Is recurrent myocarditis of unknown cause a type of arrhythmogenic left ventricular dysplasia?

No, recurrent myocarditis of unknown cause is not a type of arrhythmogenic left ventricular dysplasia, but it may be an early inflammatory presentation ("hot phase") of underlying genetic arrhythmogenic cardiomyopathy (ACM).

Recurrent acute myocarditis should trigger immediate suspicion for underlying genetic ACM, particularly desmoplakin (DSP) cardiomyopathy, as inflammatory episodes often represent early disease manifestations rather than true recurrent myocarditis. 1

Understanding the Relationship

ACM Can Mimic Recurrent Myocarditis

The critical distinction is that these are not the same disease entity, but rather:

• ACM with inflammatory "hot phases" can present clinically identical to recurrent myocarditis 2, 1
• Up to 67% of patients with recurrent acute myocarditis are later diagnosed with genetic ACM 1
• 57% of these patients harbor pathogenic mutations, most commonly in DSP (desmoplakin), PKP2 (plakophillin-2), or TTN (titin) genes 1

Key Distinguishing Features

When to suspect ACM rather than true recurrent myocarditis:

• Recurrent episodes without identified infectious or autoimmune etiology 2, 3
• Left-dominant or biventricular involvement on imaging 4, 5
• Subepicardial/mid-myocardial fibrosis predominantly affecting the posterolateral LV wall 5
• Fat infiltration on cardiac MRI, particularly subepicardial posterolateral location 5
• Ventricular arrhythmias with left ventricular origin on ECG 5
• Family history of cardiomyopathy or early sudden cardiac death (88% positive predictive value for genetic mutation) 1

Diagnostic Algorithm

Initial Presentation of "Recurrent Myocarditis"

1. Complete infectious/autoimmune workup - if negative, proceed immediately to:

2. Cardiac MRI with specific attention to:

   • Subepicardial late gadolinium enhancement in posterolateral LV wall 5
   • Fat infiltration patterns (highly specific for ACM vs myocarditis) 5
   • Distribution: circumferential vs focal patterns 6

3. Genetic testing should be performed early, not delayed 2, 1, 3

   • Comprehensive cardiomyopathy panel including desmosomal genes (DSP, PKP2, DSG2, DSC2, JUP)
   • Non-desmosomal genes (LMNA, TMEM43, DES, PLN, FLNC, TTN) 7

4. Endomyocardial biopsy when diagnosis remains uncertain 2, 3

   • Can show chronic inflammation with interstitial fibrosis in ACM
   • Distinguishes from acute lymphocytic myocarditis

Critical Timing Considerations

The "hot-to-cold" transition phase represents the highest arrhythmogenic risk 8. During active inflammation (hot phase), patients require:

• Aetiology-targeted treatment if ACM is suspected
• Arrhythmia monitoring with Holter and exercise ECG 9
• ICD consideration for high-risk features even during inflammatory phase 8

Management Implications

If ACM is Diagnosed

The diagnosis fundamentally changes management from immunosuppression to:

1. ICD implantation for documented sustained VT/VF 10
2. ICD consideration for extensive disease with LV involvement, family history of SCD, or unexplained syncope 10
3. Restriction from competitive sports and strenuous exercise 11, 9
4. Antiarrhythmic therapy (amiodarone or sotalol) as adjunct 10
5. Family screening with genetic testing and clinical evaluation 7
6. Genetic counseling for reproductive planning 7

Common Pitfalls to Avoid

• Do not assume recurrent episodes are infectious myocarditis without genetic evaluation 3
• Do not delay genetic testing until after multiple recurrences 1
• Do not miss DSP-associated ACM - it presents with left-dominant disease and may not meet traditional ARVC Task Force Criteria 3
• Do not overlook family history - it has 88% PPV for genetic mutation 1
• Do not continue immunosuppression if ACM is diagnosed, as this is ineffective and delays appropriate therapy 2

Specific High-Risk Scenarios

DSP truncating variants are associated with:

• Fulminant arrhythmic progression 3
• Left-dominant presentation mimicking myocarditis 2, 4
• Rapid disease progression requiring heart transplantation 3, 6

Women with DSP variants particularly present with myocarditis-like phenotype 3

The Bottom Line

In any patient with recurrent myocarditis of unknown cause, particularly with left ventricular involvement, negative infectious/autoimmune workup, or family history of cardiomyopathy/SCD, genetic ACM must be actively excluded through comprehensive genetic testing and specialized cardiac imaging. 1 These inflammatory episodes represent early ACM disease manifestations requiring entirely different therapeutic strategies focused on arrhythmia prevention and sudden death risk mitigation rather than immunosuppression. 2, 8