Homogeneous human complex-type oligosaccharides in correctly folded intact glycoproteins: evaluation of oligosaccharide influence on protein folding, stability, and conformational properties.

The N-glycosylation of proteins is generated at the consensus sequence NXS/T (where X is any amino acid except proline) by the biosynthetic process, and occurs in the endoplasmic reticulum and Golgi apparatus. In order to investigate the influence of human complex-type oligosaccharides on counterpart protein conformation, crambin and ovomucoide, which consist of 46 and 56 amino acid residues, respectively, were selected for synthesis of model glycoproteins. These small glycoproteins were intentionally designed to be glycosylated at the α-helix (crambin: 8 position), ß-sheet (crambin: 2 position) and loop position between the antiparallel ß-sheets (ovomucoide: 28 position), and were synthesized by using a peptide-segment coupling strategy. After preparation of these glycosylated polypeptide chains, protein folding experiments were performed under redox conditions by using cysteine-cystine. Although the small glycoproteins bearing intentional glycosylation at the α-helix and ß-sheet exhibited a suitable folding process, glycosylation at the loop position between the antiparallel ß-strands caused multiple products. The conformational differences in the isolated homogeneous glycoproteins compared with non-glycosylated counterparts were evaluated by circular dichroism (CD) and NMR spectroscopy. These analyses suggested that this intentional N-glycosylation did not result in large conformational changes in the purified protein structures, including the case of glycosylation at the loop position between the antiparallel ß-strands. In addition to these experiments, the conformational properties of three glycoproteins were evaluated by CD spectroscopy under different temperatures. The oligosaccharides on the protein surface fluctuated considerably; this was dependent on the increase in the solution temperature and was thought to disrupt the protein tertiary structure. Based on the measurement of the CD spectra, however, the glycoproteins bearing three disulfide bonds did not exhibit any change in their protein tertiary structure. These results suggest that the oligosaccharide conformational fluctuations were not disruptive to protein tertiary structure, and the tertiary structure of glycoproteins might be stabilized by the disulfide bond network.

Molecular characterization and gene disruption of a novel zinc-finger protein, HIT-4, expressed in rodent brain.

To identify a novel regulatory factor involved in brain development or synaptic plasticity, we applied the differential display PCR method to mRNA samples from NMDA-stimulated and un-stimulated neocortical cultures. Among 64 cDNA clones isolated, eight clones were novel genes and one of them encodes a novel zinc-finger protein, HIT-4, which is 317 amino acid residues (36-38 kDa) in length and contains seven C2H2 zinc-finger motifs. Rat HIT-4 cDNA exhibits strong homology to human ZNF597 (57% amino acid identity and 72% homology) and identity to rat ZNF597 at the carboxyl region. Furthermore, genomic alignment of HIT-4 cDNA indicates that the alternative use of distinct promoters and exons produces HIT-4 and ZNF597 mRNAs. Northern blotting revealed that HIT-4 mRNA (approximately 6 kb) is expressed in various tissues such as the lung, heart, and liver, but enriched in the brain, while ZNF597 mRNA (approximately 1.5 kb) is found only in the testis. To evaluate biological roles of HIT-4/ZNF597, targeted mutagenesis of this gene was performed in mice. Homozygous (-/-) mutation was embryonic lethal, ceasing embryonic organization before cardiogenesis at embryonic day 7.5. Heterozygous (+/-) mice were able to survive but showing cell degeneration and vacuolization of the striatum, cingulate cortex, and their surrounding white matter. These results reveal novel biological and pathological roles of HIT-4 in brain development and/or maintenance.

