Arrhythmogenic Right Ventricular Cardiomyopathy Underlies Syndrome of Right Bundle Branch Block, ST-Segment Elevation, and Sudden Death

I 1992, Brugada and Brugada1 described 8 patients with right bundle branch block, persistent right precordial ST-segment elevation, and aborted cardiac death. Those investigators suggested that this combination of findings represented a distinct syndrome of idiopathic ventricular fibrillation, now called the Brugada syndrome. The etiology and pathogenesis of the syndrome is controversial. Brugada and Brugada1 found no structural abnormality of the heart and suggested the presence of a functional electrical disease, whereas Martini et al2 suggested the presence of concealed right ventricular myocardial disease. Furthermore, Corrado et al3 recently reported that a familial cardiomyopathy that mainly involves the right ventricle and the conduction system underlies this syndrome. Because it is still unclear whether morphologic or histologic abnormalities are present in patients with Brugada syndrome, we investigated the morphologic and histologic changes in 6 patients with this syndrome. • • • We evaluated retrospectively the data on 6 Japanese men, aged 28 to 63 years, with the Brugada syndrome. They had been observed for 38 6 23 months (range 5 to 72). All had normal findings on physical examination and none exhibited any evidence of cardiac or extracardiac disease. Chest radiographs and laboratory values, including serum electrolytes, and the results of renal, hepatic, and thyroid tests were normal in all patients (Table I). All 6 patients had a history of recurrent episodes of aborted sudden cardiac death. Ventricular fibrillation was documented at least once during such episodes. A syncopal episode without any prodromal effects was the initial manifestation of the disease in 5 of the 6 patients. Thus, all but 1 patient (no. 2) were apparently healthy before the first episode of aborted sudden cardiac death. Patient 2 had a history of blackouts. The father of patient 3 died suddenly at age 55 years. In 5 patients, the first attack was followed by cardiocirculatory arrest requiring cardiopulmonary resuscitation and application of directcurrent countershock. No factor that could have triggered the episode of aborted sudden cardiac death could be identified in any case. None of the patients had a history of using narcotics or amphetamines. No patient was taking medication at the time of the first episode of syncope and cardiac arrest. Patient 2 died suddenly during follow-up. All patients exhibited sinus rhythm, right bundle branch block, and right precordial ST-segment elevation of either the coved or saddle-back type (Figure 1, Table I). The morphology of the ST elevation had not changed in 4 of the 6 patients (nos. 1 and 4 to 6). It had changed over time in the remaining 2 patients (nos. 2 and 3). The PR interval, the QT interval, and the rate-corrected QT (QTc) interval were all within normal limits (Table I). The results of coronary angiography and left ventriculography were normal in all patients. The response to the intracoronary ergonovine test was negative in all patients. Resting thallium-201 scintigraphy showed no myocardial damage in any patient. To evaluate the detailed morphologic changes of the heart, electron-beam computed tomography was performed with a C-100 or C-150 scanner (Imatron, San Francisco, California) as previously described4 in 5 patients. Volume-mode scanning (scanning time, 100 ms for 512 matrix images) and cine-mode scanning (scanning time, 50 ms for 256 matrix images) were performed after administration of a nonionic contrast medium (Iopamidol 370; Nippon Schering, Osaka, Japan). Initially, we performed serial volume-mode scanning (20 contiguous sections, 6-mm section thickness, 6-mm intervals) at end-systole (40% of the RR interval on the electrocardiogram). To examine the function of the left and right ventricles, 8-level (covering the entire heart) ‘‘near short-axis’’ cine-mode scans (10 contiguous images per level) were obtained with administration of a nonionic contrast medium. A modified version of Simpson’s method was used to obtain these multisection cine-mode scans. We then calculated the right and left ventricular end-diastolic volume index and ejection fractions. As a control, 13 control subjects (10 men and 3 women; mean age 46 6 12 years) also were studied, and the findings were compared between the 2 groups. Statistical analysis utilized 1-way analysis of variance with use of the Bonferroni simultaneous multiple comparison method to evaluate the significance of the differences among the means in the 2 groups. A p level ,0.05 was considered statistically significant. Representative findings obtained on electronbeam computed tomography are shown in Figure 2. Two patients (nos. 3 and 4) demonstrated a slight From the Divisions of Cardiology, Pathology, and Radiology, National Cardiovascular Center, Osaka; the Department of Internal Medicine, Saka General Hospital, Shiogama; and Department of Cardiovascular Medicine, Okayama University Medical School, Okayama, Japan. Dr. Tada’s address is: The Third Department of Internal Medicine, Fukui Medical School, 23 Shimoaizuki, Matsuoka-cho, Fukui 910-11, Japan. Manuscript received July 17, 1997; revised manuscript received and accepted November 11, 1997.