Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region.

All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML-RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPɛ and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML.

Nationwide survey on the prevalence of anti-tuberculosis drug resistance in the Republic of Yemen, 2004.

OBJECTIVES: To determine the prevalence of resistance to the four major anti-tuberculosis drugs, isoniazid, rifampicin, streptomycin and ethambutol, in Yemen. METHODS: Cluster sampling with probability proportionate to size was applied. Susceptibility to four major anti-tuberculosis drugs was examined. The proportion method using Löwenstein-Jensen medium or Ogawa medium was carried out. RESULTS: A total of 790 primary culture isolates from tuberculosis (TB) cases enrolled at the National Tuberculosis Institute, Yemen, were examined. In the confirmation culture at the supranational reference laboratory, 227 of them failed to grow on the secondary culture or were proved to be mycobacteria other than Mycobacterium tuberculosis and were excluded from further analysis. Among 563 cultures, 510 were obtained from new cases and 53 from previously treated cases. The prevalence of resistance to any four drugs was 9.8% (95%CI 7.0-12.5) among new cases and 17.4% (95%CI 12.0-33.5) among previously treated cases. The prevalence of multidrug-resistant TB was 3.0% (95%CI 1.5-4.5) among new cases and 9.4% (95%CI 0.2-18.7) among previously treated cases. CONCLUSION: The first nationwide prevalence survey on resistance to the four major anti-tuberculosis drugs in Yemen showed a relatively low prevalence of drug-resistant cases, but a high prevalence of multidrug resistance among new cases.

The national tuberculosis drug resistance survey in Cambodia, 2000-2001.

SETTING: Cambodia has a high incidence of tuberculosis (TB). Hospital-based DOTS was predominant throughout the country from 1994 to 2002. OBJECTIVES: To determine the prevalence of resistance to four major anti-tuberculosis drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SM), among new cases as a baseline before a new National Tuberculosis Programme strategy with decentralised ambulatory DOTS was widely implemented. DESIGN: A cluster sampling of TB diagnostic centres with probability proportional to the number of new cases in a diagnostic centre in 1999 was used. Intake of cases took place from October 2000 to April 2001. RESULTS: From 734 isolates collected, drug susceptibility test results were obtained for 638 new cases. The prevalence of resistance to any of four drugs was 10.1% (95%CI 7.7-13). Resistance to INH was 6.1% (95%CI 4.3-8.4) and resistance to RMP 0.6% (95%CI 0.2-1.6). No multidrug-resistant (MDR) case was found among the new cases (95%CI 0.0-0.6). Three of 96 previously treated cases had MDR (3.1%, 95%CI 1.0-9.0). CONCLUSION: The first survey indicates that the current prevalence of MDR is low. It is necessary to track resistance trends when restructuring a DOTS-based programme.

Operational conditions influencing the proficiency of AFB microscopy services in the Philippines.

SETTING: The microscopy services of the Philippine National Tuberculosis Programme (NTP). OBJECTIVE: To investigate how operational conditions in field microscopy centres (MC) affect proficiency. DESIGN: In 2004, a newly developed external quality assessment system (blinded rechecking) for acid-fast bacilli (AFB) microscopy employing lot quality assurance sampling (LQAS) was introduced into the NTP by the Philippine government. Performance reported by the quality assurance centres (QACs) of the four provinces and four cities was analysed. RESULT: There was no significant difference in rechecking results between small MCs examining fewer than 166 slides (500 slides/3 sputum samples per suspect) and larger MCs in the provinces. City MCs recorded better performance than those of the provinces. A city QAC covers only five MCs in average, whereas a provincial QAC covers 38. The average distance between city QACs and MCs is much shorter (3.2 km) than in the provinces (60.5 km). CONCLUSION: The number of MCs to be covered by each QAC and the distances between QAC and MCs are the dominant factors influencing the quality of AFB microscopy. Combining a few neighbouring MCs to reduce the number of MCs and/or provision of sufficient travel funds and timely use of vehicles, particularly in the provinces, are recommended.

Preparation of mycobacteria-containing artificial sputum for TB panel testing and microscopy of sputum smears.

