Arrhythmogenic right ventricular cardiomyopathy

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Arrhythmogenic cardiomyopathy is an inherited myocardial disease in which ventricular arrhythmia may precede structural dysfunction. The traditional RV-predominant label remains clinically useful, but systematic LV assessment is essential.

A specialist diagnosis combines phenotype criteria, pedigree and carefully interpreted genomic evidence. Overdiagnosis from an athletic RV or incidental CMR fat is as harmful as missed disease.

Management focuses on exercise modification, arrhythmia surveillance and suppression, ICD selection, heart-failure care and cascade family management.

Key points

ARVC is a genetic arrhythmogenic cardiomyopathy with fibrofatty myocardial replacement; biventricular and left-dominant disease occur.
Diagnosis is multiparametric: no single ECG, echo, CMR or genetic finding is sufficient in isolation.
Clues include T-wave inversion V1-V3 beyond the expected age, terminal activation abnormalities and VT with left-bundle morphology.
CMR must assess regional motion and quantitative RV/LV size and function; isolated fat is non-specific.
Exercise can accelerate penetrance and arrhythmia: competitive and high-intensity exercise is generally discouraged in affected people and pathogenic-variant carriers.
A negative family history does not exclude disease; penetrance and expression vary markedly.
Risk assessment integrates prior arrest/VT, syncope, ventricular function, arrhythmia burden, genotype and extent of disease.
Inflammatory 'hot phases', especially with desmosomal variants, can mimic myocarditis and should prompt inherited-disease reassessment.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Desmosomal genetic disease

Many cases reflect pathogenic variants in proteins that maintain mechanical adhesion between cardiomyocytes. Inheritance is often autosomal dominant with incomplete penetrance, so a parent may carry the variant with little apparent disease; other inheritance patterns also occur.

Broader arrhythmogenic cardiomyopathy genes

Other inherited myocardial variants can produce biventricular or left-dominant phenotypes. A negative panel does not exclude a clinical diagnosis, and a variant of uncertain significance cannot establish one.

Exercise as a disease modifier

Repeated high-intensity endurance exercise increases mechanical stress on susceptible myocardium, promoting penetrance, scar progression and ventricular arrhythmia. It modifies inherited risk rather than acting as a sufficient cause alone.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Impaired cell-to-cell integrity
In many desmosomal forms, impaired junctional integrity and signalling make cardiomyocytes vulnerable to injury during mechanical strain. Other arrhythmogenic-cardiomyopathy genes can reach a similar phenotype through different cellular mechanisms.
2
Myocyte injury and inflammation
Myocyte injury may be accompanied by inflammatory episodes in some phenotypes, particularly desmoplakin-related disease. These hot phases can present with chest pain and troponin release, sometimes resembling acute myocarditis.
3
Patchy scar replacement
Injured myocardium is replaced by patchy fibrosis with variable fatty replacement, creating regional wall-motion abnormalities, ventricular dilatation and a heterogeneous electrical substrate in the RV, LV or both.
4
Re-entrant ventricular arrhythmia
Slow and discontinuous conduction around patchy scar supports re-entry, producing ventricular ectopy and VT that may precede obvious structural dysfunction and can deteriorate into VF.
5
Progressive pump failure
If myocardial loss and remodelling progress, RV and sometimes LV contractility decline, potentially causing biventricular heart failure and poorer tolerance of ventricular arrhythmias.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Electrical presentation

Palpitations, ventricular ectopy, VT or syncope in a young adult may occur before obvious structural disease.

ECG clues

T-wave inversion in right precordial leads, prolonged terminal activation and epsilon-like late potentials can support diagnosis but require age and conduction context.

VT morphology

VT arising from the RV commonly has left-bundle-branch-block morphology; axis and morphology help localise but are not diagnostic alone.

Structural phenotype

Regional RV akinesia/dyskinesia or aneurysm with RV dilatation/dysfunction is characteristic; LV fibrosis or dysfunction may coexist.

Hot phaseRed flag

Chest pain and troponin rise with non-ischaemic scar, recurrent 'myocarditis' or a DSP family history should raise arrhythmogenic cardiomyopathy.

High-risk symptomsRed flag

Exercise-related syncope, sustained VT or aborted sudden death needs urgent risk assessment and exercise cessation.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
12-lead and signal-averaged ECGFirst step
Why
Identify repolarisation/depolarisation criteria and conduction alternatives.
Interpretation and limitations
Interpret T-wave inversion by age, sex and bundle-branch block; epsilon waves have limited sensitivity and observer reproducibility.
02
Ambulatory ECG and exercise testing
Why
Quantify PVC/NSVT burden and relate arrhythmia to exertion.
Interpretation and limitations
Frequent or complex ventricular ectopy supports electrical disease and contributes to risk; testing must be supervised, not an invitation to unrestricted exercise.
03
TTE
Why
Assess regional RV motion, RVOT/dimensions, fractional area change and LV involvement.
Interpretation and limitations
Regional abnormality plus quantitative dysfunction is more specific than subjective RV enlargement alone.
04
CMR
Why
Quantify both ventricles and map scar/tissue.
Interpretation and limitations
Regional motion, volumes, ejection fractions and non-ischaemic LGE support phenotype; fat alone is not diagnostic.
05
Genetic counselling and panel testing
Why
Confirm a molecular cause and enable family testing.
Interpretation and limitations
Only pathogenic/likely pathogenic variants should drive predictive testing; genotype must be reconciled with phenotype.
06
Coronary/inflammatory evaluation when presenting with myocardial injury
Why
Exclude ACS and alternative myocarditis causes.
Interpretation and limitations
A recurrent scar pattern or family/genetic signal can reclassify an apparent myocarditis episode as a hot phase.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Athlete's heart

Physiological RV enlargement is usually proportionate, with preserved regional motion and no convincing scar or familial electrical phenotype. Deconditioning and expert quantitative imaging may resolve borderline findings.

