Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
29 Efficacy of Antiarrhythmic Drugs in Patients With Arrhythmogenic Right Ventricular Disease Results in Patients With Inducible and Noninducible Ventricular Tachycardia Thomas Wichter, MD; Martin Borggrefe, MD; Wilhelm Haverkamp, MD; Xu Chen, MD; and Gunter Breithardt, MD, FESC, FACC Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 Background. Ventricular tachyarrhythmias are the major clinical manifestation of arrhythmogenic right ventricular disease. Although antiarrhythmic therapy has been widely advocated, there is only limited information available on the efficacy of antiarrhythmic drugs in these patients. Methods and Results. The short- and long-term efficacies of various antiarrhythmic agents were retrospectively and prospectively analyzed in 81 patients (mean age, 39+14 years; range, 16-68 years; 61.7% males) with arrhythmogenic right ventricular disease. In 42 patients with inducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were obtained: class Ia and lb drugs (n=18), 5.6%; class Ic drugs (n=25), 12%; 1-blockers (n=8), 0%o; sotalol (n=38), 68.4%; amiodarone (n=13), 15.4%; verapamil (n=5), 0%o; and drug combinations (n=26), 15.4%. Only one of the 10 patients not responding to sotalol was treated effectively by amiodarone, whereas the remaining nine patients proved to be drug refractory toward all other drugs tested (3.8±2.3 drugs, including amiodarone in five cases) and underwent nonpharmacological therapy. During a follow-up of 34±25 months, three of the 31 patients (9.7%) discharged on pharmacological therapy had nonfatal recurrences of ventricular tachycardia after 0.5, 51, and 63 months, respectively. In 39 patients with noninducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were observed: class Ia and Ib drugs (n=16), 0%1; class Ic agents (n=23), 17.4%; 13-blockers (n=7), 28.6%; sotalol (n=35), 82.8%; amiodarone (n=4), 25%; verapamil (n=24), 50%1; and drug combinations (n=11), 9.1%. During a follow-up of 14±+13 months, four of 33 patients (12.1%) discharged on antiarrhythmic drugs had nonfatal relapses of their clinical ventricular arrhythmia. Conclusions. Thus, in arrhythmogenic right ventricular disease, sotalol proved to be highly effective in patients with inducible as well as noninducible ventricular tachycardia. Patients with inducible ventricular tachycardia not responding to sotalol are likely to not respond to other antiarrhythmic drugs and should be considered for nonpharmacological therapy without further drug testing. Amiodarone did not prove to be more effective than sotalol and may not be an alternative because of frequent side effects during long-term therapy, especially in young patients. Verapamil and 1-blockers were effective in a considerable number of patients with noninducible ventricular tachycardia and may be a therapeutic alternative in this subgroup. Class I agents appear to be rarely effective in the treatment of both inducible and noninducible ventricular tachycardia in arrhythmogenic right ventricular disease. (Circulation 1992;86:29-37) KEY WoRDs * right ventricle * dysplasia, right ventricular * antiarrhythmics * ventricular tachycardia rrhythmogenic right ventricular disease (ARVD) is a rare myocardial disorder characterized by ventricular tachyarrhythmias originating from the right ventricle, frequent repolarization abnormalities in the right precordial leads of the surface ECG, and localized or diffuse right ventricular contraction abnormalities detectable by two-dimensional echocardiography, gated nuclear scintigraphy, or right ventricular A From the Hospital of the Westfalische Wilhelms-University, Department of Cardiology and Angiology, Munster, Germany. Address for correspondence: Thomas Wichter, MD, Medizinische Klinik und Poliklinik, Innere Medizin C (Kardiologie und Angiologie), Westfalische Wilhelms-Universitat Munster, AlbertSchweitzer Strasse 33, D-4400 MIunster, Germany. Received August 26, 1991; revision accepted March 13, 1992. angiography.1-5 The underlying structural cardiac abnormalities may be examined by endomyocardial biopsy or, more recently, magnetic resonance imaging.6-'1 Patients with arrhythmogenic right ventricular disease and inducible ventricular tachycardia normally present with spontaneous sustained monomorphic ventricular tachycardia. They frequently exhibit more extensive global or regional right ventricular contraction abnormalities detectable by various imaging techniques. In contrast, patients with noninducible ventricular tachycardia normally present with frequent ventricular runs or repetitive nonsustained ventricular tachycardia and only circumscribed contraction abnormalities of the right ventricle,12-"5 mostly not reducing global right ventricular ejection fraction. 30 Circulation Vol 86, No 1 July 1992 TABLE 1. Clinical Characteristics of Study Patients VT inducible VT noninducible (n=42) (n=39) p <0.001 85.7 35.9 Male (%) NS 34±13.5 34±14.1 Age at onset of symptoms (mean+SD, years) 40±13.3 NS 38±14.5 Age at diagnosis (mean±SD, years) <0.0001 20.5 92.9 Presenting arrhythmia: sustained VT (%) <0.0001 79.5 7.1 Presenting arrhythmia: nonsustained VT (%) NS 3.9±2.8 4.3±3.5 Antiarrhythmic drugs tested (mean±SD) NS 64.7 43.3 (n=34) (n=30) Abnormal fibrolipomatosis (%) <0.0001 56±6.1 45±8.3 RV-EF (mean±SD, %) NS 70±11.2 74±8.7 LV-EF (mean+SD, %) VT, ventricular tachycardia; RV-EF, right ventricular ejection fraction; LV-EF, left ventricular ejection fraction. Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 Antiarrhythmic drug therapy frequently is considered to be indicated in patients with arrhythmogenic right ventricular disease to prevent serious arrhythmic symptoms or complications including sudden cardiac death, which has been reported in both subgroups.'6,17 Although various authors have reported on successful antiarrhythmic therapy with various drugs and drug combinations in small numbers of patients, pharmacological treatment still is empiric.14"15"18-23 Recommendations concerning the most effective drugs and dosages have not been established. Therefore, we analyzed retrospectively and prospectively the short- and longterm efficacies of different antiarrhythmic drugs in 81 patients with arrhythmogenic right ventricular disease and inducible or noninducible ventricular tachycardia during programmed ventricular stimulation. Methods Study Patients The study population comprised 81 patients (50 males and 31 females) ranging in age from 16 to 68 years (mean, 39±13.9 years) with proven or highly suspected arrhythmogenic