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.

Elucidating left atrial electrical potential with microelectrode catheter: A case of coronary sinus ostial atresia with small persistent left superior vena cava.

A 51-year-old woman presented with recurring palpitations. Electrocardiography revealed narrow QRS tachycardia with short RP configuration. Computed tomography showed coronary sinus (CS) ostial atresia along with a small persistent left superior vena cava (PLSVC). Electrophysiological study identified the retrograde earliest atrial activation site (EAAS) at the CS ostium without decremental properties, and para-Hisian pacing suggested retrograde atrioventricular nodal conduction. Using a 1.6-Fr microelectrode catheter distally placed in the CS via the PLSVC, EAAS was confirmed within the left atrium, not the CS ostium. Transseptal approach revealed a left lateral accessory pathway, which was successfully eliminated.

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.

Ethanol infusion therapy for peri-mitral atrial tachycardia through the Marshall bundle with electrical irrelevance of left atrial appendage and mitral isthmus.

A 62-year-old man with a history of catheter ablation for atrial fibrillation and atrial tachycardia (AT) received a line of block of the mitral isthmus (MI) and electrical isolation of the left atrial appendage (LAA). Upon entrainment pacing, AT recurred and was diagnosed as peri-mitral AT (PMAT) with electrical irrelevance of MI, LAA, and left pulmonary vein, having a critical isthmus identified as Marshall bundle (MB). MB was then infused with ethanol, leading to the successful treatment of the PMAT.

Unusual QRS complexes associated with the simultaneous presence of a right-sided accessory pathway, fasciculoventricular pathway, and incomplete right bundle branch block.

A 52-year-old man presented with delta waves on a body surface electrocardiogram, which suggested the presence of a right-sided accessory pathway (AP). Patients with right-sided APs generally have an rS pattern in leads V1-2, while he had an rS in lead V1 but an Rs in lead V2, which could not rule out the possibility of the presence of a septal AP or fasciculoventricular pathway (FVP). On the other hand, patients with septal APs or FVPs generally have a QS pattern in lead V1 instead of an rS pattern. An electrophysiological study demonstrated that the simultaneous presence of a right-sided posterolateral AP and FVP with incomplete right bundle branch block (ICRBBB) generated those unusual QRS complexes. The FVP arose distal to the site with ICRBBB, and the ICRBBB delayed the initiation of the FVP conduction. The delayed QS and Rs waves in leads V1-2 generated by the FVP conduction with ICRBBB appeared to produce rS and Rs patterns in leads V1-2, respectively. A radiofrequency application along the posterolateral tricuspid annulus eliminated the right-sided AP conduction. If the localization of APs based on the QRS morphology is difficult, multiple APs or an FVP with a conduction system disturbance should be noted. Learning objective: Patients with right-sided posterolateral accessory pathways (APs) generally have an rS pattern in lead V2, while patients with fasciculoventricular pathways (FVPs) generally have a QS pattern in lead V1. The present case with a suspected right-sided posterolateral AP had unusual QRS complexes, an rS in lead V1, Rs in lead V2, and monophasic R in leads V3-6, which were associated with the simultaneous presence of a right-sided posterolateral AP, FVP, and incomplete right bundle branch block.

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.

Impact of the size of non-ablated left atrial posterior wall area on outcomes after extensive encircling pulmonary vein isolation.

The aim of this study was to evaluate the impact of the size of the isolated surface area and non-ablated left atrial posterior area after extensive encircling pulmonary vein isolation (EEPVI) for non-paroxysmal atrial fibrillation (AF) on arrhythmia recurrence. This study included 132 consecutive persistent AF patients who underwent EEPVI guided by Ablation Index (AI). The isolated antral surface area (IASA) excluding the pulmonary veins, the non-ablated left atrial (LA) posterior wall surface area (PWSA), the ratio of IASA to LA surface area (IASA/LA ratio), and the ratio of PWSA to LA surface area (PWSA/LA ratio) were assessed using CARTO3 and the association with AF and atrial tachycardia (AT) recurrence was examined. At a mean follow-up of 13.2 ± 7.3 months, sinus rhythm was maintained in 115 (87%) patients. In the univariate Cox regression analysis, the factors that significantly predicted AT/AF recurrence were a history of heart failure, a higher CHA2DS2-VASc score, a larger LA diameter, and a larger PWSA/LA ratio. Multivariate Cox regression analysis revealed that the independent predictors of AT/AF recurrence were LA diameter [hazard ratio (HR) 1.120 per 1 mm increase; 95% confidence interval (CI) 1.006-1.247; P = 0.039] and PWSA/LA ratio (HR 1.218 per 1% increase; 95% CI 1.041-1.425; P = 0.014). Receiver operating characteristics curve analysis yielded an optimal cut-off value of 8% for the PWSA/LA ratio. The Kaplan-Meier survival curve showed that patients with a larger PWSA/LA ratio had poorer clinical outcomes (Log-rank P = 0.001). A larger PWSA/LA ratio was associated with a high AT/AF recurrence rate in patients with non-paroxysmal atrial fibrillation.

