A unique association of arrhythmogenic right ventricular dysplasia and acute myocarditis, as assessed by cardiac MRI: a case report
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Arrhythmogenic right ventricular dysplasia (ARVD), is a genetic disorder of the heart, which mainly involves the right ventricle. It is characterized by hypokinetic areas at the free wall of the right ventricle (RV) or both ventricles, where myocardium is replaced by fibrous or fatty tissue. ARVD is an important cause of ventricular arrhythmias in children and young adults. Although the transmission of the disease is based on hereditary, in young adults it may not show any symptoms. The main differential diagnoses with other frequent etiological causes of sudden arrhythmia are: idiopathic outflow tract ventricular tachycardia of the RV, myocarditis, dilated cardiomyopathy and sarcoidosis.
We describe an unusual case of a 44-year-old woman who was hospitalized for ventricular tachycardia, deep asthenia and dyspnoea with no previous history of cardiac disease. The patient had a ten-year history of palpitations, which started immediately after her last pregnancy. She was diagnosed with both acute/subacute viral myocarditis and arrhythmogenic right ventricular dysplasia, based on established clinical and cardiac MRI criteria. After the diagnosis the patient received an automatic implantable cardioverter defibrillator. Currently, she is on clinical follow-up with no apparent further complications.
Analyzing this rare case, we have shown the link between myocarditis and arrhythmogenic right ventricular dysplasia, and how important is to perform a cardiac MRI, in the context of acute myocarditis and ventricular arrhythmia.
KeywordsMyocarditis Cardiac Magnetic resonance imaging Right ventricle Case report
Automatic implantable cardioverter defibrillator
Arrhythmogenic right ventricular dysplasia
Body surface area
Coronary care unit
Right ventricular ejection fraction
Short time inversion recovery
Arrhythmogenic right ventricular dysplasia (ARVD), is a genetic disorder of the heart, that mainly involves the right ventricle [1, 2]. It is characterized by hypokinetic areas at the free wall of the right ventricle (RV) or both ventricles, where myocardium is replaced by fibrous or fatty tissue. ARVD is an important cause of ventricular arrhythmias in children and young adults. Although the transmission of the disease is based on hereditary, in young adults it may not show any symptoms. The main differential diagnoses with other frequent etiological causes of sudden arrhythmia are: idiopathic outflow tract ventricular tachycardia of the RV, myocarditis , dilated cardiomyopathy and sarcoidosis. We hereby describe a rare case of a patient with both acute viral myocarditis and ARVD, as assessed by echocardiography and cardiac MR (CMR).
ARVD is predominantly a genetically determined heart muscle disorder, pathologically characterized by fibro-fatty replacement of the right ventricular myocardium [1, 2]. This pathology predisposes to ventricular arrhythmias and sudden cardiac death and it can be divided in three progressive phases: in the early “concealed phase” patients are often asymptomatic; in the overt “electrical phase” patients present with symptomatic arrhythmias; finally, in the diffuse disease patients may present with right, left or biventricular heart failure with associated ventricular arrhythmias. Current Task Force Criteria for ARVD diagnosis include, repolarization or depolarization abnormalities on electrocardiography (ECG), presence of ventricular arrhythmias, morphological and functional changes, in addition to histopathology, family history, and genetic findings . Our patient fulfilled the major criteria set by the Task Force [2, 3]: repolarization abnormalities (inverted T waves in right precordial leads in the absence of complete right bundle-branch block), sustained ventricular tachycardia of left bundle-branch morphology with superior axis, RV EDV to BSA ≥ 100 mL/m2 and RVEF ≤ 40%, as assessed by echocardiography and CMR. In addition, the patient fulfilled two of the Lake-Louise criteria for CMR in acute myocarditis . Infact, CMR showed the presence of myocardial edema on STIR-T2W sequences and sub-epicardial necrosis on post-contrast T1W sequences; therefore, these imaging findings added to troponin I and CK-MB release and an elevation of CRP and white blood cells, strongly suggested an acute myocarditis. Several studies have demonstrated that myocarditis may affect the RV, causing structural abnormalities, including microaneurysms, as well as the arrhythmic manifestations that are typical of ARVD. Some cardiotropic viruses (enterovirus or adenovirus), detected in patients with sporadic ARVD, were considered to have a potential role for the disease; in fact the activation of inflammatory mediators, determined by the myocardial infection, could damage the cardiac adherents junctions and the T-tubule system, resulting in ventricular irritability and/or ion channel disruption and consequent ARVD symptomatology . However, this hypothesis is controversial, because the inflammation could be a secondary event; infact, an already diseased myocardium could have an increased susceptibility to viral infection with resulting myocardial inflammation . Therefore, the precise relationship between ARVD and acute myocarditis is not yet determined .