SETTING: Panel testing, blinded cross rechecking and on-site evaluation are the three methods for external quality assessment (EQA) of acid-fast bacilli (AFB) smear microscopy. Panel testing can provide data on laboratory capabilities prior to implementing a rechecking programme, assess the current status of laboratory performance and detect problems associated with diagnostic performance. Thus far, two methods for preparing panel test slides have been reported: these use real AFB-positive and -negative sputum treated with sodium hydroxide (NaOH) or N-acetyl-L-cysteine (NALC). OBJECTIVE: To evaluate the above methods and to develop a new method to prepare panel test slides with artificial sputum. DESIGN: Panel test slides were prepared using the NaOH and NALC methods. New artificial sputum preparation methods were developed and examined using a cultured monocyte cell line, cultured avirulent mycobacteria and methylcellulose or polyacrylamide gel as substrate. Smears prepared by the four methods were compared. RESULTS: Panel test slides prepared with NaOH and NALC methods are not macroscopically or microscopically similar to real smears. Our new artificial sputum is similar to real sputum in viscosity and macroscopic and microscopic appearance; it is also consistent in panel positivity grades. CONCLUSION: The artificial sputum described here could contribute to the EQA and training in tuberculosis laboratories or microscopy centres.

Tuberculosis drug resistance and treatment outcomes under DOTS settings in large cities in the Philippines.

SETTING: Two large cities in the Philippines. OBJECTIVES: To describe the problems of drug-resistant tuberculosis (TB) in an urban setting, with special emphasis on their potential impact on the treatment services provided by the National TB Control Programme. DESIGN: Cross-sectional survey and cohort analysis of treatment outcomes. METHODS: All patients with positive sputum smear examination results in Cebu and Mandaue cities during the survey period were included. The survey procedures of the World Health Organization and the International Union Against Tuberculosis and Lung Disease were strictly applied. Treatment outcome data were also collected. RESULTS: Of 306 cases enrolled, 255 were new cases, 28 were previously treated and for 23 treatment history was unknown. Of the new cases, 72.2% were pan-susceptible to all four first-line anti-tuberculosis drugs. Resistance in new cases was 16.9% to isoniazid (INH), 4.7% to rifampicin (RMP), 3.1% to ethambutol, 18.0% to streptomycin, and 3.9% to at least both INH and RMP (multidrug-resistant [MDR]). Over 90% of the new cases, either pan-susceptible or mono-resistant, were successfully treated with the standard regimen, but four of nine MDR new cases could not be cured. CONCLUSION: The drug resistance level was high in this population, but treatment outcome using the standard treatment regimen was not seriously affected unless the patients were MDR.

New quantitative methods for evaluation of dynamic changes in QT interval on 24 hour Holter ECG recordings: QT interval in idiopathic ventricular fibrillation and long QT syndrome.

OBJECTIVES: To introduce a nomogram of the normal QT interval at various heart rates measured from 24 hour Holter ECG recordings in healthy subjects with respect to age and sex and to use the nomogram to characterise dynamic changes in QT interval in patients with idiopathic ventricular fibrillation (IVF) and the long QT syndrome (LQT). METHODS: The study group consisted of 422 subjects: 249 healthy men ranging in age from 21-88 years (mean (SD) 47 (20) years) and 173 healthy women ranging in age from 21-85 years (47 (19) years). In addition, seven men with IVF ranging in age from 33-53 years (43 (9) years) and five women with LQT ranging in age from 20-55 years (37 (14) years) were studied. For each subject, QT interval and heart rate were determined automatically from 24 hour Holter ECG digital data-namely, QT interval was measured from signal averaged ECG waves obtained by averaging consecutive sinus beats during each 15 second period over 24 hours. Data were grouped and averaged at an interval of 5 beats/min for heart rates ranging from 46-120 beats/min. RESULTS: In healthy subjects aged < 50 years and > or = 50 years QT intervals were longer in women than in men. QT intervals were longer in both men and women aged > or = 50 years than in ages < 50 years. From these findings a nomogram of QT interval at varying heart rates adjusted for age (younger group aged < 50 years or older group aged > or = 50 years) and sex was determined. In patients with IVF, QT intervals were significantly shorter at slower heart rates than normal values obtained from the nomogram. In patients with LQT, QT intervals were significantly longer at both faster and slower heart rates than normal values. CONCLUSIONS: The nomogram of QT interval at varying heart rates adjusted for sex and age could be used to assess dynamic changes of QT interval of various pathological conditions. For example, patients with IVF had shorter QT interval at slower heart rates, a finding suggestive of arrhythmogenicity of this specific syndrome at night. Patients with LQT had prolonged QT interval at specific heart rate ranges depending on their genotype.

