Transseptal puncture and catheter ablation via the superior vena cava approach for persistent atrial fibrillation in a patient with polysplenia syndrome and interruption of the inferior vena cava: contact force-guided pulmonary vein isolation.

AIMS: We sought to establish the technical feasibility of transseptal puncture and left atrial (LA) ablation through the right internal jugular vein via the superior vena cava (SVC) approach in patients with an interrupted inferior vena cava (IVC). METHODS AND RESULTS: A 34-year-old man with persistent atrial fibrillation (AF) and polysplenia syndrome (hypoplasia of the left kidney, aplasia of the pancreas tail, bilaterally bilobed lungs, and an interrupted IVC) was referred to our hospital for radiofrequency ablation. Because transseptal puncture and LA ablation would be impossible by a standard IVC approach via the femoral vein, we performed transseptal puncture and LA ablation through the right internal jugular vein via the SVC approach using a manually curved Brockenbrough needle and intracardiac echocardiographic guidance. We accomplished pulmonary vein (PV) isolation using a deflectable guiding sheath and a contact force-sensing ablation catheter to monitor the contact force and the force-time integral of the tip of the ablation catheter. No complications occurred during or after the procedure. The patient was discharged home without recurrence of AF 3 days after the procedure. He had no recurrence of AF and was taking no medication 5 months after ablation. CONCLUSIONS: We successfully performed transseptal puncture in a patient with persistent AF, polysplenia syndrome, and complete interruption of the IVC using the superior route through the internal jugular vein. We also accomplished PV isolation using a deflectable guiding sheath and real-time monitoring of the contact force of the ablation catheter.

Externalization of a stiff guide wire via the radial artery: a new technique to facilitate advancement of an Inoue balloon across the aortic valve in patients with aortic stenosis undergoing antegrade balloon aortic valvuloplasty.

An 84-year-old woman with aortic stenosis underwent antegrade balloon aortic valvuloplasty (BAV). After transseptal puncture, we introduced a 7-Fr wedge catheter into the left ventricle and across the aortic valve. We then inserted a 0.032-inch soft guide wire, and the tip of the guide wire was advanced into the brachial artery and exchanged for a stiff guide wire. We externalized the tip of the stiff guide wire from the radial artery. Finally, we advanced an Inoue balloon (Toray, Tokyo, Japan) across the aortic valve and inflated the balloon. Transradial externalization makes antegrade BAV an even less invasive procedure.

Overexpression of zinc-finger protein 777 (ZNF777) inhibits proliferation at low cell density through down-regulation of FAM129A.

Krüppel-associated box-containing zinc finger proteins (KRAB-ZFPs) regulate a wide range of cellular processes. KRAB-ZFPs have a KRAB domain, which binds to transcriptional corepressors, and a zinc finger domain, which binds to DNA to activate or repress gene transcription. Here, we characterize ZNF777, a member of KRAB-ZFPs. We show that ZNF777 localizes to the nucleus and inducible overexpression of ZNF777 inhibits cell proliferation in a manner dependent on its zinc finger domain but independent of its KRAB domain. Intriguingly, ZNF777 overexpression drastically inhibits cell proliferation at low cell density but slightly inhibits cell proliferation at high cell density. Furthermore, ZNF777 overexpression decreases the mRNA level of FAM129A irrespective of cell density. Importantly, the protein level of FAM129A strongly decreases at low cell density, but at high cell density the protein level of FAM129A does not decrease to that observed at low cell density. ZNF777-mediated inhibition of cell proliferation is attenuated by overexpression of FAM129A at low cell density. Furthermore, ZNF777-mediated down-regulation of FAM129A induces moderate levels of the cyclin-dependent kinase inhibitor p21. These results suggest that ZNF777 overexpression inhibits cell proliferation at low cell density and that p21 induction by ZNF777-mediated down-regulation of FAM129A plays a role in inhibition of cell proliferation.

Cdk1-mediated phosphorylation of human ATF7 at Thr-51 and Thr-53 promotes cell-cycle progression into M phase.

