- Email: [email protected]
Prevalence and time of appearance of Brugada electrocardiographic pattern in young male adolescents from a three-year follow-up study
Prevalence and Time of Appearance of Brugada Electrocardiographic Pattern in Young Male Adolescents from a Three-Year Follow-Up Study Masao Yoshinaga, MD, Ryuichiro Anan, MD, Yuichi Nomura, MD, Yasuhiro Tanaka, MD, Yuji Tanaka, MD, Jav Sarantuya, MD, Shozo Oku, MD, Seiji Nishi, MD, Yoshifumi Kawano, MD, Chuwa Tei, MD, and Katsura Arima, MD The prevalence of Brugada’s electrocardiographic (ECG) pattern in 7,022 male adolescents in the seventh grade was determined, and the same subjects were reexamined 3 years later, while in tenth grade. Two subjects (0.03%) and 7 subjects (0.10%) showed Brugada’s ECG pattern by the conventional criterion (J point or STsegment >0.1 mV in leads V1 to V3), and no subjects (0%) and 2 subjects (0.03%) fulfilled the recent criterion (J point or ST-segment >0.2 mV) in the seventh and tenth grades, respectively, indicating that Brugada’s ECG pattern begins to appear during junior high school and increases until late adulthood. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:1186 –1189)
he purpose of the present study was to determine the prevalence of Brugada’s electrocardiographic T (ECG) pattern by the conventional and recent criteria in 7,022 male adolescents in seventh grade who participated in a screening program for heart disease in Kagoshima City, Japan. The electrocardiograms of the same subjects were examined 3 years later, while they were in tenth grade, to determine the time of the appearance of Brugada’s ECG pattern. •••
Subjects were seventh grade male adolescents who were participating in a screening program for heart disease in Kagoshima City from 1996 to 1999 and who also participated in the same screening program when they were in tenth grade, from 1999 to 2002, 3 years after their initial participation, in Kagoshima City. We obtained permission to use and analyze these data from the Committee for Ethics of the Kagoshima City Medical Association, under the condition that confidentiality regarding all personal data would be maintained. Kagoshima City is located in the southern part of Japan, and it has a population of approximately 550,000. In the screening program for heart disease in Kagoshima City, all students in first, seventh, and tenth grades were enrolled to examine 12-lead electrocarFrom the Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City; and the Kagoshima City Medical Association, Kagoshima City, Japan. Dr. Yoshinaga’s address is: Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima, 890-8520, Japan. E-mail: [email protected]. Manuscript received April 30, 2004; revised manuscript received and accepted July 15, 2004.
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©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 November 1, 2004
diograms at a study speed of 25 mm/s. A questionnaire was also administered, including history regarding the presence or absence of a heart murmur, cardiac diseases, cardiac symptoms (chest pain, palpitations, and syncope), and a family history of sudden cardiac death. Japanese adolescents enter junior high school in April, when they are 12 years old. The electrocardiograms in this study were obtained from April to May each year. Therefore, almost all of the seventh graders were 12 years old, with a small number being ⬎12 years old, at the time of the examination. Similarly, almost all of the tenth graders were 15 years old, with a small number being ⬎15 years old, at the time of the examination. Approximately 99% of the subjects of a parent population participated in the screening program in Kagoshima City each year. Five cardiologists blinded to the study objectives screened the 12-lead electrocardiograms of the subjects and assessed them as indicating Brugada’s ECG pattern when they demonstrated ST-segment elevation in the right precordial leads.1 ST-segment elevation was defined as an increase in the J point or ST segment of ⱖ0.1 mV in leads V1 to V3 (the conventional criterion)2 to compare the prevalence of Brugada’s ECG pattern in the present data with the previously reported prevalence.3–9 Five readers (also blinded to the study objectives) read the electrocardiograms screened by ⱖ1 reader. The diagnosis of Brugada’s ECG pattern was made when 4 of the 5 readers considered an electrocardiogram to demonstrate Brugada’s ECG pattern. According to the configuration, ST-segment elevations were designated as either coved or saddleback type. The recent criterion of J point or ST-segment elevation of ⱖ0.2 mV in leads V1 to V3 was also used for evaluation.10 The screening of Brugada’s ECG pattern in tenth grade was done using the same method as for seventh graders. The diagnosis of Brugada’s ECG pattern was made when 4 of 5 readers found Brugada’s ECG pattern on the electrocardiogram. Of the 13,283 male subjects who participated in the screening program during seventh grade, from 1996 to 1999, in Kagoshima City, all 7,022 male subjects who again participated in the program in tenth grade, from 1999 to 2002, in Kagoshima City were included in the present study. The remaining subjects had moved outside Kagoshima City and participated in the screening programs of their new places of residence. Two of 7,022 subjects (0.03%) were diagnosed as having Brugada’s ECG pattern in seventh grade. All 5 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.07.092