right ventricular disease on the basis of the 12-lead surface ECG during sinus rhythm and documented sustained or nonsustained ventricular tachycardia (n=81), noninvasive imaging techniques such as two-dimensional echocardiography (n=81) and magnetic resonance imaging (n=50), right and left ventricular angiography and coronary angiography (n=81), and endomyocardial biopsy (n=64). The first patient included in this study was diagnosed in 1977. The baseline characteristics of the patients are summarized in Table 1. Diagnosis ofArrhythmogenic Right Ventricular Disease Arrhythmogenic right ventricular disease was diagnosed in the presence of documented sustained or nonsustained ventricular tachycardia of left bundle branch block morphology, repolarization abnormalities in the right precordial leads of the surface ECG in sinus rhythm, and evidence of characteristic right ventricular contraction abnormalities. Coronary artery disease, dilative or hypertrophic cardiomyopathy, and congenital or acquired valvular heart disease were excluded. The more specific diagnosis of arrhythmogenic right ventricular dysplasia was made in the presence of the abovementioned criteria and the additional evidence of ab- normal fibrolipomatous infiltration of the right ventricular myocardium,34 which was detected by endomyocardial biopsy in 35 of 64 patients (54.7%). Patients with idiopathic ventricular tachycardia that was diagnosed after exclusion of morphological, functional, and structural heart disease3 were not included in this study. Characteristic angiographic findings suggestive of arrhythmogenic right ventricular disease were localized akinesia, dyskinesia, aneurysms, bulgings, or outpouchings,24-27 which may also be detectable by two-dimensional echocardiography.28-32 In addition, nonspecific angiographic findings like horizontal fissures and slow dye evacuation frequently were observed. Angiographic global ejection fractions were determined uniplane for the left ventricle by calculation according to the arealength method and biplane for the right ventricle according to Boak's formula.33 Endomyocardial biopsies were taken from different right ventricular areas (3.4±1.6 samples per patient; range, one to eight) by preference of regions of documented contraction abnormalities. Electrophysiological Study All patients underwent an invasive electrophysiological study with programmed ventricular stimulation off antiarrhythmic drugs in the nonsedated state after written informed consent was obtained. Single and double extrastimuli were delivered at two right ventricular stimulation sites (apex and outflow tract) at twicediastolic threshold during sinus rhythm and basic drive cycle lengths of 500, 430, 370, and 330 msec.34 If no sustained ventricular tachyarrhythmia was inducible, a third extrastimulus was introduced during 500-msec drive cycle length. If still no ventricular tachycardia was inducible, the entire sequence was repeated after intravenous isoprenaline infusion titrated to achieve an increase of basic heart rate by 25% or more. Definitions Spontaneous and induced ventricular tachyarrhythmias were classified according to the definitions listed in Table 2. Criteria of Drug Efficacy Various antiarrhythmic drugs of different classes of action according to the classification of Vaughan-Williams35 were used in both patient groups. The drugs and Wichter et al Antiarrhythmic Drug Efficacy in ARVD TABLE 2. Definitions 3-10 consecutive ventricular beats Ventricular run Nonsustained VT >10 consecutive ventricular beats, <30 seconds' duration Sustained VT >30 seconds' duration or prior termination because of hemodynamic deterioration Inducible VT Sustained VT inducible by PVS at baseline or after isoprenaline infusion No sustained VT inducible by PVS including isoprenaline infusion VT, ventricular tachycardia; PVS, programmed ventricular stimulation. Noninducible VT Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 corresponding mean daily dosages are listed in Tables 3 and 4. In the retrospective part of data analysis, information on all previously administered drugs were extracted from the records of the referring physicians and hospitals and by interviewing the patients. Clinical drug failure was defined as recurrence of ventricular tachycardia despite regular drug intake and adequate dosages. Blood levels were not available. In the prospective part of data analysis, patients with inducible ventricular tachycardia underwent antiarrhythmic drug testing guided by serial programmed ventricular stimulation. Drug efficacy was judged according to criteria previously reported34 and shown in Figure 1. In patients with noninducible ventricular tachycardia, drug therapy was guided by repeated 48hour Holter monitoring and symptom-limited treadmill exercise tests. The efficacy criteria used for analysis are shown in Figure 2. Follow-up End points for follow-up were either spontaneous recurrences of ventricular tachycardia or sudden death TABLE 3. Drugs and Dosages Used in Patients With Inducible Ventricular Tachycardia No. of Dosage (mg/day) patients Class Drug 594±138 10 Ia Disopyramide 600 1 Quinidine 800 1 Tocainide Ib 16 700± 135 Mexiletine 728±196 20 Ic Propafenone 250±50 17 Flecainide 113±23 8 Aprindine 107±41 7 Prajmaline 333±153 3 Lorcainide 1 600 Diprafenone 450 1 Barucainide 38 459±100 Sotalol III 13 400±155* Amiodarone 5 300±120 IV Verapamil *After a loading phase of 1000 mg/day for 21 days. Values are given as mean+SD. 31 TABLE 4. Drugs and Dosages Used in Patients With Noninducible Ventricular Tachycardia No. of Dosage (mg/day) patients 6 480± 130 2 600+0 5 1,400±283 Ib 13 600±85 19 644± 174 Ic 13 227±65 100 1 Aprindine 67±12 5 Prajmaline 3 300±150 Diprafenone III 35 440±69 Sotalol 4 533±115* Amiodarone IV 24 371±79 Verapamil *After a loading phase of 1,000 mg/day for 21 days. Values are given as mean±SD. Class Ia Drug Disopyramide Quinidine Tocainide Mexiletine Propafenone Flecainide and cardiac or noncardiac death or the time of study closure. No patient was lost to follow-up. In patients who discontinued electrophysiologically or clinically tested and effective antiarrhythmic drug therapy, follow-up ended at the time of drug withdrawal. The follow-up data were obtained by regular follow-up visits at our institution and telephone contact with the patients and their physicians at regular intervals. Results Results of Control Electrophysiological Study During the control electrophysiological study, 42 of 81 patients (36 men; mean age at diagnosis, 38±14.5 years) had inducible sustained