The nationwide tuberculosis drug resistance survey in Mongolia, 1999.

SETTING: Mongolia, a country in the Western Pacific Region burdened with many cases of tuberculosis, with rapid expansion of DOTS over the last several years. OBJECTIVE: To determine the prevalence of resistance to major anti-tuberculosis drugs among tuberculosis patients who have never been treated previously. DESIGN: Sputum specimens were collected from all smear-positive tuberculosis patients identified from 1 November 1998 to 1 May 1999. RESULTS: Resistance to any of the four major drugs (streptomycin, isoniazid, rifampicin, and ethambutol) was as high as 28.9% (95%CI 24.7-33.5), primarily due to high streptomycin resistance of 24.2% (95%CI 20.3-28.6). Isoniazid resistance was also high, at 15.3% (95%CI 12.1-19.1). Resistance levels to ethambutol and rifampicin were relatively low, at 1.7% (95%CI 0.8-3.5) and 1.2% (95%CI 0.5-2.9), presumably because these drugs were only recently introduced into Mongolia. Multidrug resistance was also rare, at 1.0% (95%CI 0.1-1.8). Drug resistance rates were higher in middle-aged patients than in younger and older age groups combined (P = 0.006). Males tended to have higher resistance than females, although this was of statistically marginal significance (P = 0.08). No significant regional differences in drug resistance were found. CONCLUSION: While multidrug resistance was rare, isoniazid resistance was very common, which necessitates closer monitoring of the treatment outcomes of individual patients as well as long-term follow-up for drug resistance on a nationwide scale.

Quality control of sputum smear examination in Cebu Province.

SETTING: Rural Health Units (RHUs) in Cebu Province, Philippines. OBJECTIVE: To assess and improve the on-going quality control of tuberculosis activities in Cebu Province. METHODS: During the period of the study, from January 1996 to December 1997, positive slides (100% in 1996 and 20% or 100% in 1997) and 20% of negative slides selected from all of the slides examined at the RHUs were assessed on the quality of smear preparation. The readings were blindly cross-checked by the provincial assessors. RESULTS: In 1997, 1) 90% of RHUs participated in the quality control activity; 2) the proportion of good quality smears increased markedly; and 3) the false positive and false negative rates did not change during the period, but most of the false positives were observed among the scanty positives of the field reading, and no false negatives were noted among the heavily positive slides. CONCLUSION: Although the false positive and negative rates did not decrease during the period, the quality control procedure resulted in marked improvements in smear preparation, a high participation of RHUs in the quality control programme and the elimination of large discrepancies between readers on positive slides in 1997. It is considered to have significantly improved the NTP's smear microscopy service in Cebu Province.

Radiofrequency ablation at the coronary sinus ostium interrupts the vagal efferent input to the atrioventricular node in the canine heart.

The fat pad at the junction of the inferior vena cava and inferior left atrium is the area of convergence of vagal projections into the atrioventricular node (AVN) region. The present study investigated whether radiofrequency (RF) ablation applied to the area around the coronary sinus (CS) ostium would impair vagal input to the AVN in the canine heart. Twenty-four dogs were anesthetized by sodium pentobarbital and RF energy was delivered at 20W for 5-10s. In the baseline state without vagal stimulation (10Hz, 2ms), the electrophysiological variables did not change significantly after RF ablation. Vagally induced changes in the sinus cycle length and effective refractory period of the right atrium and left ventricle did not differ after RF ablation. However, the effects of vagal stimulation on the AVN function were impaired after RF ablation to the CS area from the ostium to 10mm within the ostium. After ablation was applied to the fast pathway area, the vagally induced changes in the AVN function decreased, but these changes were not affected after RF ablation in the slow pathway area. RF ablation in the vicinity of the CS would attenuate vagal input to the AVN.

