Case report

 

Arrhythmogenic right ventricular cardiomyopathy

Abstract  Arrhythmogenic right ventricular dysplasia  or cardiomyopathy is a heart muscle disorder of unknown cause that is  characterized by fibro fatty replacement of the right ventricular myocardium and ventricular arrhythmias Clinical manifestations of the disease include various arrhythmias generally of right ventricular origin including isolated extra systoles, non sustained or sustained ventricular tachycardia and ventricular fibrillation leading to sudden death. Congestive heart failure is also observed in the most severe forms of the disease. Diagnosis of ARVD is often a very difficult task as there is no single test which can be used either to establish or exclude this diagnosis. A careful history, physical examination, and a number of specific cardiac tests can be used to establish the diagnosis of ARVC. We report a case of  ARVC which was diagnosed  from ECG, echocardiographic and MRI findings.

 

 

Key words Arrhythmogenic right ventricular dysplasia  , Arrhythmogenic right ventricular cardiomyopathy, ARVD,ARVC

 

 

 

 

 

 

 

 

 

 

Introduction

Arrhythmogenic right ventricular dysplasia  or cardiomyopathy is a heart muscle disorder of unknown cause that is  characterized by fibro fatty replacement of the right ventricular myocardium and ventricular arrhythmias. Recognition of this disease is hampered by the fact that it is an unusual condition and not well known to most physicians or pathologists. Even though the predominant involvement is right ventricular myocardium, it is known to involve left ventricular involvement in late stages. Familial occurrence is common with autosomal dominant transmission in 50 % of patients¹. Clinical manifestations of the disease include various arrhythmias generally of right ventricular origin including isolated extra systoles, non sustained or sustained ventricular tachycardia and ventricular fibrillation leading to sudden death. Congestive heart failure is also observed in the most severe forms of the disease. Diagnosis of ARVD is often a very difficult task as there is no single test which can be used either to establish or exclude this diagnosis. A careful history, physical examination, and a number of specific cardiac tests can be used to establish the diagnosis of ARVD

 

 

 

 

 

 

 

 

 

 

 

Case report

             40 year old male patient was admitted in a nursing home with palpitations. ECG recorded during the same episode showed a broad complex tachycardia, regular at a rate of 166 bpm. Patient was treated with IV xylocaine and was started on oral amiodarone . Patient was shifted to this tertiary care centre for further management. When ECG during tachycardia was analyzed it showed LBBB configuration with inferior axis(Fig 1). His baseline ECG during sinus rhythm revealed I RBBB with inverted T waves in the V1-V5 along with prolonged QRS duration in the leads V1-V4( Fig 2). A provisional diagnosis of ARVD was made and further evaluation was carried out. He denied any previous history of the similar episodes. There was no family history of any sudden deaths or any cardiac disorders. His X ray showed cardiomegaly with prominent right heart border.  His ECHO revealed localized aneurysmal dilatation of RVOT, depressed RV function  and mild primary tricuspid regurgitation.(Fig 3,4) As patient had fulfilled 2 major and 2 minor criteria diagnosis of ARVD was confirmed. Patient’s two brothers were evaluated with ECG and ECHO. Both had normal ECG and ECHO. A cardiac MRI was performed which revealed aneurysmally dilated RVOT with thinning and fatty deposition of right ventricular myocardium.(Fig 5,6,7) Patient was continued on amiodarone. Patient had no more episode of palpitation during the second month of follow up.

                                                            ECG

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ECHO 1

ECHO 2

 

Discussion 

   In 1977, Fontaine and colleagues ² provided an anatomical and clinical description of several cases of ARVD discovered during surgical treatment of ventricular tachycardia.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disease, often familial, that is characterized pathologically by fibro fatty replacement of the right ventricular myocardium, and clinically by ventricular arrhythmias of right ventricular origin which may lead to sudden death, mostly in young people and athletes. The word dysplasia is been replaced by the term cardiomyopathy with the recognisation of the fact that it is a non-ischemic, ongoing atrophy of the right ventricular myocardium, most likely genetically determined, which becomes symptomatic in adolescents and young adults.