Activating transcription factor 2 (ATF2) and its homolog ATF7 are phosphorylated at Thr-69/Thr-71 and at Thr-51/Thr-53, respectively, by stress-activated MAPKs regulating their transcriptional functions in G1 and S phases. However, little is known about the role of ATF2 and ATF7 in G2/M phase. Here, we show that Cdk1-cyclin B1 phosphorylates ATF2 at Thr-69/Thr-71 and ATF7 at Thr-51/Thr-53 from early prophase to anaphase in the absence of any stress stimulation. Knockdown of ATF2 or ATF7 decreases the rate of cell proliferation and the number of cells in M-phase. In particular, the knockdown of ATF7 severely inhibits cell proliferation and G2/M progression. The inducible expression of a mitotically nonphosphorylatable version of ATF7 inhibits G2/M progression despite the presence of endogenous ATF7. We also show that mitotic phosphorylation of ATF7 promotes the activation of Aurora kinases, which are key enzymes for early mitotic events. These results suggest that the Cdk1-mediated phosphorylation of ATF7 facilitates G2/M progression, at least in part, by enabling Aurora signaling.

v-Src inhibits the interaction between Rad17 and Rad9 and induces replication fork collapse.

ATR-dependent DNA damage checkpoint is crucial to maintain genomic stability. Recently, we showed that Src family kinases suppress ATR-dependent checkpoint signaling in termination of DNA damage checkpoint. However, the precise molecular mechanism is unclear. Therefore, we examined the role of oncogenic v-Src on ATR-Chk1 signaling. We show that v-Src suppresses thymidine-induced Chk1 phosphorylation and induces replication fork collapse. v-Src inhibits interaction between Rad17 and Rad9 in chromatin fraction. By contrast, v-Src does not inhibit RPA32 phosphorylation, ATR autophosphorylation, or TopBP1-Rad9 interaction. These data suggest that v-Src attenuates ATR-Chk1 signaling through the inhibition of Rad17-Rad9 interaction.

Activation of the prereplication complex is blocked by mimosine through reactive oxygen species-activated ataxia telangiectasia mutated (ATM) protein without DNA damage.

Mimosine is an effective cell synchronization reagent used for arresting cells in late G1 phase. However, the mechanism underlying mimosine-induced G1 cell cycle arrest remains unclear. Using highly synchronous cell populations, we show here that mimosine blocks S phase entry through ATM activation. HeLa S3 cells are exposed to thymidine for 15 h, released for 9 h by washing out the thymidine, and subsequently treated with 1 mM mimosine for a further 15 h (thymidine → mimosine). In contrast to thymidine-induced S phase arrest, mimosine treatment synchronizes >90% of cells at the G1-S phase boundary by inhibiting the transition of the prereplication complex to the preinitiation complex. Mimosine treatment activates ataxia telangiectasia mutated (ATM)/ataxia telangiectasia and Rad3-related (ATR)-mediated checkpoint signaling without inducing DNA damage. Inhibition of ATM activity is found to induce mimosine-arrested cells to enter S phase. In addition, ATM activation by mimosine treatment is mediated by reactive oxygen species (ROS). These results suggest that, upon mimosine treatment, ATM blocks S phase entry in response to ROS, which prevents replication fork stalling-induced DNA damage.

Nuclear ErbB4 signaling through H3K9me3 is antagonized by EGFR-activated c-Src.

The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR)/ErbB1, HER2/ErbB2, ErbB3 and ErbB4, and plays roles in signal transduction at the plasma membrane upon ligand stimulation. Stimulation with neuregulin-1 (NRG-1) cleaves ErbB4 and releases the ErbB4 intracellular domain (4ICD) that translocates into the nucleus to control gene expression. However, little is known about the regulation of 4ICD nuclear signaling through tyrosine phosphorylation. We show here that 4ICD nuclear signaling is antagonized by EGF-induced c-Src activation through EGFR. Generation of 4ICD by NRG-1 leads to increased levels of trimethylated histone H3 on lysine 9 (H3K9me3) in a manner dependent on the nuclear accumulation of 4ICD and its tyrosine kinase activity. Once EGF activates c-Src downstream of EGFR concomitantly with NRG-1-induced ErbB4 activation, c-Src associates with phospho-Tyr950 and phospho-Tyr1056 on 4ICD, thereby decreasing nuclear accumulation of 4ICD and inhibiting an increase of H3K9me3 levels. Moreover, 4ICD-induced transcriptional repression of the human telomerase reverse transcriptase (hTERT) is inhibited by EGF-EGFR-Src signaling. Thus, our findings reveal c-Src-mediated inhibitory regulation of ErbB4 nuclear signaling upon EGFR activation.

