#arrhythmogenic-cardiomyopathy #ARVC #ALVC #diagnostic-criteria #cardiac-magnetic-resonance #late-gadolinium-enhancement

Evolving Diagnostic Criteria for Arrhythmogenic Cardiomyopathy

Authors, Journal, Affiliations, Type, DOI

Authors: Domenico Corrado, Alessandro Zorzi, Alberto Cipriani, Barbara Bauce, Riccardo Bariani, Giorgia Beffagna, Manuel De Lazzari, Federico Migliore, Kalliopi Pilichou, Alessandra Rampazzo, Ilaria Rigato, Stefania Rizzo, Gaetano Thiene, Martina Perazzolo Marra, Cristina Basso
Journal: Journal of the American Heart Association, 2021;10:e021987 (Contemporary Review)
Affiliations: Department of Cardiac, Thoracic and Vascular Sciences and Public Health, and Department of Biology, University of Padova, Italy
Type: Review article
DOI: https://doi.org/10.1161/JAHA.121.021987

Overview

A single-group historical review tracing ACM diagnosis from the 1994 Task Force criteria through the 2010 revision to the 2020 Padua criteria, with a detailed category-by-category comparison and the post-hoc reclassification of a Padua cohort. Its value is the explicit account of why each revision happened: 1994 was qualitative and insensitive to early disease, 2010 added quantitative imaging and molecular genetics but remained RV-only, and 2020 added CMR tissue characterisation and LV criteria. It also supplies a cautionary mapping study showing that most RBBB-morphology VT in ACM does not originate from the LV.

Keywords

Arrhythmogenic cardiomyopathy; ARVC; ALVC; Task Force criteria; Padua criteria; cardiac magnetic resonance; late gadolinium enhancement; diagnosis; repolarisation; ventricular arrhythmia

Key Takeaways

1994 Task Force Criteria

Six categories — global/regional dysfunction and structural alteration, tissue characterisation, repolarisation, depolarisation/conduction, arrhythmias, family history — with major and minor criteria; definite diagnosis required 2 major, 1 major + 2 minor, or 4 minor from different categories.
Designed for specificity in overt RV disease, at the cost of sensitivity in early and familial disease.
Limitations: qualitative RV size and function (mild/severe by standard deviations, with "moderate" undefined), subjective wall-motion assessment, no definition of fibro-fatty replacement, no definition of epsilon wave, and ventricular arrhythmia deliberately classified as minor to avoid mislabelling benign RVOT VT.
Morpho-functional criteria required no or only mild LV impairment, a prerequisite that excluded biventricular disease by construction.

2010 Revised Task Force Criteria

Quantitative imaging reference values by sex and body surface area were introduced, and global RV dilatation/dysfunction had to accompany regional wall-motion abnormality. Severity separated major from minor.
New "borderline" and "possible" diagnostic tiers were added.
EMB morphometry defined residual myocyte thresholds (<60% major, 60–75% minor).
Molecular genetics entered the family-history category: a pathogenic variant in a first-degree relative or the proband became major.
T-wave inversion V1–V3 became major, and LBBB VT with superior/indeterminate axis became major; RVOT-pattern VT and >500 PVCs/24 h remained minor.
CMR tissue characterisation was deliberately excluded because of limited experience and low perceived specificity at the time.
The criteria remained RV-only, so biventricular and left-dominant disease could not be diagnosed.

2020 Padua Criteria

Tissue characterisation by CMR became the central innovation. Transmural RV LGE in ≥1 region is major; LV LGE in a stria pattern in ≥1 Bull's Eye segment is the major structural criterion for left-sided disease. Septal junctional LGE is excluded as non-pathological.
LV morpho-functional criteria are minor because they overlap with DCM; regional LV hypokinesia/akinesia is also minor.
LV ECG criteria: lateral T-wave inversion (V4–V6) and low limb-lead QRS voltages (<0.5 mV) are minor.
LV arrhythmia criterion: RBBB-morphology PVCs/VT, excluding the fascicular pattern, is minor.
Epsilon wave was downgraded to minor because of filtering/sampling dependence and interobserver variability; signal-averaged ECG was removed.
Diagnosis requires ≥1 morpho-functional or structural criterion; genetic, ECG or arrhythmic findings alone are insufficient.
ALVC requires a pathogenic variant in addition to LV phenotype, because LV findings alone cannot separate ACM from DCM, myocarditis or sarcoidosis.

Why RBBB VT Is a Weak Localising Sign

In a mapping/ablation series, two-thirds of RBBB-morphology VT in ACM originated from the apical or inferior septum of a dilated RV, with early transition to a negative QRS by V3. Only 17% actually arose from the LV, and those showed a broad positive V1, absent precordial transition and rightward axis.
This is why the LV arrhythmia criterion is minor, and why a dilated, displaced RV can produce "left-sided" T-wave inversion in V4–V6 without LV disease.

ALVC versus DCM

The relationship between LVEF and LGE differs. In ALVC, LVEF reduction correlates linearly with the percentage of LV LGE; in DCM, systolic dysfunction and LGE are unrelated, because DCM dysfunction reflects impaired myocyte force generation and LGE is an epiphenomenon.
The typical ALVC remodelling pattern is a hypokinetic or normokinetic, non-dilated or mildly dilated LV with subepicardial/mid-myocardial inferolateral LGE, often with septal involvement and a "ring-like" pattern.
LGE may be the only abnormality — global systolic dysfunction and wall-motion abnormality can both be absent, so LV involvement cannot be excluded by normal echo or cine-CMR.

Clinical Impact of the Padua Criteria

In 112 consecutive Padua patients (2015–2019): 87 definite, 15 borderline, 9 possible by 2010 criteria.
51 of 87 definite ARVC were reclassified as biventricular after LV criteria were applied.
5 of 15 borderline became definite (RV LGE) and 6 became biventricular (LV LGE).
7 of 9 possible cases became ALVC on the LV LGE criterion; all 9 had a pathogenic desmosomal or FLNC variant (4 DSP, 3 FLNC, 2 DSG).
The authors conclude the criteria increase diagnostic accuracy and improve phenotypic characterisation, but require external validation.

Genetic Testing Indications

Recommended in a proband already meeting right-dominant or biventricular ACM, to enable cascade testing.
May be considered in borderline phenotypes, provided interpretation is by ACM genetics experts.
Mandatory for ALVC without RV involvement under the 2020 criteria, because the variant is the most specific link between LV phenotype and ACM.

Limitations of the document

Written by the criteria's authors, so the historical narrative and the justification for the Padua upgrade are not independent; no competing criteria set is given equivalent space.
The reclassification data are post hoc and single-centre, drawn from the same Padua cohort that generated the criteria, which inflates apparent improvement.
No diagnostic-accuracy statistics (sensitivity, specificity, predictive values) are reported against an independent gold standard.
Published in 2021, before the 2023 European Task Force revision, so it presents the 2020 genetic requirement for ALVC as settled — a requirement since removed.
The review is diagnosis-only and does not address risk stratification, therapy or outcomes.
The RBBB-VT mapping study is small, and its 17% LV-origin figure should not be treated as a stable estimate.

Key Concepts Mentioned

Key Entities Mentioned

Wiki Pages Updated

The ingest entry is in log.md.