This patient with recurrent acute myocarditis developed regional dyskinesis, extensive fibrosis of the RV myocardium, and fatty infiltration of the LV myocardium. These imaging findings raise concern for arrhythmogenic cardiomyopathy (ACM) (previously termed arrhythmogenic right ventricular cardiomyopathy, or ARVC) with LV and RV involvement. Genetic testing is recommended in patients with clinically suspected ACM.¹ Genetic testing aids in risk stratification and informs testing in relatives. Genes commonly associated with ACM include plakophilin 2 (PKP2), desmoglein 2 (DSG2), desmoplakin (DSP), and desmocollin 2 (DSC2).

As this patient's clinical findings were most consistent with a nonischemic cardiomyopathy (NICM), a CT angiogram of the coronary arteries would be low-yield. PET CT can be a useful adjunct modality for diagnosis of infective endocarditis. However, this patient's clinical presentation was not suggestive of endocarditis. Sodium channel blocker testing can unmask diagnosis of Brugada syndrome, but this diagnosis would be unlikely based on the history and cMRI findings.

ACM is an NICM characterized by fibrofatty replacement of the myocardium. Clinical manifestations include progressive ventricular wall motion abnormalities, ventricular dilation, and ventricular arrhythmias (VAs). Proposed criteria for diagnosis include the 2010 International Task Force Criteria and the 2020 Padua Criteria, which were updated to include LGE findings and to better reflect potential for LV involvement.^2,3 Most heritable forms of ACM are caused by desmosome gene mutations. Specifically, variants in DSP have been associated with recurrent episodes of myocarditis, which may precede recognition of the diagnosis.^4-8 These episodes are characterized by chest pain and troponin level elevations. A cMRI during an episode will often reveal myocardial edema and LGE, thus meeting the modified Lake Louise Criteria for acute myocarditis.

Recurrent myocarditis-like episodes reflect an uncommon presentation of ACM, are more frequently seen in pediatric than adult patients, and are theorized to represent progression in disease.^4,8 This presentation has been termed hot phase arrhythmogenic cardiomyopathy. Genetic testing for desmosomal variants should be strongly considered in children with recurrent myocarditis or a single episode of myocarditis in addition to a first-degree family history of cardiomyopathy.⁹

Hemodynamically unstable VA is a feared manifestation of ACM. Beta-blockers are often prescribed, and an implantable cardioverter-defibrillator may be indicated for patients who have experienced cardiac arrest or hemodynamically unstable sustained ventricular tachycardia, or in those with high-risk combinations of clinical and imaging data. Importantly, exercise restriction is often recommended given the association of high-intensity exercise with increased VAs and disease progression.¹ Overall, ACM prognosis is variable. However, increasing understanding of specific underlying genetic abnormalities may help better risk-stratify patients. cMRI is useful to define the cardiovascular ACM phenotype, monitor disease progression, and inform risk stratification and prognosis.

References

1. Towbin JA, McKenna WJ, Abrams DJ, et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm 2019;16:e301-e372.
2. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Circulation 2010;121:1533-41.
3. Corrado D, Perazzolo Marra M, Zorzi A, et al. Diagnosis of arrhythmogenic cardiomyopathy: the Padua criteria. Int J Cardiol 2020;319:106-14.
4. Smith ED, Lakdawala NK, Papoutsidakis N, et al. Desmoplakin cardiomyopathy, a fibrotic and inflammatory form of cardiomyopathy distinct from typical dilated or arrhythmogenic right ventricular cardiomyopathy. Circulation 2020;141:1872-84.
5. Martins D, Ovaert C, Khraiche D, Boddaert N, Bonnet D, Raimondi F. Myocardial inflammation detected by cardiac MRI in arrhythmogenic right ventricular cardiomyopathy: a paediatric case series. Int J Cardiol 2018;271:81-6.
6. Surget E, Maltret A, Raimondi F, et al. Clinical presentation and heart failure in children with arrhythmogenic cardiomyopathy. Circ Arrhythm Electrophysiol 2022;15:[ePub ahead of print].
7. Bariani R, Cipriani A, Rizzo S, et al. 'Hot phase' clinical presentation in arrhythmogenic cardiomyopathy. Europace 2021;23:907-17.
8. Ammirati E, Raimondi F, Piriou N, et al. Acute myocarditis associated with desmosomal gene variants. JACC Heart Fail 2022;10:714-27.
9. Piriou N, Marteau L, Kyndt F, et al. Familial screening in case of acute myocarditis reveals inherited arrhythmogenic left ventricular cardiomyopathies. ESC Heart Fail 2020;7:1520-33.