Mechanistic Insight into the TBHP-Mediated Decarboxylative Condensation of α-Ketoacids: Reaction Development and Application to Oligopeptide Synthesis.

With the aim of achieving the convergent elongation of peptide chains, an amide bond formation reaction that enables a peptide fragment coupling has long been pursued. The decarboxylative amidation recently reported by our group is a potential solution to this problem. In this article, a mechanistic analysis of the t-butyl hydroperoxide (TBHP) mediated-decarboxylative amidation of α-ketoacids that results in a significant advance in convergent peptide synthesis is described. Despite the observation of epimerization with low bulk substrates in preliminary studies, a systematic examination and understanding of the reaction mechanism enabled the development of a modified epimerization-free reaction whereby peptide fragment couplings using peptide α-ketoacids were successfully achieved.

Esophageal thermal lesions in radiofrequency ablation for atrial fibrillation: A prospective comparative study of thermal sensors.

BACKGROUND: Esophageal thermal lesion (ETL) is a complication of radiofrequency ablation for atrial fibrillation (RFAF). To prospectively compare the incidence of ETL, we used two linear, five- and three-sensor esophageal thermal monitoring catheters (ETMC5 and ETMC3). We also evaluated the predictors of ETL. METHODS: Patients receiving their first RFAF (n = 106) were randomized into two groups, ETMC5 (n = 52) and ETMC3 (n = 54). Ablation was followed by esophagogastroduodenoscopy within 3 days. RESULTS: Esophageal thermal lesion was detected in 7/106 (6.6%) patients (ETMC5: 3/52 [5.8%] vs. ETMC3: 4/54 [7.4%]; p = 1.0). The maximum temperature and number of measurements > 39.0°C did not differ between the groups (ETMC5: 40.5°C and 5.4 vs. ETMC3: 40.6°C and 4.9; p = .83 and p = .58, respectively). In ETMC5 group, the catheter had to be moved significantly less often (0.12 vs. 0.42; p = .0014) and fluoroscopy time was significantly shorter (79.2 min vs. 101.7 min; p = .0038) compared with ECMC3 group. The total number of ablations in ETMC5 group was significantly greater (50.2 vs. 37.7; p = .030) and ablation time was significantly longer (52.1 min vs. 40.1 min; p = .0039). Only body mass index (BMI) was significantly different between patients with and without ETL (21.4 ± 2.5 vs. 24.3 ± 3.4; p = .022). CONCLUSIONS: The incidence of ETL was comparable between ETMC5 and ETMC3 groups; however, fluoroscopy time, total ablation time, and total number of ablations differed significantly. Lower BMI may increase the risk of developing ETL.

Clinical predictors for bradycardia and supraventricular tachycardia necessitating therapy in patients with unexplained syncope monitored by insertable cardiac monitor.

BACKGROUND: Insertable cardiac monitors (ICMs) improve diagnostic yield in patients with unexplained syncope. The most of cardiac syncope is arrhythmic causes include paroxysmal bradycardia and supraventricular tachycardia (SVT) in patients with unexplained syncope receiving ICM. Predictors for bradycardia and SVT that necessitate therapy in patients with unexplained syncope are not well known. HYPOTHESIS: This study aimed to investigate predictors of bradycardia and SVT necessitating therapy in patients with unexplained syncope receiving ICMs. METHODS: We retrospectively reviewed medical records of consecutive patients who received ICMs to monitor unexplained syncope. We performed Cox's stepwise logistic regression analysis to identify significant independent predictors for bradycardia and SVT. RESULTS: One hundred thirty-two patients received ICMs to monitor unexplained syncope. During the 17-month follow-up period, 19 patients (14%) needed pacemaker therapy for bradycardia; 8 patients (6%) received catheter ablation for SVT. The total estimated diagnostic rates were 34% and 48% at 1 and 2 years, respectively. Stepwise logistic regression analysis indicated that syncope during effort (odds ratio [OR] = 3.41; 95% confidence interval [CI], 1.21 to 9.6; p = .02) was an independent predictor for bradycardia. Palpitation before syncope (OR = 9.46; 95% CI, 1.78 to 50.10; p = .008) and history of atrial fibrillation (OR = 10.1; 95% CI, 1.96 to 52.45; p = .006) were identified as significant independent predictors for SVT. CONCLUSION: Syncope during effort, and palpitations or history of atrial fibrillation were independent predictors for bradycardia and for SVT. ICMs are useful devices for diagnosing unexplained syncope.

Relationship between device-detected subclinical atrial fibrillation and heart failure in patients with cardiac resynchronization therapy defibrillator.