Phosphorylation-dependent Akt-Inversin interaction at the basal body of primary cilia.

A primary cilium is a microtubule-based sensory organelle that plays an important role in human development and disease. However, regulation of Akt in cilia and its role in ciliary development has not been demonstrated. Using yeast two-hybrid screening, we demonstrate that Inversin (INVS) interacts with Akt. Mutation in the INVS gene causes nephronophthisis type II (NPHP2), an autosomal recessive chronic tubulointerstitial nephropathy. Co-immunoprecipitation assays show that Akt interacts with INVS via the C-terminus. In vitro kinase assays demonstrate that Akt phosphorylates INVS at amino acids 864-866 that are required not only for Akt interaction, but also for INVS dimerization. Co-localization of INVS and phosphorylated form of Akt at the basal body is augmented by PDGF-AA Akt-null MEF cells as well as siRNA-mediated inhibition of Akt attenuated ciliary growth, which was reversed by Akt reintroduction. Mutant phosphodead- or NPHP2-related truncated INVS, which lack Akt phosphorylation sites, suppress cell growth and exhibit distorted lumen formation and misalignment of spindle axis during cell division. Further studies will be required for elucidating functional interactions of Akt-INVS at the primary cilia for identifying the molecular mechanisms underlying NPHP2.

Lysosomal interaction of Akt with Phafin2: a critical step in the induction of autophagy.

Autophagy is an evolutionarily conserved mechanism for the gross disposal of intracellular proteins in mammalian cells and dysfunction in this pathway has been associated with human disease. Although the serine threonine kinase Akt is suggested to play a role in this process, little is known about the molecular mechanisms by which Akt induces autophagy. Using a yeast two-hybrid screen, Phafin2 (EAPF or PLEKHF2), a lysosomal protein with a unique structure of N-terminal PH (pleckstrin homology) domain and C-terminal FYVE (Fab 1, YOTB, Vac 1, and EEA1) domain was found to interact with Akt. A sucrose gradient fractionation experiment revealed that both Akt and Phafin2 co-existed in the same lysosome enriched fraction after autophagy induction. Confocal microscopic analysis and BiFC analysis demonstrated that both Akt and Phafin2 accumulate in the lysosome after induction of autophagy. BiFC analysis using PtdIns (3)P interaction defective mutant of Phafin2 demonstrated that lysosomal accumulation of the Akt-Phafin2 complex and subsequent induction of autophagy were lysosomal PtdIns (3)P dependent events. Furthermore, in murine macrophages, both Akt and Phafin2 were required for digestion of fluorescent bacteria and/or LPS-induced autophagy. Taken together, these findings establish that lysosomal accumulation of Akt and Phafin2 is a critical step in the induction of autophagy via an interaction with PtdIns (3)P.

Environment-sensitive fluorophores with benzothiadiazole and benzoselenadiazole structures as candidate components of a fluorescent polymeric thermometer.

An environment-sensitive fluorophore can change its maximum emission wavelength (λ(em)), fluorescence quantum yield (Φ(f)), and fluorescence lifetime in response to the surrounding environment. We have developed two new intramolecular charge-transfer-type environment-sensitive fluorophores, DBThD-IA and DBSeD-IA, in which the oxygen atom of a well-established 2,1,3-benzoxadiazole environment-sensitive fluorophore, DBD-IA, has been replaced by a sulfur and selenium atom, respectively. DBThD-IA is highly fluorescent in n-hexane (Φ(f) =0.81, λ(em) =537 nm) with excitation at 449 nm, but is almost nonfluorescent in water (Φ(f) =0.037, λ(em) =616 nm), similarly to DBD-IA (Φ(f) =0.91, λ(em) =520 nm in n-hexane; Φ(f) =0.027, λ(em) =616 nm in water). A similar variation in fluorescence properties was also observed for DBSeD-IA (Φ(f) =0.24, λ(em) =591 nm in n-hexane; Φ(f) =0.0046, λ(em) =672 nm in water). An intensive study of the solvent effects on the fluorescence properties of these fluorophores revealed that both the polarity of the environment and hydrogen bonding with solvent molecules accelerate the nonradiative relaxation of the excited fluorophores. Time-resolved optoacoustic and phosphorescence measurements clarified that both intersystem crossing and internal conversion are involved in the nonradiative relaxation processes of DBThD-IA and DBSeD-IA. In addition, DBThD-IA exhibits a 10-fold higher photostability in aqueous solution than the original fluorophore DBD-IA, which allowed us to create a new robust molecular nanogel thermometer for intracellular thermometry.