ventricular tachyarrhythmias (monomorphic ventricular tachycardia, n=39 [92.8%]; mean cycle length, 291±71 msec [190-530 msec]; polymorphic ventricular tachycardia, n = 1 [2.4%]; ventricular fibrillation, n=2 [4.8%]). These ventricular tachyarrhythmias were induced from the right ventricular apex in 37 patients (88.1%) and from the right ventricular outflow tract in the remaining five patients (11.9%). Their induction required single extrastimuli in six patients (14.3%), double in 31 (73.8%), triple in five (11.9%), and isoprenaline infusion in four VT iduciblity during PVS compared to bascline none more difficult unc ange (:;p2 steps in basic drive) I Icomp.letcsuppressson IPaponsI drug failure FIGURE 1. Chart of criteria of drug efficacy in patients with inducible ventricular tachycardia (VT). A response to a drug was considered to be present if VT was no longer inducible or rendered more difficult to induce. Drug failure was present if there was unchanged inducibility or a spontaneous recurrence of VT. PVS, programmed ventricular stimulation. 32 Circulation Vol 86, No 1 July 1992 48 hour Holter and xercise tests sVTw v- J <100% 100% coupu~PVCB >70% <70%reduction |completearth reppesson failure Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 FIGURE 2. Chart of criteria of drug efficacy in patients with noninducible ventricular tachycardia (VT). Complete suppression was defined as abolition of sustained VT (sVT), nonsustained VT (nsVT), and ventricular runs (v-runs). A partial response was present if v-runs were not completely abolished. Drugfailure was present if either there was a < 70% reduction in v-runs, couplets, or premature ventricular complexes (PVCs) or a spontaneous recurrence of VT. of 42 patients (9.5%). Ventricular tachyarrhythmias terminated by ventricular extrastimuli in eight patients (19.5%), overdrive pacing in 25 patients (61.0%), or cardioversion in five patients (12.2%). In the remaining three patients (7.3%), ventricular tachycardia terminated spontaneously after 95+± 78 seconds (range, 40-150 seconds). In 39 of 81 patients (14 men; mean age, 40±13 years), no sustained ventricular tachyarrhythmia was inducible during programmed ventricular stimulation including isoprenaline provocation. In nine patients (23.1%), nonsustained (n=4) or sustained (n=5) ventricular tachyarrhythmias occurred spontaneously during administration of intravenous isoprenaline infusion. were Efficacy of Antiarrhythmic Drugs in Inducible Ventricular Tachycardia Acute response. In 42 patients with inducible ventricular tachycardia, a total of 174 drug tests were performed (Table 5). Prospective analysis of drug efficacy included 128 drug tests in these 42 patients, whereas the remaining 46 drug tests were evaluated retrospectively in 20 patients. Sotalol treatment resulted in the highest overall effirate (68.4%). Complete suppression was achieved in 22 of 38 patients (57.9%), and partial response was achieved in another four patients (10.5%). In only three of 12 patients not responding to monotherapy with oral sotalol, ventricular tachycardia induction was suppressed completely by amiodarone (n = 1) or a combination of sotalol with class I agents (n=2), whereas the remaining nine patients proved drug refractory after serial testing with 3.8±2.3 drugs, including amiodarone in five cases. Nonpharmacological therapy was performed in eight of these patients. The remaining patient was discharged on sotalol despite persistent ventricular tachycardia induction. Amiodarone proved to be effective according to the electrophysiological criteria in only two of 13 patients (15.4%). Ventricular tachycardia induction was unchanged in nine patients, six of whom had spontaneous ventricular tachycardia recurrences after 7±7 months (range, 1-18 months) during a total follow-up of 17±19 months (range, 1-51 months). The remaining two patients were followed clinically without programmed ventricular stimulation after the loading phase. Both had spontaneous ventricular tachycardia relapses after 3 and 12 months, respectively, and amiodarone treatment was discontinued. Class Ia and lb drugs as well as class Ic agents were effective in only 5.6% and 12.0%, respectively. Because several patients received more than one drug of the same group, the total number of drug tests exceeded the number of patients. Only one of 28 tests (3.6%; disopyramide) performed with class Ia or lb drugs and three of 57 tests (5.3%; flecainide, propafenone, aprindine) with class Ic agents were successful. }3-Blockers (n=7) and verapamil (n=5) failed in all patients treated. Drug combinations were effective in four of 26 patients (15.4%) in whom the individual agents had previously failed. Combinations of class I drugs with sotalol (n=10) or amiodarone (n=4) were effective in two patients each, whereas combinations of two class I drugs (n=5) or class I drugs with P-blockers (n=7) showed no beneficial effect. Follow-up. Thirty-one of 42 patients (73.8%) with inducible ventricular tachycardia were discharged on pharmacological treatment guided by serial drug testing, whereas the remaining 11 patients (26.2%) were cacy TABLE 5. Efficacy of Antiarrhythmic Drugs in Patients With Inducible Ventricular Tachycardia Drug Class Ia/b Class Ic 3-Blockers Sotalol Amiodarone Verapamil Combinations Two class I drugs Class I+/3-blocker Class I+sotalol Class I+amiodarone No. of patients 18 25 7 38 13 5 26 5 7 10 4 Overall efficacy No. S 1 5.6 3 12.0 0 0 26 68.4 2 15.4 0 0 4 15.4 0 0 0 0 2 20.0 2 50.0 Complete suppression No. S 0 0 1 4.0 Partial response No. S 1 5.6 2 8.0 22 2 57.9 15.4 4 0 10.5 0 2 7.7 2 7.7 0 2 0 50.0 2 0 20 0 Wichter et al Antiarrhythmic Drug Efficacy in ARVD 33 TABLE 6. Efficacy of Antiarrhythmic Drugs in Patients With Noninducible Ventricular Tachycardia Drug Class Ia/b Class Ic ,B-Blockers Sotalol Amiodarone Verapamil Combinations Two class I drugs Class I+3-blocker Class I+sotalol Class I+amiodarone No. of patients 16 23 7 35 4 24 11 1 5 3 2 Overall efficacy No. % 0 0 4 17.4 2 28.6 29 82.8 1 25.0 12 50.0 1 9.1 0 0 0 0 0 0 1 50.0 Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 considered drug refractory and were treated with alternative modalities such as catheter ablation (n=9), antitachycardia surgery (n =1), or implantation of a cardioverter-defibrillator (n = 1). At the time of discharge, 21 patients received oral sotalol alone, and four patients received sotalol in combination with a class I drug (aprindine, n=3; mexiletine, n= 1). The remaining six patients were treated with amiodarone (n =2), class Ic