- Email: [email protected]
Arrhythmogenic right ventricular dysplasia
Diagnostics
Arrhythmogenic Right Ventricular Dysplasia ABDULHALIM J. KINSARA, MD,* LIAQAT ZAMAN, MD,1- AND ANTON GORGELS, MDI Right ventricular dysplasia (RVD) is a disease entity of unknown cause that is characterised by partial or total replacement of RV-muscle by adipose or fibrous tissue. It is a well-recognized cause of arrhythmia and premature sudden death, but usually underdiagnosed. Several noninvasive and invasive diagnostic modalities have been used, however, all may not be positive in a given case. Drug therapy with class lc, betablocker, and amiodarone in variable combination produce varying success rates in preventing recurrent ventricular tachycardia. Failure of the above measures calls for insertion of implantable cardioverter defibrillator. The attention of emergency physicians is drown to this disease as they are the first medical personnel to be presented with this disease as an emergency. Hence their recognition of RVD will ensure early and proper management. (Am J Emerg ied 2001;19:67-70. Copyright ~ 2001 by W.B. Saunders Company) Osier was the first to describe right ventricular dysplasia (RVD) and in 1950 Segall presented a picture of the disease. It is a well-recognized cause of arrhythmia and premature sudden death, but is diagnosed infrequently. We describe two clinical cases of this disease and its unique clinical features, so that when emergency physicians are presented with this disease, it will be easily recognized and proper investigations and management is promptly instituted. CASE REPORT Case 1: A 34-year-old woman presented at her local hospital with several attacks of fast regular palpitations associated with headache, dizziness, and shortness of breath for the last 6 months. Her attacks were variable in frequency, on the average 2 to 3 times per week, lasting 10 to 15 minutes. Neither her past medical history, nor her family history was significant. On examination, she was euthyroid with normal physical examination of cardiovascular system. Her investigation showed normal baseline blood indices. Her thyroid function test was normal. Electrocardiogram (ECG) on admission showed sinus rhythm with negative T in VI_2 (Fig 1) ECG during tachycardia was ventricular tachycardia (VT) of left
From *King Khalid National Guard Hospital, Jeddah and i-King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Manuscript received April 29, 2000, returned May 4, 2000, revision received May 16, 2000, accepted June 6, 2000. Address reprint requests to Abdulhalim J. Kinsara, MD, P.O. Box 4409, Jeddah 21491, Saudi Arabia. E-mail: [email protected] Key Words: right ventricular dysplasia, therapy, diagnosis. Copyright © 2001 by W.B. Saunders Company 0735-6757/01/1901-0018510.00/0
doi:10.1053/ajem.2001.18131
bundle branch block morphology with normal axis (Fig 2). She was treated with intravenous procainamide during VT and was maintained on Verapamil, but her symptoms recurred a few weeks later and she was referred to our hospital. Her echocardiogram did not show wall motion abnormalities in fight ventricle (RV). Signal averaged ECG showed a borderline abnormality (duration of filtered QRS complex was > 120 ms but other parameters were normal). On a heart magnetic resonance image (MR/), the RV was slightly dilated but normal otherwise. Holter monitor showed nonsustained VT, variable bigeminy and trigeminy. Subsequent electrophysiologic study showed inducible VT by burst pacing. Mapping showed that ventricular activation was in the septum near the RV apex. This was ablated by radiofrequency but it was only partially successful, as the tachycardia was inducible after high dose of isoproterenol. Hence, she was started on Atenolol and on follow-up 2 months later, she was free of symptoms. Case 2: A 35-year-old woman experienced dizzy spells and collapsed at home. She was transferred on an emergency basis to a hospital where she was found to have VT at a rate of 300 beats/min for which she was D/C shocked and commenced on Amiodarone therapy. On her subsequent course she did well. There was no history of deafness and no family history of sudden death. Her 12-lead ECG, showed sinus rhythm, normal QT, with no significant T changes. Signal averaged ECG showed evidence of late potential, which is a duration of filtered QRS complex after the voltage decreased to <40/zv was > 4 0 ms and rootmean-square voltage during the last 40 ms of the filtered QRS complex was <20p, v. Echocardiogram was normal and MRI showed high signal intensity throughout the entire free wall of the RV measuring 6 m m in thickness consistent with arrhythmogenic RVD (Fig 3). RV biopsy confirmed the diagnosis of RVD (Fig 4). Her electrophysiological study showed easily induced VT by both atrial and ventricular stimulation. She was commenced on amiodarone and scheduled for implantable cardioverter defibrillator placement. DISCUSSION RVD is a disease entity of unknown cause that is characterized by partial or total replacement of muscle by adipose or fibrous tissue. It is primarily a disorder of the RV particularly the apex, infundibular and posterobasal wall, 1 but associated left ventricle involvement has been reported. No single factor was claimed to have a causal relationship, however, it occurs in both sporadic and familial forms with recognized abnormal gene; chromosome number 14. 2 67
68
AMERICAN JOURNAL OF EMERGENCY MEDICINE • Volume 19, Number 1 • January 2001
FIGURE i. Base line ECG showing characteristic negative T in V1-2.
