An unusual case of severe myocarditis in a genetic cardiomyopathy: a case report

Abstract

Background: Myocarditis is an inflammatory disease of the myocardium caused by infectious pathogens, immune-mediated conditions, or toxic agents. This report explores a rare case of severe myocarditis occurring in an inherited cardiomyopathy.

Case summary: A 24-year-old female patient presented with progressing dyspnoea and chest discomfort. Echocardiography and cardiac magnetic resonance imaging revealed dilated cardiomyopathy (DCM) with severe biventricular dysfunction [left ventricle ejection fraction (LV-EF) 10%]. Myocardial inflammation was suspected due to extensive subendocardial to transmural late gadolinium enhancement. Endomyocardial biopsy (EMB) showed severe chronic lymphocytic myocarditis. As inflammatory DCM was assumed, immunosuppressive therapy with prednisolone was initiated in addition to standard heart failure therapy. Endomyocardial biopsy after 3 months showed resolving inflammation. However, a marked architectural disarray observed in all biopsies raised the suspicion of an inherited cardiomyopathy. Genetic testing revealed a de novo mutation with effect on splicing of lysosome-associated membrane protein 2, as found in Danon disease. Periodic acid-Schiff (PAS) staining confirmed a glycogen storage disorder. Immunosuppressive therapy was intensified due to reactivation of myocardial inflammation and led to improvement of LV-EF and to significant symptom relief over a 16-month follow-up period.

Discussion: This is the first report of Danon disease initially presenting as a severe myocarditis. It illustrates the clinical value of EMB for diagnosis and immunosuppressive therapy monitoring in chronic myocarditis. Increasing evidence suggests that myocardial inflammation may modify disease progression and prognosis in inherited cardiomyopathies. The causal role of cardiac protein mutations in the pathophysiology of myocarditis remains to be determined.

Keywords: Case report; Danon disease; Dilated cardiomyopathy; Endomyocardial biopsy; Inherited cardiomyopathies; Lymphocytic myocarditis.

Figure 1

Twelve-lead electrocardiogram at initial presentation. (A) Atrial fibrillation with wide QRS complexes (170 ms) presenting both right and left bundle branch block pattern (64 b.p.m.), indicative of severe conduction abnormalities and ventricular extrasystoles. (B) Electrocardiogram after spontaneous conversion to sinus rhythm. The partial atrioventricular dissociation (P-waves indicated by arrows) and deformed QRS complexes are suggestive of complete heart block with junctional escape rhythm (47 b.p.m.).

Figure 2

Representative transthoracic echocardiogram images. Severely dilated left ventricle shown in parasternal long axis (PLAX) end-diastolic (A) and end-systolic (B) view. Interventricular septal wall thickness in diastole 11 mm, left ventricular end-diastolic diameter 64 mm, left ventricular end-systolic diameter 57 mm, and posterior wall thickness in end-diastole 8 mm. Severe functional mitral regurgitation (four-chamber view) with broad regurgitation jet as seen in colour Doppler (C), quantified using the proximal isovelocity surface area method (D).

Figure 3

Representative cardiac magnetic resonance images in short-axis view and four-chamber view. Dilated left ventricle with markedly reduced global ejection fraction (10%) and akinesia of the thin basal anteroseptal and apical inferior wall. Both areas show transmural late enhancement. In addition, subendocardial and subepicardial enhancement can be observed in the anterolateral and inferolateral wall, respectively. The inferior septum presents predominantly mid-myocardial enhancement. Furthermore, a marked increase in extracellular volume is observed in these areas (up to 60%). T2-TSE shows an increased signal intensity in the mid-cavity septum (three-fold increase compared to the pectoral muscle). The T2-relaxation time (54 ms) determined in T2-mapping is in the normal range. 4ch, four-chamber view; ECV, extracellular volume; LGE, late gadolinium enhancement; SAX, short-axis view.

Figure 4

Histological findings in endomyocardial biopsies. Immunohistochemical staining detects numerous CD3+ T cells (A and C). Masson trichrome stain reveals myofiber disarray, loss of myofibrils, and fibrosis (B and D). PAS staining illustrates glycogen deposits within cardiomyocytes without (E and G) and with (F and H) diastase digestion. Magnification A–D, G and H ×200, E and F ×400. EMB, endomyocardial biopsy; IHC, immunohistochemistry; PAS, periodic acid-Schiff.