Impact of high frequency stimulation to confirm a complete box isolation in catheter ablation of non-paroxysmal atrial fibrillation.

INTRODUCTION: Pulmonary vein (PV) isolation (PVI) including the left atrial posterior wall (LAPW) (Box-PVI) is proposed as an additional strategy for non-paroxysmal atrial fibrillation (NPAF), however, the efficacy remains controversial. The more reliable and durable the Box-PVI we can create, the better the rhythm outcomes might be than with a conventional PVI alone. This study focused on the potential exit conduction of the box lesion and investigated whether the conventional Box-PVI would be sufficient. METHODS AND RESULTS: We enrolled 350 consecutive patients with NPAF that underwent a conventional encircling Box-PVI and examined whether latent exit conduction and dormant "exit" conduction independently remained on the LAPW and in the PVs using high frequency stimulation (HFS) and an adenosine triphosphate (ATP) injection. All electrograms inside the box lesion were eliminated in all cases, however, HFS inside the box propagated outward in 23 cases (6.6%) without any exit conduction by conventional burst stimulation, and 24 cases (6.9%) exhibited only dormant "exit" conduction of the LAPW. Additional ablation where positive HFSs were observed created a complete bidirectional Box-PVI in 43 (41.3%) of the cases without a first pass Box-PVI. The recurrence rates depended on the groups classified according to the HFS response. CONCLUSION: HFS delivered with an ATP injection on the LAPW and in the PVs following a Box-PVI could not only elucidate true exit block but also identified possible incomplete lesions or connections outside the ablation line, whose elimination could achieve a complete Box-PVI leading to a better rhythm outcome.

Effect of beta-blockade on quantitative microvolt T-wave alternans in 24-hour continuous 12-lead ECG recordings in patients with long QT syndrome.

BACKGROUND: The aim of study was to investigate effects of beta-blockade on microvolt T-wave alternans (TWA), a precursor of lethal arrhythmia, in patients with long QT syndrome (LQTS). METHODS: Eleven consecutive LQTS patients, types 1 (n = 6), 3 (n = 2), and "non-1, non-2, non-3" (n = 3) were enrolled. All patients underwent 24-hr continuous 12-lead ECG monitoring before and after initiation of beta-blockade therapy. TWA was measured using the modified moving average method. RESULTS: Seven (63.6%) of the 11 patients studied were symptomatic, with history of cardiac arrest or documented Torsade de Pointes (TdP) in 4 and syncope in three patients. After a median follow-up of 34 months, beta-blockade reduced the number of symptomatic patients to 1 with TdP (p < 0.02), in whom TdP frequency decreased from 25 events/60 months (0.42 event/month) to seven events/69 months (0.1 event/month). In association with this reduction in symptoms, peak TWA decreased by 47% in the cohort after a median of eight months of beta-blockade therapy [from 95 (74-130) to 50 (39.5-64.5) µV, p = 0.01]. All patients exhibited TWA ≥42 µV before beta-blockade therapy, which eliminated these episodes in four patients. Daily frequency of TWA ≥42 µV episodes decreased by 87% [from 15 (6-26) to 2 (0-5) episodes/day, p = 0.009]. CONCLUSIONS: This study is limited by the small sample size and is mainly hypothesis generating. TWA monitoring deserves further evaluation as a risk marker and a guide to therapy in LQTS patients in future large-scale studies.

Significance of T-wave inversion triggered by spontaneous atrial premature beats in patients with long QT syndrome.

