Arrhythmogenic Right Ventricular Cardiomyopathy Presenting as Clinical Myocarditis in Women

doi:10.1016/j.amjcard.2020.12.090

The American Journal of Cardiology

Volume 145, 15 April 2021, Pages 128-134

https://doi.org/10.1016/j.amjcard.2020.12.090 Get rights and content

HIGHLIGHTS

•
Myocarditis is a distinct presenting phenotype of ARVC.
•
ARVC diagnostic criteria can make myocarditis phenotype difficult to diagnose.
•
Genetic testing a subset of myocarditis patients aids in diagnosis.
•
Early and accurate ARVC diagnosis is important for patient and family members.

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) classically initially present with ventricular arrhythmias or, less commonly, heart failure. Myocardial inflammation has been implicated in pathogenesis, but clinical myocarditis in ARVC is less described. We therefore studied clinical myocarditis as an initial ARVC presentation, and hypothesized that these patients have distinct clinical and genetic characteristics. Using the Johns Hopkins ARVC Registry, we identified 12 patients (all female, median age 20) referred between 2014 and 2019 diagnosed with myocarditis at presentation who were subsequently diagnosed with ARVC by Task Force Criteria. Majority presented with chest pain (n = 7, 58%) or ventricular arrhythmia (n = 3, 25%). All patients had troponin elevations and left ventricular (LV) function was reduced in 5 (42%). Magnetic resonance imaging demonstrated LV delayed gadolinium enhancement and/or pericardial enhancement in 10 (83%); only 3 (25%) patients had right ventricular abnormalities. Pathogenic genetic variants were identified in 11 (92%) patients: 10 desmoplakin (DSP) and 1 desmoglein-2 (DSG2). Thus, nearly 1/3 (10/32, 31%) of overall DSP ARVC patients were originally diagnosed with myocarditis. Patients were diagnosed with ARVC 1.8 years (IQR 2.7 years) after presentation and 8 (75%) patients did not meet Task Force Criteria without genetic testing. ARVC diagnosis led to an additional 5 (42%) patients referred for implantable cardiac defibrillator and 17 family member diagnoses. In conclusion, ARVC may initially present as myocarditis and these patients have distinct characteristics including female gender, LV involvement and DSP gene variants. Genetic testing is key to ARVC diagnosis and should be considered in select myocarditis patients.

Section snippets

Methods

The Johns Hopkins ARVC Program evaluates patients referred for possible ARVC and their family members. The ARVC Registry prospectively enrolls those affected or at risk for ARVC. The registry includes detailed medical records obtained at time of referral, dating back to the original clinical presentation. The registry data for each patient is updated regularly with information gathered through either direct clinical contact with the ARVC Program or communication with patients supplemented with

Results

Of the 520 patients enrolled in the Johns Hopkins ARVC Registry during the study period, 236 met ARVC TFC. Of those, we identified 12 female Caucasian patients (referred to as Patient 1 – 12) who were originally diagnosed with clinical myocarditis. The presenting characteristics and subsequent diagnostic work-up for each patient is presented in Table 1. The median age at presentation was 20 years (IQR 14.5). The most common presenting symptom was chest pain and all patients had elevated serum

Discussion

We describe a cohort of patients initially presenting with clinical myocarditis who were subsequently diagnosed with ARVC. Our findings highlight the unique demographic, clinical and genetic characteristics of a myocarditis presentation of ARVC. In our cohort, patients commonly presented with a classic myocarditis syndrome (chest pain, troponin elevation), there was a female predominance, myocarditis primarily involved the LV, and most patients had a DSP genetic variant. Genetic testing results

Credit Author Statement

Paul Scheel: conceptualization, methodology, formal analysis, data curation, writing – original draft, writing – review & editing, visualization. Brittney Murray: conceptualization, investigation, methodology, resources, writing – original draft, writing – review & editing. Crystal Tichnell: supervision, project administration, writing – review & editing. Cynthia James: conceptualization, metholdogy, formal analysis, investigation, writing – review & editing. Harikrishna Tandri: supervision,

Declaration of Interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study.

Acknowledgement

We are grateful to the ARVC/D patients and families who have made this work possible.

REFERENCES (34)

S Belkaya et al.
Autosomal recessive cardiomyopathy presenting as acute myocarditis
J Am Coll Cardiol
(2017)
LT Cooper et al.
The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology and the European Society of Cardiology
J Am Coll Cardiol
(2007)
NA Gilotra et al.
Outcomes and predictors of recovery in acute onset cardiomyopathy: a single-center experience of patient undergoing endomyocardial biopsy for new heart failure
Am Heart J
(2016)
NE Bowles et al.
The detection of cardiotropic viruses in the myocardium of patient with arrhythmogenic right ventricular dysplasia/cardiomyopathy
J Am Coll Cardiol
(2002)
JM Lopez-Ayala et al.
Genetics of myocarditis in arrhythmogenic right ventricular dysplasia
Heart Rhythm
(2015)
M Pieroni et al.
High prevalence of myocarditis mimicking arrhythmogenic right ventricular cardiomyopathy
J Am Coll Cardiol
(2009)
JA Towbin et al.
2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy
Heart Rhythm
(2019)
D Corrado et al.
Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study
J Am Coll Cardiol
(1997)
D Fairweather et al.
Sex differences in autoimmune disease from a pathological perspective
Am J Pathol
(2008)
LT Cooper
Myocarditis
N Engl J Med
(2009)

AL Caforio et al.

Current state of knowledge of aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on myocardial and pericardial diseases

Eur Heart J

(2013)

M Bennett et al.

Evaluation of the role of endomyocardial biopsy in 851 patients with unexplained heart failure from 2000-2009

Circ Heart Fail

(2013)

EE Brown et al.

Genetic aetiologies should be considered in paediatric cases of acute heart failure presumed to be myocarditis

Cardiol Young

(2019)

D Corrado et al.