Keisuke Kuga

Prevention of atrial fibrillation recurrence with corticosteroids after radiofrequency catheter ablation: a randomized controlled trial.

OBJECTIVES We sought to clarify the efficacy of corticosteroid therapy for preventing atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). BACKGROUND The inflammatory process may cause acute AF recurrence after PVI. However, no studies have examined the relationship between corticosteroid administration and AF recurrence after PVI. METHODS A total of 125 patients with paroxysmal AF were randomized to receive either corticosteroids (corticosteroid group) or a placebo (placebo group). In the corticosteroid group, intravenous hydrocortisone (2 mg/kg) was given the day of the procedure, and oral prednisolone (0.5 mg/kg/day) was administered for 3 days after the PVI. The body temperature and high-sensitivity C-reactive protein level were measured before and on each of the first 3 days after ablation. RESULTS The prevalence of immediate AF recurrence (≤3 days after the PVI) was significantly lower in the corticosteroid group (7%) than in the placebo group (31%). The maximum body temperature and C-reactive protein during the initial 3 days after ablation and the increase in the body temperature and C-reactive protein level from baseline were significantly lower in the corticosteroid group than in the placebo group. Corticosteroid treatment did not decrease AF recurrences between 4 and 30 days after ablation. The AF-free rate at 14 months post-ablation was greater in the corticosteroid group (85%) than in the placebo group (71%, p=0.032 by the log-rank test). CONCLUSIONS Transient use of small amounts of corticosteroids shortly after AF ablation may be effective and safe for preventing not only immediate AF recurrences but also AF recurrences during the mid-term follow-up period after PVI.

Comparison of Characteristics and Significance of Immediate Versus Early Versus No Recurrence of Atrial Fibrillation After Catheter Ablation

Atrial fibrillation (AF) recurrences after catheter ablation are common within the first month after AF ablation, and inflammatory processes may be related to AF genesis. This study aimed to clarify the relation between inflammatory processes and recurrence of AF after ablation and to characterize AF recurring within 3 days after ablation (immediate AF recurrence).The study included 186 patients with drug-refractory paroxysmal AF who underwent extensive pulmonary vein isolation. Body temperature and C-reactive protein level were measured before and consecutively on the first 3 days after ablation. Signs of pericarditis or atrial arrhythmias within 3 days after ablation were also monitored. Forty-five patients (24%) had immediate AF recurrence (immediate-AF-recurrence group), 27 (14%) had early recurrence 4 to 30 days after ablation (early-AF-recurrence group), and the remaining 114 (61%) had no AF recurrence within 1 month after ablation (no-AF-recurrence group). Increases in body temperature and C-reactive protein level from baseline in the immediate-AF-recurrence group were the highest among the 3 groups, and signs of pericarditis were observed in 15 of the 45 patients (33%) in the immediate-AF-recurrence group. Atrial premature contractions and nonsustained AF occurred most frequently in the early-AF-recurrence group. After 6-month follow-up, the AF-free rate was greater in the immediate-AF-recurrence group (76%) than in the early-AF-recurrence group (30%). In conclusion, immediate AF recurrence has an apparently different mechanism and impact on midterm outcomes than does early AF recurrence. Acute inflammatory changes after ablation may be responsible for immediate AF recurrence.

Prevalence and characteristics of asymptomatic excessive transmural injury after radiofrequency catheter ablation of atrial fibrillation.

BACKGROUND Even with a low energy setting, radiofrequency energy applications on the left atrial (LA) posterior wall may cause excessive transmural injury (ETI) during catheter ablation of atrial fibrillation (AF). OBJECTIVE The purpose of this study was to clarify the prevalence and characteristics of ETI. METHODS This study included 104 patients with AF who underwent extensive encircling pulmonary vein isolation (EEPVI) followed by an endoscopic examination (≤48 hours after EEPVI). EEPVI was performed under conscious sedation, and the ablation settings at the LA posterior wall were a maximum energy of 20 to 25 W and duration of ≤30 seconds. The ETI was defined as any injury that resulted from EEPVI, including esophageal damage or periesophageal nerve injury. RESULTS ETIs were found in 10 (9.6%) patients and were all asymptomatic; esophageal damage in 4 patients and periesophageal nerve injury in the remaining 6. All patients with ETI were below normal weight (body mass index [BMI] < 24.9 kg/m(2)), and consisted of 17% of those below normal weight. The procedural parameters such as the type of energy source, total duration of energy applications to the LA posterior wall, additional LA linear ablation, and biochemical markers were not related to the ETI. In the logistic multiadjusted model, the BMI (per 1 kg/m(2)) was the only independent predictor of ETI (odds ratio = 0.76; 95% confidence interval = 0.59 to 0.97, P < .05). CONCLUSION Asymptomatic ETIs were not rare even with a low energy setting in patients below normal weight. Tailored energy settings based on the patients BMI may be required when performing EEPVI.

