Published papers

BACKGROUND Strokes develop even in patients with low CHADS2 scores, and the left atrial appendage (LAA) is the embolic source 90% of the time. We focused on the LAA morphology as a new predictor of strokes. OBJECTIVE To clarify the anatomical characteristics of the LAA for risk stratification of strokes in patients with nonvalvular atrial fibrillation (AF) who have low CHADS2 scores. METHODS Among 80 patients who underwent catheter ablation of AF with contrast-enhanced computed tomography, the LAA characteristics were compared between 30 patients with histories of strokes and 50 age-matched controls. The LAA anatomy was classified into 4 types-"cactus," "cauliflower," "chicken wing," and "windsock"- discriminated by the computed tomography measurements of the length, angle, and number of lobes of the LAA. RESULTS The average CHADS2 score did not differ significantly between patients with stroke and controls (0.8 ± 0.8 vs 0.6 ± 0.7; P = .277). Eight (26.7%) patients with stroke had CHA2DS2-VASc scores of 0. The left atrial size, LAA flow velocity, left ventricular function, and serum brain natriuretic peptide level were also unable to predict strokes. However, a "cauliflower" LAA, defined as a main lobe of less than 4 cm long without forked lobes, was significantly more common in patients with stroke (odds ratio 3.857; 95% confidence interval 1.482-10.037; P = .005). The CHA 2DS2-VASc score-adjusted logistic regression analysis revealed the cauliflower LAA as an independent predictor of a stroke (odds ratio 3.355; 95% confidence interval 1.243-9.055; P = .017). CONCLUSIONS The LAA anatomy might be useful for predicting strokes in patients with nonvalvular AF who have low CHADS2 scores. © 2013 Heart Rhythm Society. All rights reserved.

Background: Patients with coronary spasm generally have a good prognosis, although it can result in sudden cardiac arrest (SCA) and syncope. We hypothesized that the nature of coronary spasm triggering lethal arrhythmias may be different from that which induces angina-only. Methods: Clinical characteristics were examined in patients who had experienced SCA (n = 18) or syncope (n = 28) triggered by coronary spasm. These characteristics were compared to those of patients who had coronary spastic angina-only (n = 52). Results: SCA and syncope occurred frequently during daytime in 57% and 68%, respectively. Spontaneous ST-segment changes during daytime were recorded more often in patients with SCA (50%) and syncope (39%) than angina-only patients (4%, p < 0.01 for each). Nocturnal angina occurred less frequently in patients with SCA (33%) and syncope (32%) than angina-only patients (83%, p < 0.01 for each). Severe multivessel spasm, daytime ST-segment changes, and younger age were significant predictors of SCA. Daytime ST-segment changes and active smoking were related to syncope. Conclusions: The circadian variance of coronary spasm triggering SCA or syncope may be different from that inducing typical coronary spastic angina. The coronary spasm should be evaluated for patients with aborted SCA or recurrent syncope of unknown cause, even though the patients have not experienced the typical nocturnal angina. © 2011 Elsevier Ireland Ltd. All rights reserved.

Atrial fibrillation (AF) and coronary artery disease (CAD) can be comorbid with each other, because they can develop based on common risk factors such as aging, hypertension, diabetes mellitus and obesity. The management for stroke prevention in patients with AF and CAD needs some cautions. The vascular disease including CAD has been approved as one of the risk developing stroke in the CHA2DS2-VASc score for patients with AF. Patients with AF and CAD often should take antiplatelet and anticoagulant and sometimes take double antiplatelets and anticoagulant, which associates with increased bleeding risk. On terms of the management of AF, the medications of the rhythm control therapy for the AF would be limited if a patient has CAD. A K channel blocker would be selected for the 1st line therapy.

Background: The efficacy and safety of rigid pericardial endoscopy as the promising minimally invasive approach to the pericardial space was evaluated. Techniques for cell transplantation, epicardial pacemaker lead implantation, and epicardial ablation were developed.Methods: Two swine and 5 canines were studied to evaluate the safety and efficacy of rigid pericardial endoscopy. After a double pericardiocentesis, a transurethral rigid endoscope was inserted into the pericardial space. The technique to obtain a clear visual field was examined, and acute complications such as hemodynamic changes and the effects on intra-pericardial pressure were evaluated. Using custom-made needles, pacemaker leads, and forceps, the applications for cell transplantation, epicardial pacemaker lead implantation, and epicardial ablation were also evaluated. Results: The use of air, the detention of a stiff guide wire in the pericardial space, and the stretching of the pericardium with the rigid endoscope were all useful to obtain a clear visual field. A side-lying position also aided observation of the posterior side of the heart. As a cell transplantation methodology, we developed an ultrasonography-guided needle, which allows for the safe visualization of transplantation without major complications. Pacemaker leads were safely and properly implanted, which provides a better outcome for cardiac resynchronizing therapy. Furthermore, the success of clear visualization of the pulmonary veins enabled us to perform epicardial ablation. Conclusions: Rigid pericardial endoscopy holds promise as a safe method for minimally invasive cell transplantation, epicardial pacemaker lead implantation, and epicardial ablation by allowing clear visualization of the pericardial space. © 2012 Kimura et al.; licensee BioMed Central Ltd.

