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

Diagnosis of arrhythmogenic cardiomyopathy: the Padua criteria

Authors, Journal, Affiliations, Type, DOI

Authors: Domenico Corrado, Martina Perazzolo Marra, Alessandro Zorzi, Giorgia Beffagna, Alberto Cipriani, Manuel De Lazzari, Federico Migliore, Kalliopi Pilichou, Alessandra Rampazzo, Ilaria Rigato, Stefania Rizzo, Gaetano Thiene, and international collaborators including Aris Anastasakis, Angeliki Asimaki, Chiara Bucciarelli-Ducci, Kristine H. Haugaa, Francis E. Marchlinski, Andrea Mazzanti, William J. McKenna, Antonis Pantazis, Antonio Pelliccia, Christian Schmied, Sanjay Sharma, Thomas Wichter, Barbara Bauce and Cristina Basso
Journal: International Journal of Cardiology, 2020;319:106–114
Affiliations: University of Padova (lead); Onassis Cardiac Surgery Centre Athens; St George's University of London; Bristol Heart Institute; Oslo University Hospital; University of Pennsylvania; University of Pavia; University College London; Royal Brompton and Harefield; Institute of Sports Medicine and Science Rome; University Heart Center Zurich; Osnabrück
Type: International expert consensus document
DOI: https://doi.org/10.1016/j.ijcard.2020.06.005

Overview

The Padua criteria are an international expert consensus that upgrades the 2010 Task Force criteria from a right-ventricular disease model to the full arrhythmogenic cardiomyopathy spectrum — dominant-right (ARVC), biventricular and dominant-left (ALVC). The central innovation is tissue characterisation by contrast-enhanced cardiac magnetic resonance: late gadolinium enhancement becomes a diagnostic criterion in both ventricles, and LV LGE is the major structural criterion for left-sided disease. New LV-specific ECG and arrhythmia criteria are added, and the diagnosis is made only when at least one morpho-functional or structural criterion is present, because ACM is a structural heart disease. For ALVC without RV involvement the criteria require a pathogenic ACM gene variant, a restriction the 2023 European Task Force later removed.

Keywords

Arrhythmogenic cardiomyopathy; ARVC; ALVC; biventricular ACM; Padua criteria; cardiac magnetic resonance; late gadolinium enhancement; desmosome; task force criteria; diagnosis

Key Takeaways

Definition and Classification

ACM is defined as a genetic heart muscle disease affecting the RV, LV or both, whose most distinctive feature is myocardial scar — fibrous or fibro-fatty replacement — underlying global and/or regional dysfunction and predisposing to scar-related ventricular arrhythmias regardless of the severity of systolic dysfunction.
Three phenotypic variants: dominant-right (classic ARVC, no or minor LV abnormality), biventricular (parallel RV and LV involvement), and dominant-left (ALVC, no or minor RV abnormality).
The authors reject the HRS 2019 umbrella definition that includes sarcoidosis, amyloidosis, myocarditis, Chagas disease, lamin A/C, filamin C, phospholamban and ion-channel diseases. In their view, an "arrhythmic clinical presentation" is not a pathobiological basis for grouping heterogeneous diseases; ACM remains a nosographically distinct cardiomyopathy.

The Six Categories

I. Morpho-functional ventricular abnormalities
- RV major: regional akinesia, dyskinesia or bulging plus global RV dilatation or systolic dysfunction, regardless of severity. The previous major/minor severity split is abolished as more useful prognostically than diagnostically.
- RV minor: regional wall motion abnormality alone, recognising the segmental nature of fibro-fatty lesions.
- LV minor: global LV systolic dysfunction (reduced EF or global longitudinal strain) with or without dilatation; LV minor: regional hypokinesia or akinesia of the free wall, septum or both.
II. Structural myocardial abnormalities
- RV major: transmural LGE in a stria pattern in ≥1 RV region (inlet, outlet, apex) in two orthogonal views.
- RV major: fibrous replacement with or without fatty tissue in ≥1 endomyocardial biopsy sample.
- LV major: LV LGE in a stria pattern in ≥1 Bull's Eye segment of the free wall (subepicardial or mid-myocardial), septum or both, excluding septal junctional LGE.
III. Repolarisation
- RV major: inverted T waves in V1–V3 or beyond after completed puberty, without complete RBBB.
- RV minor: inverted T waves in V1–V2; or V1–V4 with complete RBBB.
- LV minor: inverted T waves in V4–V6 without complete LBBB.
IV. Depolarisation/conduction
- RV minor: epsilon wave; terminal activation duration ≥55 ms in V1–V3 without complete RBBB.
- LV minor: low QRS voltages (<0.5 mV peak-to-peak) in limb leads, after excluding obesity, emphysema and pericardial effusion.
V. Ventricular arrhythmias
- RV major: >500 PVCs/24 h, non-sustained or sustained VT with LBBB morphology (non-inferior axis).
- RV minor: the same with inferior axis — the RVOT pattern — which is commonly idiopathic.
- LV minor: >500 PVCs/24 h, non-sustained or sustained VT with RBBB morphology, excluding the fascicular pattern.
VI. Family history/genetics
- Major: ACM in a first-degree relative meeting criteria; ACM confirmed pathologically at autopsy or surgery in a first-degree relative; identification of a pathogenic or likely pathogenic ACM variant in the patient.
- Minor: history of ACM in a first-degree relative who cannot be classified; premature SCD (<35 years) from suspected ACM in a first-degree relative; ACM confirmed in a second-degree relative.

