5th July 2026

Arrhythmogenic cardiomyopathy

• Prevalence: 1 in 1,000 to 1 in 5,000 people.
• Age: It is most commonly diagnosed in adolescents and young adults, often presenting with arrhythmias or sudden cardiac death in athletes.
• Gender: male-to-female ratio of approximately 2:1.

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease characterised by replacement of myocardial tissue with fatty or fibrofatty scar tissue. It predisposes affected individuals, typically young adults and athletes, to malignant ventricular arrhythmias and sudden cardiac death. Disease prevalence is estimated at 1 in 5000, and pattern of inheritance in the majority of ACM-affected families is autosomal dominant. Penetrance of the disease in genetic carriers is variable depending on age, sex and physical activity. Mutations to genes encoding proteins such as desmoplakin (DSP), plakophilin-2 (PKP2) and desmoglein-2 (DSG2) are implicated in ACM. This is usually inherited in an autosomal dominant pattern with variable penetrance. Rare cases can be autosomal recessive. ARVC most commonly affects genes encoding desmosomal proteins, crucial for cell adhesion and structural integrity of cardiac muscle cells. Without effective cell-cell-adhesion, the myocardium becomes susceptible to mechanical stress, leading to cell death and fibrofatty replacement. This fibrofatty replacement is characterised by the infiltration of fibrous tissue, which disrupts normal myocardial architecture and contributes to electrical instability. The structural irregularities result ultimately in re-entrant circuits and ventricular arrhythmias. 

ACM was originally described as a disease that favours the right ventricular (RV) myocardium, with only mild or no involvement of the left ventricle (LV). LV disease was once regarded as a result of disease progression associated with advanced RV disease. This led to the designation of the term ‘arrhythmogenic right ventricular cardiomyopathy (ARVC)’. In recent years, however, there has been increased recognition of biventricular and left dominant phenotyping variants owing to autopsy findings and emergence of tissue characterisation using contrast-enhanced cardiac magnetic resonance (CMR). As such, the generic term ACM is now preferred. 

Diagnosis and Diagnostic Criteria

Diagnostic Criteria

One of the most common underdiagnosed causes of sudden cardiac death in young people, ARVC is diagnosed with either two major criteria, one major and two minor criteria, or four minor criteria, summarised in Table 1 below.

Table 1. Diagnostic Criteria of AVRC, adapted from Escardio.org/Journals/E-journal-of-cardiology-practice/Volume-1/Arrhythmogenic-right-ventricualr-cardiomyopathy-Title-Arrhythmogenic-right-ve

The standard of reference for diagnosis of ARVC is the histologic demonstration of transmural fibrofatty replacement of the right ventricular myocardium at autopsy or surgery, with criteria of greater than 3% fat and less than 40% fibrous tissue replacing the myocardial muscle.

Signs and symptoms

• Palpitations and syncope: most frequently experienced symptoms in patients with ACM. These are often triggered by exercise, and related to ventricular arrhythmias which include premature ventricular complexes, sustained or non-sustained ventricular tachycardia (NSVT) and ventricular fibrillation.

• Sudden cardiac death (SCD) can be the first presenting feature in patients subsequently diagnosed with ACM. Over half of affected individuals (estimated at 60%) may be asymptomatic prior to mortality. 
• Progressive heart failure affecting the right, left or both ventricles, is also observed in some patients and is a common indication for heart transplant. 
• Angina, fatigue, and dyspnoea may also be reported.

Clinical examination may be normal, or signs that may be elicited include: 

• split S2
• S3 gallop during rapid ventricular phase of diastole, indicating ventricular dilatation
• S4

Investigations

Primary investigations for patients with ARVC include:

• Bloods: BNP elevation, FBC, U+Es, thyroid function, LFTs and troponin
• ECG: 
  • May have T wave inversion in leads V1-V3 suggests abnormal repolarisation in the right ventricle. 
  • Epsilon waves represent delayed depolarisation in the right ventricular outflow tract. They are characterised by small positive deflections at the end of QRS complexes in leads V1-V4 (figure 1). 
  • Ventricular ectopy and recurrent monomorphic VT with an LBBB pattern indicate abnormal ventricular electrical activity. 
  • Late potentials on a signal-averaged ECG reflect delayed conduction, all pointing to electrical instability in ARVC.
• Echocardiogram: may show a right ventricular dilatation or demonstrate aneurysmal projections from the right ventricular wall.

