Background There are few studies on the clinical profile of Chinese patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The purpose of this study was to describe the clinical characteristics of ARVD/C patients from China, particularly to define the features of electrocardiograph and treatment outcomes.

Methods Thirty-nine patients hospitalized in Fu Wai Cardiovascular Hospital from 1998 to 2006 were included. The data were obtained from the medical archive and the follow-up records.

Results Of these patients 33 were male and 6 female (age at the first presentation was (34.9 ± 9.8) years). The most common symptoms were palpitation (62%) and syncope (44%). Right precordial QRSd ≥ 110 ms was detected in 69% of the patients, epsilon wave in 59%, and a ratio of QRSd in V₁+V₂+V₃/V₄+V₅+V₆ ≥ 1.2 in 82%. The most frequent features of electrocardiogram in patients without right bundle-branch block were T-wave inversions and S-wave upstroke in V₁–V₃ ≥55 ms (96% and 90% of 28 patients, respectively). Radiofrequency catheter ablation (RFCA) for ventricular tachycardia (VT) was successful in 15 (68%) of 22 patients. The recurrence rate of VT was 46% (7/15) during the follow-up of (16.7 ± 11.2) months. Seven patients had cardioverter/defibrillator (ICD) implanted plus drug therapy and 17 patients took antiarrhythmic drugs alone. During the follow-up of (35.6 ± 19.0) months, all patients with ICD implanted received at least one appropriate ICD shock. One patient died of ventricular fibrillation suddenly and one patient underwent heart transplantation for progressive biventricular heart failure during the drug therapy alone.

Conclusions This study demonstrated the clinical and ECG features of the 39 ARVD/C Chinese patients. ICD provided life-saving protection by effectively terminating malignant arrhythmias, and the high recurrence of VT was the major problem of RFCA therapy.

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Arrhythmogenic right ventricular dysplasia/ cardiomyopathy (ARVD/C) is an inherited disease pathologically characterized by progressive replacement of the right ventricular myocardium with adipose and fibrous tissue, which often induces ventricular arrhythmias in the early phase or leads to heart failure in the later stage. It has been recognized as an important cause for sudden cardiac death among young individuals,¹ especially in competitive athletes. ^2,3

Since the first description of ARVD/C 24 years ago,⁴ remarkable progress has been made in pathogenesis, genetics and diagnosis. However, the natural history of ARVD/C reported varies greatly, especially in different races. The majority of studies in the literature have involved western populations,^5-7 except one which described 11 Chinese patients from Hong Kong, China.⁸ In this paper, we characterized the clinical profiles of 39 ARVD/C Chinese patients, particularly focused on the diagnostic values of specific electrocardiograph (ECG) patterns and the outcomes of these patients under the current invasive and noninvasive treatments.

Diagnosis of ARVD/C
The diagnosis of ARVD/C was based on the criteria established by the Task Force of the Working Group of Myocardial and Pericardial Disease of the European Society of Cardiology and the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology.⁹ Briefly, the criteria are subdivided into major and minor criteria and are classified into 6 categories: (1) global and/or regional dysfunction and structural alterations; (2) fibrofatty replacement of the myocardium; (3) repolarization abnormalities; (4) depolarization/conduction abnormalities; (5) arrhythmias; and (6) family history. The diagnosis of ARVD/C can be established when 2 major criteria or 1 major plus 2 minor criteria, or at least 4 minor criteria have been met.

Study population and clinical data
Thirty-nine patients hospitalized in Fu Wai Cardio- vascular Hospital from 1998 to 2006 were included. The data obtained from their medical archive included demographic data (age, sex, race), clinical data (familial history, presentation of the disease, age at onset of symptoms, physical examination), and ECG recordings (12-lead ECG and 24-hour Holter recordings). Structure and function of the ventricular myocardium were assessed by noninvasive (echocardiography, magnetic resonance imaging (MRI)) and invasive (ventricular angiography, electrophysiological study (EPS)) examinations.

Diffuse lesion was defined when imaging study revealed a widespread right ventricular (RV) involvement resulting in global RV dilatation and a reduction in ejection fraction. Regional lesion was diagnosed when the disease was localized in the RV, such as segmental wall-motion abnormalities (hypokinetic or dyskinetic areas) with mild or no decrease in RV ejection fraction.