Circumferential pulmonary vein ablation of atrial fibrillation via superior vena cava approach in a patient with interruption of the inferior vena cava.

Interruption of the inferior vena cava (IVC) is a very rare congenital abnormality. Such patients have many difficulties during ablation procedures. We report a case of successful ablation of paroxysmal atrial fibrillation using the superior vena cava in a patient with interruption of the IVC.

Automated template matching to pinpoint the origin of right ventricular outflow tract tachycardia.

BACKGROUND: Template matching, a technique that examines the similarity between two QRS complexes, has not been broadly applied clinically. METHODS: The 16 patients enrolled in this study underwent radiofrequency catheter ablation (RFCA) at the site of five ventricular tachycardias (VT) and of premature ventricular contractions (PVC) arising from 25 sites in the right ventricular outflow tract (RVOT), under the guidance of conventional pace and activation mapping. After RFCA, (a) a template-matching score using a correlation coefficient, and (b) a pace-map score were calculated at 30 successful and 48 unsuccessful ablation sites. RESULTS: The template-matching score at successful ablation sites (94 +/- 4%) was significantly higher than at unsuccessful (85 +/- 9%) ablation sites (P < 0.001). A > or = 90% average matching score identified successful ablation sites with a sensitivity of 90% and specificity of 69%. While there was a significant correlation between the template-matching score and visually judged pace-map score (r = 0.63, P < 0.0001), the area under the receiver operating characteristic curve of the template matching score was larger than that of the pace-map score (0.80 vs. 0.67). CONCLUSIONS: Automated template matching was useful for localizing the optimal ablation site during RFCA of RVOT-VT/PVC.

Cavotricuspid isthmus conduction split by pouch-like recesses during typical atrial flutter.

A 58-year-old man had typical cavotricuspid-isthmus-dependent atrial flutter (AFL). Right atrial angiography and multidetector computed tomography revealed a deep pouch-like recess in the mid-isthmus region. Linear ablation from the pouch to the edge of the inferior vena cava resulted in widely split double potentials without any change in the AFL cycle length. This observation suggested that the pouch played an electrophysiological role by dividing the flutter wavefront into 2 parallel conduction wave fronts through both sides of the pouch along the isthmus during typical AFL. When a widely split potential is created on 1 side of the pouch, the other side of the pouch should be targeted.

Electrophysiologic and histopathologic findings of the ablation sites for ventricular fibrillation in a patient with ischemic cardiomyopathy.

We examined autopsy specimens from a patient with ischemic cardiomyopathy who underwent radiofrequency catheter ablation of ventricular fibrillation. There was site specific arrhythmogenesis of the trigger ventricular premature contractions (VPCs) and Purkinje potentials were recorded before the onset of the QRS. In postmortem examination, fibromuscular bands connecting the posterior papillary muscle and ventricular septum were recognized at the successful ablation sites of the trigger VPCs and the microscopic examinations revealed Purkinje cells in the center of that fibromuscular band.

Effect of cardiac resynchronization therapy in isolated ventricular noncompaction in adults: follow-up of four cases.

BACKGROUND: An isolated ventricular noncompaction (IVNC) is an unclassified cardiomyopathy and, despite the increasing awareness of and interest in this disorder, the role of cardiac resynchronization therapy (CRT) remains obscure. OBJECTIVE: The purpose of this study was to clarify the long-term effect of CRT on IVNC in adult patients. METHODS: Four cases of IVNC were included in this study. Before the CRT device was implanted, all four patients (54 +/- 16-year-old, 4 males) presented with symptomatic congestive heart failure. Echocardiography revealed their systolic dysfunction and their left ventricular ejection fraction (LVEF) was 21 +/- 8%. There was also mechanical dyssynchrony observed between the LV septum and free wall area. The QRS duration was "narrow" (112 and 120 ms) in two patients. One patient had been resuscitated from ventricular fibrillation (VF) and two had nonsustained ventricular tachycardia (VT). A CRT defibrillator (CRT-D) was implanted in three patients with VT/VF and a CRT pacemaker (CRT-P) in a patient without VT/VF. The LV lead was positioned in a lateral branch of the coronary sinus where a thickened noncompacted wall existed. RESULTS: During the follow-up period (28 +/- 23 months), their congestive heart failure had improved in terms of the cardiothoracic ratio on the chest X-ray, B-type natriuretic peptide level, LV systolic dimension, and LVEF. No episodes of defibrillation shocks were observed. CONCLUSION: CRT may improve the prognosis and quality-of-life in patients with an IVNC with mechanical dyssynchrony.