history of heart murmur or cardiac symptoms or a family history of sudden cardiac death. Of 2 patients (cases 1 and 2 in Figure 1) who showed Brugada’s ECG pattern in seventh grade, only 1 patient (case 2 in Figure 1) showed Brugada’s ECG pattern again 3 years later in tenth grade by the conventional criteria. Patient 1 did not show Brugada’s ECG pattern in tenth grade. Of 7 patients who showed Brugada’s ECG pattern in tenth grade (cases 2 to 8 in Figure 1), 5 had not shown Brugada’s ECG pattern 3 years previously, in seventh grade (cases 4 to 8 in Figure 1). Two of 7 subjects (29%) with Brugada’s ECG pattern by the conventional criterion in tenth grade fulfilled the recent criterion (cases 2 and 3 in Figure 1). Patient 2 showed type 1 ST-segment abnormalities, and patient 3 showed type 3 STsegment abnormalities.7 No subject fulfilled the recent criterion in seventh grade. •••
The results of the present study indicate that the prevalence of Brugada’s ECG pattern in young adolescents 12 and 15 years of age was 0.03% (2 of 7,022) and 0.10% (7 of 7,022), respectively, by the conventional criterion of J point or ST-segment elevation of ⱖ0.1 mV in leads V1 to V3. Two subjects (0.03%) fulfilled the recent criterion of J point or ST-segment elevation of ⱖ0.2 mV in leads V1 to V3 in tenth grade. This is FIGURE 1. Electrocardiograms of 8 male adolescents in seventh grade (A) and tenth the first report of observed longitudigrade (B). Two subjects in seventh grade (cases 1 and 2 in A) and 7 subjects in tenth nal changes of adolescents’ electrograde (cases 2 to 8 in B) fulfilled the conventional criterion of Brugada’s ECG pattern cardiograms concerning Brugada’s (J point or ST-segment elevation of >0.1 mV in leads V1 to V3). The electrocardioECG pattern. Brugada’s ECG pattern grams of patient 2 in the seventh and tenth grades fulfilled the conventional criterion. may appear during junior high None of the electrocardiograms of patient 1 in tenth grade and patients 3 to 8 in seventh grade fulfilled the criterion. Patients 2 and 3 in tenth grade fulfilled the recent school. criterion of J point or ST-segment elevation of >0.2 mV in leads V1 to V3. Brugada’s ECG pattern is not a rare condition in adult populations in southeastern Asia. Japanese investireaders agreed that these 2 subjects fulfilled the con- gators have reported a different prevalence of subjects ventional criterion. Of those, 2 subjects (cases 1 and 2 with Brugada’s ECG pattern in different populations in Figure 1) showed the saddleback- and coved-type by the conventional criterion.3,4,7–9 Atarashi et al3 and ST-segment elevations, respectively. None had a his- Furuhashi et al9 reported that the prevalence of Brutory of heart murmur or cardiac symptoms or a family gada’s ECG pattern was 0.18% (Table 1) in a large history of sudden cardiac death. Seven of 7,022 sub- number of working men aged 40 to 49 years (8,913 jects (0.10%; patients 2 to 8) were diagnosed as hav- and 5,987 men, respectively). When subjects are liming Brugada’s ECG pattern in tenth grade. All 5 ited, however, the prevalence is found to be greater readers agreed that 2 subjects (cases 2 and 7) fulfilled than suggested by these reports. Matsuo et al7 reported the conventional criterion, and 4 of 5 readers agreed that 7 of 1,956 subjects (0.36%) showed Brugada’s that the remaining 5 subjects fulfilled the criterion. Of ECG pattern in a follow-up program of the Radiation those, 2 subjects (cases 3 and 8 in Figure 1) showed Effects Research Foundation. Miyasaka et al8 found saddleback-type ST-segment elevations. None had a 14 men (2.14%) with Brugada’s ECG pattern in 3,691 BRIEF REPORTS
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needed for subjects who showed Brugada’s ECG pattern in tenth grade. In the present study, the final diNo. and Prevalence agnosis of Brugada’s ECG pattern Reference Total Subjects Mean Age Coved Total was made when 4 of 5 readers considered an electrocardiogram to demJapanese population onstrate the pattern. We chose this Tohyou et al11 5,175 9 ND 1 (0.02%) Yamakawa et al17 10,434 9.7 ⫾ 3.2* 8 (0.08%) 10 (0.10%) method because we sought to avoid Present study 7,022 12 1 (0.01%) 2 (0.03%) the overdiagnosis of Brugada’s ECG Present study 7,022 15 5 (0.06%) 7 (0.10%) pattern. A similar prevalence of Atarashi et al5 8,913 42 ⫾ 9* ND 16 (0.18%) Brugada’s ECG pattern in the Furuhashi et al16 5,987 49.2* 4 (0.07%) 11 (0.18%) Matsuo et al14 1,956 ND ND 7 (0.36%) present data and in former studMiyasaka et al15 3,691 58 ⫾ 10* 14 (0.38%) 79 (2.14%) ies3,4,7 may justify this method, alWestern population though the method should be furViskin et al12 346 36 ⫾ 10* 0 0 ther examined. 