RVD is a polymorphic condition with a wide spectrum of clinical presentation and findings on physical examination? The usual presentation is that of healthy adult with palpitation. Different types of arrhythmia has been described, some of which may be exercise induced and hence catecholamine mediated. The common and the most dangerous is recurrent VT resulting from microreentry at the sites of morphologic abnormalities, usually of left bundle branch morphology. 4 The tachycardia with inferior axis originates near the infundibulum, while those with a superior axis originate near the mid-inferior area at the RV. Other modes of presentation include right-sided heart failure and sudden death. Physical examination is usually normal. There may be signs of RV dilatation, functional tricuspid regurgitation or wide split second heart sound (because of prolonged RV ejection).
There are several noninvasive and invasive diagnostic modalities available to make the diagnosis. However, all may not be positive in a given case. The four main features are negative T in precordial leads on surface ECG, electrical instability, morphologic abnormalities of RV (diffuse or localized) and area of fibrous or fibrous-fatty infiltration of myocardium on endomyocardial biopsy. In our first case the noninvasive findings in ECG gave the clue, but in the second patient, the clue was in signal averaged ECG and MRI. ECG classically shows anterior precordial T waves inversion, particularly in lead v~ and/or QRS complex duration -> 110 ms in the right precordial leads} Other findings include right axis deviation, incomplete fight bundle branch block. An Epsilon wave, a deflection at the terminal portion of the QRS is the characteristic wave seen in 25% of cases.
FIGURE 2. Ventricular tachycardia of left bundle branch morphology.
KINSARA, ZAMAN, AND GORGELS • ARRHYTHMOGENIC RVD
FIGURE 3. MRI of the heart showing fat surrounding the heart similar to subcutaneous tissue signals. This delayed potential can be confirmed on signal averaged ECG particularly the one which combines the time and frequency domain, with >97% sensitivity and 94% specificity. 6 Exercise test may disclose malignant arrhythmia particularly VT, interestingly, well tolerated. The holter monitor may disclose the arrhythmia or premature ventricular configuration of left bundle branch morphology. On echocardiography, the size and unexplained wall motion abnormalities of the RV whether diffuse or localized are useful in confirming the diagnosis. 7 These include mild dilatation of RV, localized bulge and dyskine-
FIGURE 4. Myocardial biopsy showing extensive fatty infiltrate.
69
sia of the inferobasal wall, structural changes of the moderator band, isolated enlargement of RV outflow tract, apical dyskinesia, and trabecular disarrangement. Various radiologic diagnostic procedures have been used, such as lateral view of chest X-ray film which may reveal enlarged RV, radionuclide angiogram may show a broad spectrum from minor wall motion abnormality to diffuse disease. Other modalities are computed tomography (CT) scan using volume mode and cinMR1. The latter shows promise in earlier clarification of the diagnosis and determining the extent of infiltrate, 8 but contrast RV angiography remains the standard technique for the diagnosis. Biopsy revealed the characteristic pathologic features with fibrosis and/or fat replacement of intramyocardial and subepicardial layers and almost normal subendomyocardium. 9 These myocytes are usually surrounded by lymphoplasmocytic infiltrate. Under electron microscopy, abnormal intercalated disc that is attenuated and flattened with decreased Z band material is seen in both ventricles. 1° In the first case, biopsy was not done because had enough clinical data, supported by the known segmental pattern of the disease and the paucity of the endocardium involvement. Treatment is directed towards controlling or preventing the arrhythmia. Drug therapy usually consists of antiarrhythmic therapy, and can achieve varying success rates in preventing recurrent VT4; especially the catecholamineinduced VT. Such drugs include class lc, beta-blocker, calcium-channel blocker, and amiodarone in variable combinations. Failure of the above measures may call for insertion of implantable cardioverter defibrillator. For resistant cases or intolerant patients, ablation with radiofrequency or direct current energy has been applied with variable rate of success [up to 60%] and high rate of relapse. This may call for adding antiarrhythmic drugs or repeat ablation. Various surgical approaches like disarticulation of the RV has been reported to be helpful, but is rarely used
70
AMERICAN JOURNAL OF EMERGENCY MEDICINE • Volume 19, Number 1 • January 2001
nowadays} However, favorable long-term results have been reported with myocardial excision, on the basis of the epicardial mapping with cryocoagulation of surrounding myocardium. 11 However, this may be technically difficult because of the diffuse nature of RV involvement. At present there are limited data on long-term prognosis of this disease. Bad prognostic indicators are: effort syncope, premature ventricular contractions that increase with exercise, dilated RV, and sustained VT.