Preservation of renal function in response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) has recently been introduced as a new option for patients with severe heart failure, but its effect on renal function remains unclear. METHODS AND RESULTS: Twenty-three patients receiving CRT were studied. Responders were those who showed >0% increase in left ventricular ejection fraction after CRT by echocardiography. Clinical parameters, echocardiographic measurement, renal function, and prescriptions were examined before and 3 months after CRT, and the relationship between the response to CRT and renal function was examined. The responders had a better prognosis than the non-responders (p<0.05). There was a significant difference in the change in the estimated glomerular filtration rate between the responders and non-responders (p<0.05), even in patients with renal dysfunction before CRT (p<0.01). Prescriptions of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) were 100% in the CRT responders and 60% in the non-responders (p<0.05). Up-titration of beta-blockers could be significantly achieved in the CRT responders compared with the non-responders (p<0.05). CONCLUSIONS: Preservation of renal function was observed in the responders to CRT, even in patients with renal dysfunction. Prescription of ACEI/ARB and up-titration of beta-blockers increased in the CRT responders. These results may contribute to the beneficial effects of CRT.

Clinical characteristics, treatment, and outcome of tachycardia induced cardiomyopathy.

Tachycardia-induced cardiomyopathy is characterized by ventricular systolic dysfunction and congestive heart failure resulting from persistent or highly frequent tachyarrhythmias with uncontrolled heart rate. While reversible and often considered benign, few studies have examined the outcome of the disorder. The clinical characteristics, treatment, and long-term outcomes of 12 consecutive patients with tachycardia-induced cardiomyopathy (9 men, age, 51.9 +/- 17.6 years) were studied. The mean period between the occurrence of tachyarrhythmias and the development of congestive heart failure was 26.0 +/- 34.3 days. The mean heart rate on admission was 156.3 +/- 28.7 beats/min. All patients had severe heart failure with a NYHA functional class of 2.3 +/- 0.5, left ventricular ejection fraction of 0.32 +/- 0.10, and brain natriuretic peptide level of 505.7 +/- 449.1 pg/mL. In all patients, cardiac dysfunction recovered after 53.5 +/- 61.3 days. During the follow-up of 53 +/- 24 months, 2 patients had a recurrence of heart failure with uncontrolled tachyarrhythmia and 1 patient died suddenly. In tachycardia-induced cardiomyopathy, recurrent heart failure with uncontrollable tachyarrhythmia and sudden death were observed after recovery from cardiac dysfunction. A substrate for heart failure and/or life-threatening arrhythmia might persist, and careful, long-term follow-up seems required.

Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies.

The chemical synthesis of complex glycoproteins is an ongoing challenge in protein chemistry. We have examined the synthesis of a single glycoform of monocyte chemotactic protein-3 (MCP-3), a CC-chemokine that consists of 76 amino acids and one N-glycosylation site. A three-segment native chemical ligation strategy was employed using unprotected peptides and glycopeptide. Importantly, the synthesis required the development of methods for the generation of sialylglycopeptide-alphathioesters. For the sialylglycopeptide-alphathioester segment, we examined and successfully implemented approaches using Fmoc-SPPS and Boc-SPPS. To avoid use of hydrogen fluoride, the Boc approach utilized minimal side chain protection and direct thiolysis of the resin bound peptide. Using these strategies, we successfully synthesized a glycoprotein having an intact and homogeneous complex-type sialyloligosaccharide.

Effect of dl-sotalol on mortality and recurrence of ventricular tachyarrhythmias: ischemic compared to nonischemic cardiomyopathy.

OBJECTIVE: We compared the effectiveness of sotalol on mortality and the recurrence of ventricular tachyarrhythmia (VTA) between idiopathic dilated cardiomyopathy (IDCM) and coronary artery disease (CAD). PATIENTS: Forty patients with spontaneous VTA and induced VTA associated with CAD (n = 23) and IDCM (n = 17) were studied. In all patients, sotalol was prescribed and an electrophysiologic study (EPS) was performed to evaluate its effect on the induction of VTA. There were no significant differences in left ventricular ejection fraction (LVEF) between CAD and IDCM (35%+/- 10% vs. 35%+/- 12%). RESULTS: After sotalol, there were no significant differences in the QTc interval on electrocardiogram (ECG) or in the effective refractory period in the apex of the right ventricle between the two groups, but sotalol was more effective in preventing the induction of VTA in CAD than in IDCM (65% vs. 29%; P < 0.05). During a mean follow-up period of 47 +/- 27 months, the overall VTA recurrence rate was significantly lower in CAD than in IDCM (P < 0.01). The all-cause mortality rate tended to be lower in CAD than in IDCM, but the difference was not significant (P = 0.07). Electrical storm (ES) occurred more frequently in IDCM than in CAD, (41% vs. 13%; P < 0.05), and all patients with ES (n = 10) failed to respond to sotalol as assessed by EPS. CONCLUSION: Sotalol reduced the overall VTA recurrence rate and all-cause mortality more in CAD than in IDCM.

