A case of mistaken identity of arrhythmogenic right ventricular dysplasia in a 75-year-old patient

Abstract

We present an uncommon case of a 75-year-old woman who was admitted to our department for the evaluation of her double valvular disease that hid a diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). In the course of preoperative workup, a mass of tissue substituting the right ventricular free wall was identified and documented with transthoracic echocardiography, computed tomography scanning, and nuclear magnetic resonance imaging. This pathology was not identified as ARVD. Before and after surgery (double valve replacement), malignant arrhythmias were observed and treated with an implantable cardioverter-defibrillator. The patient underwent reoperation 24 days later for endocarditis and died in the immediate postoperative period from untreatable ventricular arrhythmias. At autopsy the histological characteristics of ARVD were detected. This report highlights the difficulty in diagnosing ARVD in patients who do not fulfil the McKenna criteria.

Background

Arrhythmogenic right ventricular dysplasia, a cardiomyopathy inherited as an autosomal dominant disease, is characterised by fibro-fatty substitution of the right ventricular myocardium. The condition was originally called Uhl’s disease, after Henry Uhl who reported the first case in 1952. In 1979, Fontaine and colleagues described a condition which they called “arrhythmogenic right ventricular dysplasia”, characterised by a gradual loss of myocytes and replacement by adipose and fibrous tissue in the right ventricular myocardium. In the literature a variety of descriptive names were embraced by these two apparently distinct conditions, which included ectasia, congenital aplasia and congenital hypoplasia of the right ventricle, idiopathic right ventricular myocardial dysplasia, absence of the right ventricular myocardium, fatty infiltration, and lipomatosis.

The disease is an uncommon cardiac disorder characterised by varying degrees of replacement of the right ventricular myocardium by fibrous and adipose tissue. It is the cause of isolated right ventricular enlargement and failure with partial or total absence of right ventricular myocardium.

The clinical course is characterised by ventricular arrhythmias, heart failure, syncope and sudden death.

Arrhythmogenic right ventricular dysplasia was first considered to be a result of abnormal embryologic development. However, more recent publications incriminate chromosomal anomalies.^1–3 Few cases have been reported in the literature, with few affected individuals reaching their fourth decade of life.

We report a case of a patient with severe and diffuse right ventricular dysfunction similar to arrhythmogenic right ventricular dysplasia.

Case presentation

A 75-year-old woman was referred to our cardiovascular department for evaluation of mitral and aortic valve disease. She had a history of hypertension, dyslipidaemia, chronic obstructive pulmonary disease, and paroxysmal atrial fibrillation. She had no family history of cardiovascular disease, no chronic alcohol abuse, and no muscular dystrophy.

Her cardiac history began approximately 7 years previously with onset of mild dyspnoea and chest pain on exertion and syncopal episodes.

Just before her present admission the dyspnoea had begun to worsen, progressing to New York Heart Association (NYHA) functional class III. She had also orthopnoea, paroxysmal nocturnal dyspnoea, oedema of her lower extremities, and frequent syncopal episodes.

Cardiovascular examination revealed a grade III–IV pansystolic murmur at the apex and a diastolic murmur at the third left parasternal border. The electrocardiogram (ECG) demonstrated a left anterior hemiblock (fig 1) and no clear epsilon waves in V1–V3 (fig 2); no other signs were remarkable. Paroxysmal atrial fibrillation was identified. Coronary angiography was normal.

Figure 1.

Electrocardiogram (ECG) showing left anterior hemiblock.

Figure 2.

ECG showing no clear epsilon waves in V1–V3.

During her hospital stay the patient described a sudden onset of rapid, regular and forceful heart activity; the monitor showed at first a ventricular tachycardia that rapidly degenerated into a torsade de point (fig 3) and ventricular fibrillation (fig 4). Resuscitation was performed and the patient was successfully defibrillated electrically.

Figure 3.

ECG showing torsade de point and ventricular fibrillation.

Figure 4.

ECG showing ventricular fibrillation.

Transthoracic echocardiography at that time demonstrated a very large dilation of the right atrium and a hypokinetic right ventricle with severe mitral and aortic regurgitation. The right ventricle (24 mm end diastolic diameter) was thin walled and without trabeculation. The right atrium was dilated and hypertrophied. Notably an unambiguous large pericardial thickening above the right ventricle was evident (fig 5).

Figure 5.

Transthoracic echocardiogram showing non-homogeneous mass of 1.9 cm diameter in continuity with the right ventricular free wall.

In order to evaluate the nature of the pericardial thickening, the patient underwent computed tomography (CT) scanning, which revealed enlargement of the cardiac silhouette with a prominent right ventricle contour. The images were suggestive of a lipomatous structure of the free wall of the right ventricle. No other structural abnormalities were found (fig 6).

Figure 6.

Computed tomography image showing tissue infiltrating the right ventricle free wall with a density typical of fat. Multilobular aspect of the fat tissue substituting the right ventricular free wall partially occupies the right ventricular chamber.

Thoracic nuclear magnetic resonance imaging (MRI) showed a diffuse bright signal from the right ventricular wall, interpreted as lipomatous tissue in the cardiac surface, and in particular visualised the mistakable presence of some fat in the right ventricular myocardium. There was no demonstration of global and regional functional abnormalities of the right ventricle and right ventricular outflow tract (fig 7).

Figure 7.