ECG analysis
Standard 12-lead ECG was registered at 25 mm/s and 1 mV/cm. ECG parameters and standards for measure- ments are described in Table 1. All parameters were measured in 3 consecutive beats; the mean value was used for analysis.

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Table 1. ECG parameters and definitions

Treatment and follow-up
Clinical treatment included antiarrhythmic drugs, radiofrequency catheter ablation (RFCA), implantable cardioverter-defibrillator (ICD) and heart transplantation. Patients were followed up in out-patient clinic every 6 to 12 months with regard to the recurrence of cardiac arrhythmias and assessment of cardiac structure and function. Cardiac events recorded by ICD were also collected.

Statistical analysis
Categorical variables were expressed as frequency (percentage). Continuous variables were expressed as mean ± standard deviation (SD). Statistical analyses were performed with SPSS statistical software (version 11.0). P < 0.05 was considered statistically significant.

Clinical characteristics
The clinical data of the 39 patients are summarized in Table 2. All the patients were Chinese Han ethnic, 33 males and 6 females (5.5:1). Their mean age at the first presentation was (34.9 ± 9.8) years (range 17–60 years). All of the patients met the international standardized diagnostic criteria. Twenty (51%) of the patients presented with 2 major diagnostic criteria, 12 (31%) patients with 1 major criterion plus at least 2 minor criteria, and 7 (18%) patients with 4 minor criteria. Four (11%) of the patients had a family history of either sudden cardiac death (3 patients) or ventricular tachycardia (VT) (1 patient).

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Table 2. Clinical characteristics of 39 patients with ARVD/C

The most common symptoms of the patients were palpitation (62%) and/or syncope (44%). In more than half (54%) of the patients, the symptoms were induced by physical exercise. Ventricular fibrillation (VF) as the first manifestation was seen in 2 patients.

Ventricular tachycardia with left bundle-branch block (LBBB-VT) was the most frequent arrhythmic event. Sustained VT was documented by 24 hours Holter recording in 36 patients with a 2:1 ratio of monomorphic VT to polymorphic VT.

Dilated RV and wall thinning were detected in 34 patients by echocardiography or MRI with global RV involvement in 18 (53%) and regional lesion in 16 (47%) patients. Twenty-four patients (71%) showed right ventricular outflow tract (RVOT) dilation and 6 patients (18%) exhibited left ventricle (LV) involvement. Typical morphologic changes were seen in the RV of the patient with the episode of polymorphic VT (Figures 1, 2). Abnormalities of the RV demonstrated by echocardiography could also be detected by MRI, but minor lesions were only revealed by MRI in 12 patients (35%).

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Figure 1. ECGs from a 44-year-old man diagnosed with ARVD/C at 40 years of age. A: His baseline ECG demonstrated sinus rhythm with T-wave inversion in leads V1 to V4, epsilon wave and S-wave upstroke prolongation in right precordial leads. B: Episode of polymorphic VT.

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Figure 2. Magnetic resonance imaging of the same patient in Figure 1, showing RV wall thinning and dilation with the enlarged RVOT as well as the regional thinning (marked by slim arrow) and the fatty replacement (marked by wide arrow) of LV myocardium. RA: right atrium. RV: right ventricle. RVOT: right ventricle outflow tract. LV: left ventricle.

In 21 patients older than 35 years or with chest pain, coronary angiography revealed no significant coronary artery disease.

In 22 patients who underwent EPS study, more than one type of VT was induced in 19 patients (86%) from multi-site origins in RV. At least one of them matched clinical VT morphologically. The fragmented potentials could be registered in 13 patients (59%) by ablation catheter before energy delivery.

ECG analysis
The detailed ECG features of all patients are summarized in Table 3, and the typical ECG recordings are shown in Figures 1, 3, 4. Complete and incomplete right bundle-branch blocks (RBBBs) were present in 11 patients (30%). In 28 patients (72%) without RBBB, the T-wave inversion was the most prominent findings (27/28, 96%), which were limited to V₁–V₃ in 14 patients (52%) and beyond V₃ in the remaining 13 patients (48%). Prolonged S-wave upstroke in V₁ through V₃ ≥ 55 ms was another common feature (25 patients, 90%).