BACKGROUND: Atrial fibrillation (AF) is a leading preventable cause of heart failure (HF) for which early detection and treatment is critical. Subclinical-AF is likely to go untreated in the routine care of patients with cardiac resynchronization therapy defibrillator (CRT-D). HYPOTHESIS: The hypothesis of our study is that subclinical-AF is associated with HF hospitalization and increasing an inappropriate therapy. METHODS: We investigated 153 patients with an ejection fraction less than 35%. We divided into three groups, subclinical-AF (n = 30), clinical-AF (n = 45) and no-AF (n = 78). We compared the baseline characteristics, HF hospitalization, and device therapy among three groups. The follow-up period was 50 months after classification of the groups. RESULTS: The average age was 66 ± 15 years and the average ejection fraction was 26 ± 8%. Inappropriate therapy and biventricular pacing were significantly different between subclinical-AF and other groups (inappropriate therapy: subclinical-AF 13% vs clinical-AF 8.9% vs no-AF 7.7%: P = .04, biventricular pacing: subclinical-AF 81% vs clinical-AF 85% vs no-AF 94%, P = .001). Using Kaplan-Meier method, subclinical-AF group had a significantly higher HF hospitalization rate as compared with other groups. (subclinical-AF 70% vs clinical-AF 49% vs no-AF 38%, log-rank: P = .03). In multivariable analysis, subclinical-AF was a predictor of HF hospitalization. CONCLUSIONS: Subclinical-AF after CRT-D implantation was associated with a significantly increased risk of HF hospitalization. The loss of the biventricular pacing and increasing an inappropriate therapy might affect the risk of HF hospitalization.

Idiopathic basal crux ventricular arrhythmias with left bundle branch block and superior axis: A comparison with inferior-septal valvular arrhythmias.

INTRODUCTION: Left bundle branch block (LBBB) with superior axis is common in patients with idiopathic-ventricular arrhythmia (VA) originating from the tricuspid annulus (TA) and rarely from the cardiac basal crux and mitral annulus (MA). We described the electrocardiography and electrophysiological findings of idiopathic-VA presenting with LBBB and superior axis. METHODS AND RESULTS: We described 42 idiopathic-VA patients who had an LBBB and superior axis; 15 basal crux-VA, 17 TA-VA, and 10 MA-VA. No patient had a structural heart disease. Among patients with idiopathic-VA referred for ablation, we investigated the electrocardiogram and clinical characteristics of basal crux-VA as compared with other LBBB and superior axis-VA. The left ventricular ejection fraction with MA-VA was significantly lower in comparison with basal crux-VA (P = .01). All patients had a positive R wave in lead I and aVL. The maximum deflection index with basal crux-VA was significantly higher in comparison with TA-VA or MA-VA (P = .01). Patients with basal crux-VA presented with QS wave in lead II more frequently as compared with TA-VA or MA-VA (P = .001). All MA-VA patients had Rs wave in V6, and basal crux-VA, and TA-VA patients had a monophasic R wave or Rs wave in V6. Basal crux-VA patients underwent ablation in the middle cardiac vein (MCV) or coronary sinus (success rate: 94%, recurrence rate: 6%). CONCLUSIONS: We could distinguish basal crux-VA, TA-VA, and MA-VA, using a combination of clinical and electrocardiographic findings. These findings might be useful for counseling patients about an ablation strategy. Ablation via the MCV is effective for eliminating basal crux-VA.

Association left ventricular lead and ventricular arrhythmias after upgrade to cardiac resynchronization therapy in patients with implantable cardioverter defibrillators.

BACKGROUND: There are some controversial reports related to the pro-arrhythmic or anti-arrhythmic potential of cardiac resynchronization therapy (CRT) and little is known about the relationship between ventricular arrhythmia (VA) and left ventricular (LV)-lead threshold. HYPOTHESIS: Upgrade CRT is anti-arrhythmic effect of VA with implantable cardioverter-defibrillator (ICD) patients and has a relationship with the incident of VA and LV-lead threshold. METHODS: Among 384 patients with the implantation of CRT-defibrillator (CRT-D), 102 patients underwent an upgrade from ICD to CRT-D. We divided patients into three groups; anti-arrhythmic effect after upgrade (n = 22), pro-arrhythmic effect (n = 14), and unchanging-VA events (n = 66). The VA event was determined by device reports. We described the electrocardiography parameters, LV-lead characteristics, and clinical outcomes. RESULTS: Before upgrade, the numbers of VA were 305 episodes and the numbers of ICD therapy were 157 episodes. While after upgrade, the numbers of VA were 193 episodes and the number of ICD therapy were 74 episodes. Ventricular tachycardia cycle length (VT-CL) after upgrade was significantly slower as compared to those with before upgrade. Pro-arrhythmic group was significantly higher with delta LV-lead threshold (after 1 month-baseline) as compared to those with anti-arrhythmic group (0.74 vs -0.21 V). Furthermore, pro-arrhythmic group was significantly bigger with delta VT-CL (after 3 months-before 3 months) as compared to those with anti-arrhythmic group (P = .03). CONCLUSIONS: We described upgrade-CRT was associated with reduction of VA, ICD therapies and VT-CL. While 14 patients had a pro-arrhythmic effect and LV lead threshold might be associated with VA-incidents.