drugs (n=2; propafenone, flecainide), or a combination of amiodarone and class Ic drugs (n=2; propafenone, flecainide). During a mean follow-up of 34±25 months (range, 2-103 months), there were no sudden cardiac deaths or cardiac or noncardiac deaths in these 31 patients discharged on pharmacological therapy. Three patients (9.7%) had nonfatal recurrences of ventricular tachycardia after 0.5, 51, and 63 months, one of which was associated with hypokalemia. Efficacy of Antiarrhythmic Drugs in Noninducible Ventricular Tachycardia Acute response. In 39 patients with noninducible ventricular tachycardia, a total of 148 drug tests were performed (Table 6). Prospective analysis of drug efficacy included 91 drug tests in these 39 patients, whereas the remaining 57 drug tests were evaluated retrospectively in 17 patients. The overall efficacy rate for sotalol was 82.8% with a complete suppression of frequent ventricular runs and nonsustained or sustained ventricular tachycardia in 23 of 35 patients (65.7%) and a partial response in an additional six patients (17.1%). Only one of four patients was effectively treated with amiodarone. 1-Blockers showed a partial effect in two of seven patients (28.6%), and verapamil was effective in 12 of 24 patients (50.0%), half of them meeting the criteria of complete arrhythmia suppression. Class Ia and Ib antiarrhythmic drugs were not effective in any of 16 patients (total number of drug tests, 26), whereas class Ic agents were effective in four of 23 patients (17.4%) in a total number of 41 drug tests (9.8% effective tests; propafenone, n=2; flecainide, n=2). Drug combinations showed partial response in one of 11 patients (9.1%; amiodarone with flecainide) despite previous failure of the individual drugs. Follow-up. At the time of discharge, 33 of 39 patients (84.6%) with noninducible ventricular tachycardia were treated pharmacologically. Twenty-four patients re- Complete suppression S No. Partial response No. % 1 0 23 0 7 0 4.4 0 65.7 0 29.2 0 3 2 6 1 5 1 13.0 28.6 17.1 25.0 20.8 9.1 0 0 1 50.0 ceived oral sotalol, seven patients received verapamil, and two patients received class Ic agents (propafenone, flecainide). Two patients with clinically asymptomatic short ventricular runs were discharged without treatment. Both are doing well after 6 and 21 months of follow-up. The remaining four patients with symptomatic ventricular tachycardia did not respond to pharmacological treatment and underwent catheter ablation. During a mean follow-up of 14±13 months (range, 2-65 months), there were no sudden cardiac deaths and no cardiac or noncardiac deaths in these 33 patients discharged on antiarrhythmic drug therapy. Four patients (12.1%) had nonfatal recurrences of ventricular tachycardia. Recurrences occurred in two of 24 patients (8.3%) discharged on sotalol and in two of seven patients (28.6%) discharged on verapamil. At the time of discharge, drug therapy had been judged as completely effective in three of them and partially effective in the remaining patient. Side Effects During treatment with class I drugs, gastrointestinal side effects demanded discontinuation of therapy in five of 54 patients (9.3%) or five of 152 drug tests (3.3%). Sotalol had to be withdrawn in four of 73 patients (5.5%) because of symptomatic bradycardia (n= 1), hypotension (n=l), pulmonary congestion (n=1), and QT prolongation with torsade de pointes (n = 1). Atrioventricular conduction disturbances were not observed. In all except one patient, side effects occurred during the first days of therapy during hospital stay. Thus, during a total follow-up of 25+±22 months, only one of 49 patients discharged on sotalol developed serious side effects (symptomatic hypotension) after discharge. Amiodarone treatment was discontinued in five of 17 patients (29.4%) because of serious side effects (hyperthyroidism, n=3; hepatotoxicity, n=1; ophthalmic toxicity with symptomatic corneal deposits, n=1) during longterm therapy after 24±+ 24 months (range, 2-51 months). No serious adverse effects were observed during treatment with 8-blockers or verapamil. Discussion Ventricular tachyarrhythmias are the major clinical manifestation of arrhythmogenic right ventricular disease. The documented arrhythmia may range from frequent premature ventricular complexes, ventricular 34 Circulation Vol 86, No 1 July 1992 runs, and nonsustained ventricular tachycardia to sustained ventricular tachycardia.12'36,37 Primary ventricular fibrillation has been reported in single cases but appears to be rare.38-41 The right ventricular origin of the arrhythmias is suggested by the left bundle branch block morphology of ventricular tachycardia and can be confirmed by detailed endocardial catheter mapping Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 techniques. Although some patients do not report any symptoms suggestive of arrhythmias, the majority of patients present clinically with either palpitations, dizziness, syncope, or even sudden death. Patients with inducible ventricular tachycardia during programmed ventricular stimulation normally present with spontaneous sustained monomorphic ventricular tachycardia. They frequently exhibit pronounced global or regional right ventricular contraction abnormalities detectable by various imaging techniques. In contrast, patients with noninducible ventricular tachycardia normally present with repetitive ventricular runs or nonsustained ventricular tachycardia and only mild or moderate right ventricular contraction abnormalities, which may only be detectable by biplane right ventricular angiography.12-'5 However, due to the variable appearance of a normal right ventricle, differentiation of abnormal from normal right ventricular contractions may be difficult in patients with very mild angiographic findings. Because circumscribed right ventricular contraction abnormalities do not necessarily result in a reduction of global right ventricular function, the right ventricular ejection fraction is within normal limits in most patients with noninducible ventricular tachycardia. The need for antiarrhythmic therapy has been advocated in both subgroups of arrhythmogenic right ventricular disease because of symptoms and possibly prognostic aspects since sudden cardiac death may occur in both patient groups.16"7 However, specific risk factors for the selection of patients at high risk of sudden cardiac death have not been defined. The experiences with the use of antiarrhythmic drugs in patients with coronary artery disease or cardiomyopathies are not necessarily transferable