Diagnostic Algorithm

A diagnosis of ACM requires at least one criterion, major or minor, from category I or II — morpho-functional or structural. Genetic, ECG or arrhythmic findings alone cannot diagnose a structural heart disease, by analogy with HCM requiring demonstration of hypertrophy.
ARVC: definite = 2 major, or 1 major + 2 minor, or 4 minor from different categories; borderline = 1 major + 1 minor, or 3 minor; possible = 1 major, or 2 minor. At least one morpho-functional or structural criterion is required at every level.
Biventricular ACM: ≥1 morpho-functional and/or structural abnormality in both RV and LV; the total criteria across both ventricles determine definite, borderline or possible. The concurrent RV criteria supply disease specificity to the LV findings.
ALVC: 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 morpho-functional and LGE findings overlap with DCM, myocarditis and sarcoidosis.

What Changed from 2010

CMR tissue characterisation enters the criteria for the first time, in both ventricles. RV LGE was excluded in 2010 because of poor spectral resolution and contrast-to-noise ratio in the thin RV wall, but yield up to 88% and a 98% diagnostic accuracy when combined with wall-motion assessment justified inclusion.
The severity-based major/minor split for RV dilatation/dysfunction is removed — one major criterion remains, with the minor criterion redefined as isolated regional wall-motion abnormality.
Epsilon wave is downgraded from major to minor, because identification varies with filtering, sampling rate and observer.
Signal-averaged ECG is removed entirely.
LV criteria are new, including LGE, low limb-lead voltages, lateral T-wave inversion and RBBB-morphology arrhythmia.
EMB major/minor grading is abolished; any replacement-type fibrosis in ≥1 sample is major, and biopsy is reserved for sporadic genotype-negative probands in whom a phenocopy must be excluded.

Clinical Impact

In 112 Padua patients previously classified by the 2010 criteria (87 definite, 15 borderline, 9 possible), 51 of 87 definite ARVC were reclassified as biventricular after LV criteria were applied. Of 15 borderline, 5 became definite (RV LGE) and 6 biventricular (LV LGE). Of 9 possible cases diagnosed on a desmosomal or FLNC variant alone, 7 became ALVC on the LV LGE criterion. (sources/acm-evolving-criteria-jaha-2021, rating: high)
The authors state the criteria require prospective validation in large cohorts; the document is a working framework, not a validated score.

Limitations Acknowledged

LV abnormalities are non-specific and overlap with DCM, myocarditis and sarcoidosis, which is why ALVC requires genetic confirmation.
CMR is mandatory in practice, limiting deployment where access or expertise is lacking.
The cardiomyocyte-level definition of "fibro-fatty replacement" remains imperfect, and biopsy suffers sampling error.
Athlete RV dilatation can exceed population nomograms, so athlete-specific reference values are needed.

Limitations of the document

Consensus, not validated criteria. The authors explicitly call for validation; no prospective diagnostic-accuracy study underpins the thresholds, and sensitivity/specificity are unknown.
The ALVC genetic requirement creates a paradox: a patient with extensive subepicardial LGE, RBBB VT and a positive family history but a negative panel remains undiagnosed, even though the phenotype is typical. The 2023 European Task Force removed this requirement for exactly that reason.
Single-centre derivation. The criteria derive from 30 years of Padua practice and were then shared with international experts; the evidence base is therefore concentrated in one institution's cohort.
CMR dependency makes the criteria difficult to apply in centres without advanced tissue-characterisation expertise, and the document gives no minimum protocol standard.
No risk-stratification or management content — the document is purely diagnostic.
The HRS umbrella definition is rejected without a formal comparison of outcomes between the narrow and broad ACM constructs.

Key Concepts Mentioned

Key Entities Mentioned

Wiki Pages Updated

The ingest entry is in log.md.