-Cardiomyopathy
- Clinical: concepts/Cascade-Family-Screening · concepts/Sudden-Cardiac-Death · concepts/Exercise-Restriction-in-ARVC · concepts/Phenotypic-Approach-to-Cardiomyopathy · concepts/Channelopathies