REFERENCES 1. Lobo FV, Heggtveit HA, Butany J, et ah Right ventricular dysplasia: Morphological findings in 13 cases. Can J Cardio11992;8:261-8 2. Nava A, Thiene G, Canciani B, et ah Familial occurrence of right ventricular dysplasia: A study involving nine families. J Am Coil Cardiol 1988;12:1222-8 3. Chauhan A, More R: Arrhythmogenic right ventricular dysplasia. Int J Cardiol 1996;56:107-112 4. Hoch DH, Rosenfeld LE: Tachycardias of right ventricular origin. Cardiol Clin 1992;10:151-64
5. Marcus FI, Fontaine G: Arrhythmogenic right ventricular dysplasia/cardiomyopathy: A review. Pacing Clin Electrophysiol 1995; 18:1298-314 6. Kinoshita O, Fontaine G, Rosas F, et al: Time- and frequencydomain analyses of the signal-averaged ECG in patients with arrhythmogenic right ventricular dysplasia. Circulation 1995;91:715721 7. Kisslo J: Two-dimensional echocardiography in arrhythmogenic right ventricular dysplasia. Eur Heart J 1989;10: 22-6 8. Blake LM, Scheinman MM, Higgins CV: MR features of arrhythmogenic right ventricular dysplasia. AJR Am J Roentgenol 1994;162:809-12 9. Fontaine G, Frank R, Tonet JL, et al: Arrhythmogenic right ventricular dyspiasia: A clinical model for the study of chronic ventricular tachycardia. Jap Circul J 1984;48:515-38 10. Guiraudon CM: Histological diagnosis of right ventricular dysplasia: A role for electron microscopy? Eur Heart J 1989;10: 95-6 11. Misaki T, Watanabe G, Iwa T, et ah Surgical treatment of arrhythmogenic right ventricular dysplasia: Long-term outcome. Ann Thoracic Surg 1994;58:1380-5
Arrhythmogenic Right Ventricular Dysplasia ABDULHALIM J. KINSARA, MD,* LIAQAT ZAMAN, MD,1- AND ANTON GORGELS, MDI Right ventricular dysplasia (RVD) is a disease entity of unknown cause that is characterised by partial or total replacement of RV-muscle by adipose or fibrous tissue. It is a well-recognized cause of arrhythmia and premature sudden death, but usually underdiagnosed. Several noninvasive and invasive diagnostic modalities have been used, however, all may not be positive in a given case. Drug therapy with class lc, betablocker, and amiodarone in variable combination produce varying success rates in preventing recurrent ventricular tachycardia. Failure of the above measures calls for insertion of implantable cardioverter defibrillator. The attention of emergency physicians is drown to this disease as they are the first medical personnel to be presented with this disease as an emergency. Hence their recognition of RVD will ensure early and proper management. (Am J Emerg ied 2001;19:67-70. Copyright ~ 2001 by W.B. Saunders Company) Osier was the first to describe right ventricular dysplasia (RVD) and in 1950 Segall presented a picture of the disease. It is a well-recognized cause of arrhythmia and premature sudden death, but is diagnosed infrequently. We describe two clinical cases of this disease and its unique clinical features, so that when emergency physicians are presented with this disease, it will be easily recognized and proper investigations and management is promptly instituted. CASE REPORT Case 1: A 34-year-old woman presented at her local hospital with several attacks of fast regular palpitations associated with headache, dizziness, and shortness of breath for the last 6 months. Her attacks were variable in frequency, on the average 2 to 3 times per week, lasting 10 to 15 minutes. Neither her past medical history, nor her family history was significant. On examination, she was euthyroid with normal physical examination of cardiovascular system. Her investigation showed normal baseline blood indices. Her thyroid function test was normal. Electrocardiogram (ECG) on admission showed sinus rhythm with negative T in VI_2 (Fig 1) ECG during tachycardia was ventricular tachycardia (VT) of left
From *King Khalid National Guard Hospital, Jeddah and i-King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Manuscript received April 29, 2000, returned May 4, 2000, revision received May 16, 2000, accepted June 6, 2000. Address reprint requests to Abdulhalim J. Kinsara, MD, P.O. Box 4409, Jeddah 21491, Saudi Arabia. E-mail: [email protected] Key Words: right ventricular dysplasia, therapy, diagnosis. Copyright © 2001 by W.B. Saunders Company 0735-6757/01/1901-0018510.00/0
doi:10.1053/ajem.2001.18131
