Don't
Miss
SCD can be the first signA young adult or athlete with exertional syncope, palpitations, or sustained VT (LBBB morphology) — think AC before labeling "idiopathic RVOT VT".
Family history mattersAutosomal-dominant desmosomal disease — SCD in a young relative or a known familial variant is a major clue. Cascade-screen first-degree relatives.
"Hot phase" mimics myocarditisChest pain + troponin rise + normal coronaries, esp. with DSP variants — recurrent "myocarditis" can be left-dominant AC.
Two parallel jobsProtect from arrhythmia (risk-stratify ± ICD) and restrict exercise — endurance sport accelerates the disease. Neither replaces the other.
01
When to Suspect
Phenotype & red flags
Presentations
- Ventricular arrhythmia palpitations, sustained VT (often LBBB morphology), frequent PVCs, aborted SCD.
- RV / biventricular failure late; RV dilation & dysfunction, regional wall-motion abnormality.
- Athlete with syncope exertional syncope or arrest — AC is a leading cause of young-athlete SCD.
ECG clues
- T-wave inversion V1–V3 (beyond age 14, no RBBB).
- Epsilon wave; terminal activation delay; low QRS voltage (left-dominant).
- PVC/VT of LBBB morphology (RV origin).
Three phenotypes Classic RV-dominant (ARVC), biventricular, and left-dominant (ALVC) — the modern umbrella is arrhythmogenic cardiomyopathy. Left-dominant forms are easily missed.
02
2010 Task Force Criteria
6 categories · major/minor
- I · Structure/function RV dysfunction & regional abnormality (echo / CMR / angiography).
- II · Tissue fibrofatty replacement on biopsy.
- III · Repolarization T-wave inversion V1–V3.
- IV · Depolarization epsilon wave, terminal activation delay, SAECG late potentials.
- V · Arrhythmia VT (LBBB), frequent PVCs.
- VI · Family/genetics first-degree relative, pathogenic desmosomal variant.
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, from different categories.
03
Padua Upgrade & Imaging
CMR · left-dominant
- Padua criteria add left-ventricular & biventricular phenotypes and CMR tissue characterization (nonischemic LGE) to the diagnostic scheme.
- CMR RV/LV volumes & wall motion; LGE (often subepicardial LV in left-dominant disease). Fat alone is nonspecific and not a diagnostic CMR criterion.
- Always exclude mimics idiopathic RVOT VT, sarcoidosis, myocarditis, athlete's heart.
Don't call it RVOT VT
Apparently "idiopathic" RV VT in a young patient with any ECG/imaging/family clue deserves a full AC workup (CMR + genetics) before reassurance.
▶
2010 Task Force Criteria — selected major / minor items
MAJOR MINOR
| Category | Major | Minor |
|---|
Structure / function
(echo · CMR · RV angio) | Regional RV akinesia/dyskinesia/aneurysm plus RVOT ↑ or RV EF ↓ (severe thresholds). | Same regional abnormality with milder dilation / dysfunction thresholds. |
| Tissue (biopsy) | Residual myocytes <60% by morphometry (<50% estimated) with fibrous replacement of RV free wall ± fatty tissue. | Residual myocytes 60–75% by morphometry (50–65% estimated), with fibrous replacement. |
| Repolarization | TWI V1–V3 (age >14 y, no complete RBBB). | TWI V1–V2 (no RBBB); or TWI V4–V6; or TWI V1–V4 with complete RBBB. |
| Depolarization | Epsilon wave in V1–V3. | Late potentials on SAECG; terminal activation duration ≥55 ms (no RBBB). |
| Arrhythmia | NSVT/sustained VT of LBBB morphology with superior axis. | VT LBBB with inferior/unknown axis; or >500 PVC/24 h. |
| Family / genetics | Confirmed AC in 1st-degree relative; pathogenic desmosomal variant; or AC at autopsy/surgery in relative. | History suggestive of AC, premature SCD (<35 y), or confirmed AC in 2nd-degree relative. |
2▲Definite: 2 major
1+2or 1 major + 2 minor
4▽or 4 minor (diff. categories)
B/PBorderline / possible = fewer
Items counted from different categories; criteria validated for the classic RV-dominant phenotype, so the Padua upgrade adds CMR tissue characterization and LV/biventricular forms.