13 Hermida et al 632 39 ⫾ 10* 1 (0.16%) ND A limitation of the present study *The mean age of the total subjects (men and women) was used. is that Brugada’s ECG pattern does ND ⫽ not described. not represent Brugada’s syndrome. We did not examine drug-induced ST-segment elevation by a sodium channel blocker, an electrophysisubjects suspected of having cardiac abnormalities ologic study, or a molecular genetic study. We also did not begin therapy for the subjects identified as during physical examinations in 1 city. In contrast, the prevalence of Brugada’s ECG pat- having Brugada’s ECG pattern. We should follow tern in young adolescents is unclear. Recently, Ya- these patients to determine if they present cardiac makawa et al11 reported that 10 male subjects (0.10%) symptoms related to Brugada’s syndrome. Finally, this is the first longitudinal study of the and 1 male subject (0.01%) showed Brugada’s ECG pattern by the conventional and recent criteria, respec- prevalence of Brugada’s ECG pattern under baseline tively, in a population of 10,434 Japanese male chil- conditions in young adolescents by the conventional dren and adolescents (age range 6 to 17 years). In the and recent criteria, and this will be a good reference present study, the prevalence of Brugada’s ECG pat- for the prevalence of Brugada’s ECG pattern in adulttern in young male adolescents was found to be 0.03% hood. in seventh grade (about 12 years old) and 0.10% in tenth grade (about 15 years old) by the conventional criterion. The prevalence was 0% and 0.03% in sevBrugada P, Brugada J. Right bundle branch block, persistent ST segment enth and tenth grades, respectively, by the recent 1. elevation and sudden cardiac death: a distinct clinical and electrocardiographic criterion. Because the ages of patients in the parent syndrome. A multicenter report. J Am Coll Cardiol 1992;20:1391–1396. 2. Surawicz B. Brugada syndrome: manifest, concealed, “asymptomatic,” suspopulation were unclear in the former study,11 we were pected and simulated. J Am Coll Cardiol 2001;38:775–777. not able to calculate the prevalence of Brugada’s ECG 3. Atarashi H, Ogawa S, Harumi K, Toyama J, Hayakawa H, Idiopathic pattern at each age. These 2 large-scale studies, how- Ventricular Fibrillation Investigators. Three-year follow-up of patients with bundle branch block and ST segment elevation in the right precordial ever, showed that the prevalence of Brugada’s ECG right leads: Japanese Registry of Brugada Syndrome. J Am Coll Cardiol 2001;37: pattern in children and adolescents might be similar in 1916 –1920. 4. Tohyou Y, Nakazawa K, Ozawa A, Tanaka O, Watanuki M, Takagi A, Akagi Japan. Masui Y, Matsumoto N, Miyake F, et al. A survey in the incidence of right In Kagoshima City, approximately 99% of the par- T, bundle branch block with ST-segment elevation among normal population. Jpn J ent population participated in the screening program, Electrocardiol 1995;15:223–226. Viskin S, Fish R, Eldar M, Zeltser D, Lesh MD, Glick A, Belhassen B. suggesting that the prevalence in the present study 5. Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy represents that of the young population of the same controls. Heart 2000;84:31–36. age in Japan. Supposing that the reports of Atarashi et 6. Hermida JS, Lemoine JL, Aoun FB, Jarry G, Rey JL, Quiret JC. Prevalence of Brugada syndrome in an apparently healthy population. Am J Cardiol 2000; al3 and Furuhashi et al9 are based on the prevalence in the 86:91–94. the entire working male population, we can hypothe- 7. Matsuo K, Akahoshi M, Nakashima E, Suyama A, Seto S, Hayano M, Yano size that more than half (0.10%/0.18%) of men aged K. The prevalence, incidence and prognostic value of the Brugada-type electrocardiogram: a population-based study of four decades. J Am Coll Cardiol 2001; 40 to 49 years with Brugada’s ECG pattern show the 38:765–770. pattern at the age of 15 years. 8. Miyasaka Y, Tsuji H, Yamada K, Tokunaga S, Saito D, Imuro Y, Matsumoto Iwasaka T. Prevalence and mortality of the Brugada-type electrocardiogram in In the present study, 2 and 7 subjects fulfilled the N, one city in Japan. J Am Coll Cardiol 2001;38:771–774. conventional criterion of Brugada’s ECG pattern in 9. Furuhashi M, Uno K, Tsuchihashi K, Nagahara D, Hyakukoku M, Ohtomo seventh and tenth grades, respectively. It is well T, Satoh S, Nishimiya T, Shimamoto K. Prevalence of asymptomatic ST elevation in right precordial leads with right bundle branch block known that the ST-segment abnormalities of Bruga- segment (Brugada-type ST shift) among the general Japanese population. Heart 2001; da’s ECG pattern show a dynamic change.10 One of 2 86:161–166. subjects who fulfilled the conventional criterion in 10. Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada Corrado D, Hauer RN, Kass RS, Nademanee K, et al. Proposed diagnostic seventh grade did not show Brugada’s ECG pattern in P, criteria for the Brugada syndrome: consensus report. Circulation 2002;106: tenth grade, suggesting that a third ECG recording is 2514 –2519. TABLE 1 Prevalence of an Idiopathic Brugada’s ECG Pattern in Healthy Male Subjects, as Assessed by the Conventional Criterion of J Point or ST-segment Elevation of ⱖ0.1 mV in Leads V1 to V3
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11. Yamakawa Y, Ishikawa T, Uchino K, Mochida Y, Ebina T, Sumita S, Kobayashi T, Matsushita K, Matsumoto K, Ohkusu Y, et al. Prevalence of right bundle-branch block and right precordial ST-segment elevation (Brugada-type electrocardiogram) in Japanese children. Circ J 2004;68:275–279. 12. Atarashi H, Ogawa S, Harumi K, Hayakawa H, Sugimoto T, Okada R, Murayama M, Toyama J. Characteristics of patients with right bundle branch block and ST-segment elevation in right precordial leads: Idiopathic Ventricular Fibrillation Investigators. Am J Cardiol 1996;78:581–583. 13. Brugada J, Brugada R, Brugada P. Right bundle-branch block and STsegment elevation in leads V1 through V3: a marker for sudden death in patients without demonstrable structural heart disease. Circulation 1998;97: 457– 460.