Other investigations to consider include:

• Ambulatory monitoring
  • Represents a major criterion in detecting frequent ventricular extrasystoles (>500) across 24 hours, non-sustained or sustained ventricular tachycardia of left bundle branch block morphology. 
• Cardiac MRI: 
  • On T1-weighted images, the right ventricular free wall often shows increased signal intensity due to the replacement of normal heart muscle with fatty or fibrous tissue. Thinning refers to the reduction in thickness of the right ventricular free wall, which can be a result of structural damage or atrophy. Akinesis may also be a result of this due to poor movement, and over time, this can be the predisposing cause of aneurysms, which can also be detected on MRI. In particular, ARVC may affect the triangle of dysplasia particularly, including the right ventricular outflow tract, the apex, and the inflow tract.
• Cardiac catheterisation
  • May show right ventricular enlargement or right ventricular wall motion abnormalities.
• Exercise stress testing
  • Might demonstrate any exercise-related ventricular tachyarrhythmias
• Endomyocardial biopsy
  • Used to detect fibro-fatty replacement of myocardium.

Management

General Management 

Patients diagnosed with ACM are advised against intense exercise or competitive sports to avoid triggering fatal arrhythmias and decelerate disease progression. Genetic counselling and testing may be offered to patients and their families to identify genetic mutations associated with ARVC and assess the risk of transmission to offspring. Annual ECG monitoring may aid in diagnosis, management and risk stratification.  

Medical Management

• Beta-blockers are the recommended first-line pharmacological therapy in patients with ACM to reduce arrhythmia burden. 
• Antiarrhythmics such as sotalol (non-selective beta-blocker with class III antiarrhythmic properties) and mexiletine (class Ib antiarrhythmic) can be used to manage arrhythmia-related symptoms not controlled by conventional beta-blocker therapy alone. 
• Caution should be exercised when prescribing amiodarone to young patients with ACM due to its long-term adverse effects.
• For patients with ARVC with phenotypic LV dysfunction, HFrEF RCTs have suggested inclusion of ACEi/angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRA), and sodium–glucose co-transporter 2 inhibitors (SGLT2i).

Surgical Management

• Catheter ablation can be considered in refractory cases or when appropriate ICD interventions for ventricular arrhythmia is recurrent despite pharmacological therapy.
• Implantable cardiac defibrillator (ICD) is implicated in the secondary prevention of sudden cardiac death in patients with ACM who have survived a cardiac arrest or recovered from a ventricular arrhythmia resulting in haemodynamic instability. High-risk features, including unexplained syncope, ventricular dysfunction and non-sustained VT, should be considered to inform individualised decision-making for primary prevention ICD implantation. 
• Left Ventricular Assist Devices (LVADs) may be considered in advanced cases of ARVC with biventricular dysfunction, advanced heart failure, or life-threatening arrhythmias, while awaiting heart transplantation or as destination therapy.
• Heart Transplantation is considered in end-stage ARVC patients with refractory heart failure, recurrent ventricular arrhythmias, or poor prognosis despite optimal medical and surgical management.

Complications

• Ventricular arrhythmias
  • ARVC is characterised by an increased risk of ventricular arrhythmias, including VT and VF, which may lead to syncope, cardiac arrest, or sudden cardiac death
• Heart failure
  • Progressive fibrofatty replacement of the right ventricular myocardium leads to right ventricular dysfunction and heart failure.
• Thromboembolism 
  • Right ventricular dysfunction and blood stasis may predispose individuals with ARVC to thrombus formation and subsequent thromboembolic events such as pulmonary embolism.
• Risk of sudden cardiac death
  • ARVC carries a significant risk of sudden cardiac death, often attributed to ventricular arrhythmias occurring in the setting of structural abnormalities and fibrofatty infiltration of the myocardium.