Relation of fibrillatory wave amplitude with hemostatic abnormality and left atrial appendage dysfunction in patients with chronic nonrheumatic atrial fibrillation.

Large left atrium (LA) and LA appendage (LAA) dysfunction are known to relate to cardiogenic thromboembolism, so the present study investigated the relation of the atrial fibrillatory wave (F wave) amplitude to hemostatic markers and LAA function. Transthoracic and transesophageal echocardiographic studies were performed in 82 consecutive patients with chronic, nonrheumatic atrial fibrillation (AF). Patients were divided into 2 groups according to F wave amplitude in lead V1 on the 12-lead ECG: coarse AF (the greatest amplitude of F wave > or =1 mm, n=44) and fine AF (<1 mm, n=38). Plasma levels of thrombin-antithrombin III complex, D-dimer, platelet factor 4 and beta-thromboglobulin were determined. Compared with patients with coarse AF, those with fine AF had lower LAA peak flow velocity (p<0.05) and higher prevalence of embolic cerebral infarction (50% vs 27%, p<0.05). Platelet activity did not differ between the 2 groups; however, plasma levels of thrombin-antithrombin III complex and D-dimer were significantly higher in patients with fine AF than in those with coarse AF (p<0.05). Multiple logistic regression analysis showed that fine AF was independently associated with cerebral embolism. Therefore, the presence of fine F wave in V1 would be a useful marker of LAA dysfunction and hypercoagulability, and indicate a risk for cerebral embolism in patients with chronic, nonrheumatic AF.

Modulation of ventricular repolarization and R-R interval is altered in patients with globally impaired cardiac 123I-MIBG uptake.

BACKGROUND: Cardiac (123)I-metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. METHODS: Twenty-nine patients with prior myocardial infarction were divided into two groups by a heart-to-mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M >or= 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holter recording and a standard 12-lead electrocardiography were used for evaluation of HRV, QT-RR relation, and QT dispersion. RESULTS: Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT-RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 +/- 25 msec) than in group II (43 +/- 19 msec) and group III (28 +/- 9 msec). CONCLUSION: These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.

Spectral characteristics of human atrial fibrillation waves of the right atrial free wall with respect to the duration of atrial fibrillation and effect of class I antiarrhythmic drugs.

The aim of this study was to use fast Fourier transform analysis to clarify the characteristics of human atrial fibrillation (AF) waves with respect to the duration of AF and the effect of class I antiarrhythmic drugs. Twenty-two patients (10 paroxysmal AF, 12 persistent AF) without organic heart disease were studied by conventional electrophysiological methods. Electrograms were recorded from the right atrial free wall during AF and spectral analysis was performed for 35s (16 consecutive 4096-ms epochs with 50% overlap) and the fibrillation cycle length (FCL) was calculated from the peak frequency. Mean FCL and SD were determined from 16-epoch data, and the temporal variability of FCL was defined as the SD of FCL. Paroxysmal AF had a longer mean FCL than persistent AF (178+/-26ms vs 139+/-16 ms, p<0.001) and AF duration had a significant inverse correlation with mean FCL (r=-0.79, p<0.001). The temporal variability of FCL was significantly greater in paroxysmal AF than in persistent AF (p<0.05) and there was a significant positive correlation between the mean FCL and the temporal variability of FCL (r=0.66, p<0.001). In 8 of 18 patients given a class I antiarrhythmic drug (cibenzoline or procainamide), AF was terminated and in those patients the mean FCLs before administration of class I drugs were significantly greater than in patients without AF termination. With respect to mean FCL before drug administration, conversion occurred in 100% of patients with FCL > or =168 ms and in 17% of those with FCL <168 ms. A longer duration of AF shortens the mean FCL, which is consistent with atrial electrical remodeling. Class I drugs prolong the mean FCL above a critical level and will terminate AF, which can be estimated from the mean FCL before drug administration.