In a previous manuscript, Mavrogeni et al. described the case of a patient with Naxos disease, a recessively inherited arrhythmogenic cardiomyopathy (ACM), characterized by woolly hair and palmo-plantar keratoderma . This patient was asymptomatic and presented with chest pain and increased troponin I. A deletion in plakoglobin (cell adhesion protein) gene (Pk2157del2TG) was identified as the cause of Naxos disease ; therefore, it has been proposed that a defect in proteins involved in cell–cell adhesion, particularly under mechanical stress conditions, could result in cell death and progressive myocardial fibro-fatty replacement . Moreover, myocardial inflammatory infiltrates, frequently detected in patients with ARVD, have been assumed as a reaction to cell death rather than a consequence of an infective process . As described in recent papers, the reactive nature of myocarditis in ARVD has been supported by the massive inflammatory cell infiltrates found after acute myocardial necrosis in early stages of disease in desmoglein-2 transgenic animal model . In particular, Kant et al. have shown the etiologic role of a deletion of the adhesive extracellular domain of the desmosomal cadherin in mice with an arrhythmogenic right ventricular cardiomyopathy like phenotype, with ventricular dilation and fibrosis. Disturbed sarcomer structure, multiple autophagic vacuoles and swollen mitochondria are typical findings of this cardiomyopathy, inducing cardiomyocyte death, aseptic inflammation and fibrotic replacement, with consequent impairment of the cardiac function .
It must be underlined that in our case the patient started to suffer of palpitations and fatigue for light efforts after giving birth her third child in 2009. Therefore, it is reasonable to raise the hypothesis that pregnancy, the hormonal changes and/or inflammatory stress occurring during pregnancy may unmask ARVD. Due to the rarity of cases, the relation between the two events is not yet established. Furthermore, idiopathic right ventricular outflow tract ventricular tachycardia, right ventricular myocardial infarction, dilated cardiomyopathy, myocarditis, pulmonary hypertension, atrial and ventricular septal defects are possible differential diagnoses including a dilated right ventricle. Moreover, sarcoidosis with cardiac involvement can mimic ARVC, making the differential diagnosis very challenging. Uhl’s disease, an unusual cardiac disorder with almost complete absence of right ventricular myocardium, should also be considered as differential diagnosis . ARVD and myocarditis have often different prognosis and treatment; in fact, the former is a complex and progressive entity that requires major clinical intervention, as AICD implantation, or heart transplantation, while the latter is often a self-limited pathology responding to a conservative approach.
To the best of our knowledge, only one case has been published in the English literature showing in a 23 years old man this rare linkage between ARVD and acute myocarditis, based on echocardiography and CMR findings . In agreement with this article, in our case and according to the current international task force consensus statement for ARVD  the patient underwent an AICD implantation and is currently in clinical follow up, with no further complications.
In the case presented, CMR allowed the correct identification of the two different clinical entities; in addition, the enhancement pattern as shown on delayed CMR images, may also serve as a map for the exact location of ablation or an endomyocardial biopsy .
This case shows the rare association between acute myocarditis and ARVD, highlighting the importance of a complete RV assessment through a CMR study in the context of ventricular arrhythmia. CMR is the most accurate and reproducible technique for assessing the morphology and segmental wall motion of the RV; in addition, it can evaluate the presence of myocardial inflammation with specific STIR-T2W sequences and myocardial fibrosis or necrosis with post-contrast T1W sequences, leading the physician to the correct final diagnosis and to the most appropriate management of patients presenting with ventricular arrhythmias.
Gennaro Fraia and Fabio Garbino (Technologists) for their contribution in making this study possible.
Availability of data and materials
data regarding this manuscript are available at the Department of Advanced Biomedical Sciences, at the University Federico II, Naples, Italy; Via Pansini 5.
MI, MP, AP, AC and BT: Study design and conception, Cardiac MR interpretation and manuscript preparation; CM, MS, LS and AR: acquisition of data, coronary care unit, drafting the manuscript; LB, MP, AP and MI: acquisition of cardiac MR data and interpretation of images. AC and BT: manuscript critical revision. All authors read and approved the final manuscript.
All authors belong to the Department of Advanced Biomedical Sciences, University “Federico II”, Via Pansini 5, 80123, Naples, Italy.
Consent for publication
The patient gave written informed consent to publish this manuscript.
Ethics approval and consent to participate
This case report was approved by the local institutional review board and the patient gave written informed consent to partecipate for this manuscript.
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