Comparison of conduction delay in the right ventricular outflow tract between Brugada syndrome and right ventricular cardiomyopathy: investigation of signal average ECG in the precordial leads.

BACKGROUND: In both Brugada syndrome (BS) and arrhythmogenic right ventricular cardiomyopathy (ARVC), electrical abnormalities in the right ventricular outflow tract (RVOT) are important for arrhythmogenesis. OBJECTIVES: The aim of this study was to compare conduction delay in the right ventricular in BS with that in ARVC using the signal-averaged electrocardiogram. METHODS: Twenty patients with BS (18 men and 2 women; 55 +/- 12 years old; 9 symptomatic and 11 asymptomatic) and eight patients with ARVC (six men and two women; 53 +/- 16 years old) were included. We assessed the presence of late potentials (LPs) and the filtered QRS duration (fQRSd) in V(2) and V(5) using a high-pass filter of 40 Hz (fQRSd:40) and 100 Hz (fQRSd:100). RESULTS: In ARVC, there was no significant difference in fQRSd:40 between V2 and V5 (158 +/- 19 vs. 145 +/- 17 ms, respectively): however, in BS, fQRSd:40 in V2 was significantly longer than fQRSd:40 in V5 (147 +/- 15 vs. 125 +/- 10 ms, P < 0.001). In ARVC, there was no significant difference between fQRSd:40 and fQRSd:100 in V(2) and V(5) (158 +/- 19 vs. 142 +/- 23 ms and 145 +/- 17 vs. 132 +/- 9 ms, respectively). In contrast, in BS, fQRSd:100 was significantly shorter than fQRSd:40 in V2 (110 +/- 8 ms vs. 147 +/- 15, P < 0.001). The relative decrease in fQRSd:100 compared with fQRSd:40 in V2 was significantly greater in BS than in ARVC. CONCLUSION: The dominant prolongation of the fQRSd in the right precordial lead in BS was different from the characteristics of ARVC, which may be caused by the conduction delay due to fibro-fatty replacement in RV.

Incidence and initial characteristics of pilsicainide-induced ventricular arrhythmias in patients with Brugada syndrome.

BACKGROUND: In patients with Brugada syndrome, class I antiarrhythmic drugs can trigger ventricular arrhythmias (VA). The incidence and initial characteristics of VA that developed after pilsicainide was examined in 28 patients with Brugada-type electrocardiographic (ECG) abnormalities and with a positive response in the pilsicainide test. The clinical outcome was also compared between patients with and without pilsicainide-induced VA. METHODS AND RESULTS: In all patients, pilsicainide increased ST segment elevation and accentuated type 1 ECG changes. Ventricular tachycardia (VT) developed in 3 patients and premature ventricular complexes (PVC) in 2 other patients. These 5 patients (group I) had higher ST segment elevation in lead V2 on the ECG at baseline and after pilsicainide and showed a longer QTc interval after pilsicainide than the other 23 patients (group II). However, there was no difference between the 2 groups regarding incidence of prior cardiac events, results of signal-averaged ECG, HV interval, inducibility of ventricular fibrillation by programmed electrical stimulation, or QRS duration. In 1 patient, PVC originated from 3 sites, 2 of which triggered polymorphic VT. The right ventricular (RV) outflow tract was the origin of 2 types of PVC, and other RV sites of 5 other types. During a 45 +/- 37 months follow-up, polymorphic VT recurred in 2 patients in group II. CONCLUSIONS: Pilsicainide induced VA in some patients with Brugada syndrome, but this result may not be used as a parameter of the risk stratification of Brugada syndrome. Multiple PVC induced by pilsicainide and triggering polymorphic VT originated from several RV sites is an important factor when considering patients for treatment with catheter ablation.