Idiopathic RV outflow-tract tachycardia

This can produce left-bundle-pattern VT in an otherwise normal heart, but lacks progressive regional RV dysfunction, characteristic scar and the broader familial phenotype of arrhythmogenic cardiomyopathy.

Myocarditis

A single inflammatory episode without evolving familial or structural features favours myocarditis, but recurrent hot phases may represent arrhythmogenic cardiomyopathy; CMR, pedigree and genetics require integrated interpretation.

Cardiac sarcoidosis

High-grade AV block, extracardiac sarcoidosis, active patchy inflammatory uptake or granulomatous tissue may support sarcoidosis. Multimodality assessment is often needed because scar patterns and ventricular arrhythmias overlap.

Brugada syndrome

Brugada usually has a structurally normal heart with a coved right-precordial ST pattern and fever-related events, rather than regional ventricular dilatation, wall-motion abnormality and replacement scar.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnosisSuspected ARVCFirst stepArrhythmic symptoms, suggestive ECG/CMR or family diagnosis.

1Stop competitive/high-intensity exercise pending assessment; obtain a three-generation pedigree and details of sudden deaths or recurrent myocarditis.
2Perform ECG, ambulatory monitoring, expert TTE and CMR with quantitative biventricular assessment.
3Exclude mimics including athlete remodelling, RV volume/pressure loading, cardiac sarcoidosis, myocarditis and congenital shunts.
4Apply accepted multiparametric criteria in an inherited-cardiac service; add genomic counselling rather than treating a genetic result as a standalone diagnosis.

02EmergencyVT or arrhythmic syncopeSustained broad-complex tachycardia, arrest or high-risk collapse.

1Treat unstable VT with immediate synchronised cardioversion and pulseless VT/VF with the Resuscitation Council UK arrest algorithm.
2Correct reversible electrolytes/drugs and assess acute myocardial injury, but do not attribute exertional syncope to vasovagal causes without rhythm review.
3Refer urgently to electrophysiology/inherited-cardiac specialists for secondary-prevention ICD and arrhythmia strategy.
4Use antiarrhythmic drugs or ablation to reduce recurrence/ICD therapies when needed; neither substitutes for an indicated ICD.

03PreventionRisk and exercise managementConfirmed phenotype or causal variant.

1Advise against competitive and high-intensity exercise; agree lower-intensity activity individually using phenotype, arrhythmia and symptoms.
2Integrate previous VT/arrest, syncope, RV/LV dysfunction, ventricular ectopy/NSVT, scar and genotype in shared ICD decisions.
3Treat ventricular or biventricular heart failure using the corresponding NICE HF pathway, with transplant referral for refractory advanced disease.
4Reassess risk longitudinally because structural and electrical disease can progress.

04FamilyCascade carePathogenic variant or familial ARVC phenotype.

1Offer first-degree relatives genetic counselling, targeted testing when a causal variant is known, and ECG/imaging surveillance.
2Continue age-appropriate clinical surveillance for genotype-positive relatives even when initial imaging is normal; advise exercise restriction.
3DefinitiveFor genotype-negative relatives, discharge from variant-specific surveillance only after specialist confirmation that the familial variant is causal and testing is definitive.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Sustained VT, VF and sudden death

Scar-related re-entry causes sustained ventricular tachycardia, while unstable VT can degenerate into ventricular fibrillation. Life-threatening arrhythmia may be the first recognised manifestation.

Arrhythmic syncope and injury

Transient low output during rapid VT can cause abrupt loss of consciousness, often during exercise, with secondary trauma and a strong implication for sudden-death risk assessment.

Right or biventricular heart failure

Progressive myocardial replacement causes chamber dilatation, functional tricuspid regurgitation and systemic venous congestion; LV involvement adds pulmonary congestion and worsens prognosis.

Intracardiac thrombus and embolism

Severe ventricular dilatation and regional akinesia promote stasis and mural thrombus. Resulting pulmonary or systemic embolism is less characteristic than arrhythmia but clinically important in advanced disease.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review syncope, palpitations, exercise exposure and family events at every visit.
Repeat ECG, ambulatory monitoring and biventricular imaging at phenotype-appropriate intervals or sooner after symptoms.
Interrogate an ICD for arrhythmia burden, therapies and programming; investigate shocks promptly.
Monitor LV/RV failure, functional TR, congestion and end-organ function.
Track cascade testing and clinical screening of relatives.
Revisit exercise advice explicitly; absence of symptoms does not make high-intensity training safe.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Electrical disease can lead

Ventricular ectopy or VT may be the first manifestation before RV dilatation is obvious.

Think beyond the RV

DSP and other genotypes may cause prominent LV scar or biventricular disease.

Fat is non-specific

CMR fat signal without regional/quantitative abnormalities can occur with age or obesity and should not anchor diagnosis.

Exercise modifies disease

Endurance and high-intensity exposure can increase penetrance and adverse events; exercise history is part of diagnosis and treatment.

Ablation is not a cure

Epicardial/endocardial substrate may recur as disease progresses; successful ablation does not remove ICD or surveillance needs.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing ARVC from an epsilon wave, athletic RV enlargement or CMR fat alone.
02
Ignoring LV imaging because the historical name emphasises the RV.
03
Recommending unrestricted competitive exercise to an asymptomatic variant carrier.
04
Using a VUS to diagnose relatives.
05
Assuming ablation or antiarrhythmic medication replaces an indicated ICD.