BACKGROUND: In patients with the long QT syndrome (LQTS), a sudden increase in heart rate can cause T-wave alternans (TWA) with beat-to-beat alternating polarity of T wave. We hypothesized that LQTS patients at high risk for torsades de pointes (TdP) may exhibit momentary atrial or sinoatrial premature beat-induced T-wave inversion (APB-TWI). OBJECTIVE: The purpose of this study was to assess the association of APB-TWI with TdP history and with microvolt TWA. METHODS: Twenty-four-hour continuous 12-lead electrocardiograms (ECGs) were recorded in 18 healthy subjects and 39 consecutive patients with LQTS types 1 (n = 21), 2 (n = 4), 3 (n = 4), and unidentified (n = 10). Peak TWA was determined by the modified moving average method. RESULTS: The 39 LQTS patients were divided into 2 groups: 10 LQTS patients with TdP history (TdP group) and 29 without (non-TdP group). None of the healthy subjects showed APB-TWI, whereas 38.5% of the LQTS patients (15/39) exhibited APB-TWI. The incidences of APB-TWI and TWA ≥42 µV were significantly higher in the TdP group than in the non-TdP group (APB-TWI: 80% vs 24.1%, P = .006; TWA ≥42 µV: 100% vs 65.5%, P = .04). APB-TWI was inferior in sensitivity for an association with TdP history to TWA ≥42 µV (80% vs 100%) but superior in specificity (75.9% vs 51.7%). Patients with APB-TWI exhibited significantly higher TWA values than those without [median (interquartile range) 73 (55-106.5) vs 48 (37.5-71.8) µV, P = .02]. CONCLUSION: APB-TWI is an easily measurable ECG pattern and is strongly associated with TdP history as well as TWA ≥42 µV in LQTS patients. APB-TWI and TWA may share pathophysiological mechanisms.

Incidence of Persistent Left Superior Vena Cava in the Normal Population and in Patients with Congenital Heart Diseases Detected Using Echocardiography.

Reports on the incidence of persistent left superior vena cava (PLSVC) in the normal population are limited to studies involving pacemaker implantation candidates and cadavers. The incidence in patients with congenital heart diseases (CHDs) is estimated to be higher than that in the normal population; however, the details are unclear. To investigate the incidence of PLSVC in the normal population and in patients with CHDs, subjects were examined prospectively using echocardiography. Normal subjects consisted of 2841 successive neonates without intra-cardiac or congenital anomalies born in Gifu Prefectural General Medical Center. Additionally, 1920 patients with CHDs were evaluated. The incidence of PLSVC in normal neonates was 0.21% (95% confidence interval 0.042-0.38%). A high incidence (more than 7.0 times the incidence in normal subjects) was observed in all CHD patients. The high incidence group included coarctation of the aorta (CoA) (23.7%) and double outlet right ventricle (DORV) patients (24.6%). The second group consisted of CHD patients with ventricular septal defect (VSD), with an incidence ranging from 5.1 to 6.1%. The low incidence group comprised patients with other CHDs, with an incidence between 1.5 and 3.1%. The incidence of PLSVC in trisomy 21 and atrial septal defect patients was significantly higher than that in normal neonates. The incidence of PLSVC in the normal population and in patients with CHDs was systematically evaluated for the first time. The incidence in CHD patients appeared to be positively influenced by the type of CHD, particularly by DORV, CoA, and VSD.

Arrhythmia risk and ß-blocker therapy in pregnant women with long QT syndrome.

BACKGROUND: Pregnancy is one of the biggest concerns for women with long QT syndrome (LQTS). OBJECTIVES: This study investigated pregnancy-related arrhythmic risk and the efficacy and safety of ß-blocker therapy for lethal ventricular arrhythmias in pregnant women with LQTS (LQT-P) and their babies. METHODS: 136 pregnancies in 76 LQT-P (29±5 years old; 22 LQT1, 36 LQT2, one LQT3, and 17 genotype-unknown) were enrolled. We retrospectively analysed their clinical and electrophysiological characteristics and pregnancy outcomes in the presence (BB group: n=42) or absence of ß-blocker therapy (non-BB group: n=94). RESULTS: All of the BB group had been diagnosed with LQTS with previous events, whereas 65% of the non-BB group had not been diagnosed at pregnancy. Pregnancy increased heart rate in the non-BB group; however, no significant difference was observed in QT and Tpeak-Tend intervals between the two groups. In the BB group, only two events occurred at postpartum, whereas 12 events occurred in the non-BB group during pregnancy (n=6) or postpartum period (n=6). The frequency of spontaneous abortion did not differ between the two groups. Fetal growth rate and proportion of infants with congenital malformation were similar between the two groups, but premature delivery and low birthweight infants were more common in those taking BB (OR 4.79, 95% CI 1.51 to 15.21 and OR 3.25, 95% CI 1.17 to 9.09, respectively). CONCLUSIONS: Early diagnosis and ß-blocker therapy for high-risk patients with LQTS are important for prevention of cardiac events during pregnancy and the postpartum period, and ß-blocker therapy may be tolerated for babies in LQT-P cases.