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Table 3. ECG features of patients with ARVD/C

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Figure 3. A: ECG from a patient characterized by the T-wave inversion in leads V1 to V4, epsilon wave (as indicated with an arrow) and S-wave upstroke prolongation in right precordial leads. B: The epsilon wave on ECG with cRBBB from another patient.

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Figure 4. ECGs from a 40-year-old man diagnosed with ARVD/C and diffuse RV involvement at 38 years of age. A: Baseline ECG shows sinus rhythm with RBBB. B: Monomorphic VT with LBBB was documented during his syncope event.

QRS duration (QRSd) ≥ 110 ms in V₁–V₃ was present in 67% of all patients. The ratio of QRSd in V₁+V₂+V₃/V₄+V₅+V₆ ≥ 1.2 (called localized right precordial QRS prolongation) was detected in 32 patients (82%). Another marker indicating delayed activation was the presence of parietal block (defined as the QRSd in leads V₁ to V₃ that exceeded the QRSd in lead V₆ by ≥ 25 ms). A parietal block was more commonly observed in patients with RBBB than in those without RBBB (72% (8/11), versus 54% (15/28), P < 0.05). The prevalence of epsilon waves was 59%. Mean QRS dispersion was (35.0 ± 13.9) ms and QRS dispersion ≥ 40 ms was detected in 46% of all patients.

Treatment and follow-up
The acute success was achieved in 15 (68%) out of 22 patients who underwent RFCA for VT. During the follow-up of (16.7 ± 11.2) months, VT recurred in 7 patients (47%). There were 24 patients under sotalol/amiodarone therapy for prevention of VT including 7 patients implanted with an ICD and 7 patients for RFCA failure. During the follow-up of (35.6 ± 19.0) months, all patients implanted with ICD received at least one appropriate shock. All patients taking drugs only experienced 1 or more episodes of VT and most of VTs were terminated by external cardioversion. One patient died of VF and one underwent heart transplantation because of the progressive biventricular heart failure during a later follow-up. The follow-up data are summarized in Table 4.

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Table 4. Treatment and outcomes

We have described in detail the clinical and ECG features of the 39 ARVD/C Chinese patients, a large cohort of ARVD/C patients. The results of the study are representative, and comparable with those of the studies in the western populations. The results also provide important insights into the natural history and the efficacy of current treatments for this life-threatening cardiomyopathy.

The most common symptoms in our patients were palpitation and syncope. The age at the first presentation of these symptoms ranged from 17 to 60 years and the majority of the patients typically showed the symptoms during the third and fourth decade of life. It was notable that the patients presented with syncope or resuscitated VF cardiac arrest at the first onset (total 13 patients) were younger than those with repeated palpitations. It was also worth pointing out that the documented VT/VF events were triggered by sports activity in 54% of the patients with symptoms. This observation may confirm the previous findings in other studies that the incidence of sudden cardiac death (SCD) in ARVD/C patients declined after the fourth decade of life.^1,10 This also suggests the higher risk in the young patients and the potential role of physical activity in triggering cardiac arrhythmia in ARVD/C.

A familial history of sudden cardiac death or LBBB-VT was found in 4 patients in our series. The incidence was less than the range of 15% to 50% reported in the literature.^11,12 It might be underestimated in our study because we did not perform systematic screening of all family members for ARVD/C. The higher prevalence in male than female (5.5:1) in our cohort was similar to that reported elsewhere. ^5-8

Our study suggested that MRI is more sensitive than echocardiography to find the structural abnormalities in the early stage of ARVD/C. However, the advantage is limited in patients with a larger amount of fibrosis, and the specificity is also challenged in the situation such as pure lipomatosis, which is completely different in pathology from ARVD/C. ¹³

Marcus et al⁴ first reported the ECG features of patients with ARVD/C 24 years ago. Subsequently, several specific ECG features were introduced by McKenna et al⁹ to the diagnostic criteria for ARVD/C including (1) T-wave inversions in V₁ through V₃, (2) QRS duration (QRSd) ≥ 110 ms in V₁ through V₃, and (3) the presence of an epsilon wave. In our study, 95% of the patients (all except two) showed 1 or more ECG features of the criteria.