            Most important pathological feature of this condition is diffuse or segmental loss of right ventricular myocardium and its replacement with fibro fatty tissue.

In 50 % of the patients it involves the the diaphragmatic, apical,and infundibular regions (so called “triangle of dysplasia)³. Histologically fibrofatty tissue is seen with islands of myocardial cells mainly confined to the subendocardial region. In two thirds of the patients patchy  inflammatory infiltrates may be seen. Apoptosis , inflammation or genetically determined muscle dystrophy are the proposed mechanism for this fibrofatty replacement ⁴ .

A familial background have been demonstrated in nearly 50% of ARVC cases, with an autosomal dominant pattern of inheritance. The involved genes and the molecular defects causing the disease are still unknown. However, seven ARVC loci have been identified so far, two of which are in close proximity of chromosome 14 (14q23-q24 and 14q12-q22),and the others on chromosome 1 (1q42-q43),chromosome 2 (2q32.1-q32.2), chromosome 3 (3p23), and chromosome 10 (p12-p14)¹.

The most common clinical manifestations of ARVC consist of ventricular arrhythmias with left bundle branch block (LBBB) morphology. Uncommonly, the first manifestation of ARVD may be sudden cardiac death. Patients may be diagnosed because of ECG or echocardiographic findings on routine examination. In late stage they may present with right heart failure or biventricular failure.

The physician should consider ARVD in the differential diagnosis if the ventricular arrhythmias have a left bundle branch block configuration with an inferior, horizontal or superior QRS axis. The probability that the ventricular arrhythmias are due to ARVD is enhanced if there are inverted T waves in the right precordial leads beyond V₁ in individuals over the age of 12. Fontaine et al, ⁵ in 1994, reported that a QRS duration of > 110 msec in V₁, V₂, or V₃ in association with a negative T wave in lead V₂, had an 84% sensitivity and 100% specificity for the diagnosis of patients with ARVD who had sustained ventricular tachycardia. Peters, et al.⁶ reported a 93% sensitivity, 96% specificity and 98% positive predictive value for the diagnosis of ARVD if the QRS duration in V₂ + V₃/V₄ or V₅ was >1.2. They stated that there was an even greater sensitivity if there is a QRS prolongation of > 100 msec in addition to the above criteria

The Signal Averaged Electrocardiogram (SAECG) is usually markedly abnormal in patients with ARVD who have sustained ventricular tachycardia, particularly if the tachycardia has a superior QRS axis.

The echocardiogram is extremely useful to detect right ventricular enlargement or wall motion abnormalities that would confirm the diagnosis of ARVD. The left ventricle is normal or not severely involved with regard to increased size or functional abnormalities except in the advanced stages of this disease. Manyari et al ⁷. assessed the sensitivity and specificity of 2D echocardiography to detect right ventricular dysplasia in 44 patients suspected of having this condition. ARVD was present in 14 patients and absent in 30 patients as determined by cardiac catheterization including right ventricular angiography. A ratio of > 0.5 for the RV/LV end diastolic diameter had a sensitivity of 86%, specificity of 93% and positive predictive value of 86% for the diagnosis of ARVD.The negative predictive value was 93%.ECHO is also useful in diagnosis of asymptomatic family members of the patient.

                Right ventricular angiography is usually regarded as the gold standard for the diagnosis of ARVC. Angiographic evidence of akinetic or dyskinetic bulgings localised in infundibular, apical, and subtricuspidal regions has a high diagnostic specificity (over 90%).Large areas of dilatation akinesia with an irregular and “mamillated” aspect, most often involving the inferior right ventricular wall, are also significantly associated with the diagnosis of ARVC ⁸. However, considerable interobserver variability regarding the visual assessment of right ventricular wall motion abnormalities by contrast angiography has been reported.