Effects of CYP2D6 genotypes on age‐related change of flecainide metabolism: involvement of CYP1A2‐mediated metabolism

AIMS The aim of this study was to clarify the effects of CYP2D6 genotype on age-related change in flecainide metabolism in patients with supraventricular tachyarrhythmias. An in vitro study using microsomes was performed to identify other CYPs responsible for age-related change in flecainide metabolism. METHODS The study population comprised 111 genotyped patients: CYP2D6-homozygous extensive metabolizers (hom-EMs, n= 34), heterozygous EMs (het-EMs, n= 56), and intermediate and poor metabolizers (IMs/PMs, n= 21). Serum concentrations of flecainide and its metabolites [m-O-dealkylated flecainide (MODF) and m-O-dealkylated lactam of flecainide] were determined by use of a high-performance liquid chromatography. Metabolic ratio (MR) was expressed as serum concentrations of flecainide to its metabolites. In vitro formation of MODF was examined in human liver microsomes and cDNA-expressed CYP isoforms. RESULTS MR was higher in elderly patients (> or =70 years) than in middle-aged patients (<70 years). The increase of MR in elderly patients differed among CYP2D6 genotypes: 1.6-fold in het-EMs [4.3, 95% confidence interval (CI) 2.8, 5.7 vs. 2.7, 95% CI 2.3, 3.1, P < 0.05], 1.5-fold in IMs/PMs (6.0, 95% CI 4.5, 7.6 vs. 4.1, 95% CI 2.9, 5.4, P < 0.05), and no change in hom-EMs. The in vitro study using microsomes revealed that both CYP2D6 and CYP1A2 were involved in the formation of MODF. MODF formation in CYP2D6 PM microsomes increased as CYP1A2 activity increased. CONCLUSIONS The results suggest that patients with poor CYP2D6-mediated metabolism (het-EMs and IMs/PMs) showed age-related reduction in flecainide metabolism because metabolism was taken over by CYP1A2, whose activity decreases with age.

Ventricular fibrillation during anesthesia in association with J waves in the left precordial leads in a child with coarctation of the aorta.

A 14-year-old boy with coarctation of the aorta who showed repeat ventricular fibrillation during anesthesia, and ultimately sudden cardiac death in school, is presented. Electrocardiography showed J waves in the left precordial leads, which became prominent after an episode of ventricular fibrillation. While some of the clinical features and electrophysiological findings were similar to those seen in Brugada syndrome, others were inconsistent. J waves in the left precordial leads should be recognized as a possible waveform change inducing ventricular fibrillation predominantly at rest.

High Washout Rate of Iodine-123-Metaiodobenzylguanidine Imaging Predicts the Outcome of Catheter Ablation of Atrial Fibrillation

123 I‐MIBG and Ablation for Atrial Fibrillation. Introduction: Excessive sympathetic nervous activity may contribute to atrial fibrillation (AF) recurrences after ablation, but its precise role remains controversial. The goals of this study were to assess the effects of AF on the iodine‐123‐metaiodobenzylguanidine (123I‐MIBG) findings and to elucidate its impact on the procedural outcome in patients undergoing a first‐time catheter ablation to treat AF.

Noninvasive, direct visualization of macro-reentrant circuits by using magnetocardiograms: initiation and persistence of atrial flutter

AIMS We analysed the cardiac magnetic fields on the body surface to visualize electrical currents noninvasively during reentrant arrhythmias. METHODS AND RESULTS Seven patients with counterclockwise atrial flutter (AFL) were studied during 17 episodes of AFL using 64-channel magnetocardiograms (MCGs) and electrophysiological study. Eight of the episodes were paroxysmal AFL, in which MCGs were recorded from the time of spontaneous onset to the time of termination. We constructed iso-magnetic field maps of the tangential components and produced MCG animations. With respect to AFL initiation, an atrial premature complex induced AFL. Prior to the initiation of AFL, atrial fibrillation (AF) transiently occurred. The cardiac magnetic fields revealed a single peak during sinus rhythm or with premature complexes but a disorganized pattern during AF. When AF transformed to AFL, the magnetic fields changed from a disorganized pattern to a single peak at first and then evolved to a circular pattern. During persistent AFL, the magnetic source moved in a counterclockwise circuit. CONCLUSION MCG animation can be used to visualize the sequence in which a premature complex transforms sinus rhythm to AFL via AF. Our findings indicate that MCGs can be used to identify noninvasively the mechanisms responsible for atrial tachyarrhythmias.