Bepridil for drug-refractory ventricular tachyarrhythmias.

AIMS: To avoid frequent discharges of implantable cardioverter defibrillators, antiarrhythmic drugs may be needed in some patients with ventricular tachyarrhythmias. For ventricular tachyarrhythmias refractory to conventional antiarrhythmic drugs, we evaluated the efficacy of bepridil, a multiple ion-channel blocker. METHODS AND RESULTS: Sixteen patients with structural heart disease and ventricular tachyarrhythmias refractory to multiple antiarrhythmic drugs (4.1+/-1.6 drugs including class III drugs) were enrolled. Bepridil was prescribed at a mean dose of 156+/-40 mg/day. Bepridil prolonged the QT/QTc interval without affecting heart rate or the QRS duration. During a mean follow-up of 52+/-44 months, bepridil completely suppressed ventricular tachyarrhythmias in 6 of the 16 patients (38%) and the drug decreased the frequency of ventricular tachyarrhythmia recurrences by >75% in 3 of the other 10 patients. The markers of complete suppression of ventricular tachyarrhythmias during bepridil treatment included a smaller number of VT morphologies, a better NYHA functional class, and a greater drug-induced prolongation of the QT/QTc interval. The result of electrophysiologic study-guided evaluation of bepridil was closely associated with the clinical efficacy of bepridil in 7 of 8 patients. CONCLUSION: Bepridil appears to be useful to suppress drug-refractory ventricular tachyarrhythmia recurrence.

Over-expression of Kv1.5 in rat cardiomyocytes extremely shortens the duration of the action potential and causes rapid excitation.

BACKGROUND: Genetically abnormal action potential duration (APD) can be a cause of arrhythmias that include long and short QT interval syndrome. PURPOSE: The aim of this study was to evaluate the arrhythmogenic effect of short QT syndrome induced by the over-expression of Kv1.5 in rat. METHODS: From Sprague-Dawley rats on fetal days 18-19, cardiomyocytes were excised and cultured with and without transfection with the Kv-1.5 gene using an adenovirus vector. The expression of Kv1.5 was proven by immunohistochemistry and Western blot analysis. In the culture dish and in the whole cells, the electrical activities were recorded using the whole-cell patch-clamp technique and the effects of 4-AP and verapamil were tested. RESULTS: After transfection with Kv1.5 for 12h, immunohistochemical staining and Western blot analysis were positive for Kv1.5 while they were negative in the control transfected with only Lac-Z. In the culture dish, the myocytes showed spontaneous beating at 115beats/min (bpm) just prior to the transfection with Kv1.5 and increased to 367bpm at 24h. The control myocytes showed stable beating rates during culturing. 4-AP at 200microM slowed down the rate and verapamil abolished the beating. In the whole cells, the maximal resting membrane potential was slightly depolarized and APD was extremely abbreviated both at 50% and 90% of repolarization compared with those of the control. Rapid spontaneous activities were found in a single myocyte with Kv1.5 transfection and 4-AP slowed down the frequency of the activities with a reversal of the shortened APD. CONCLUSION: The over-expression of Kv1.5 induced short APD and triggered activities in rat cardiomyocytes. This model can be used to study the arrhythmogenic substrate of short QT syndrome.

Comparison of efficacy of sotalol and nifekalant for ventricular tachyarrhythmias.