14. Alings M, Wilde A. “Brugada syndrome” clinical data and suggested pathophysiological mechanism. Circulation 1999;99:666 – 673. 15. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002;105: 1342–1347. 16. Antzelevitch C, Brugada P, Brugada J, Brugada R, Shimizu W, Gussak I, Perez Riera AR. Brugada syndrome: a decade of progress. Circ Res 2002;91: 1114 –1118. 17. Antzelevitch C, Brugada P, Brugada J, Brugada R, Towbin JA, Nademanee K. Brugada syndrome: 1992-2002: a historical perspective. J Am Coll Cardiol 2003;41:1665–1671.
Usefulness of Pindolol for Treatment of Neurocardiogenic Syncope Nandini Nair,
MD, PhD,
Farooq A. Padder, MD, Steven P. Kutalek, Bharat K. Kantharia, MD
This study evaluated the efficacy of pindolol, a noncardioselective  blocker with intrinsic sympathetic activity, on neurocardiogenic syncope using a head-up tilt-table test in 66 patients. Pindolol was equally effective in men and women and the 2 age groups (>60 and <60 years) of the study cohort. The earliest benefit was seen <3 days after initiating treatment. Side effects were better tolerated in younger patients (age <60 years). 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:1189–1191)
eta blockers have been used in clinical practice to prevent recurrent neurocardiogenic syncope. B Beta blockers with intrinsic sympathetic activity have 1–11
been considered to be more efficacious, with fewer adverse effects.6 – 8 Overall, the outcomes of -blocker therapy in the treatment of neurocardiogenic syncope have widely varied.3–11 In this study, we used the head-up tilt-table (HUT) test, an established method for the evaluation of syncope,1,12,13 and clinical follow-up to assess the efficacy of pindolol, a noncardioselective  blocker with intrinsic sympathetic activity properties, as a single-agent therapy in the treatment of neurocardiogenic syncope. •••
The study population consisted of 66 patients (42 women [aged 25 to 91 years] and 24 men [aged 17 to 86 years]), who presented with ⱖ1 unexplained syncopal attack. There were 25 patients ⬎60 years of age (group A) and 41 patients ⬍60 years of age (group B). All patients underwent clinical evaluation by detailed histories and physical examinations, 12-lead electrocardiograms, transthoracic echocardiograms, and other noncarFrom the Department of Cardiology, Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, Pennsylvania; and the Division of Cardiac Electrophysiology, Albert Einstein Medical Center, Philadelphia, Pennsylvania. Dr. Kantharia’s address is: Division of Cardiac Electrophysiology, Albert Einstein Medical Center, 5501 Old York Road, Levy 3 East, Philadelphia, Pennsylvania 19141. E-mail: [email protected]. Manuscript received May 6, 2004; revised manuscript received and accepted July 7, 2004. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 November 1, 2004
MD,
and
diac investigations when deemed necessary. All patients subsequently underwent the HUT test. The protocol for the HUT test included 20 minutes of baseline rest in the supine position, followed by 30 minutes in the head-up position at a tilt angle of 70° to 80°. If the test results were negative during the passive phase, sublingual nitroglycerin 0.4 mg was administered to provoke features of neurocardiogenic syncope. Patients were further observed for 30 minutes. The end point was determined after 60 minutes of the test protocol or at the point of the appearance of symptoms, whichever occurred first. Treatment with pindolol as a single pharmacologic agent was started at the smallest dose of 2.5 mg orally twice daily and then increased, depending on the recurrence of symptoms. Pindolol was continued at a maintenance dose unless the patients developed intolerable side effects. The patients were not given behavior modification or tilt training. The patients were followed up clinically for ⱕ24 months (mean 10.5) and with repeat HUT tests. In those patients who underwent repeat HUT tests, the tests were performed at an interval of 3 days to 3 months, depending on the patient. The patients were considered to be free of syncope if they remained clinically asymptomatic at the follow-up visits or if repeat HUT test results were negative. Statistical analyses of the data were performed using chi-square analysis, and a p value ⬍0.05 was considered significant. Sixty-six patients (24 men and 42 women) with a history of syncope were enrolled in the study (Table 1). Group A consisted of 8 men (age range 64 to 86 years) and 17 women (age range 60 to 91 years). Group B included 16 men (age range 17 to 59 years) and 25 women (age range 25 to 59 years). They were treated with varying doses of pindolol (2.5 to 10 mg orally twice daily), as tolerated. The drug was discontinued in 17 patients secondary to intolerable side effects, such as paraesthesia, cramps, and fatigue. As listed in Table 1, in group A (age ⬎60 years), 13 patients (59%) had no side effects due to pindolol 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.07.093