Background: Phrenic nerve (PN) injury is a potential complication that can occur during superior vena cava (SVC) isolation to cure atrial fibrillation (AF). Avoiding radiofrequency (RF) energy delivery is the safer alternative but may result in failed isolation. High-output PN pacing above the ablation site (upstream PN pacing) to confirm whether the PN is intact is a promising technique to avoid PN injury. This study was conducted to elucidate the safety of delivering RF energy at the site of capture of the right PN using upstream high-output pacing during electrical SVC isolation. Methods: SVC isolation was conducted in 41 drug-resistant AF patients. When high-output pacing (25 mA) from the distal tip of the ablation catheter captured the PN at the right atrial-SVC junction, upstream PN pacing (cycle length: 1000-1500 ms) was applied during RF delivery. The application of RF energy was stopped upon the failure or weakness of diaphragmatic twitching. The feasibility of SVC isolation using upstream PN pacing was investigated. Results: In all 41 patients, SVC isolation was successfully achieved. RF energy was delivered at the PN capture site in 26 patients (154 138 second, 18 5 W), and upstream PN pacing was successfully applied in all of the patients. Out of 46 SVC isolations, including five repeated sessions, PN injury occurred in one patient, who recovered spontaneously within 2 weeks. Conclusions: Upstream PN pacing may be effective for the safe completion of SVC isolation and to reduce the severity of PN injury. (PACE 2012; 35:1053-1060) ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Aims Long QT syndrome (LQTS) is an inheritable and life-threatening disease; however, it is often difficult to determine disease characteristics in sporadic cases with novel mutations, and more precise analysis is necessary for the successful development of evidence-based clinical therapies. This study thus sought to better characterize ion channel cardiac disorders using induced pluripotent stem cells (iPSCs). Methods and resultsWe reprogrammed somatic cells from a patient with sporadic LQTS and from controls, and differentiated them into cardiomyocytes through embryoid body (EB) formation. Electrophysiological analysis of the LQTS-iPSC-derived EBs using a multi-electrode array (MEA) system revealed a markedly prolonged field potential duration (FPD). The IKr blocker E4031 significantly prolonged FPD in control- and LQTS-iPSC-derived EBs and induced frequent severe arrhythmia only in LQTS-iPSC-derived EBs. The IKs blocker chromanol 293B did not prolong FPD in the LQTS-iPSC-derived EBs, but significantly prolonged FPD in the control EBs, suggesting the involvement of IKs disturbance in the patient. Patch-clamp analysis and immunostaining confirmed a dominant-negative role for 1893delC in IKs channels due to a trafficking deficiency in iPSC-derived cardiomyocytes and human embryonic kidney (HEK) cells. ConclusionsThis study demonstrated that iPSCs could be useful to characterize LQTS disease as well as drug responses in the LQTS patient with a novel mutation. Such analyses may in turn lead to future progress in personalized medicine. © 2012 The Author.

Background and Objective Contact laser irradiation is generally used in therapeutic laser procedures such as plastic surgery and laser catheter lead removal. However, it may induce blood charring on the surface of the optical window in blood circumstance so that the laser beam might be blocked. Various charring detection methods have been proposed, but they detect charring only after charring has occurred. This study investigates the transient behavior of red blood cells (RBCs) prior to the charring on the surface of an optical window during red laser irradiation in blood circumstance. Materials and Methods The backscattering light power was continuously measured to investigate the transient behavior of a 1-mm-thick porcine blood model (hematocrit: 40%) during continuous laser irradiation (center wavelength: 663 nm; irradiance: 81 W/cm2). A rabbit blood model was microscopically observed after irradiation. The absorption coefficient (μa) and the reduced scattering coefficient (μs) were measured using a double integrating sphere setup and the inverse adding-doubling method. The backscattering light power was continuously measured in vivo during contact laser irradiation via a laser catheter in a porcine heart cavity. Results The results reveal that it may be possible to detect a precursory state of charring from a time course of the backscattering light power. μa increased monotonically by 15% until charring occurred. μs decreased by 10% followed a broad peak until charring occurred. These changes in the optical property correspond to changes in the morphology of RBCs. Changes in the backscattering light power measured in vivo were similar to those measured ex vivo. Conclusions The transient optical changes in blood prior to charring may be caused by changes in the morphology of RBCs on the optical window surface. Backscattering light power measurements may be a practical method to detect the precursor state of charring. Copyright © 2012 Wiley Periodicals, Inc.