▶
One-line pathophysiology
Desmosomal failure → fibrofatty scar → re-entry
Why the heart fibrillates before it fails
Pathogenic desmosomal variants weaken cell–cell adhesion; mechanical stress (amplified by endurance exercise) drives myocyte death and fibrofatty replacement, beginning in the RV (the "triangle of dysplasia") and, with DSP and other variants, the LV. The scar is an arrhythmogenic substrate for re-entrant VT — so sudden death can precede any decline in pump function. Management therefore protects against arrhythmia and removes the accelerant (exercise) long before heart failure appears.
Mostly desmosomal, autosomal dominant More than half of probands carry a pathogenic desmosomal variant; inheritance is autosomal dominant with reduced penetrance & variable expression. A negative genetic test does not exclude AC.
A
Genotype → phenotype
▲ = high arrhythmic-risk gene
| Gene · protein | Phenotype | Practical note |
|---|
| PKP2 · plakophilin-2 | Classic RV-dominant | Most common desmosomal cause; predominantly RV, arrhythmia often precedes dysfunction. |
| DSP · desmoplakin ▲ | Left-dominant / biventricular | LV subepicardial LGE; recurrent "hot-phase" myocarditis-like chest pain + troponin with normal coronaries; arrhythmia at near-normal EF. |
| DSG2 · desmoglein-2 | RV ± biventricular | Can be biventricular; more often double/compound variants. |
| DSC2 · desmocollin-2 · JUP · plakoglobin | RV; recessive syndromes | Biallelic JUP/DSP = Naxos / Carvajal — cardiocutaneous: woolly hair, palmoplantar keratoderma. |
| PLN · phospholamban ▲ | Left-dominant / DCM overlap | Low QRS voltage; high VA + HF risk; founder variants. |
| FLNC · filamin-C ▲ | Arrhythmogenic DCM | Truncating variants: malignant VA, often before severe LV dysfunction. |
| TMEM43 ▲ · LMNA ▲ · DES | Biventricular / conduction | TMEM43 (founder, male-predominant) & LMNA: highly arrhythmic, lower ICD threshold; LMNA adds conduction disease/AV block. |
A negative panel does not exclude AC; ~40–50% of probands are gene-elusive. Report a VUS cannot drive clinical decisions or cascade testing — segregation/reclassification first.
01
Genetic Testing
Proband first
- Test the proband multigene desmosomal/cardiomyopathy panel once AC is clinically suspected/diagnosed.
- Counsel a pathogenic variant enables cascade testing; variable penetrance means genotype ≠ certain disease.
- Genotype informs risk some genes (PLN, FLNC, DSP, LMNA, TMEM43) carry higher arrhythmic risk and influence ICD decisions.
02
Family Screening
Cascade & surveillance
- First-degree relatives clinical screen (ECG, signal-averaged ECG, echo ± CMR, ambulatory monitor) + cascade genetic testing.
- Genotype-positive / phenotype-negative serial evaluation through adolescence/adulthood — penetrance is age-dependent.
- Genotype-negative clinically unaffected relatives who test negative for the causal familial P/LP variant can usually leave serial screening.
B
Cascade screening & serial surveillance of relatives
Penetrance is age-dependent
| Relative status | Evaluation | Re-screen interval |
|---|
| 1st-degree relative (variant in family) | Cascade genetic test for the familial variant. | Drives the two rows below. |
| Genotype + / phenotype − | ECG · SAECG · echo · ambulatory monitor; CMR at baseline; exercise restriction counseling. | Every 1–3 yr through adolescence & adulthood (more often if symptoms or athletic). |
| Genotype − (known familial variant) | Usually discharge only after normal phenotyping and confirmation that the family variant is causal. | Released from surveillance. |
| Gene-elusive family (no variant found) | Screen 1st-degree relatives clinically (ECG, echo ± CMR, monitor). | Every 2–3 yr; sooner with symptoms. |
| Any new symptom | Syncope, palpitations, presyncope → prompt re-evaluation. | Do not wait for the scheduled visit. |
Begin screening in childhood/early adolescence for higher-risk genotypes; intervals individualized by age, genotype, and athletic exposure.
KEYIdentify the variant, cascade the family, and re-screen the gene-positive over time. AC is a family disease with age-dependent penetrance — a normal study today does not clear a genotype-positive relative for life.
Secondary prevention is clear-cut Prior cardiac arrest, VF, or hemodynamically significant sustained VT → ICD. The hard work is primary prevention — weigh risk markers and use a validated calculator.