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he purpose of the present study was to determine the prevalence of Brugada’s electrocardiographic T (ECG) pattern by the conventional and recent criteria in 7,022 male adolescents in seventh grade who participated in a screening program for heart disease in Kagoshima City, Japan. The electrocardiograms of the same subjects were examined 3 years later, while they were in tenth grade, to determine the time of the appearance of Brugada’s ECG pattern. •••
Subjects were seventh grade male adolescents who were participating in a screening program for heart disease in Kagoshima City from 1996 to 1999 and who also participated in the same screening program when they were in tenth grade, from 1999 to 2002, 3 years after their initial participation, in Kagoshima City. We obtained permission to use and analyze these data from the Committee for Ethics of the Kagoshima City Medical Association, under the condition that confidentiality regarding all personal data would be maintained. Kagoshima City is located in the southern part of Japan, and it has a population of approximately 550,000. In the screening program for heart disease in Kagoshima City, all students in first, seventh, and tenth grades were enrolled to examine 12-lead electrocarFrom the Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City; and the Kagoshima City Medical Association, Kagoshima City, Japan. Dr. Yoshinaga’s address is: Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima, 890-8520, Japan. E-mail: [email protected]. Manuscript received April 30, 2004; revised manuscript received and accepted July 15, 2004.
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©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 November 1, 2004
diograms at a study speed of 25 mm/s. A questionnaire was also administered, including history regarding the presence or absence of a heart murmur, cardiac diseases, cardiac symptoms (chest pain, palpitations, and syncope), and a family history of sudden cardiac death. Japanese adolescents enter junior high school in April, when they are 12 years old. The electrocardiograms in this study were obtained from April to May each year. Therefore, almost all of the seventh graders were 12 years old, with a small number being ⬎12 years old, at the time of the examination. Similarly, almost all of the tenth graders were 15 years old, with a small number being ⬎15 years old, at the time of the examination. Approximately 99% of the subjects of a parent population participated in the screening program in Kagoshima City each year. Five cardiologists blinded to the study objectives screened the 12-lead electrocardiograms of the subjects and assessed them as indicating Brugada’s ECG pattern when they demonstrated ST-segment elevation in the right precordial leads.1 ST-segment elevation was defined as an increase in the J point or ST segment of ⱖ0.1 mV in leads V1 to V3 (the conventional criterion)2 to compare the prevalence of Brugada’s ECG pattern in the present data with the previously reported prevalence.3–9 Five readers (also blinded to the study objectives) read the electrocardiograms screened by ⱖ1 reader. The diagnosis of Brugada’s ECG pattern was made when 4 of the 5 readers considered an electrocardiogram to demonstrate Brugada’s ECG pattern. According to the configuration, ST-segment elevations were designated as either coved or saddleback type. The recent criterion of J point or ST-segment elevation of ⱖ0.2 mV in leads V1 to V3 was also used for evaluation.10 The screening of Brugada’s ECG pattern in tenth grade was done using the same method as for seventh graders. The diagnosis of Brugada’s ECG pattern was made when 4 of 5 readers found Brugada’s ECG pattern on the electrocardiogram. Of the 13,283 male subjects who participated in the screening program during seventh grade, from 1996 to 1999, in Kagoshima City, all 7,022 male subjects who again participated in the program in tenth grade, from 1999 to 2002, in Kagoshima City were included in the present study. The remaining subjects had moved outside Kagoshima City and participated in the screening programs of their new places of residence. Two of 7,022 subjects (0.03%) were diagnosed as having Brugada’s ECG pattern in seventh grade. All 5 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.07.092
history of heart murmur or cardiac symptoms or a family history of sudden cardiac death. Of 2 patients (cases 1 and 2 in Figure 1) who showed Brugada’s ECG pattern in seventh grade, only 1 patient (case 2 in Figure 1) showed Brugada’s ECG pattern again 3 years later in tenth grade by the conventional criteria. Patient 1 did not show Brugada’s ECG pattern in tenth grade. Of 7 patients who showed Brugada’s ECG pattern in tenth grade (cases 2 to 8 in Figure 1), 5 had not shown Brugada’s ECG pattern 3 years previously, in seventh grade (cases 4 to 8 in Figure 1). Two of 7 subjects (29%) with Brugada’s ECG pattern by the conventional criterion in tenth grade fulfilled the recent criterion (cases 2 and 3 in Figure 1). Patient 2 showed type 1 ST-segment abnormalities, and patient 3 showed type 3 STsegment abnormalities.7 No subject fulfilled the recent criterion in seventh grade. •••