BACKGROUND: Suppression of implantable defibrillator discharges associated with ventricular tachyarrhythmia (VTA) has been reported for sotalol. This study aimed to investigate the efficacy of intravenous nifekalant hydrochloride in predicting the effects of oral sotalol. METHODS AND RESULTS: The present study included 14 patients who had sustained VTA associated with structural heart disease. All patients also had inducible VTA. To compare the effects of nifekalant and sotalol, programmed electrical stimulation was performed, in the basal state, after nifekalant administration, and after sotalol administration. Nifekalant and sotalol similarly prolonged the corrected QT interval and ventricular effective refractory periods, but the heart rate was slowed by sotalol only. In 4 of 5 patients whose VTA became non-inducible by nifekalant, subsequent treatment with sotalol also suppressed the inducible VTA. In all of the 9 patients non-responding to nifekalant, VTA remained inducible during sotalol treatment. Nifekalant accurately predicted the response to sotalol during electrophysiologic study in 13 of 14 patients. Of 11 patients who remained on sotalol, VTA recurred in 3 non-responders during a follow-up of 46 +/- 11 months. CONCLUSIONS: Nifekalant and sotalol had similar effects on inducible VTA. The response of inducible VTA to nifekalant may predict the clinical efficacy of sotalol.

Ventricular tachycardia late after repair of congenital heart disease: efficacy of combination therapy with radiofrequency catheter ablation and class III antiarrhythmic agents and long-term outcome.

OBJECTIVE: This study investigated the treatment of ventricular tachycardia (VT) after repair of tetralogy of Fallot or double outlet of the right ventricle. BACKGROUND: The ideal antiarrhythmic therapy for VT in patients after repair of congenital heart disease, especially without left ventricular dysfunction, has not yet been established. METHODS: Seven consecutive patients (2 women and 5 men) with stable monomorphic sustained VT were investigated. The mean age was 25 +/- 7 years (range, 16-35 years). Four patients had undergone surgical repair of tetralogy of Fallot, and 3 had surgical correction of double outlet of the right ventricle at the mean age of 18 +/- 7 years (range, 9-27 years) before documentation of the arrhythmia. RESULTS: The mean ejection fraction of the left ventricle was 60% +/- 8% (range, 50-72). Fourteen sustained monomorphic VTs were induced in 7 patients using programmed electrical stimulation. The mean cycle length of tachycardia was 346 +/- 77 milliseconds (range, 260-480 seconds). The site of the surgical correction of the right ventricle was associated with the origin of VT in all patients. Radiofrequency catheter ablation was attempted in 8 VTs in 7 patients: 7 clinical and 1 nonclinical VTs. In 6 patients, class III antarrhythmic agents were added because VT remained inducible after ablation. During a follow-up of 61 +/- 29 months (range, 15-110 months), there were no recurrences of VT. CONCLUSION: In patients with drug-refractory VT originating from the right ventricle late after congenital heart disease, and when their left ventricular function do not deteriorate, combined therapy for radiofrequency catheter ablation with class III antiarrhythmic agents might effective and should be considered as a therapeutic option.

Elimination of late potentials by quinidine in a patient with Brugada syndrome.

The beneficial effects of quinidine on ST-segment elevation, inducible ventricular tachyarrhythmias, and episodes of ventricular tachyarrhythmia have been reported in Brugada syndrome. This is the first report describing quinidine-induced elimination of the late potential, which is considered one of the parameters for an arrhythmic event, in a patient with Brugada syndrome.

Nifekalant hydrochloride suppresses severe electrical storm in patients with malignant ventricular tachyarrhythmias.