bundle branch block morphology with normal axis (Fig 2). She was treated with intravenous procainamide during VT and was maintained on Verapamil, but her symptoms recurred a few weeks later and she was referred to our hospital. Her echocardiogram did not show wall motion abnormalities in fight ventricle (RV). Signal averaged ECG showed a borderline abnormality (duration of filtered QRS complex was > 120 ms but other parameters were normal). On a heart magnetic resonance image (MR/), the RV was slightly dilated but normal otherwise. Holter monitor showed nonsustained VT, variable bigeminy and trigeminy. Subsequent electrophysiologic study showed inducible VT by burst pacing. Mapping showed that ventricular activation was in the septum near the RV apex. This was ablated by radiofrequency but it was only partially successful, as the tachycardia was inducible after high dose of isoproterenol. Hence, she was started on Atenolol and on follow-up 2 months later, she was free of symptoms. Case 2: A 35-year-old woman experienced dizzy spells and collapsed at home. She was transferred on an emergency basis to a hospital where she was found to have VT at a rate of 300 beats/min for which she was D/C shocked and commenced on Amiodarone therapy. On her subsequent course she did well. There was no history of deafness and no family history of sudden death. Her 12-lead ECG, showed sinus rhythm, normal QT, with no significant T changes. Signal averaged ECG showed evidence of late potential, which is a duration of filtered QRS complex after the voltage decreased to <40/zv was > 4 0 ms and rootmean-square voltage during the last 40 ms of the filtered QRS complex was <20p, v. Echocardiogram was normal and MRI showed high signal intensity throughout the entire free wall of the RV measuring 6 m m in thickness consistent with arrhythmogenic RVD (Fig 3). RV biopsy confirmed the diagnosis of RVD (Fig 4). Her electrophysiological study showed easily induced VT by both atrial and ventricular stimulation. She was commenced on amiodarone and scheduled for implantable cardioverter defibrillator placement. DISCUSSION RVD is a disease entity of unknown cause that is characterized by partial or total replacement of muscle by adipose or fibrous tissue. It is primarily a disorder of the RV particularly the apex, infundibular and posterobasal wall, 1 but associated left ventricle involvement has been reported. No single factor was claimed to have a causal relationship, however, it occurs in both sporadic and familial forms with recognized abnormal gene; chromosome number 14. 2 67
68
AMERICAN JOURNAL OF EMERGENCY MEDICINE • Volume 19, Number 1 • January 2001
FIGURE i. Base line ECG showing characteristic negative T in V1-2.
RVD is a polymorphic condition with a wide spectrum of clinical presentation and findings on physical examination? The usual presentation is that of healthy adult with palpitation. Different types of arrhythmia has been described, some of which may be exercise induced and hence catecholamine mediated. The common and the most dangerous is recurrent VT resulting from microreentry at the sites of morphologic abnormalities, usually of left bundle branch morphology. 4 The tachycardia with inferior axis originates near the infundibulum, while those with a superior axis originate near the mid-inferior area at the RV. Other modes of presentation include right-sided heart failure and sudden death. Physical examination is usually normal. There may be signs of RV dilatation, functional tricuspid regurgitation or wide split second heart sound (because of prolonged RV ejection).
There are several noninvasive and invasive diagnostic modalities available to make the diagnosis. However, all may not be positive in a given case. The four main features are negative T in precordial leads on surface ECG, electrical instability, morphologic abnormalities of RV (diffuse or localized) and area of fibrous or fibrous-fatty infiltration of myocardium on endomyocardial biopsy. In our first case the noninvasive findings in ECG gave the clue, but in the second patient, the clue was in signal averaged ECG and MRI. ECG classically shows anterior precordial T waves inversion, particularly in lead v~ and/or QRS complex duration -> 110 ms in the right precordial leads} Other findings include right axis deviation, incomplete fight bundle branch block. An Epsilon wave, a deflection at the terminal portion of the QRS is the characteristic wave seen in 25% of cases.
FIGURE 2. Ventricular tachycardia of left bundle branch morphology.