to patients with arrhythmogenic right ventricular disease. Because information on the use of antiarrhythmic drugs in these patients is limited, this study was performed to analyze and discuss the short- and long-term effects of antiarrhythmic drug therapy in 81 patients with arrhythmogenic right ventricular disease. Overall, 64 of 81 patients (79.0%) who were referred for further treatment, responded acutely to antiarrhythmic drug therapy without limiting side effects, whereas 15 patients (18.5%) were subjected to nonpharmacological therapy, and two patients (2.5%) were discharged without treatment. Class I antiarrhythmic drugs have been demonstrated to be effective during electrophysiological testing in the treatment of life-threatening ventricular tachyarrhythmias in various underlying heart diseases. Most available data refer to postmyocardial infarction ventricular tachyarrhythmias and less frequently to patients with dilative cardiomyopathy.42-45 However, in patients with arrhythmogenic right ventricular disease, varying results have been reported.13"14'19,2' In our patients with inducible as well as noninducible ventricular tachycardia, class I antiarrhythmic drugs proved effective in only a minority of patients. Effective treatment with class I agents was achieved in only four of 85 drug tests (4.7%) performed in 27 patients with inducible ventricular tachycardia and in only five of 67 drug tests (7.5%) in 27 patients with noninducible ventricular tachycardia. The overall efficacy rates were 14.8% and 18.5% of patients, respectively, markedly lower than those reported in the treatment of ischemic ventricular tachycardia, although various class I agents were tested, and some patients received three or more different class I drugs successively without satisfactory therapeutic effect. Class Ic agents appeared to be slightly more effective than class Ia and Ib drugs; this has also been reported by others.45,46 ,B-Blockers, which were tested in only a small group of patients, did not have sufficient antiarrhythmic effect in those with inducible ventricular tachycardia but were at least partially effective in a small number of patients with noninducible ventricular tachycardia (28.6%). This corresponds to studies in patients with idiopathic ventricular tachycardia, possibly by an inhibition of catecholamine-induced increase of intracellular cyclic AMP mediated by GTP-dependent regulatory proteins.4749 Our results demonstrate that oral sotalol administered in dosages ranging from 320 to 480 mg/day (up to 640 mg/day in selected cases) appears to be the most effective antiarrhythmic drug in the treatment of both inducible and noninducible ventricular tachycardia in arrhythmogenic right ventricular disease. The overall efficacy rates were 68.4% and 82.8%, respectively. Side effects demanding withdrawal of sotalol treatment were rare (5.5%) and mostly occurred within the first days of therapy. High efficacy rates of sotalol compared with other antiarrhythmic agents may not be unique in the condition of arrhythmogenic right ventricular disease because similar overall efficacy rates of 61% were observed in our group of 171 patients with inducible ventricular tachycardia and various underlying heart diseases (68% coronary artery disease).50 Serious side effects were observed in only nine of these 171 patients (5.3%) despite considerably high dosages of sotalol, which also confirms the low rate of adverse effects reported in the present study. Sotalol dosages of more than 320-480 mg/day clearly exceed the dosage necessary for pl-blockade,5' so that its antiarrhythmic efficacy may predominantly be attributed to its class III activity. All except one patient with inducible ventricular tachycardia not responding to oral sotalol or combinations with sotalol proved refractory against all other antiarrhythmic agents tested (including amiodarone). Therefore, nonpharmacological therapy without further serial drug testing should be considered in sotalol nonresponders with inducible ventricular tachycardia. Amiodarone did not seem to be superior to sotalol. Of 12 patients receiving both drugs successively, one of eight sotalol nonresponders was effectively treated with amiodarone, whereas two of nine amiodarone nonresponders were effectively treated with sotalol. With regard to its potential side effects during long-term therapy,52 amiodarone does not appear to be the drug of first choice in the treatment of young patients requiring long-term antiarrhythmic drug therapy. Verapamil has been reported to be effective in a considerable percentage of patients with various forms of nonischemic ventricular tachycardia, especially right Wichter et al Antiarrhythmic Drug Efficacy in ARVD Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 ventricular outflow tract tachycardia.19,20,53-57 In our study group, 50% of patients with noninducible ventricular tachycardia responded to verapamil, and 92% of them met the criteria of repetitive nonsustained ventricular tachycardia originating in the right ventricular outflow tract. The mechanism of these tachycardias is postulated to be due to catecholamine-induced delayed afterdepolarizations dependent on intracellular calcium overload. Adenosine appears to be highly effective in specifically inhibiting cyclic AMP through an inhibitory G protein and therefore is effective only in the termination of ventricular tachycardia due to cyclic AMPmediated triggered activity. By blocking the slow-inward calcium current and therefore preventing intracellular calcium overload, verapamil is effective in calciuminduced, ouabain-induced, and catecholamine-cyclic AMP-mediated triggered activity.47,58 Only a few of our patients with inducible ventricular tachycardia received verapamil, which does not permit any definite conclusions. However, none of the patients in this group responded to verapamil. A combination of antiarrhythmic drugs may result in electrophysiological and antiarrhythmic properties that may be different from the actions of the individual agents. Drug combination may cause enhanced or decreased antiarrhythmic efficacy but also may increase or decrease the incidence of side effects, depending on the dosage of the individual drugs.59-M In this regard, our experience with antiarrhythmic drug combinations in patients with arrhythmogenic right ventricular disease is limited. These limited observations in patients on combination therapy did not appear to be promising. Drug combinations with class I drugs and amiodarone or sotalol were effective in a minority of