The epsilon wave, a marker of delayed right ventricular activation, is considered a major diagnostic criterion for ARVD/C. Although this criterion is highly specific, it is observed in only 25% to 35% of patients in previous studies.^14-16 The minor criterion of T-wave inversion in the right precordial leads (in the absence of RBBB) is reported in 55% to 95% of patients.^14,16-18 The higher prevalence of epsilon wave and T-wave inversion in our study (59% and 96%, respectively) indicated the later stage of the disease. Most of our patients showed RV anatomic abnormalities, particularly diffuse RV involvement in 18 patients (53%). Nava et al¹⁸ reported that the extent of right precordial T-wave inversion correlates with the degree of RV involvement. In our study, T-wave inversion beyond V₃ lead was seen in 78% (14/18) of patients with diffuse RV disease and in 38% (6/16) of patients with localized form (P < 0.05). Hence T-wave inversion is not specific for ARVD/C, and it can be seen in normal individuals, particularly in children under 12 years of age.

QRSd ≥ 110 ms in V₁–V₃, a major criterion for the diagnosis of ARVD/C, indicates delayed right ventricular activation. In one study, QRSd ≥ 110 ms in lead V₁ measured during sinus rhythm had a sensitivity of 55% and a specificity of 100% for the diagnosis of ARVD/C. If QRSd ≥ 110 ms appeared in both V₁ and V₃, the sensitivity would increase to 60% but the specificity decreased to 82%. ¹⁹ Another study ¹⁴ reported that QRSd ≥ 110 ms in V₁ through V₃ was presented in 64% of patients. This finding is comparable with that in our study.

The additional ECG features of ARVD/C we have analyzed include QRS dispersion, parietal block and a ratio of the QRSd in leads V₁+V₂+V₃/V₄+V₅+V₆ ≥ 1.2. We did not find any significant difference in the prevalence of these predictors between our study and other studies.^11,14-16

Recently, Nasir et al¹⁴ described a novel ECG finding termed as “delayed S-wave upstroke” in the right precordial leads. Prolonged S-wave upstrokes ≥ 55 ms in leads V₁ through V₃ were observed in 95% of patients in the absence of RBBB, and became the most prevalent ECG pattern for ARVD/C during the sinus rhythm. In our study, this ECG feature was seen in 90% of patients and showed a significant relationship with the degree of RV involvement.

QRS dispersion was considered to represent regional inhomogeneity of depolarization as a consequence of a ventricular conduction defect. QRS dispersion ≥ 40 ms was the strongest independent predictor of sudden death in ARVD/C. ¹⁵ In the present study, we found 80% of the patients presenting with syncope (13/17) and two patients with SCD showed QRS dispersion ≥ 40 ms, which further confirmed that this ECG feature is a strong predictor for malignant arrhythmic events.

Currently, no guidelines are available for the best management of patients with ARVD/C. Most therapeutic protocols target to prevent ventricular arrhythmia or sudden cardiac death. Current treatment choices include antiarrthymic drugs such as beta-blockers or amiodarone, ICD therapy, and radiofrequency catheter ablation. Our study indicated that the success of catheter ablation was limited by the progressive and diffuse nature of the disease, resulting in multiple arrhythmogenic foci, which are difficult to be abolished. The high recurrence rate of VT should be the major problem associated with RFCA. Although our study highlighted the benefit of ICD therapy with respect to terminating arrhythmic events and preventing sudden death, a larger clinical trial is needed to prove the long-term benefit and to evaluate the side-effects.²⁰ The efficacy of antiarrhythmic drug therapy is difficult to assess because of the individual variability on drug combination.

In conclusion, our study demonstrated the clinical characteristics of 39 ARVD/C Chinese patients. Ninety-five percent of the patients had 1 or more ECG features described in the task force criteria, and other ECG markers once reported for ARVD/C were also observed in our series. The majority of patients experienced LBBB-VT, and ICD therapy provided life-saving protection by effectively terminating life-threatening arrhythmias. Low acute success and high recurrence of VT were the major problem for RFCA therapy. The small number of patients and short follow-up period are the two major limitations of this study.

1. Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 1988; 318: 129-133.

2. Corrado D, Thiene G, Nava A, Rossi L, Pennelli N. Sudden death in young competitive athletes: clinicopathologic correlations in 22 cases. Am J Med 1990; 89: 588-596.

