The optimal slow pathway ablation site in atrioventricular nodal reentrant tachycardia cases with an inferiorly located His bundle.

INTRODUCTION: The optimal slow pathway (SP) ablation site in cases with an inferiorly located His bundle (HIS) remains unclear. METHODS AND RESULTS: In 45 patients with atrioventricular nodal reentrant tachycardia, the relationship between the HIS location and successful SP ablation site was assessed in electroanatomical maps. We assessed the location of the SP ablation site relative to the bottom of the coronary sinus ostium in the superior-to-inferior (SPSI), anterior-to-posterior (SPAP), and right-to-left (SPRL) directions. The HIS location was assessed in the same manner. The HIS location in the superior-to-inferior direction (HISSI), SPSI, SPAP, and SPRL were 17.7 ± 6.4, 1.7 ± 6.4, 13.6 ± 12.3, and -1.0 ± 13.0 mm, respectively. The HISSI was positively correlated with SPSI (R2 = 0.62; P < .01) and SPAP (R2 = 0.22; P < .01), whereas it was not correlated with SPRL (R2 = 0.01; P = .65). The distance between the HIS and SP ablation site was 17.7 ± 6.4 mm and was not affected by the location of HIS. The ratio of the amplitudes of atrial and ventricular potential recorded at the SP ablation site did not differ between the high HIS group (HISSI ≥ 13 mm) and low HIS group (HISSI < 13 mm) (0.10 ± 0.06 vs. 0.10 ± 0.06; P = .38). CONCLUSION: In cases with an inferiorly located HIS, SP ablation should be performed at a lower and more posterior site than in typical cases.

Incidence, distribution, and electrogram characteristics of endocardial-epicardial connections identified by ultra-high-resolution mapping during a left atrial posterior wall isolation of atrial fibrillation.

PURPOSE: The left atrial posterior wall (LAPW) can be a target for atrial fibrillation (AF) catheter ablation but is sometimes difficult to completely isolate due to the presence of endocardial-epicardial connections. We aimed to investigate the incidence and distribution of epicardial residual connections (epi-RCs) and the electrogram characteristics at epi-RC sites during an initial LAPW isolation. METHODS: We retrospectively studied 102 AF patients who underwent LAPW mapping before and after a first-pass linear ablation along the superior and inferior LAPW (pre-ablation and post-ablation maps) using an ultra-high-resolution mapping system (Rhythmia, Boston Scientific). RESULTS: Epi-RCs were observed in 41 patients (40.2%) and were widely distributed in the middle LAPW area and surrounding it. The sites with epi-RCs had a higher bipolar voltage amplitude and greater number of fractionated components than those without (median, 1.09 mV vs. 0.83 mV and 3.9 vs. 3.4 on the pre-ablation map and 0.38 mV vs. 0.27 mV and 8.5 vs. 4.2 on the post-ablation map, respectively; P < 0.001). Receiver operating characteristic analyses demonstrated that the number of fractionated components on the post-ablation map had a larger area under the curve of 0.847 than the others, and the sensitivity and specificity for predicting epi-RCs were 95.4% and 62.1%, respectively, at an optimal cutoff of 5.0. CONCLUSIONS: Among the patients with epi-RCs after a first-pass LAPW linear ablation, areas with a greater number of fractionated components (> 5.0 on the post-ablation LAPW map) may have endocardial-epicardial connections and may be potential targets for touch-up ablation to eliminate the epi-RCs.

Catheter ablation of the left-sided variant of right top pulmonary vein in a case with persistent left superior vena cava.

A 50-year-old woman underwent catheter ablation for atrial fibrillation. Preoperative computed tomography revealed a left-sided variant of the right top pulmonary vein (PV) and a persistent left superior vena cava. The right top PV was successfully isolated through a wide antral circumferential ablation line simultaneously with the right PVs.

Bilateral Cardiac Sympathetic Denervation for Treatment-Resistant Ventricular Arrhythmias in Heart Failure Patients with a Reduced Ejection Fraction.