patients in whom the individual drugs had previously failed, whereas combinations of two class I drugs and class I drugs with p3-blockers were not effective in any of the patients treated. This contrasts with the results of French authors who reported satisfactory therapeutic effects of combined therapy with class I agents and p-blockers.23 Our experience in the use of drug combinations with amiodarone is supported by the same authors who also found an increase of amiodarone efficacy by additional therapy with class I drugs in single patients. The combination of amiodarone with p-blockers may be more effective than the individual drugs.22'23 In a study by Leclercq et al,23 all of the six patients previously insufficiently treated by class I agents, amiodarone, or p-blockers alone or by combinations of class I agents with p-blockers or amiodarone proved to be effectively treated with the combination of amiodarone and p-blockers. These observations should be viewed in the light of our positive results with high dosages of sotalol. Both therapeutic regimen consist in a combination of class III and p-blocking antiarrhythmic properties, which appears to act synergistically in patients with arrhythmogenic right ventricular disease. This may be due to the strong catecholamine dependence as a triggering factor for ventricular arrhythmia in many of these patients, uncovered by stress tests or isoprenaline infusion.65-68 The low incidence of recurrences of ventricular tachyarrhythmias and the absence of sudden deaths during follow-up of our patients with inducible ventricular tachycardia who were discharged on drugs considered 35 effective confirms the predictive value of electrophysiologically controlled serial drug testing. Although there have been no studies on the reproducibility of programmed ventricular stimulation in arrhythmogenic right ventricular disease, our results indicate that electrophysiological study and successful serial drug testing may select patients at lower risk of sudden cardiac death. Of the 11 patients with drug-refractory inducible ventricular tachycardia, one patient with multiple origins of right ventricular tachycardia and a progressive and extensive form of arrhythmogenic right ventricular dysplasia died suddenly 3 months after successful repeated catheter ablation. In patients with noninducible ventricular tachycardia, serial drug testing controlled by Holter monitoring and exercise testing may be sufficiently safe, provided there is no history of life-threatening events. In case of survived cardiac arrest or recurrent syncope and noninducibility of ventricular tachyarrhythmia, the implantation of a cardioverter-defibrillator should be considered. Recurrences of ventricular tachycardia may not necessarily reduce the reliability of electrophysiologically or Holter controlled serial drug testing because they also may be due to metabolic abnormalities (such as hypokalemia in one of our patients) or progression of the underlying disease. The latter should especially be considered in case of late recurrences during long-term follow-up of arrhythmogenic right ventricular disease. Study Limitations To our knowledge, this is the first large-scale report on the effect of various antiarrhythmic drugs in arrhythmogenic right ventricular disease. However, several limitations of the present study should be addressed. The study was a nonrandomized, partly retrospective analysis of drug efficacy. All available information concerning previous antiarrhythmic drug therapy was prospectively documented, but the decision to treat a patient with a given antiarrhythmic drug was based on clinical grounds that were sometimes arbitrary. The data may be biased by the selection of drugs during serial antiarrhythmic testing in our institution since the favorable response to sotalol later resulted in a first-line application of this specific drug in the treatment of patients with arrhythmogenic right ventricular disease. As drug administration was not randomized, this may have influenced the efficacy rates in this study. In addition, there was no standard antiarrhythmic drug dosing, and blood levels usually were not available. Furthermore, most of the patients were referred to our department for further antiarrhythmic treatment of severe symptoms and were preselected insofar as many had undergone previous antiarrhythmic drug therapy that had failed. With the exception of verapamil, differences between the two patient groups concerning the response rates to antiarrhythmic drugs may be due at least in part to the methods of drug testing used in this study. Patients with inducible ventricular tachycardia were evaluated using the more rigorous method of serial electrophysiologic testing, which may have resulted in lower efficacy rates compared with patients with noninducible ventricular tachycardia in whom drug testing was controlled by repeated Holter and exercise tests. 36 Circulation Vol 86, No 1 July 1992 Clinical Implications Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 The low recurrence rates of ventricular tachycardia and the absence of sudden death during long-term follow-up of patients after successful serial drug testing indicates the predictive value of electrophysiologically guided serial drug testing in patients with arrhythmogenic right ventricular disease and inducible ventricular tachycardia. In patients with noninducible ventricular tachycardia, serial drug testing guided by repeated Holter and exercise tests may be sufficiently safe, provided there is no history of life-threatening arrhythmias necessitating the implantation of a cardioverter-defibrillator. Oral sotalol may be a first-line antiarrhythmic agent in the treatment of both inducible and noninducible ventricular tachycardia in patients with arrhythmogenic right ventricular disease. Patients with inducible ventricular tachycardia not responding to sotalol are likely to prove to be drug refractory and may be candidates for early nonpharmacological therapy without extensive serial drug testing. Amiodarone did not prove to be more effective than sotalol and may not be an alternative because of frequent side effects during long-term therapy. ,3-Blockers and verapamil may be an alternative in the treatment of noninducible ventricular tachycardia in arrhythmogenic right ventricular disease. Class I antiarrhythmic drugs appear to be rarely effective in both inducible and noninducible ventricular tachycardias of right ventricular origin. A prospective randomized study has been started to further elucidate