The results of the present study indicate that the prevalence of Brugada’s ECG pattern in young adolescents 12 and 15 years of age was 0.03% (2 of 7,022) and 0.10% (7 of 7,022), respectively, by the conventional criterion of J point or ST-segment elevation of ⱖ0.1 mV in leads V1 to V3. Two subjects (0.03%) fulfilled the recent criterion of J point or ST-segment elevation of ⱖ0.2 mV in leads V1 to V3 in tenth grade. This is FIGURE 1. Electrocardiograms of 8 male adolescents in seventh grade (A) and tenth the first report of observed longitudigrade (B). Two subjects in seventh grade (cases 1 and 2 in A) and 7 subjects in tenth nal changes of adolescents’ electrograde (cases 2 to 8 in B) fulfilled the conventional criterion of Brugada’s ECG pattern cardiograms concerning Brugada’s (J point or ST-segment elevation of >0.1 mV in leads V1 to V3). The electrocardioECG pattern. Brugada’s ECG pattern grams of patient 2 in the seventh and tenth grades fulfilled the conventional criterion. may appear during junior high None of the electrocardiograms of patient 1 in tenth grade and patients 3 to 8 in seventh grade fulfilled the criterion. Patients 2 and 3 in tenth grade fulfilled the recent school. criterion of J point or ST-segment elevation of >0.2 mV in leads V1 to V3. Brugada’s ECG pattern is not a rare condition in adult populations in southeastern Asia. Japanese investireaders agreed that these 2 subjects fulfilled the con- gators have reported a different prevalence of subjects ventional criterion. Of those, 2 subjects (cases 1 and 2 with Brugada’s ECG pattern in different populations in Figure 1) showed the saddleback- and coved-type by the conventional criterion.3,4,7–9 Atarashi et al3 and ST-segment elevations, respectively. None had a his- Furuhashi et al9 reported that the prevalence of Brutory of heart murmur or cardiac symptoms or a family gada’s ECG pattern was 0.18% (Table 1) in a large history of sudden cardiac death. Seven of 7,022 sub- number of working men aged 40 to 49 years (8,913 jects (0.10%; patients 2 to 8) were diagnosed as hav- and 5,987 men, respectively). When subjects are liming Brugada’s ECG pattern in tenth grade. All 5 ited, however, the prevalence is found to be greater readers agreed that 2 subjects (cases 2 and 7) fulfilled than suggested by these reports. Matsuo et al7 reported the conventional criterion, and 4 of 5 readers agreed that 7 of 1,956 subjects (0.36%) showed Brugada’s that the remaining 5 subjects fulfilled the criterion. Of ECG pattern in a follow-up program of the Radiation those, 2 subjects (cases 3 and 8 in Figure 1) showed Effects Research Foundation. Miyasaka et al8 found saddleback-type ST-segment elevations. None had a 14 men (2.14%) with Brugada’s ECG pattern in 3,691 BRIEF REPORTS
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needed for subjects who showed Brugada’s ECG pattern in tenth grade. In the present study, the final diNo. and Prevalence agnosis of Brugada’s ECG pattern Reference Total Subjects Mean Age Coved Total was made when 4 of 5 readers considered an electrocardiogram to demJapanese population onstrate the pattern. We chose this Tohyou et al11 5,175 9 ND 1 (0.02%) Yamakawa et al17 10,434 9.7 ⫾ 3.2* 8 (0.08%) 10 (0.10%) method because we sought to avoid Present study 7,022 12 1 (0.01%) 2 (0.03%) the overdiagnosis of Brugada’s ECG Present study 7,022 15 5 (0.06%) 7 (0.10%) pattern. A similar prevalence of Atarashi et al5 8,913 42 ⫾ 9* ND 16 (0.18%) Brugada’s ECG pattern in the Furuhashi et al16 5,987 49.2* 4 (0.07%) 11 (0.18%) Matsuo et al14 1,956 ND ND 7 (0.36%) present data and in former studMiyasaka et al15 3,691 58 ⫾ 10* 14 (0.38%) 79 (2.14%) ies3,4,7 may justify this method, alWestern population though the method should be furViskin et al12 346 36 ⫾ 10* 0 0 ther examined. 13 Hermida et al 632 39 ⫾ 10* 1 (0.16%) ND A limitation of the present study *The mean age of the total subjects (men and women) was used. is that Brugada’s ECG pattern does ND ⫽ not described. not represent Brugada’s syndrome. We did not examine drug-induced ST-segment elevation by a sodium channel blocker, an electrophysisubjects suspected of having cardiac abnormalities ologic study, or a molecular genetic study. We also did not begin therapy for the subjects identified as during physical examinations in 1 city. In contrast, the prevalence of Brugada’s ECG pat- having Brugada’s ECG pattern. We should follow tern in young adolescents is unclear. Recently, Ya- these patients to determine if they present cardiac makawa et al11 reported that 10 male subjects (0.10%) symptoms related to Brugada’s syndrome. Finally, this is the first longitudinal study of the and 1 male subject (0.01%) showed Brugada’s ECG pattern by the conventional and recent criteria, respec- prevalence of Brugada’s ECG pattern under baseline tively, in a population of 