            MRI is an attractive imaging method because it is non-invasive and has the unique ability to characterise tissue, specifically by differentiating fat from muscle. In ARVD, the right ventricular wall is infiltrated with fatty tissue. The excessive fat is displayed as a white area as compared with a gray color that is characteristic of normal ventricular muscle. In addition, there may be myocardial thinning. ⁹ The cine MRI can be used to define localized dyskinetic regions of the myocardium. Although attractive there are several fallacies in this technique. The right ventricular free wall is only 4–5 mm thick and the motion artifacts often result in insuYcient quality/ spectral resolution to quantify right ventricular wall thickness accurately. The normal presence of epicardial and pericardial fat also makes

identification of true intramyocardial fat difficult. Some areas—such as the subtricuspidal region—are not easily distinguished from the atrioventricular sulcus which is rich in fat. There has been recent emphasis on functional  methods such as right ventricular volume estimation with cine MRI. This approach also permits accurate assessment of right ventricular wall motion abnormalities and focal areas of dilatation with or without dyskinesia .Despite these limitations, the MRI is a valuable technique for diagnostic evaluation of right ventricular dysplasia as well as the extent of involvement of the right and left ventricles in this condition

The confirmation of the diagnosis of ARVD by endocardial biopsy lacks sensitivity because the typical pathological changes are not consistently seen in the septum, the usual site of biopsy. The right ventricular free wall is not usually biopsied because of possible myocardial perforation. Biopsy performed at the junction of the septum and the free wall may increase the sensitivity. However, this requires experience to be certain that the bioptome is in this location. Using this latter site and performing a quantitative analysis of fat in the biopsy specimen Angellini et al.¹⁰ found a 67% sensitivity and 92% specificity for this diagnosis .On a practical basis however, myocardial biopsy can not be routinely recommended to confirm the diagnosis of ARVD.

Mckenna et al. described criteria for the diagnosis of the ARVD in 1994¹¹ (Table1)

Table 1 Criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy(ARVC) I. Family history Major Familial disease confirmed at necropsy or surgery Minor Family history of premature sudden death (< 35 years) caused by suspected ARVC Family history (clinical diagnosis based on present criteria) II.ECG depolarisation/conduction abnormalities Major Epsilon waves or localised prolongation (> 110 ms) of the QRS complex in the right precordial leads (V1–V3) Minor Late potentials seen on signal averaged ECG III.ECG repolarisation abnormalities Minor Inverted T waves in right precordial leads (V2 and V3) in people >12 years and in the absence of right bundle branch block IV.Arrhythmias Minor Sustained or non-sustained left bundle branch block type ventricular tachycardia documented on the ECG, Holter monitoring or during exercise testing Frequent ventricular extrasystoles (more than 1000/24 hours on Holter monitoring) V. Global and/or regional dysfunction and structural alterations* Major Severe dilatation and reduction of right ventricular ejection fraction with no (or only mild) left ventricular involvement Localised right ventricular aneurysms (akinetic or dyskinetic areas with diastolic bulgings) Severe segmental dilatation of the right ventricle Minor Mild global right ventricular dilatation and/or ejection fraction reduction with normal left ventricle Mild segmental dilatation of the right ventricle Regional right ventricular hypokinesia VI. Tissue characteristics of walls Major Fibrofatty replacement of myocardium on endomyocardial biopsy

*Detected by echocardiography, angiography, magnetic resonance imaging, or radionuclide

scintigraphy

 

                                                                        MRI 1

MRI2

MRI 3

 

 

 

 

Therapy with beta blockers, sotalol or amiodarone¹² may be effective in suppressing ventricular arrhythmias and possibly in preventing sudden cardiac death. Implantation of an ICD may also be indicated to prevent sudden death. Catheter ablation of ventricular tachycardia may be useful in patients with refractory symptoms despite antiarrhythmic therapy. It has acute success rate of 60 -90%.  However, ventricular arrhythmias may recur from other areas in 60 % of patients.¹³

Patients should also be advised not to perform vigorous exercise or engage in competitive sports. Surgical disarticulation of the right ventricular free wall from its attachments to the left ventricle and septum can prevent the electrical propagation of ventricular arrhythmias from the right to the left ventricle. This was an effective means to prevent sudden death prior to the availability of the ICD, but resulted in severe right ventricular failure. Management of heart failure includes standard medical therapy with consideration of heart transplantation if severe ventricular, especially biventricular, dysfunction is present.

