Clin Res Cardiol DOI 10.1007/s00392-015-0849-9
LETTER TO THE EDITORS
Cardiac magnetic resonance imaging reveals extensive biventricular fibrosis and inflammation challenging the diagnosis of ARVC Julia Koch1 • Arash Arya1 • Gerhard Hindricks1 • Charlotte Eitel1
Received: 24 August 2014 / Accepted: 23 March 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Sirs: A 53-year-old female was admitted with recurrent palpitations and syncope at rest. Her medical history included arterial hypertension and atrial tachycardia and her family history was negative for sudden cardiac death. The physical examination did not reveal any pathologic findings. On electrocardiogram, sinus rhythm with an atypical right bundle branch block (RBBB) pattern with Q waves in lead V 1–3 and negative T-waves as well as epsilon waves in lead V1 to V4 were found (Fig. 1, top). The coronary angiogram did not show any relevant stenosis. Echocardiography revealed mildly impaired left ventricular (LV) ejection fraction (EF) as well as significantly impaired right ventricular (RV) function and mild dilatation of the RV body and outflow tract, though, areas of akinesia or dyskinesia could not be identified. The next day, the patient’s previously reported symptoms could be correlated to incessant ventricular tachycardia (VT) with two different morphologies (Fig. 1, bottom), suggesting an origin in the RV (Fig. 1, bottom right). The VT could successfully be terminated by intravenous application of amiodarone. According to the modified Task Force criteria for ARVC two major criteria [1]: repolarization disorder (negative T-waves in V1-4 in the presence of RBBB) and depolarization disorder (epsilon waves in V1–3), as well as one
Electronic supplementary material The online version of this article (doi:10.1007/s00392-015-0849-9) contains supplementary material, which is available to authorized users. & Julia Koch
[email protected] 1
Department of Electrophysiology, Heart Center, University of Leipzig, Struempellstrasse 39, 04289 Leipzig, Germany
minor criteria, sustained VT of RV outflow tract configuration (left BBB morphology with inferior axis) were met, leading to the diagnosis of ARVC. Cardiac magnetic resonance (CMR) imaging was performed for further substrate analysis and comprehensive assessment of RV anatomy, structure, and function. Cine CMR imaging revealed a mildly impaired LV function, whereas the RV function was significantly reduced with dyskinesia of the free wall (EF 33%), also significant RV dilatation was found (139 ml/qm). Late gadolinum enhancement (LGE) images demonstrated areas of extensive fibrosis of the anterolateral RV wall and a significant transmural fibrosis/necrosis of the anterior LV and nontransmural intramyocardial LGE of the LV septum with corresponding focal edema in these regions and no evidence of fatty tissue infiltration in the LV and RV (Fig. 2, top left and right). Moreover, evidence of global myocardial hyperemia as a marker of myocardial inflammation on T1 weighted images (global early enhancement) could be detected. Consequently, the CMR findings were consistent with myocarditis as three diagnostic CMR criteria for myocardial inflammation are met: (1) irreversible myocardial injury in a non-ischemic regional distribution pattern in LGE images, (2) hyperemia/capillary leakage as defined by an increased early gadolinium uptake and (3) global or regional edema [2]. Yet, all these criteria are nonspecific to myocarditis and can occur in various conditions. One important differential diagnosis is sarcoidosis, where this pattern of pronounced LGE notably in the basal septum can be found. However, there were no clinical or histological signs of sarcoidosis, making this diagnosis very unlikely. For further evaluation, biventricular endomyocardial biopsy was conducted, revealing moderate diffuse fibrosis, histologic proof of chronic lymphocytic myocarditis and
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Fig. 1 The 12-lead surface ECG in sinus rhythm (top) of the clinical ventricular tachycardias CL 400 ms (bottom left) and CL 370 ms as a dual tachycardia (ventricular tachycardia and atrial flutter, bottom right)
just under 500 viral copies of human herpes virus 6 (HHV 6) per microgram of myocardial nucleic acids (Fig. 2, bottom).
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Due to recurrent hemodynamic unstable VT and the extensive LGE suggesting the irreversibility of the arrhythmic substrate in this patient, an ICD implantation
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Fig. 2 Parasternal short axis showing delayed gadolinium enhancement in the basal anterior and anteroseptal aspects of the LV and anterolateral aspects of the RV (top left) and T2 weighed stir sequence with focal edema in the anterior and anteroseptal aspects of the LV and RV (top right). Histopathology and immunohistology of
endomyocardial biopsies: Masson trichrome staining with blue areas corresponding to interstitial fibrosis (bottom left), presence of CD 3 T cells (bottom middle) and CD 68 positive macrophages (bottom right) indicating chronic lymphocytic myocarditis
was indicated for secondary prevention of SCD. The patient was discharged with heart failure medication including sotalol. On 6 months follow-up, the patient still presented with New York Heart Association class II symptoms and echocardiography did not show any changes in RV or LV function. Device interrogation revealed adequate ICD therapies, for the medication was switched to amiodarone; there were no more therapies at 18 months follow-up. This case underlines that establishing a clear-cut diagnosis in such a scenario can be extremely challenging despite the application of extensive diagnostic work-up modalities. There are various conditions that can mimic ARVC, such as myocarditis or sarcoidosis [3]. The applicability of the modified Task Force criteria for ARVC in the presence of other pathologies affecting the RV is questionable [1]. One of the most important differential diagnoses is myocarditis as depicted in this case. But ARVC and myocarditis might not be that clearly distinguishable. In more than half of ARVC cases inflammation with or without cardiotropic virus presence can be found in the biopsy [5–7]. It is well possible that ARVC has two components:
(1) a predisposition of fibrofatty displacement of the right and left ventricle and (2) myocardial inflammation secondary to viral myocarditis (either as a trigger of disease progression or secondary due to increased susceptibility). This also suggests two conceivable pathologies in this case: (a) a progressive-infiltrative, inherited disease, which was triggered and deteriorated by an additional HHV 6 infection of the myocardium and (b) a HHV 6 associated myocarditis, presenting with the phenotype of ARVC. Importantly, there was no fibrofatty displacement in the RV biopsies, also the genetic testing for ARVC associated genes and family history were unremarkable. On the other hand, biopsy can miss the area of interest and genetic testing is positive in only 30–50 % of ARVC cases [4]. In summary, this case revealed extensive HHV 6 associated chronic myocarditis mimicking the phenotype of ARVC. Despite a definite diagnosis of ARVC according to the modified Task Force Criteria [1] the diagnosis was challenged by CMR, which revealed extensive LGE and additional signs of inflammation. Because of these findings, endomyocardial biopsy was performed resulting in the final diagnosis of severe chronic myocarditis.
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None. 4.
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