10,434 Japanese male chil- conditions in young adolescents by the conventional dren and adolescents (age range 6 to 17 years). In the and recent criteria, and this will be a good reference present study, the prevalence of Brugada’s ECG pat- for the prevalence of Brugada’s ECG pattern in adulttern in young male adolescents was found to be 0.03% hood. in seventh grade (about 12 years old) and 0.10% in tenth grade (about 15 years old) by the conventional criterion. The prevalence was 0% and 0.03% in sevBrugada P, Brugada J. Right bundle branch block, persistent ST segment enth and tenth grades, respectively, by the recent 1. elevation and sudden cardiac death: a distinct clinical and electrocardiographic criterion. Because the ages of patients in the parent syndrome. A multicenter report. J Am Coll Cardiol 1992;20:1391–1396. 2. Surawicz B. Brugada syndrome: manifest, concealed, “asymptomatic,” suspopulation were unclear in the former study,11 we were pected and simulated. J Am Coll Cardiol 2001;38:775–777. not able to calculate the prevalence of Brugada’s ECG 3. Atarashi H, Ogawa S, Harumi K, Toyama J, Hayakawa H, Idiopathic pattern at each age. These 2 large-scale studies, how- Ventricular Fibrillation Investigators. Three-year follow-up of patients with bundle branch block and ST segment elevation in the right precordial ever, showed that the prevalence of Brugada’s ECG right leads: Japanese Registry of Brugada Syndrome. J Am Coll Cardiol 2001;37: pattern in children and adolescents might be similar in 1916 –1920. 4. Tohyou Y, Nakazawa K, Ozawa A, Tanaka O, Watanuki M, Takagi A, Akagi Japan. Masui Y, Matsumoto N, Miyake F, et al. A survey in the incidence of right In Kagoshima City, approximately 99% of the par- T, bundle branch block with ST-segment elevation among normal population. Jpn J ent population participated in the screening program, Electrocardiol 1995;15:223–226. Viskin S, Fish R, Eldar M, Zeltser D, Lesh MD, Glick A, Belhassen B. suggesting that the prevalence in the present study 5. Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy represents that of the young population of the same controls. Heart 2000;84:31–36. age in Japan. Supposing that the reports of Atarashi et 6. Hermida JS, Lemoine JL, Aoun FB, Jarry G, Rey JL, Quiret JC. Prevalence of Brugada syndrome in an apparently healthy population. Am J Cardiol 2000; al3 and Furuhashi et al9 are based on the prevalence in the 86:91–94. the entire working male population, we can hypothe- 7. Matsuo K, Akahoshi M, Nakashima E, Suyama A, Seto S, Hayano M, Yano size that more than half (0.10%/0.18%) of men aged K. The prevalence, incidence and prognostic value of the Brugada-type electrocardiogram: a population-based study of four decades. J Am Coll Cardiol 2001; 40 to 49 years with Brugada’s ECG pattern show the 38:765–770. pattern at the age of 15 years. 8. Miyasaka Y, Tsuji H, Yamada K, Tokunaga S, Saito D, Imuro Y, Matsumoto Iwasaka T. Prevalence and mortality of the Brugada-type electrocardiogram in In the present study, 2 and 7 subjects fulfilled the N, one city in Japan. J Am Coll Cardiol 2001;38:771–774. conventional criterion of Brugada’s ECG pattern in 9. Furuhashi M, Uno K, Tsuchihashi K, Nagahara D, Hyakukoku M, Ohtomo seventh and tenth grades, respectively. It is well T, Satoh S, Nishimiya T, Shimamoto K. Prevalence of asymptomatic ST elevation in right precordial leads with right bundle branch block known that the ST-segment abnormalities of Bruga- segment (Brugada-type ST shift) among the general Japanese population. Heart 2001; da’s ECG pattern show a dynamic change.10 One of 2 86:161–166. subjects who fulfilled the conventional criterion in 10. Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada Corrado D, Hauer RN, Kass RS, Nademanee K, et al. Proposed diagnostic seventh grade did not show Brugada’s ECG pattern in P, criteria for the Brugada syndrome: consensus report. Circulation 2002;106: tenth grade, suggesting that a third ECG recording is 2514 –2519. TABLE 1 Prevalence of an Idiopathic Brugada’s ECG Pattern in Healthy Male Subjects, as Assessed by the Conventional Criterion of J Point or ST-segment Elevation of ⱖ0.1 mV in Leads V1 to V3
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11. Yamakawa Y, Ishikawa T, Uchino K, Mochida Y, Ebina T, Sumita S, Kobayashi T, Matsushita K, Matsumoto K, Ohkusu Y, et al. Prevalence of right bundle-branch block and right precordial ST-segment elevation (Brugada-type electrocardiogram) in Japanese children. Circ J 2004;68:275–279. 12. Atarashi H, Ogawa S, Harumi K, Hayakawa H, Sugimoto T, Okada R, Murayama M, Toyama J. Characteristics of patients with right bundle branch block and ST-segment elevation in right precordial leads: Idiopathic Ventricular Fibrillation Investigators. Am J Cardiol 1996;78:581–583. 13. Brugada J, Brugada R, Brugada P. Right bundle-branch block and STsegment elevation in leads V1 through V3: a marker for sudden death in patients without demonstrable structural heart disease. Circulation 1998;97: 457– 460.