and confirm these results. References 1. Marcus FI, Fontaine GH, Guiraudon G, Frank R, Laurenceau JL, Malergue C, Grosgogeat Y: Right ventricular dysplasia: A report of 24 cases. Circulation 1982;65:384-398 2. Wichter T, Borggrefe M, Breithardt G: Die arrhythmogene rechtsventrikulare Erkrankung. Z Kardiol 1991;80:107-125 3. Breithardt G, Borggrefe M, Wichter T: Editorial comment: Catheter ablation of idiopathic right ventricular tachycardia. Circulation 1990;82:2273-2276 4. Rizzon P, Breithardt G, Chiddo A: Arrhythmogenic right ventricle. Eur Heart J 1989;10(suppl D) 5. Blomstrom-Lundqvist C: The Syndrome of Arrhythmogenic Right Ventricular Dysplasia-Diagnostic and Prognostic Implications (thesis). Goteborg, University of G6teborg, 1987 6. Fontaine G, Fontaliran F, Linares-Cruz E, Chomette G, Grosgogeat Y: The arrhythmogenic right ventricle, in Iwa T, Fontaine G (eds): Cardiac Arrhythmias: Recent Progress in Investigation and Management. New York, Elsevier Science Publishers BV, 1988, pp 189-202 7. Strain JE: Adipose dysplasia of the right ventricle: Is endomyocardial biopsy useful? Eur Heart J 1989;10(suppl D):84-88 8. Strain JE, Grose RM, Factor SM, Fisher JD: Results of endomyocardial biopsy in patients with spontaneous ventricular tachycardia but without apparent structural heart disease. Circulation 1983; 68:1171-1181 9. Wichter T, Auffermann W, Breithardt G, Borggrefe M, Bongartz G, Peters PE: Magnetic resonance imaging in arrhythmogenic right ventricular disease. (abstract) Eur Heart J 1989;10(suppl):13 10. Casolo AC, Poggesi L, Boddi M, Fazi A, Bartolozzi C, Lizzadro G, Dabizzi RP: ECG-gated magnetic resonance imaging in right ventricular dysplasia. Am Heart J 1987;114:1245-1248 11. Klersy C, Raisaro A, Salerno JA, Montemartini C, Campani R: Arrhythmogenic right and left ventricular disease: Evaluation by computed tomography and nuclear magnetic resonance imaging. Eur Heart J 1989;10(suppl D):33-36 12. Martini B, Nava A, Thiene G, Buja GF, Canciani B, Miraglia G, Scognamiglio R, Boffa GM, Daliento L: Accelerated idioventricular rhythm of infundibular origin in patients with a concealed form of arrhythmogenic right ventricular dysplasia. Br Heart J 1988;59: 564-571 13. Palileo EV, Ashley WW, Swiryn S, Bauernfeind RA, Strasberg B, Petropoulos AT, Rosen KM: Exercise provocable right ventricular outflow tract tachycardia. Am Heart J 1982;104:185-192 14. Buxton AE, Waxman HL, Marchlinski FE, Simson MB, Cassidy D, Josephson ME: Right ventricular tachycardia: Clinical and electrophysiological characteristics. Circulation 1983;68:917-927 15. Proclemer A, Ciani R, Feruglio GA: Right ventricular tachycardia with ventricular dysplasia: Clinical features, diagnostic techniques, and current management. Am Heart J 1989;103:415-420 16. Rowland TW, Schweiger MJ: Repetitive paroxysmal ventricular tachycardia and sudden death in a child.AmJ Cardiol 1984;53:1729 17. Blomstrom-Lundqvist C, Sabel KG, Olsson B: A long term follow up of 15 patients with arrhythmogenic right ventricular dysplasia. Br Heart J 1987;58:477-488 18. Borggrefe M, Breithardt G: Beneficial effects of sotalol in patients with right ventricular dysplasia and drug-refractory ventricular tachycardia. Circulation 1985;72(suppl lII):III-1768 19. Wichter T, Borggrefe M, Martinez-Rubio A, Hief C, Breithardt G: Arrhythmogenic right ventricular disease: Antiarrhythmic drug therapy in patients with inducible and non-inducible ventricular tachycardia. Circulation 1990;82(suppl III):III-435 20. Woelfel A, Foster JR, McAllister RG Jr, Simpson RJ Jr, Gettes LS: Efficiacy of verapamil in exercise-induced ventricular tachycardia. Am J Cardiol 1985;53:751-756 21. Lemery R, Brugada P, Della Bella P, Dugernier T, van den Dool A, Wellens HJJ: Nonischemic ventricular tachycardia: Clinical course and long-term follow-up in patients without clinically overt heart disease. Circulation 1989;79:990-999 22. Tonet J, Frank R, Fontaine G, Grosgogeat Y: Efficacite de l'association de faibles doses de beta-bloquants a lamiodarone dans le traitment des tachycardies ventriculaires refractaires. Arch Mal Coeur 1989;82:1511-1517 23. Leclercq JF, Coumel P: Characteristics, prognosis and treatment of the ventricular arrhythmias of right ventricular dysplasia. Eur Heart J 1989;10(suppl D):61-67 24. Chiddo A, Locuratolo N, Gaglione A, Bortone A, Troito G, Musci S, Grimaldi N, Rizzon P: Right ventricular dysplasia: Angiographic study. Eur Heart J 1989;10(suppl D):42-45 25. Daubert C, Descaves C, Foulgoc JL, Bourdonnec C, Laurent M, Gouffault J: Critical analysis of cineangiographic criteria for diagnosis of arrhythmogenic right ventricular dysplasia. Am Heart J 1988;115:448-459 26. Daliento L, Rizzoli G, Thiene G, Nava A, Rinuncini M, Chioin R, Dalla Volta S: Diagnostic accuracy of right ventriculography in arrhythmogenic right ventricular cardiomyopathy. Am J Cardiol 1990;66:741-745 27. Blomstrom-Lundqvist C, Selin K, Jonsson R, Johannson SR, Schlossman D, Olsson SB: Cardioangiographic findings in patients with arrhythmogenic right ventricular dysplasia. Br Heart 1 1988; 59:556-563 28. Blomstrom-Lundqvist C, Beckmann-Suurkula M, Wallentin I, Jonsson R, Olsson SB: Ventricular dimensions and wall motion assessed by echocardiography in patients with arrhythmogenic right ventricular dysplasia. Eur Heart J 1988;9:1291-1302 29. Foale RA, Nihoyannopoulos P, Ribeiro P, McKenna WJ, Oakley CM, Krikler DM, Rowland E: Right ventricular abnormalities in ventricular tachycardia of right ventricular origin: Relation to electrophysiological abnormalities. Br Heart J 1986;56:45-54 30. Scognamiglio R, Fasoli G, Nava A, Miraglia G, Thiene G, DallaVolta S: Contribution of cross-sectional echocardiography to the diagnosis of right ventricular dysplasia at the asymptomatic stage. Eur Heart J 1989;10:538-542 31. Kisslo J: Two-dimensional echocardiography in arrhythmogenic right ventricular dysplasia. Eur Heart J 1989;10(suppl D):22-26 32. Robertson JH, Bardy GH, German LD, Gallagher JJ, Kisslo J: Comparison of two-dimensional echocardiographic and angiographic findings in arrhythmogenic right ventricular dysplasia. Am J Cardiol 1985;55:1506-1508 33. Boak JG, Bove AA, Kreulen T, Spann JF: A geometric basis for the calculation of right ventricular volume in man. Cathet Cardiovasc Diagn 1977;3:217-230 34. Borggrefe M, Trampisch HJ, Breithardt G: Reappraisal of criteria for assessing drug efficacy in patients with ventricular tachyarrhythmias: Complete versus partial suppression of inducible arrhythmias. JAm Coil Cardiol 1988;12:140-149 35. Vaughan-Williams EM: Classification