3. Furlanello F, Bertoldi A, Dallago M, Furlanello C, Fernando F, Inama G, et al. Cardiac arrest and sudden death in competitive athletes with arrhythmogenic right ventricular dysplasia. PACE Clin Electrophysiol 1998; 21 (1 Pt 2): 331-335.

4. Marcus FI, Fontaine GH, Guiraudon G, Frank R, Laurenceau JL, Malergue C, et al. Right ventricular dysplasia: a report of 24 adult cases. Circulation 1982; 65: 384-398.

5. Pinamonti B, Di Lenarda A, Sinagra G, Silvestri F, Bussani R, Camerini F, for the Heart Muscle Disease Study Group. Long-term evolution of right ventricular dysplasia- cardiomyopathy. Am Heart J 1995; 129: 412-415.

6. Berder V, Vauthier M, Mabo P, De Place C, Laurent M, Almange C, et al. Characteristics and outcome in arrhythmogenic right ventricular dysplasia. Am J Cardiol 1995; 75: 411-414.

7. Dalal D, Nasir K, Bomma C, Prakasa K, Tandri H, Piccini J, et al. Arrhythmogenic right ventricular dysplasia: a United States experience. Circulation 2005; 112: 3823-3832.

8. Fung WH, Sanderson JE. Clinical profile of arrhythmogenic right ventricular cardiomyopathy in Chinese patients. Int J Cardiol 2001; 81: 9-18.

9. McKenna WJ, Thiene G, Nava A, Fontaliran F, Blomstrom- Lundqvist C, Fontaine G, et al. Diagnosis of arrhythmogenic right ventricular dysplasia /cardiomyopathy. Br Heart J 1994; 71: 215-218.

10. Tabib A, Loire R, Chalabreysse L, Meyronnet D, Miras A, Malicier D, et al. Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia. Circulation 2003; 108: 3000-3005.

11. Fontaine G, Fontaliran F, Hébert JL, Chemla D, Zenati O, Lecarpentier Y, et al. Arrhythmogenic right ventricular dysplasia. Annu Rev Med 1999; 50: 17-35.

12. Fontaine G, Gallais Y, Fornes P, Hébert JL, Frank R. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. Anesthesiology 2001; 95: 250-254.

13. Maksimović R, Ekinci O, Reiner C, Bachmann GF, Seferović PM, Ristić AD, et al. The value of magnetic resonance imaging for the diagnosis of arrhythmogenic right ventricular cardiomyopathy. Eur Radiol 2006; 16: 560-568.

14. Nasir K, Bomma C, Tandri H, Roguin A, Dalal D, Prakasa K, et al. Electrocardiographic features of arrhythmogenic right ventricular dysplasia/cardiomyopathy according to disease severity: a need to broaden diagnostic criteria. Circulation 2004; 110: 1527-1534.

15. Turrini P, Corrado D, Basso C, Nava A, Bauce B, Thiene G. Dispersion of ventricular depolarization-repolarization: a noninvasive marker for risk stratification in arrhythmogenic right ventricular cardiomyopathy. Circulation 2001; 103: 3075-3080.

16. Peters S, Trümmel M. Diagnosis of arrhythmogenic right ventricular dysplasia-cardiomyopathy: value of standard ECG revisited. Ann Noninvasive Electrocardiol 2003; 8: 238-245.

17. Fontaine G, Umemura J, Di Donna P, Tsezana R, Cannat JJ, Frank R. Duration of QRS complexes in arrhythmogenic right ventricular dysplasia: a new non-invasive diagnostic marker. Ann Cardiol Angeiol (Paris) 1993; 42: 399-405.

18. Nava A, Canciani B, Buja G, Martini B, Daliento L, Scognamiglio R, et al. Electrovectorcardiographic study of negative T waves on precordial leads in arrhythmogenic right ventricular dysplasia: relationship with right ventricular volumes. J Electrocardiol 1998; 21: 239-245.

19. Jaoude SA, Leclercq JF, Coumel P. Progressive ECG changes in arrhythmogenic right ventricular disease. Evidence for an evolving disease. Eur Heart J 1996; 17: 1717-1722.

20. Chen RH, Chen KP, Wang FZ, Hua W, Chen X, Zhang S. Incidence and causes of inappropriate detection and therapy by implantable defibrillators of cardioversion in patients with ventricular tachyarrhythmia. Chin Med J 2006; 119: 557-563.