14. Alings M, Wilde A. “Brugada syndrome” clinical data and suggested pathophysiological mechanism. Circulation 1999;99:666 – 673. 15. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002;105: 1342–1347. 16. Antzelevitch C, Brugada P, Brugada J, Brugada R, Shimizu W, Gussak I, Perez Riera AR. Brugada syndrome: a decade of progress. Circ Res 2002;91: 1114 –1118. 17. Antzelevitch C, Brugada P, Brugada J, Brugada R, Towbin JA, Nademanee K. Brugada syndrome: 1992-2002: a historical perspective. J Am Coll Cardiol 2003;41:1665–1671.
Usefulness of Pindolol for Treatment of Neurocardiogenic Syncope Nandini Nair,
MD, PhD,
Farooq A. Padder, MD, Steven P. Kutalek, Bharat K. Kantharia, MD
This study evaluated the efficacy of pindolol, a noncardioselective  blocker with intrinsic sympathetic activity, on neurocardiogenic syncope using a head-up tilt-table test in 66 patients. Pindolol was equally effective in men and women and the 2 age groups (>60 and <60 years) of the study cohort. The earliest benefit was seen <3 days after initiating treatment. Side effects were better tolerated in younger patients (age <60 years). 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:1189–1191)
eta blockers have been used in clinical practice to prevent recurrent neurocardiogenic syncope. B Beta blockers with intrinsic sympathetic activity have 1–11
been considered to be more efficacious, with fewer adverse effects.6 – 8 Overall, the outcomes of -blocker therapy in the treatment of neurocardiogenic syncope have widely varied.3–11 In this study, we used the head-up tilt-table (HUT) test, an established method for the evaluation of syncope,1,12,13 and clinical follow-up to assess the efficacy of pindolol, a noncardioselective  blocker with intrinsic sympathetic activity properties, as a single-agent therapy in the treatment of neurocardiogenic syncope. •••
The study population consisted of 66 patients (42 women [aged 25 to 91 years] and 24 men [aged 17 to 86 years]), who presented with ⱖ1 unexplained syncopal attack. There were 25 patients ⬎60 years of age (group A) and 41 patients ⬍60 years of age (group B). All patients underwent clinical evaluation by detailed histories and physical examinations, 12-lead electrocardiograms, transthoracic echocardiograms, and other noncarFrom the Department of Cardiology, Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, Pennsylvania; and the Division of Cardiac Electrophysiology, Albert Einstein Medical Center, Philadelphia, Pennsylvania. Dr. Kantharia’s address is: Division of Cardiac Electrophysiology, Albert Einstein Medical Center, 5501 Old York Road, Levy 3 East, Philadelphia, Pennsylvania 19141. E-mail: [email protected]. Manuscript received May 6, 2004; revised manuscript received and accepted July 7, 2004. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 November 1, 2004
MD,
and
diac investigations when deemed necessary. All patients subsequently underwent the HUT test. The protocol for the HUT test included 20 minutes of baseline rest in the supine position, followed by 30 minutes in the head-up position at a tilt angle of 70° to 80°. If the test results were negative during the passive phase, sublingual nitroglycerin 0.4 mg was administered to provoke features of neurocardiogenic syncope. Patients were further observed for 30 minutes. The end point was determined after 60 minutes of the test protocol or at the point of the appearance of symptoms, whichever occurred first. Treatment with pindolol as a single pharmacologic agent was started at the smallest dose of 2.5 mg orally twice daily and then increased, depending on the recurrence of symptoms. Pindolol was continued at a maintenance dose unless the patients developed intolerable side effects. The patients were not given behavior modification or tilt training. The patients were followed up clinically for ⱕ24 months (mean 10.5) and with repeat HUT tests. In those patients who underwent repeat HUT tests, the tests were performed at an interval of 3 days to 3 months, depending on the patient. The patients were considered to be free of syncope if they remained clinically asymptomatic at the follow-up visits or if repeat HUT test results were negative. Statistical analyses of the data were performed using chi-square analysis, and a p value ⬍0.05 was considered significant. Sixty-six patients (24 men and 42 women) with a history of syncope were enrolled in the study (Table 1). Group A consisted of 8 men (age range 64 to 86 years) and 17 women (age range 60 to 91 years). Group B included 16 men (age range 17 to 59 years) and 25 women (age range 25 to 59 years). They were treated with varying doses of pindolol (2.5 to 10 mg orally twice daily), as tolerated. The drug was discontinued in 17 patients secondary to intolerable side effects, such as paraesthesia, cramps, and fatigue. As listed in Table 1, in group A (age ⬎60 years), 13 patients (59%) had no side effects due to pindolol 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.07.093
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