The natural history of ARVC remains obscure. Present evidence suggests it is a progressive disorder. Long term follow up data from clinical studies indicate that the right ventricle may become more diffusely involved with time. Later in the natural history, the left ventricle may be progressively affected with subsequent biventricular failure. Four phases have been described

a) “Concealed” phase

b) “Overt electrical disorder”

c)“Right ventricular failure”

d)“biventricular pump failure”

Sudden cardiac death may occur during any stage of the disease and remains the most dreaded complication. Young age, competitive sport activity, malignant familial background, extensive right ventricular disease with ejection fraction reduction and left ventricular involvement, syncope, and episodes of complex ventricular arrhythmias or VT have been identified as risk factors for sudden cardiac death from retrospective data¹⁴. Patients should be evaluated by noninvasive testing to identify these risk factors. But predictive value of these tests remains to be determined.

 

 

References

 

1. Nava A, Thiene G, Canciani B, et al. Familialoccurrence of right ventricular dysplasia: a study involving nine families. J Am Coll Cardiol 1988;12:1222–8.
2. Marcus FI, Fontaine G, Guiraudon G, et al. Right ventricular dysplasia. A report of 24 adult cases. Circulation 1982;65:384–98.
3. Thiene G, Nava A, Corrado D, et al. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med1988;318:129–33.
4. Basso C, Thiene G, Corrado D, et al. Arrhythmogenic right ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis? Circulation 1996;94:983–91.

5.       Fontaine G, Tsezana R, Lazarus A, Lascault G, Tonet J, Frank R. Troubles de la repolarisation et de la conduction intraventriculaire dans la dysplasie ventriculaire droite arhythmogene.   Ann Cardiol Angeiol 1994;43:5-10.

6.       Peters S, Weber B, Reil GH. Conventional electrocardiogram in arrhythmogenic right ventricular dysplasia-cardiomyopathy and idiopathic right ventricular outflow tract tachycardia. Annals of Non Invasive Cardiology 1996;1(4):400-404.

7. Manyari DE, Duff HJ, Kostuk WJ, Belenkie I, Klein GJ, Wyse DG, Mitchell LB, Boughner D, Guiraudon G, Smith ER. Usefulness of noninvasive studies for diagnosis of right ventricular dysplasia. Am J Cardiol 1986;57:1147-1153.

8.       Molinari G, Sardanelli F, Gaita F, Ottonello C, Richiard E, Parodi RC, Masperone MA, Caponnetto S. Right ventricular dysplasia as a generalized cardiomyopathy? Findings on magnetic resonance imaging. Eur Heart J 1995;16:1619-1624.

9. Daliento L, Rizzoli G, Thiene G, et al. Diagnostic accuracy of right ventriculography in arrhythmogenic right ventricular cardiomyopathy. Am J Cardiol 1990;66:741–5.

10.   Angelini A, Thiene G, Boffa GM, Calliaris I, Daliento L, Valente M, Chioin R, Nava A, Volta SD. International Journal of Cardiology 1993;40:273-282.

11. McKenna WJ, Thiene G, Nava A, et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Br Heart J 1994;71:215–18.
12. Marcus FI, Fontaine G. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: a review. Pacing Clin Electrophysiol 1995; 18:1298-314
13. Corrado, Cristina Basso, Gaetano Thiene Arrhythmogenic right ventricular

      cardiomyopathy: diagnosis, prognosis,and treatment Heart 2000;83:588-595

14. Thiene G, Nava A, Corrado D, et al. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med1988;318:129–33.