Changes in the isolated delayed component as an endpoint of catheter ablation in arrhythmogenic right ventricular cardiomyopathy: predictor for long-term success.

INTRODUCTION: Although successful ablation of ventricular tachycardia (VT) is feasible in arrhythmogenic right ventricular cardiomyopathy (ARVC), long-term recurrence is common. The aim of this study was to assess the usefulness of a change in the isolated delayed component (IDC) as an endpoint of the catheter ablation in ARVC. METHODS AND RESULTS: Eighteen patients (48 +/- 11 years) with ARVC were studied. Detailed endocardial mapping of the right ventricle (RV) was performed during sinus rhythm. IDCs were recorded in 16 patients and the latest IDCs were related to the VT circuit. Catheter ablation was carried out in the areas with the IDCs. At the end of the session, the IDC was electrically dissociated in one, disappeared in five, exhibited second-degree block in one, was significantly delayed (>or=50 ms) in three, and remained unchanged in six. The change in the IDC was correlated with the change in the type II/III late potentials in the signal-averaged electrocardiography (ECG) and the inducibility of the clinical VT after the ablation. During a follow-up of 61 +/- 38 months, VT recurred in six. The patients with a changed IDC had a significantly lower VT recurrence than those with no IDC or an unchanged IDC (P < 0.02). CONCLUSION: In patients with ARVC, (1) the IDCs during sinus rhythm are related to the clinical VT and can be a target for the ablation, (2) a change in the IDC can be used as an endpoint, and (3) qualitative analyses of the serial signal-averaged ECGs may be useful for the long-term follow-up.

Swallowing-induced atrial tachyarrhythmias: prevalence, characteristics, and the results of the radiofrequency catheter ablation.

BACKGROUND: Detailed information on swallowing-induced tachyarrhythmias has been lacking. METHODS: The prevalence, characteristics, and results of the radiofrequency catheter ablation (RFCA) of swallowing-induced tachyarrhythmias were examined in 544 patients with symptomatic premature atrial contractions (PACs), paroxysmal atrial tachycardia (AT), and/or paroxysmal atrial fibrillation (AF). We also conducted a search of the medical literature on swallowing-induced tachyarrhythmias. Further, we presented an in-depth review of the literature and investigated the published data on swallowing-induced tachyarrhythmias. RESULTS: The prevalence of swallowing-induced tachyarrhythmias was 0.6% (three patients). An analysis of the published literature and our three cases demonstrated that (1) males predominated 9:1 over females, (2) most cases occurred over 35 years of age, (3) tachyarrhythmias occurred consistently and reproducibly shortly after each swallow, (4) 90% of the patients had PACs and/or AT as the manifesting arrhythmia, (5) the PACs provoked by swallowing usually had the same P-wave morphology as the first beat of the AT and AF, and (6) RFCA procedures performed in five cases resulted in success with no recurrence or complications. CONCLUSIONS: Swallowing-induced tachyarrhythmias are rare, but have several distinct characteristics. RFCA should be considered in appropriately selected patients with reliable inducibility because such an ablation may offer a permanent cure.

Catheter ablation of tachycardias after undergoing a surgical atriotomy using a multipolar electrode catheter: conventional mapping method without an electroanatomical mapping system.