A
Primary-prevention risk markers
More markers = higher arrhythmic risk
| Marker | Why it raises risk |
|---|
| Unexplained (arrhythmic) syncope | Among the strongest predictors of subsequent sustained VA / arrest. |
| NSVT · frequent PVCs (>500–1000/24 h) | Higher PVC burden and documented NSVT track with arrhythmic events. |
| RV & LV dysfunction · disease extent | Lower RV/LV EF and more extensive disease increase risk; LV involvement is independently adverse. |
| Extent of TWI (number of leads) | More precordial/inferolateral lead involvement = greater electrical disease. |
| Male sex · proband · younger age | Male probands presenting young carry higher event rates. |
| High-risk genotype ▲ | PLN · FLNC · DSP · LMNA · TMEM43 — malignant VA, often a lower ICD threshold. |
| EP study inducibility (selected) | Adjunctive in intermediate cases; not required and not sufficient alone. |
B
Use the validated model
arvcrisk.com — Cadrin-Tourigny / EHJ 2019
ARVC risk calculator Estimates predicted risk of incident sustained VA over a chosen horizon from age, sex, recent cardiac syncope, NSVT, 24-h PVC count, number of TWI leads, and RV function — it outperformed prior consensus algorithms for individualizing the primary-prevention ICD decision. Derived in patients with definite classic ARVC and no prior sustained VA. Do not extrapolate to isolated LV/DSP disease or use predicted sustained VA as a synonym for sudden death.
C
Translating risk to an ICD decision
Shared decision-making
| Tier | Trigger | Action |
|---|
| Secondary prevention | Prior arrest / VF / hemodynamically significant sustained VT. | ICD — clear indication. |
| High primary risk | Syncope + ≥1 marker, significant dysfunction, or high-risk genotype. | ICD generally favored. |
| Intermediate | Calculator estimate in the grey zone. | Individualize via SDM; genotype & disease extent move the decision. |
| Low | Few/no markers, preserved function. | Surveillance + exercise restriction; reassess over time. |
Device choice
TV-ICD vs S-ICD
S-ICD reasonable when no pacing/ATP/CRT need; pass the screening ECG.
Programming
Long detect + ATP
Much VT is monomorphic & ATP-terminable — long windows cut shocks.
Ablation
Adjunct, not substitute
Reduces shocks/burden but does not replace the ICD in high-risk patients.
DECIDEArrest / VT / VF → ICD. Otherwise combine the risk markers with the arvcrisk.com estimate and decide with the patient. Genotype and disease extent move borderline cases.
A
Exercise restriction — disease-modifying
Genotype · phenotype · sport
The evidence is strongest in classic ARVC / PKP2 disease
Endurance and intense exercise can accelerate clinical expression and arrhythmia. The 2019 HRS consensus counsels against competitive or frequent high-intensity endurance exercise in ARVC. The 2025 AHA/ACC sports statement makes the genotype and phenotype distinction explicit.
| Setting | Practical decision |
|---|
| Clinical PKP2 ACM | Explain that endurance/high-intensity competitive sport likely carries more risk than benefit. |
| Non-PKP2 ACM | Expert evaluation and shared decision-making. Evidence of exercise-related progression is less certain, not proof of safety. |
| Genotype positive, no phenotype | Discuss possible disease conversion, sport exposure and close surveillance. Avoid a blanket rule across every ACM gene. |
| Recreational activity | Prescribe sustainable activity with symptom/rhythm limits. Restriction from intense sport does not mean complete inactivity. |
01
Arrhythmia Therapy
Drugs & ablation
- β-blockers first-line in most; reduce adrenergic triggers.
- Antiarrhythmics sotalol or amiodarone; individualize suppression against toxicity and limited comparative evidence.
- Catheter ablation for recurrent VT / shocks — often needs an epicardial approach (scar is epicardial/mid-wall); reduces burden but adjunct to the ICD.
- VT storm β-blockade, antiarrhythmics, sedation, ablation.
02
Heart Failure & Advanced
Pump management
- GDMT HFrEF treatment when LV systolic dysfunction is present. Isolated RV failure needs individualized care.
- RV failure diuretics, manage atrial arrhythmia, anticoagulate for documented thrombus or another established indication, not aneurysm alone.
- Advanced refractory HF or intractable VT → transplant evaluation; AC has good post-transplant outcomes.
Ablation ≠ ICD Reducing VT burden does not remove the need for defibrillator protection in high-risk patients.