Effects of a bacterial probiotic on ruminal pH and volatile fatty acids during subacute ruminal acidosis (SARA) in cattle.

Effects of a bacterial probiotic (BP) on ruminal fermentation and plasma metabolites were evaluated in four Holstein cattle (body weight, 645 ± 62 kg; mean ± SD) with induced subacute ruminal acidosis (SARA). SARA was induced by feeding a SARA-inducing diet, and thereafter, 20, 50 or 100 g per head of a commercial BP was administered for 7 consecutive days during the morning feeding. Cattle without BP served as the control. The 24-hr mean ruminal pH in the control was lower, whereas those in the BP groups administered 20 or 50 g were significantly higher compared to the control from days 2 to 7. Circadian patterns of the 1-hr mean ruminal pH were identical (6.4-6.8) among all cattle receiving BP. Although the mean minimum pH in the control on day -7 and day 0 was <5.8, the pH in the treatment groups on day 7 was >5.8 and significantly higher than that of the control group ( >5.2). Ruminal volatile fatty acid (VFA) concentrations were not affected by BP treatment; however, the BP groups had lower lactic acid levels compared with the control group at 20:00 on day 7. Additionally, non-esterified fatty acid levels decreased from 8:00 to 20:00 in all BP groups on day 7. These results suggest that administration of 20 to 50 g of a multi-strain BP for 7 days might improve the low pH and high lactic acid level of the ruminal fluid in SARA cattle.

Prevalence of Microvolt T-Wave Alternans in Patients With Long QT Syndrome and Its Association With Torsade de Pointes.

BACKGROUND: Prevalence of microvolt T-wave alternans (TWA) and the strength of its association with torsade de pointes (TdP) history have not been fully investigated in patients with long QT syndrome (LQTS). METHODS AND RESULTS: Twenty-four-hour continuous 12-lead ECGs were recorded in 10 healthy subjects (5 men; median age, 21.5 years) and 32 patients (13 men; median age, 13 years) with LQTS types 1 (n=18), 2 (n=4), 3 (n=4), and unidentified (n=6). Peak TWA was determined by the Modified Moving Average method. None of the healthy subjects had TWA ≥42 µV. All 8 (100%) LQTS patients with a history of TdP exhibited TWA ≥42 µV, whereas only 14 (58.3%) of the 24 LQTS patients without TdP history reached ≥42 µV (p=0.04). Thus, the 42-µV cut point provided 100% sensitivity and 41.7% specificity for an association with TdP history. In the 22 (68.8%) LQTS patients with TWA ≥42 µV, only 2 (median; interquartile range, 1-3) leads exhibited TWA ≥42 µV. Highest TWA levels were recorded in precordial leads (V1-V6) in 30 (93.8%) patients, most frequently in lead V2 (43.8%). A single ECG lead detected only ≤63.6% of TWA ≥42 µV episodes, whereas the combined leads V2 to V5 detected 100% of TWA ≥42 µV. CONCLUSIONS: Microvolt TWA is far more prevalent in LQTS patients than previously reported and is strongly associated with TdP history. TWA should be monitored from precordial leads in LQTS patients. The use of a limited set of ECG leads in conventional monitoring has led to underestimation of TWA and its association with TdP.

Sudden paradoxical QT-interval prolongation exacerbating T-wave alternans in a patient with type 3 long QT syndrome.

We report a case with type 3 congenital long QT syndrome, who exhibited a sudden paradoxical QT-interval prolongation during a progressive increase in heart rate, which exacerbated T-wave alternans.

Simultaneous estimation of the pH of rumen and reticulum fluids of cows using a radio-transmission pH-measurement system.