BACKGROUND: Some patients with an implantable cardioverter-defibrillator (ICD) suffer from burst of inappropriate multiple discharges (severe electrical storm), and because the current therapeutic options are limited, the effect of nifekalant hydrochloride, a new class III drug, on severe electrical storm was investigated in the present study. METHODS AND RESULTS: Ninety-one consecutive patients treated with ICD were included in the study (M 70; mean age 58 years; left ventricular ejection fraction 45+/-15%). Severe electrical storm was defined as more than 10 ICD discharges within 1 h. During a mean follow-up period of 30+/-13 months, 41/91 (45%) patients had appropriate ICD therapy for arrhythmias and severe electrical storm occurred in 11 of them (12%) at 20+/-18 months after ICD implantation. The mean number of ICD discharges/h during severe electrical storm was 18+/-12. In 4 of 10 patients, severe electrical storm was successfully suppressed by a combination of deep sedation and beta-blocking agent; 6 other patients were refractory to this treatment, but severe electrical storm was successfully suppressed by intravenous administration of nifekalant hydrochloride with no adverse effects. CONCLUSIONS: Nifekalant hydrochloride is an effective and safe treatment for severe electrical storm.

Inappropriate discharges of intravenous implantable cardioverter defibrillators owing to lead failure.

We describe here the case of a 58-year-old female patient who experienced inappropriate shocks from her implantable cardioverter-defibrillator (ICD). Stored electrograms from her ICD showed high frequency noise preceding the shock. Although the pacing threshold was normal and lead fracture was not found in chest X-rays, pacing lead impedance decreased to 480 omega. Moreover, such high frequency noise was observed by electrogram telemetry, but not by routine evaluation every 3 months. ICD lead dysfunction was suspected, so we elected to replace the ICD lead system. At the time of the operation, lead impedance was 410 omega and pacing threshold was the same as it was at the time of the ICD implantation, and no lead insulation disturbances were observed in the generator pocket. However, manipulation of the lead system produced high frequency noise reproducibly. Since some of the ICD lead dysfunction initially was clinically silent at rest, dysfunction was difficult to detect before serious problems occurred. Therefore, more careful evaluation of the ICD lead system is needed during long-term follow-up of ICD implants.

Similarities between Brugada syndrome and ischemia-induced ST-segment elevation. Clinical correlation and synergy.

Vasospastic angina (VSA) and Brugada syndrome (BS) are classified into different categories of cardiac disease, but both can be causes of sudden cardiac death from ventricular fibrillation (VF). The coexistence of VSA and BS in the same patient is possible, and this raises several questions: (1) what is the incidence of the coexistence of BS and VSA in the same patient? (2) is susceptibility to VF enhanced by the coexistence of the 2 diseases? and (3) is there any possibility of Ca-antagonists being used for the treatment of VSA-aggravated BS? In our institution, VSA coexisted in 5 of the 38 patients with BS (13.1%). Anginal episodes were confirmed clinically in 4 of the 5 patients, and syncope attack occurred after the symptom of chest pain in 2 patients. However, VF did not develop during the coronary vasospasm in any of the patients. Treatment with Ca-antagonist was effective for VSA, and neither aggravation of Brugada-type electrocardiographic abnormality nor an increase in the incidence of syncope attack was observed. Although the coexistence of BS and VSA in the same patient is not rare, neither enhanced susceptibility to VF nor the proarrhythmic effect of Ca-antagonist has been confirmed in our experience. However, careful attention is required in such patients because the influence of myocardial ischemia and/or the effect of Ca-antagonist may be different in each patient with BS.

Variable electrocardiographic effects of short-term quinidine sulfate administration in Brugada syndrome.

Quinidine, a class I antiarrhythmic agent with blocking property of transient outward current, is a possible candidate for the suppression of ventricular fibrillation in patients with Brugada syndrome; although there is a concern that its ability to these effects may be proarrhythmic. Therefore, we evaluated the effect of quinidine sulfate on ST-segment elevation in Brugada syndrome. In 8 patients with Brugada syndrome, the magnitude of ST-elevation at the J-point (ST(J)), and the ST-segment configuration in leads V1-V3, were compared before and on day 2 after the initiation of quinidine administration. In 3 patients, quinidine attenuated ST(J) by > or = 0.1 mV. Of these 3 patients, ST-segment elevation was normalized in 2 patients, while the ST-segment configuration was unchanged in another. In another 3 patients, quinidine augmented ST(J) by > or = 0.1 mV without any change of ST-segment configuration, and the augmentation was returned to baseline after the discontinuation of quinidine. Quinidine exhibited no effect on the ST-segment in the remaining 2 patients. The favorable effects of quinidine on the ST-segment tended to be more pronounced in patients with prominent ST-elevation at baseline. In 1 patient, quinidine was effective in eliminating both ST-segment elevation and repetitive tachyarrhythmia episodes. In conclusion, the effects of quinidine on ST-segment elevation were variable. Quinidine may potentially augment the ST-segment elevation in some patients with Brugada syndrome.