B
Pharmacotherapy & procedures at a glance
Suppress · ablate · support
| Therapy | Role | Notes |
|---|
| β-blocker | First-line | Reduce adrenergic triggers; individualize for arrhythmia or other indications. Asymptomatic carriers do not automatically need medication. |
| Sotalol | AAD | Common antiarrhythmic choice; monitor QT & renal function. |
| Amiodarone | AAD | May suppress recurrent VT. Long-term organ toxicity limits use, especially in the young. |
| Catheter ablation | VT burden | For recurrent VT / ICD shocks; combined endo-epicardial approach often needed (scar is epi/mid-wall). Adjunct to the ICD. |
| VT storm | Acute | β-blockade (incl. IV), antiarrhythmics, sedation; urgent ablation if refractory. |
| HF GDMT | Pump | HFrEF therapy for LV systolic dysfunction. Diurese RV congestion. Evidence for isolated RV failure is limited. |
| Anticoagulation | Selected | For documented intracardiac thrombus or per AF stroke-risk; not routine on aneurysm alone. |
| Transplant | Advanced | Refractory HF or intractable VT → evaluation; AC has good post-transplant outcomes. |
REMEMBERRestrict exercise, suppress arrhythmia, protect with a device, and treat the pump — in parallel. The accelerant (endurance exercise) is modifiable; the substrate (fibrofatty scar) is permanent, which is why device protection and family screening continue regardless of how well VT is controlled.
Re-stratify often
Arrhythmic risk evolves; reassess markers + recalculate risk at routine visits.
Exercise is treatment
Review the activity plan at every visit, according to genotype, phenotype and sport (P.4).
Screen the family
Cascade genetics + serial phenotyping of first-degree relatives.
Team sport
Cardiology · EP · genetics · sports cardiology · advanced HF.
01
Surveillance
What to track
- Rhythm periodic ambulatory monitoring; device interrogation for VT/therapies.
- Imaging serial echo ± CMR for RV/LV function & progression.
- Recalculate risk update the arvcrisk.com estimate as markers change.
02
Special Situations
Pregnancy & activity
- Pregnancy most tolerate; continue β-blockers, plan delivery; counsel on inheritance (50% transmission).
- Athletes expert assessment by genotype, phenotype and sport. PKP2 disease carries strong evidence of exercise-related progression.
- Occupational consider arrhythmic-risk implications for high-consequence occupations.
A
Serial surveillance — what & how often
Risk evolves over years
| Domain | Test | Typical cadence |
|---|
| Rhythm | Ambulatory monitor; exercise test as indicated. | Periodically (≈ annually); sooner with symptoms. |
| Device | ICD interrogation — therapies, VT, lead integrity. | Per device schedule + remote monitoring. |
| Imaging | Echo for RV/LV function & size. | Serial; CMR at intervals to track progression. |
| Risk score | Recompute arvcrisk.com as markers change. | At routine visits. |
| Family | Cascade genetics + serial phenotyping of relatives. | Per relative status (see Genetics page). |
| Lifestyle | Reinforce exercise restriction; symptom review. | Every visit. |
B
Don't confuse AC with its mimics
Differential diagnosis
| Mimic | Discriminators from AC | Key test |
|---|
| Idiopathic RVOT VT | Single VT focus, structurally normal heart, no ECG/imaging/family clue, benign course. | Integrate ECG, rhythm, imaging and family context. Negative genetics does not exclude AC. |
| Cardiac sarcoidosis | AV block, patchy septal disease or extracardiac findings. Isolated cardiac sarcoidosis remains possible. | FDG-PET / CMR; biopsy. |
| Myocarditis | Acute, viral prodrome, usually self-limited — but recurrent "myocarditis" with DSP may be left-dominant AC. | CMR (LGE pattern); genetics if recurrent. |
| Athlete's heart | Balanced biventricular dilation, normal function, no regional WMA, no arrhythmia, regresses with detraining. | CMR; deconditioning; family/ECG. |
| Sarcomeric / other DCM | Global LV dysfunction without the desmosomal RV-dominant pattern. | Genetics; phenotype mapping. |
C
The multidisciplinary team
Shared longitudinal care
Cardiology · EP
Diagnosis, risk, ICD, VT ablation, programming.
Genetics
Panel testing, variant interpretation, cascade, counseling.
Sports cardiology
Exercise prescription & return-to-play decisions.
Advanced HF
Biventricular failure, MCS & transplant evaluation.
SUMMARYDiagnose with Task-Force/Padua criteria, define the genotype, stratify arrhythmic risk, protect from sudden death, and remove the accelerant. AC is a lifelong familial disease where sudden death can precede pump failure — surveillance, an individualized exercise plan, and family evaluation continue.