Spontaneous onset of torsade de pointes in long-QT syndrome and the role of sympathovagal imbalance.

The net effects of sympathetic and vagal activity on the QT interval and the mode of spontaneous onset of torsade de pointes (TdP) are still unclear in long-QT syndrome. Two patients with long-QT syndrome had syncope while undergoing Holter ECG investigation. The spontaneous onset of TdP in these patients was analyzed with respect to the relation between the RR and QT intervals. Both patients were high-school students (16- and 17-year-old boys) who had been diagnosed as long-QT syndrome and followed up without medical treatment because they had had neither a history of syncope nor arrhythmia induction by treadmill exercise tests. The first episode of syncope in both patients occurred during ordinary daily life and was not related to exercise or psychological stress. The dynamic changes between the RR and QT intervals associated with the spontaneous onset of TdP were analyzed by Holter ECG. Both patients showed sinus tachycardia followed by abrupt sinus bradycardia immediately before the onset of TdP. The enhanced rate of the adaptive response of the QT interval that occurred during the deceleration of the heart rate preceded the onset of TdP. These observations suggest that the complex situation that follows sympathovagal imbalance may have an important role in the dynamic change in the QT interval and initiation of TdP in patients with long-QT syndrome.

[Abnormal Q wave in the right precordial leads unmasked during right bundle branch block in a patient with anteroseptal myocardial infarction: a case report].

Electrocardiography in a 77-year-old woman showed small R waves in leads V1-V3 3 hours after the onset of acute anteroseptal myocardial infarction. Abnormal Q waves appeared in leads V1-V3 only during intermittent right bundle branch block. The normal septal force disappeared after transmural septal infarction and a small force of right ventricle origin became apparent as a small R wave in V1. Right bundle branch block delayed activation of right ventricle, and thereby deleted the initial R wave and unmasked the Q wave of the septal infarction. Appearance of a Q wave in leads V1-V3 with right bundle branch block should not be assumed to reflect the extension of myocardial infarction.

Electrophysiological mechanisms of conversion of typical to atypical atrioventricular nodal reentrant tachycardia occurring after radiofrequency catheter ablation of the slow pathway.

This report presents an adult patient with conversion of typical to atypical atrioventricular nodal reentrant tachycardia (AVNRT) after slow pathway ablation. Application of radiofrequency energy (3 times) in the posteroseptal region changed the pattern of the atrioventricular (AV) node conduction curve from discontinuous to continuous, but did not change the continuous retrograde conduction curve. After ablation of the slow pathway, atrial extrastimulation induced atypical AVNRT. During tachycardia, the earliest atrial activation site changed from the His bundle region to the coronary sinus ostium. One additional radiofrequency current applied 5 mm upward from the initial ablation site made atypical AVNRT noninducible. These findings suggest that the mechanism of atypical AVNRT after slow pathway ablation is antegrade fast pathway conduction along with retrograde conduction through another slow pathway connected with the ablated antegrade slow pathway at a distal site. The loss of concealed conduction over the antegrade slow pathway may play an important role in the initiation of atypical AVNRT after slow pathway ablation.

Effects of unilateral stellate ganglion block on the spectral characteristics of heart rate variability.