Nuclear magnetic resonance image showing near obliteration of the right ventricle. Fatty infiltration with multilobular aspect of the anterior right ventricle wall is evident.

Surgical intervention for mitral and aortic valve replacement was indicated for the patient. Replacement of the aortic and mitral valves with biological stented prostheses, pulmonary vein isolation with bipolar radiofrequency, and obliteration of the left atrial appendage were performed uneventfully. The length of stay in the intensive care unit was prolonged due to respiratory problems.

Amiodarone administration was started with an intravenous (iv) 300 mg bolus before cardiopulmonary bypass (CPB) termination, followed by an infusion of 900 mg/day.

In the early postoperative period, ventricular arrhythmias became a major problem, even though the amiodarone infusion had started. Treatment of the arrhythmias with different antiarrhythmic agents, such as lidocaine 200 mg iv and magnesium sulfate 1 g iv, proved unsuccessful.

An automatic cardioverter-defibrillator was then implanted on day 15 postoperatively, because of the high risk of sudden death.

Two paraprosthetic aortic leaks were documented by transoesophageal echocardiography in the following days. Because of the patient’s worsening clinical condition, on day 24 post-surgery the patient underwent reoperation to resolve the leaks. Early prosthetic aortic valve endocarditis was found (Candida parapsilosis was later isolated) and a new biological prosthesis replaced the infected one.

The patient died a few hours following the second surgical procedure from intractable ventricular arrhythmias. The autopsy demonstrated a notably dilated heart, in particular the right ventricle, covered with subepicardic adipose tissue. The thin wall of the right ventricle consisted almost entirely of adipose tissue.

Histology showed diffuse fatty infiltration of the myocardium, with fibrosis, and macrophagic inflammatory infiltrates in which myocytes were trapped (fig 8). The histological abnormalities detected included varying degrees of fibro-fatty replacement, myocardial degeneration, and myocyte hypertrophy. A diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) was made.⁴

Figure 8.

Transverse section of the myocardium showing atrophy and replacement of myocytes with adipose tissue (haematoxylin and eosin, ×20).

Discussion

Dilated congestive cardiomyopathy limited to the right ventricle is an unusual and rare disorder. The disability in patients with ARVD arises from deficiency of the right ventricular myocardium. Ineffective right ventricular contraction results in elevated right atrial pressure, right atrial enlargement, and signs of congestive heart failure.

The abnormalities of the right ventricle which were found at necropsy in previously documented cases have varied from focal deficiency of the right ventricular myocardium in adults to almost total absence in infants. In this condition, areas of fatty and fibrous tissues replace the normal myocardium of the right ventricle. The involved myocardium evokes ventricular arrhythmias of right ventricular origin.

The haemodynamic findings reflect right ventricular pump failure, and the right atrium is responsible for maintaining the pulmonary circulation. It presents as segmental areas of hypokinesis and dyskinesis rather than global right ventricular and infundibular dysfunction.

Clinical manifestations of the disease include structural and functional abnormalities of the right ventricle, specific electrocardiographic changes, and presentation with sudden death or arrhythmias of right ventricular origin. The relatively benign course in adults is, however, complicated by the occurrence of malignant ventricular dysrhythmias. ARVD is usually diagnosed at a young age (usually <40 years). In this case the patient was 75 years of age and had lived an apparently normal life, despite the presence of an advanced form of ARVD.

The diagnosis of ARVD is based on the presence of major and minor criteria,^4,5 already established and encompassing genetic, electrocardiographic, pathophysiologic, and histopathologic factors. These guidelines represent an important landmark in establishing minimal criteria for this diagnosis. It recognised that there is no single test that is diagnostic for ARVD. A combination of major and minor criteria have been proposed but these have not been evaluated prospectively.

In our case, the data did not fulfil the McKenna criteria for a diagnosis of ARVD. Retrospectively, all the patient’s imaging data were strongly suggestive of, but not diagnostic for, ARVD.

A definitive diagnosis of ARVD is based on histological demonstration of transmural fibro-fatty changes of the right ventricle, linked in part to both apoptotic cell death and patchy myocarditis.^6,7 Only by employing microscopic histology did we recognise the morphologic features of the disease—that is, the diffuse loss of myocardium in the mediomural and epicardial layers of the right ventricular free wall, with replacement by fat and fibrous tissue.

According to diagnostic criteria of McKenna, the disease is suspected in the presence of arrhythmias. All patients should be required to have an electrocardiographic pattern of ARVD and echocardiographic evidence of right ventricular dilation, with or without evidence of right ventricular thinning and/or outflow tract dilation. Patients meeting these criteria should then be evaluated by supplementary investigations: CT, nuclear MRI or even endomyocardial biopsy with immunohistochemical analysis. Immunohistochemical pattern analysis is useful in equivocal diagnoses of ARVD. This method is relatively sensitive and specific, and increases the predictability when there are ambiguous morphological characteristics.⁸

The images are presented in this report in an effort to assist others to make this difficult diagnosis in those patients who do not fulfil the McKenna criteria, particularly the patient’s age.

Learning points

• An uncommon case of arrhythmogenic right ventricular dysplasia (ARVD) in a 75-year-old woman in whom the symptomatology was indicative of an associated valvular pathology.

• This report highlights the difficult diagnosis of ARVD in patients who do not fulfil the McKenna criteria.

• The images presented in this report may help others to make this difficult diagnosis in those patients who do not fulfil the McKenna criteria, particularly the age of the patient as in our case.