The sympathetic nervous system plays an important role in life-threatening ventricular arrhythmias (VAs). Bilateral cardiac sympathetic denervation (BCSD) is performed for refractory VAs. We sought to assess our institutional experience with BCSD in managing treatment-resistant monomorphic ventricular tachycardia (MMVT) in heart failure patients with a reduced ejection fraction (HFrEF).Four patients with HFrEF (EF 30.0 ± 8.2%, New York Heart Association [NYHA] class IV 1) underwent BCSD for MMVT (VT storm 3, repetitive VT requiring implantable cardioverter defibrillator [ICD] therapy 1) refractory to antiarrhythmic drugs, catheter ablation and ICD therapy. BCSD was effective for suppressing VT in 3 patients for whom deep sedation was effective for suppressing VT. One patient remained alive after 14 months of follow-up without episodes of VT. One patient died of acute myocardial infarction before discharge and 1 patient died from unknown cause at 3 days post-discharge. In contrast, BCSD was completely ineffective for suppressing VT in a patient with NYHA class IV for whom deep sedation and stellate ganglion block were ineffective. This patient died on the 10th post-CSD day, despite left ventricular assist device implantation. In all cases, BCSD was successfully performed without procedure-related complications.Despite the limited number of cases, our results showed that BCSD in patients with HFrEF suppressed refractory MMVT in acute-phase except for a patient with NYHA class IV; however, the prognoses were not good. BCSD may be a treatment option at an earlier stage of NYHA and a bridge to orthotopic heart transplantation, even if BCSD is effective for suppressing VAs.

Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro.

1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated organic compound, was extensively used in the past in offset color proof-printing. In 2014, the International Agency for Research on Cancer (IARC) reclassified 1,2-DCP from its initial Group 3 to Group 1. Prior to the reclassification, cholangiocarcinoma was diagnosed in a group of workers exposed to 1,2 -DCP in an offset color proof-printing company in Japan. In comparison with other forms of cholangiocarcinoma, 1,2-DCP-induced cholangiocarcinoma was of early onset and accompanied by extensive pre-cancerous lesions in large bile ducts. However, the mechanism of 1,2-DCP-induced cholangiocarcinoma is poorly understood. Inflammatory cell proliferation was observed in various sites of the bile duct in the noncancerous hepatic tissues of the 1,2-DCP-induced cholangiocarcinoma. The aim of this study was to enhance our understanding of the mechanism of 1,2-DCP-related cholangiocarcinogenesis. We applied an in vitro system to investigate the effects of 1,2-DCP, using MMNK-1 cholangiocytes cultured alone or with THP-1 macrophages. The cultured cells were exposed to 1,2-DCP at 0, 0.1, 0.2, 0.4, and 0.8 mM for 24 h, and then assessed for cell proliferation, cell cytotoxicity, DNA damage, and ROS production. Exposure to 1,2-DCP increased proliferation of MMNK-1 cholangiocytes cultured alone, but not those cultured with macrophages. 1,2-DCP also increased LDH cytotoxicity, DNA damage, and ROS production in MMNK-1 cholangiocytes co-cultured with macrophages but not those cultured alone. 1,2-DCP increased TNFα and IL-1ß protein expression in macrophages. The results highlight the role of macrophages in enhancing the effects of 1,2-DCP on cytotoxicity, ROS production, and DNA damage in cholangiocytes.

1,2-Dichloropropane induces γ-H2AX expression in human cholangiocytes only in the presence of macrophages.

Recent epidemiological studies reported cases of cholangiocarcinoma in workers exposed to 1,2-dichloropropane (1,2-DCP) in an offset proof printing factory in Japan. The present study investigated the effects of 1,2-DCP on the expression of histone family member X (H2AX) phosphorylated on Ser 139 (γ-H2AX), a marker of DNA double strand break, in human immortalized cholangiocytes MMNK-1 cells. Mono-cultures of MMNK-1 cells and co-cultures of MMNK-1 cells with THP-1 macrophages were exposed to 1,2-DCP at concentrations of 100 and 500 µM for 24 h. Expression of γ-H2AX was visualized by immunofluorescence staining. Exposure to 1,2-DCP had no effect on the expression of γ-H2AX in mono-cultured MMNK-1 cells, but significantly increased the number of nuclear foci stained by γ-H2AX in MMNK-1 cells co-cultured with THP-1 macrophages. Exposure to 1,2-DCP also significantly increased the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in co-cultured MMNK-1 cells. The results suggest that macrophages play a critical role by producing cytokines in 1,2-DCP-induced DNA double strand break in MMNK-1 cells.