KINSARA, ZAMAN, AND GORGELS • ARRHYTHMOGENIC RVD
FIGURE 3. MRI of the heart showing fat surrounding the heart similar to subcutaneous tissue signals. This delayed potential can be confirmed on signal averaged ECG particularly the one which combines the time and frequency domain, with >97% sensitivity and 94% specificity. 6 Exercise test may disclose malignant arrhythmia particularly VT, interestingly, well tolerated. The holter monitor may disclose the arrhythmia or premature ventricular configuration of left bundle branch morphology. On echocardiography, the size and unexplained wall motion abnormalities of the RV whether diffuse or localized are useful in confirming the diagnosis. 7 These include mild dilatation of RV, localized bulge and dyskine-
FIGURE 4. Myocardial biopsy showing extensive fatty infiltrate.
69
sia of the inferobasal wall, structural changes of the moderator band, isolated enlargement of RV outflow tract, apical dyskinesia, and trabecular disarrangement. Various radiologic diagnostic procedures have been used, such as lateral view of chest X-ray film which may reveal enlarged RV, radionuclide angiogram may show a broad spectrum from minor wall motion abnormality to diffuse disease. Other modalities are computed tomography (CT) scan using volume mode and cinMR1. The latter shows promise in earlier clarification of the diagnosis and determining the extent of infiltrate, 8 but contrast RV angiography remains the standard technique for the diagnosis. Biopsy revealed the characteristic pathologic features with fibrosis and/or fat replacement of intramyocardial and subepicardial layers and almost normal subendomyocardium. 9 These myocytes are usually surrounded by lymphoplasmocytic infiltrate. Under electron microscopy, abnormal intercalated disc that is attenuated and flattened with decreased Z band material is seen in both ventricles. 1° In the first case, biopsy was not done because had enough clinical data, supported by the known segmental pattern of the disease and the paucity of the endocardium involvement. Treatment is directed towards controlling or preventing the arrhythmia. Drug therapy usually consists of antiarrhythmic therapy, and can achieve varying success rates in preventing recurrent VT4; especially the catecholamineinduced VT. Such drugs include class lc, beta-blocker, calcium-channel blocker, and amiodarone in variable combinations. Failure of the above measures may call for insertion of implantable cardioverter defibrillator. For resistant cases or intolerant patients, ablation with radiofrequency or direct current energy has been applied with variable rate of success [up to 60%] and high rate of relapse. This may call for adding antiarrhythmic drugs or repeat ablation. Various surgical approaches like disarticulation of the RV has been reported to be helpful, but is rarely used
70
AMERICAN JOURNAL OF EMERGENCY MEDICINE • Volume 19, Number 1 • January 2001
nowadays} However, favorable long-term results have been reported with myocardial excision, on the basis of the epicardial mapping with cryocoagulation of surrounding myocardium. 11 However, this may be technically difficult because of the diffuse nature of RV involvement. At present there are limited data on long-term prognosis of this disease. Bad prognostic indicators are: effort syncope, premature ventricular contractions that increase with exercise, dilated RV, and sustained VT.
REFERENCES 1. Lobo FV, Heggtveit HA, Butany J, et ah Right ventricular dysplasia: Morphological findings in 13 cases. Can J Cardio11992;8:261-8 2. Nava A, Thiene G, Canciani B, et ah Familial occurrence of right ventricular dysplasia: A study involving nine families. J Am Coil Cardiol 1988;12:1222-8 3. Chauhan A, More R: Arrhythmogenic right ventricular dysplasia. Int J Cardiol 1996;56:107-112 4. Hoch DH, Rosenfeld LE: Tachycardias of right ventricular origin. Cardiol Clin 1992;10:151-64
5. Marcus FI, Fontaine G: Arrhythmogenic right ventricular dysplasia/cardiomyopathy: A review. Pacing Clin Electrophysiol 1995; 18:1298-314 6. Kinoshita O, Fontaine G, Rosas F, et al: Time- and frequencydomain analyses of the signal-averaged ECG in patients with arrhythmogenic right ventricular dysplasia. Circulation 1995;91:715721 7. Kisslo J: Two-dimensional echocardiography in arrhythmogenic right ventricular dysplasia. Eur Heart J 1989;10: 22-6 8. Blake LM, Scheinman MM, Higgins CV: MR features of arrhythmogenic right ventricular dysplasia. AJR Am J Roentgenol 1994;162:809-12 9. Fontaine G, Frank R, Tonet JL, et al: Arrhythmogenic right ventricular dyspiasia: A clinical model for the study of chronic ventricular tachycardia. Jap Circul J 1984;48:515-38 10. Guiraudon CM: Histological diagnosis of right ventricular dysplasia: A role for electron microscopy? Eur Heart J 1989;10: 95-6 11. Misaki T, Watanabe G, Iwa T, et ah Surgical treatment of arrhythmogenic right ventricular dysplasia: Long-term outcome. Ann Thoracic Surg 1994;58:1380-5