The effect of unilateral stellate ganglion block on cardiovascular regulation remains controversial, so the present study used power spectral analysis of heart rate variability to investigate its effect on the autonomic neural control of the heart. In 20 young healthy volunteers (mean age: 25 years), heart rate variability was determined before and after unilateral stellate ganglion block (right side 11, left side 9) using 8 ml of 1% mepivacaine during supine rest. Using autoregressive spectrum analysis, power spectra were quantified by measuring the area in 3 frequency bands: high-frequency power (lnHF, parasympathetic influence) from 0.15 to 0.40 Hz, low-frequency power (lnLF, predominantly sympathetic influence) from 0.04 to 0.15 Hz, and total-frequency power (lnTF) less than 0.40 Hz. Right stellate ganglion block decreased not only the lnLF component from 6.55+/-0.84 to 5.77+/-0.47 but also the lnHF component from 4.40+/-0.95 to 3.42+/-1.12 (p<0.05). In contrast, left stellate ganglion block changed neither the lnLF nor the lnHF component. The lnTF component was also decreased significantly by right stellate ganglion block from 7.80+/-0.95 to 7.01+/-0.36 (p<0.05), but was unchanged following left stellate ganglion block. Neither right nor left stellate ganglion block induced any significant change in both the RR and corrected QT intervals. However, changes in the RR interval induced by right stellate ganglion block showed significant positive correlation with changes in lnHF (p<0.005) and lnTF (p<0.05). These results suggest that (1) autonomic innervation to the sinus node is mainly through the right-sided stellate ganglion, (2) pharmacological right-sided stellate ganglion block may attenuate not only sympathetic but also parasympathetic activity and (3) following right stellate ganglion block the decrease in both the sympathetic and parasympathetic influence on the sinus node may inconsistently counterbalance and change the RR interval.

Changes in autonomic nervous activity after catheter ablation of right ventricular outflow tract tachycardia.

Idiopathic right ventricular outflow tract (RVOT) tachycardia is prone to occur when sympathetic nervous activity increases. The effects of catheter ablation on the arrhythmia may be modified by changes in the sympathovagal balance induced by the ablation. In 8 patients with RVOT tachycardia, analyses of heart rate variability (HRV) were performed before, early (1-3 days, POST1) and late (7-14 days, POST2) after the ablation. From 24-h ambulatory Holter monitoring, RR intervals of a 2-h period during sleep (00.00-06.00 h) were analyzed. MSSD and pNN50 were increased along with a decrease in the frequency of ventricular arrhythmias at both POST1 and POST2 after successful ablation. In contrast, high frequency power (HF) was increased, and low frequency power (LF) and LF/HF were decreased only at POST2 in the 8 patients. In 4 patients in whom the initial ablation had been unsuccessful, the indices of HRV did not change significantly after the unsuccessful ablation, but after successful ablation they changed as in the other 4 patients. After successful catheter ablation of the RVOT tachycardia, sympathetic nervous activity was decreased and parasympathetic nervous activity was increased along with decrease in the frequency of ventricular arrhythmias. The presence of ventricular tachyarrhythmia could, therefore, elicit sympathetic predominance and consequently modify arrhythmogenesis.

Circadian variation of idiopathic ventricular tachycardia originating from right ventricular outflow tract.

We determined circadian variation of isolated ventricular premature complexes (VPCs), 2 to 4 consecutive VPCs, and ventricular tachycardia (5 consecutive VPCs) originating from the right ventricular outflow tract in patients without apparent structural heart diseases. There was apparent circadian variation with 2 prominent peaks for these ventricular arrhythmias, and blockade abolished ventricular tachycardia and attenuated the circadian variation of consecutive VPCs.

ST segment elevation in the right precordial leads induced with class IC antiarrhythmic drugs: insight into the mechanism of Brugada syndrome.

We evaluated two patients without previous episodes of syncope who showed characteristic ECG changes similar to Brugada syndrome following administration of Class IC drugs, flecainide and pilsicainide, but not following Class IA drugs. Patient 1 had frequent episodes of paroxysmal atrial fibrillation resistant to Class IA drugs. After treatment with flecainide, the ECG showed a marked ST elevation in leads V2 and V3, and the coved-type configuration of ST segment in lead V2. A signal-averaged ECG showed late potentials that became more prominent after flecainide. Pilsicainide, a Class IC drug, induced the same ST segment elevation as flecainide, but procainamide did not. Patient 2 also had frequent episodes of paroxysmal atrial fibrillation. Pilsicainide changed atrial fibrillation to atrial flutter with 2:1 ventricular response, and the ECG showed right bundle branch block and a marked coved-type ST elevation in leads V1 and V2. After termination of atrial flutter, ST segment elevation in leads V1 and V2 continued. In this patient, procainamide and quinidine did not induce this type of ECG change. In conclusion, strong Na channel blocking drugs induce ST segment elevation similar to Brugada syndrome even in patients without any history of syncope or ventricular fibrillation.