Assessment by autonomic blockade of age-related changes of the sinus node function and autonomic regulation in sick sinus syndrome

Age-related changes of the sinus node (SN) function and the autonomic influence on the SN function were evaluated in 65 patients with sick sinus syndrome (range 14 to 84 years). Heart rate (HR), corrected SN recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) autonomic blockade (propranolol 0.2 mg/kg plus atropine 0.04 mg/kg intravenously). Percent of autonomic chronotropies of the SN function were calculated by the following formulas: (1)--(intrinsic HR--basic HR/intrinsic HR) X 100; (2) (intrinsic corrected SN recovery time--basic corrected SN recovery time/intrinsic corrected SN recovery time) X 100; (3) (intrinsic sinoatrial conduction time--basic sinoatrial conduction time/intrinsic sinoatrial conduction time) X 100. Basic HR, basic corrected SN recovery time and basic sinoatrial conduction time did not vary with age. Intrinsic HR decreased with age, but this correlation was weak (r = -0.54, p less than 0.001). Intrinsic corrected SN recovery time and intrinsic sinoatrial conduction time tended to increase with age (r = 0.26, p less than 0.05; r = 0.29, p less than 0.05, respectively). Percent chronotropies of HR, corrected SN recovery time and sinoatrial conduction time were negative values in younger patients and positive values in elderly patients; they correlated positively with age (r = 0.59, p less than 0.001; r = 0.60, p less than 0.001; r = 0.43, p less than 0.001, respectively). Thus, the basic SN function did not change with age, while the intrinsic SN function deteriorated with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of serum flecainide trough levels in patients with tachyarrhythmia.

The reported therapeutic range for trough flecainide concentration is 200–1000 ng mL−1. Severe adverse events, such as ventricular arrhythmias, have occurred occasionally in patients whose serum flecainide exceeded 1000 ng mL−1. However, the lower limit remains controversial. We have evaluated blood flecainide concentrations in patients with tachyarrhythmia who received the drug to control palpitation. We measured the flecainide trough levels and incidence and frequency of palpitation of 44 outpatients receiving oral flecainide (150–300 mg daily). Mean serum flecainide trough concentrations differed significantly between patients with (n = 14) and without (n = 30) palpitation (259.5 ± 85.2 vs 462.2 ± 197.7 ng mL−1, P < 0.01). The frequency of palpitation decreased as the serum flecainide concentration increased. The incidence of palpitation was 65% at serum flecainide concentrations < 300 ng mL−1 and 11% at ≥ 300 ng mL−1. QRS values were increased significantly in patients with serum flecainide ≥ 300 ng mL−1 compared with < 300 ng mL−1 (0.110 ± 0.016s vs 0.093 ± 0.019s, P < 0.05). We concluded that to control paroxysm in patients receiving flecainide for tachyarrhythmia serum flecainide concentrations should be maintained at ≥ 300 ng mL−1.

Involvement of peptidyl-prolyl isomerase Pin1 in the inhibitory effect of fluvastatin on endothelin-1-induced cardiomyocyte hypertrophy

AIMS Cardiac hypertrophy is elicited by endothelin (ET)-1 as well as other neurohumoral factors, hemodynamic overload, and oxidative stress; HMG-CoA reductase inhibitors (statins) were shown to inhibit cardiac hypertrophy partly via the anti-oxidative stress. One of their common intracellular pathways is the phosphorylation cascade of MEK signaling. Pin1 specifically isomerizes the phosphorylated protein with Ser/Thr-Pro bonds and regulates their activity through conformational changes. There is no report whether the Pin1 activation contributes to ET-1-induced cardiomyocyte hypertrophy and whether the Pin1 inactivation contributes to the inhibitory effect of statins. The aim of this study was to reveal these questions. MAIN METHODS We assessed neonatal rat cardiomyocyte hypertrophy using ET-1 and fluvastatin by the cell surface area, ANP mRNA expression, JNK and c-Jun phosphorylation, and [(3)H]-leucine incorporation. KEY FINDINGS Fluvastatin inhibited ET-1-induced increase in the cell surface area, ANP expression, and [(3)H]-leucine incorporation; and it suppressed the signaling cascade from JNK to c-Jun. The phosphorylated Pin1 level, an inactive form, was decreased by ET-1; however, it reached basal level by fluvastatin. Furthermore, Pin1 overexpression clearly elicited cardiomyocyte hypertrophy, which was inhibited by fluvastatin. SIGNIFICANCE This is the first report that ET-1-induced cardiomyocyte hypertrophy is mediated through the Pin1 activation and that the inhibitory effect of fluvastatin on cardiomyocyte hypertrophy would partly be attributed to the suppression of the Pin1 function. This study firstly suggests that Pin1 determines the size of hypertrophied cardiomyocyte by regulating the activity of phosphorylated molecules and that statins exert their pleiotropic effects partly via Pin1 inactivation.