BACKGROUND: A variety of supraventricular tachyarrhythmias may occur in patients after undergoing a surgical atriotomy. The purpose of this study was to characterize them and determine the role of conventional mapping. METHODS AND RESULTS: In 45 patients after a surgical atriotomy, 68 atrial tachyarrhythmias were observed. A conventional mapping system with a 20-pole electrode catheter used in the electrophysiological study detected 39 atrial tachycardias (ATs). Type 1 atrial flutter (AFL) was observed in 23 and reverse type 1 AFL in 4. AT was classified into 3 subgroups, namely, incisional macroreentrant AT (n=31), incisional focal AT (n=1) and non-incisional AT (n=7). In the patients with incisional macroreentrant AT after the standard right atriotomy, the 20-pole electrode catheter placed on the incision could easily record the entire sequence of the atrial activation. Successful catheter ablation was achieved in all patients with incisional reentrant AT. The ablation site of incisional reentrant AT was the isthmus between the incision and the superior vena cava cannulation scar in 4, between the incision and the inferior vena cava cannulation scar in 22, and the area at the septal incision in 3. The remaining 2 incisional ATs were left atrial AT and right atrial transincisional AT. CONCLUSIONS: The conventional mapping system is still very useful for making an electrophysiological diagnosis in patients after a standard right atriotomy.

Idiopathic ventricular arrhythmia arising from the mitral annulus: a distinct subgroup of idiopathic ventricular arrhythmias.

OBJECTIVES: We sought to clarify the prevalence and characteristics of idiopathic ventricular tachycardia or premature ventricular contraction originating from the mitral annulus (MAVT/PVC). BACKGROUND: Recent case reports have presented patients with MAVT/PVC. METHODS: Electrocardiographic (ECG) characteristics and the results of electrophysiologic investigation and radiofrequency catheter ablation (RFCA) were analyzed in 352 patients with symptomatic idiopathic ventricular tachycardia (IVT)/premature ventricular contraction (PVC). RESULTS: Nineteen cases of IVT/PVC (5%) represented MAVT/PVC. Of these, 11 (58%) originated from the anterolateral portion of the mitral annulus (AL-MAVT/PVC), and 2 (11%) arose from the posterior portion (Pos-MAVT/PVC). The remaining six cases of MAVT/PVC (31%) had posteroseptal origin (PS-MAVT/PVC). In all patients, an S-wave was present in lead V(6). The QRS polarity in inferior leads and leads I and aVL was useful for differentiating AL-MAVT/PVC from Pos-MAVT/PVC or PS-MAVT/PVC. The Pos-MAVT/PVC had an Rs pattern in lead I and an R pattern in lead V(1), whereas PS-MAVT/PVC invariably had an R pattern in lead I and a negative QRS component in lead V(1). The AL-MAVT/PVC and Pos-MAVT/PVC showed a longer QRS duration than the PS-MAVT/PVC (p < 0.001), and all had late-phase "notching" of the QRS complex in inferior leads. In all patients, RFCA eliminated MAVT/PVC, with no recurrences during follow-up for 21 +/- 15 months. CONCLUSIONS: Mitral annular VT/PVC is a rare but distinct subgroup of IVT/PVC. MAVT/PVC origin could be determined by ECG analysis. The AL and PS sites of the MA were preferential.

Enhancement of J-ST-segment elevation by the glucose and insulin test in Brugada syndrome.

The effects of glucose and insulin on J-ST-segment elevation were evaluated in seven men (mean age 45 +/- 10 years) with Brugada syndrome. Six patients had been reanimated from VF and one patient had experienced syncope. The effects of intavenous (1) pilsicainide 50 mg, (2) glucose 50 g, and (3) glucose 50 g plus regular insulin 10 IU on the precordial ECG leads were examined. Pilsicainide significantly enhanced J-ST elevation in all patients and induced VF in 1 patient. A significant accentuation of the abnormal J-ST configuration was observed in all patients at a mean of 51 +/- 40 minutes after glucose and insulin infusion. Changes in blood glucose and serum potassium concentration were 111 +/- 158 mg/dL and -0.30 +/- 0.48 mEq/L, respectively. These changes were not directly related to the ECG changes. Glucose infusion without insulin caused a subtle increase in J-ST elevation. In conclusion, the administration of glucose and insulin safely unmasked or accentuation the J-ST-segment elevation in Brugada syndrome. Blood glucose and insulin concentrations may be factors modulating the circadian or day-to-day ECG variations in this syndrome.