Electrophysiologic study-guided therapy with sotalol for life-threatening ventricular tachyarrhythmias.

The aim of this study was to investigate the long-term efficacy and safety of electrophysiologic study (EPS)-guided sotalol administration combined with implantable cardioverter defibrillators (ICD) for ventricular tachyarrhythmias (VTA). This study enrolled 92 patients with both structural heart disease and sustained VTA. Sotalol was administered to 57 patients, and its efficacy was assessed by EPS. Long-term treatment was continued in combination with ICD in 31 patients (57%) whose VTA was no longer inducible (responder group) and in 16 patients whose VTA remained inducible (nonresponder group). The long-term outcomes were compared among the responder group, the nonresponder group, and 35 ICD recipients untreated with antiarrhythmic drugs (ICD-only group). During a mean follow-up of 44 +/- 33 months, the recurrence of VTA was not significantly different between all patients treated with sotalol (30%) and patients in the ICD-only group (46%). However, the recurrence of VTA was significantly lower in the responder (13%) than in the nonresponder (63%) or the ICD-only groups (46%). There was no significant difference in VTA recurrence between the nonresponder and the ICD-only groups. One patient each in the responder and the ICD-only groups died suddenly, and all-cause mortality was similar in the three groups. The incidence of inappropriate ICD discharges was less in the sotalol than in the ICD-only groups. No patient had to discontinue long-term sotalol treatment because of the adverse effects. In conclusion, sotalol reduced VTA recurrence in the responding patients and inappropriate ICD discharge. EPS may predict the efficacy of sotalol for VTA recurrence.

Potential candidates for cardiac resynchronization therapy in Japanese patients with idiopathic dilated cardiomyopathy--a Niigata multicenter study of DCM--.

BACKGROUND: The purpose of this study was to assess the candidates suitable for cardiac resynchronization therapy (CRT) and to examine the significance of the QRS duration in Japanese patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: The study population consisted of 357 patients. The selection criteria for candidates suitable for CRT were QRS duration =130 ms, left ventricular ejection fraction (LVEF) =35% and New York Heart Association (NYHA) functional class III or IV by ACC/AHA/NASPE 2002 guidelines. We divided the study population into 2 groups: group A with a QRS duration <130 ms, and group B with a QRS duration =130 ms. In 25 of the 375 patients (7.0%), all the criteria were fulfilled. Group B had a significantly larger left ventricular diameter end-diastole and end-systole than group A (P<0.0001). Group B had a lower LVEF (P<0.0001). There was a fair inverse correlation (r=-0.58, P<0.0001) between the length of the QRS duration and LVEF. CONCLUSION: Approximately 7% of the Japanese patients with DCM are CRT candidates. In the present study, we found that prolonged QRS duration was associated with poor systolic function.

Postprandial variations in ST-segment in a patient with Brugada syndrome and partial gastrectomy.

A 74-year-old man with a history of partial gastrectomy presented with an electrocardiogram consistent with Brugada syndrome and marked meal related fluctuations in the ST segment. ST-segment elevation was prominently attenuated at 30 minutes and increased at 120 minutes after meals. Analysis of heart rate variability revealed a relationship between postprandial heightened parasympathetic activity and increase in Brugada-type ECG abnormality. A rapid postprandial increase in blood glucose may initially stimulate sympathetic nervous activity and secondarily increase parasympathetic tone. Food intake can be associated with fluctuations in ST-segment elevation in patients with the Brugada syndrome.