of antiarrhythmic drugs, in Sandoe E, Flensted-Jensen E, Olesen K (eds): Cardiac Arrhythmias. S0destalje, Sweden, AD Astra, 1970, pp 449-473 Wichter et al Antiarrhythmic Drug Efficacy in ARVD Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 36. Rossi P, Massumi A, Gillette P, Hall RJ: Arrhythmogenic right ventricular dysplasia: Clinical features, diagnostic techniques and current management. Am Heart J 1982;103:415-420 37. Reiter MJ, Smith WM, Gallagher JJ: Clinical spectrum of ventricular tachycardia with left bundle branch morphology. Am J Cardiol 1983;51:113-121 38. Belhassen B, Shapira I, Hammerman C: Unusual manifestations of arrhythmogenic right ventricular dysplasia as ventricular fibrillation, atrial paralysis, and hypoexcitable right ventricle. Br Heart J 1988;59:263-265 39. Martini B, Nava A, Thiene G, Buja GF, Canciani B, Scognamiglio R, Daliento L, Dalla Volta S: Ventricular fibrillation without apparent heart disease: Description of six cases. Am Heart J 1989; 118:1203-1209 40. Olsson SB, Edvardsson N, Emanuelsson H, Enestrom S: A case of arrhythmogenic right ventricular dysplasia with ventricular fibrillation. Clin Cardiol 1982;5:591 41. Rizzon P: Polymorphism of the clinical picture. Eur Heart J 1989; 10(suppl D):10-12 42. Waller TJ, Kay HR, Spielman SR, Kutalek SP, Greenspan AM, Horowitz LN: Reduction in sudden death and total mortality by antiaarrhythmic therapy evaluated by electrophysiologic drug testing: Criteria of efficacy in patients with sustained ventricular tachycardia. JAm Coll Cardiol 1987;10:83-89 43. Hernandez M, Reder RF, Marinchak RA, Rials SJ, Kowey PR: Propafenone for malignant ventricular arrhythmia: An analysis of the literature. Am Heart J 1991;121:1178-1184 44. Budde T, Borggrefe M, Podczeck A, Martinez-Rubio A, Breithardt G: Acute and long-term efficacy of oral propafenone in patients with ventricular tachyarrhythmias. J Cardiovasc Pharmacol 1991; 18:254-260 45. Horowitz LN, Morganroth J: Second generation antiarrhythmic agents: Have we reached antiarrhythmic nirvana? JAm Col] Cardiol 1987;9:459-463 46. Pottage A: Clinical profiles of newer class 1 antiarrhythmic agents-tocainide, mexiletine, encainide, flecainide and lorcainide. Am J Cardiol 1983;52:24C-31C 47. Lerman BB, Belardinelli L, West A, Berne RM, DiMarco JP: Adenosine-sensitive ventricular tachycardia: Evidence suggesting cyclic AMP-mediated triggered activity. Circulation 1986;74: 270-280 48. DiCarlo LA Jr, Susser F, Winston SA: The role of P-blockade therapy for ventricular tachycardia induced with isoproterenol: A prospective analysis. Am Heart J 1990;120:1347-1355 49. Brodsky MA, Allen BJ, Luckett CR, Capparelli EV, Wolff LJ, Henry WL: Antiarrhythmic efficacy of solitary beta-adrenergic blockade for patients with sustained ventricular tachyarrhythmias. Am Heart J 1989;118:272-280 50. Martinez-Rubio A, Chen X, Hief C, Buscher A, Borggrefe M, Breithardt G: Acute and long-term efficacy of sotalol in patients with ventricular tachyarrhythmias. (abstract) Eur Heart J 1990; 11(suppl):242 51. Nattel S, Feder-Elituv R, Matthews C, Nayebpour M, Talajic M: Concentration dependence of class 3 and beta-adrenergic blocking 37 effects of sotalol in anesthetized dogs. JAm Coil Cardiol 1989;13: 1190-1194 52. Herre JM, Sauve MJ, Malone P, Griffin JC, Helmy I, Landberg JJ, Goldberg H, Scheinman MM: Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. JAm Coil Cardiol 1989;13:442-449 53. Mason JW, Swerdlow CD, Mitchell LB: Efficiacy of verapamil in chronic recurrent ventricular tachycardia. Am J Cardiol 1983;51: 1614-1617 54. Akhtar M, Tchou P, Jazayeri M: Use of calcium channel entry blockers in the treatment of cardiac arrhythmias. Circulation 1989; 80(suppl IV):IV-31-IV-39 55. Belhassen B, Horowitz LN: Use of intravenous verapamil for ventricular tachycardia. Am J Cardiol 1984;54:1131-1133 56. Strasberg B, Kusniec J, Lewin RF, Sclarovsky S, Arditti A, Agmon J: An unusual ventricular tachycardia responsive to verapamil. Am Heart J 1986;111:190-192 57. Wu D, Kou HC, Hung FS: Exercise-triggered paroxysmal ventricular tachycardia: A repetitive rhythmic activity possibly related to afterdepolarization. Ann Intern Med 1981;95:410-414 58. Lerman BB, Berlardinelli L: Cardiac electrophysiology of adenosine. Circulation 1991;83:1499-1509 59. Mendes L, Podrid PJ, Fuchs T, Franklin S: Role of combination drug therapy with a class lc antiarrhythmic drug and mexiletine for ventricular tachycardia. JAm Coll Cardiol 1991;17:1396-1402 60. Patt MV, Grossbard CL, Graboys TB, Lown B: Combination antiarrhythmic therapy for management of malignant ventricular arrhythmia. Am J Cardiol 1988;62:181-211 61. Levy S: Combination therapy for cardiac arrhythmias. Am J Cardiol 1988;61:95A-1O1A 62. Ross DL, Sze DY, Keefe DL, Swerdlow CD, Echt DS, Griffin JC, Winkle RA, Mason JW: Antiarrhythmic drug combinations in the treatment of ventricular tachycardia: Efficacy and electrophysiologic effects. Circulation 1982;66:1205-1210 63. Greenspan AM, Spielman SR, Horowitz LN: Combination antiarrhythmic drug therapy for ventricular tachyarrhythmias. PACE 1986;9:565-576 64. Breithardt G, Seipel L, Abendroth RR: Comparison of the antiarrhythmic efficacy of disopyramide and mexiletine against stimulus-induced ventricular tachycardia. J Cardiovasc Pharmacol 1981; 3:1026-1037 65. Furlanello F, Bettini R, Bertoldi A, Vergara G, Visona L, Durante GB, Inama G, Frisanco L, Antolini R, Zanuttini D: Arrhythmia patterns in athletes with arrhythmogenic right ventricular dysplasia. Eur Heart J 1989;10(suppl D):16-19 66. Lascault G, Laplaud 0, Frank R, Tonet J, Fontaine G, Grosgogeat Y: Ventricular tachycardia features in right ventricular dysplasia (RVD). Circulation 1988;78(suppl II):II-300 67. Pietras RJ, Lam W, Bauernfeind R, Sheikh A, Palieo E, Strasberg B, Swiryn S, Rosen KM: Chronic recurrent right ventricular tachycardia in patients without ischemic heart disease: Clinical, hemodynamic and angiographic findings. Am Heart J 1983;105:357-366 68. Wilber DJ, Blakeman BM, Pifarre R, Scanlon PJ: Catecholamine sensitive right ventricular outflow tract tachycardia: Intraoperative mapping and ablation of a free wall focus. PACE 1989;12: 1851-1856 Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. T Wichter, M Borggrefe, W Haverkamp, X Chen and G Breithardt Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 Circulation. 1992;86:29-37 doi: 10.1161/01.CIR.86.1.29 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1992 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/86/1/29 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/