Circadian pH changes in the fluid of the rumen (bottom and middle) and reticulum were assessed simultaneously using wireless and wired radio-transmission pH-measurement systems in cows fed a control diet (C diet) or rumen-acidosis-inducing diet (RAI diet). The pH in the three sites decreased following the morning and evening feedings. In cows fed the C diet, the bottom-rumen and reticular pH reverted to the basal level by the next morning, while the middle-rumen pH did not recover completely, suggesting that active fermentation occurred in the middle of the rumen. The mean pH at 1 hr intervals was higher in the reticulum than at the bottom and in the middle of the rumen. The relatively stable reticular pH may result from dilution due to salivation. In cows fed the RAI diet, the bottom-rumen pH fell to approximately 5.2 after the evening feeding, but returned to the basal level by the next morning. In contrast, the middle-rumen pH did not return to the basal level (6.5) within 24 hr, presumably owing to continuous, vigorous fermentation. There were positive correlations between the pH at the bottom and in the middle of the rumen and at the bottom of the rumen and in the reticulum. These findings indicate that our radio-transmission pH-measurement system may be suitable tool for simultaneous measurement of pH in the rumen and reticulum fluid.

Clinical characteristics and genetic background of congenital long-QT syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan.

BACKGROUND: Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence. METHODS AND RESULTS: Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of beta-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator. CONCLUSIONS: Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.

Enterovirus isolation from children with acute respiratory infections and presumptive identification by a modified microplate method.

OBJECTIVE: To evaluate a modified microplate method, utilizing HEF, HEp-2, Vero, MDCK and newly introduced RD-18S and GMK cell lines, for virus isolation. METHODS: From June to October 2001, 723 throat swab specimens taken from children with acute respiratory infections (ARIs) were inoculated onto these cells. To analyze cell sensitivity, we also inoculated 20 serotypes of stocked enteroviruses. RESULTS: During the period, we isolated 40 Coxsackie A2 (CoxA2), 13 CoxA4, 16 CoxA16, 1 CoxB2, 11 CoxB3, 2 CoxB5, 54 echo16, 2 entero71 and 1 polio2. By observing a cell sensitivity pattern with HEF, HEp-2, Vero, RD-18S, and GMK, we could finally differentiate five enterovirus groups: CoxA except for CoxA16, CoxA16/entero71, CoxB, echovirus, and poliovirus. CONCLUSIONS: With this system, the RD-18S cell line enabled us to isolate CoxA virus, except for CoxA16, for the first time. Differentiation of five enterovirus groups by cell sensitivity simplified the specific identification by neutralization test as a presumptive identification. A modified microplate method may be an appropriate cell combination for virus isolation, especially for enteroviruses, and is expected to be used routinely for virologic diagnosis and to clarify the epidemiology of ARI in children.

Investigation on the influx transport mechanism of pentazocine at the blood-brain barrier in rats using the carotid injection technique.

The influx transport mechanism of pentazocine (PTZ) at the blood-brain barrier (BBB) was investigated in rats using the carotid injection technique. The uptake kinetics of PTZ into the rat brain exhibited saturability, which occurred by both nonsaturable and carrier-mediated transport processes. The in vivo kinetic parameters were estimated as follows: the maximal uptake rate (Jmax), 3.6 +/- 1.2 micromol/min/g brain and the apparent Michaelis constant (K1), 3.7 +/- 1.7 mM for the saturable component of PTZ into the brain, and the nonsaturable uptake rate constant (Kd), 0.06 +/- 0.04 ml/min/g brain. The uptake of PTZ by the brain was strongly inhibited by lidocaine, imipramine and propranolol, and also by H1-antagonists such as mepyramine, diphenhydramine. In addition, narcotic-antagonist analgesic (buprenorphine, butorphanol or eptazocine) and an opioid antagonist (naloxone) significantly inhibited PTZ transport. These results suggest that PTZ permeates into the brain via a carrier-mediated transport system, which may widely recognize the cationic drugs.

Dissolution tests for self-setting calcium phosphate cement-containing nifedipine.

Nifedipine-containing calcium phosphate cement (CPC) was prepared, and nifedipine (NF) release from this preparation was evaluated by the shaking method (SK), Japanese Pharmacopoeia XIV (JPXIV) paddle method (PD), and JPXIV flow-through cell method (FT). The release of NF from the CPC preparation continued for 7 d or longer by all these methods. This suggests that the release of NF can be controlled by preparing NF-containing CPC. The release pattern of NF from CPC in these tests was found to follow the Higuchi equation. However, the Higuchi constant differed among the three dissolution tests, probably because the apparent tortuosity of capillary system (tau) varied.