A 58-year-old male was referred for catheter ablation for atrial fibrillation. He was incidentally diagnosed with cor triatriatum si nister by preoperative transesophageal echocardiography and cardiovascular computed tomography. The patient has since been free from atrial fibrillation for over 24 months following successful electrical pulmonary vein isolation. The rapidly soaring number of cases undergoing catheter ablation for atrial fibrillation and imaging investigation prior to the procedure may increase the incidental detection of asymptomatic congenital heart diseases. © Springer-Verlag 2012.

We have studied a new type of myocardial catheter ablation with photosensitization reaction to realize non-thermal therapy for atrial arrhythmia, such as atrial fibrillation. Photochemically-generated reactive oxygen species may induce myocardial electrophysiological damage without heat generation. In this study, to demonstrate photosensitization reaction-induced myocardial electrical conduction block, the inferior vena cava to tricuspid annulus (IVC-TA) isthmus linear ablation was conducted with photosensitization reaction in porcine heart in vivo, using a newly developed laser catheter (7 Fr.). The end point of the procedure was the production of IVC-TA isthmus block under the electrophysiological analysis by diagnostic catheter with 10-bipole electrodes placed in right atrium along the isthmus. Talaporfin sodium (NPe6) as a photosensitizer was injected intravenously to pigs at 2.5-5.0 mg/kg. About 15 min after the injection, the laser light at the wavelength of 663 nm with a catheter output power density of 40-60 W/cm2 in about 1.4 mm spot size was irradiated through the laser catheter point by point in line crossing the isthmus under the fluoroscopic guidance. Before the photosensitization procedure, pacing signal from the distal electrodes of the diagnostic catheter, propagated through the isthmus in order. During the irradiation, electrical potential at the irradiated area was diminished. After the completion of the irradiation line, the bidirectional conduction block on the IVC-TA isthmus was validated by pacing from the distal and proximal bipole. These results indicated that photosensitization reaction could achieve the electrical conduction block of myocardial tissue immediately after the irradiation. We think that photosensitization reaction could become a novel therapy for atrial arrhythmia. © 2011 Copyright SPIE - The International Society for Optical Engineering.

Background and Objective This study proposes photosensitization reaction for non-thermal cardiac ablation in arrhythmia therapy. Acute and chronic phase experiments were conducted in exposed porcine hearts to demonstrate the photosensitization reaction-induced myocardial electrical conduction block in vivo. Study Design/Materials and Methods The porcine left atrial appendage was exposed under an open-chest procedure. Then, a water-soluble chlorin photosensitizer, NPe6, was injected into the pigs intravenously at 5 or 10amg/kg. About 15 or 30aminutes after the injection, a 663-nm continuous-wave diode laser was irradiated on the surface of the atrial appendage through a silica optical fiber. The laser energy was delivered to the tissue point by point at an energy density of 50-208aJ/cm 2. Results Acute and chronic tissue damages as a result of the photosensitization reaction were determined by electrophysiology and histology, respectively. The change in the myocardial conduction time between two electrodes was measured immediately after the completion of the 35-mm irradiation line between the electrodes. The conduction delay of 35.5amilliseconds might be due to the change in the conduction pathway induced by transmural acute conduction block with the photosensitization reaction. The tissue temperature increase in the irradiated area was approximately 12.8°C. Azan-staining revealed about 1-mm transmural fibrosis of the atrial appendage at 2 weeks after the irradiation (50aJ/cm 2). Conclusions The results suggest that the photosensitization reaction might induce acute and chronic myocardial electrical conduction block. Cardiac ablation with the photosensitization reaction might be a non-temperature- mediated methodology for arrhythmia therapy. © 2011 Wiley Periodicals, Inc.

Objective: A nonsurgical approach from the epicardial surface is useful for various cardiac interventions, such as positioning of the left ventricular lead for cardiac resynchronization therapy and epicardial ablation. Stem cell delivery on the epicardial surface can be considered in the future if good quality of visualization can be obtained. However, because the pericardial space is limited, hemodynamic conditions may deteriorate with pericardial endoscopy. Therefore, the feasibility and efficacy of pericardial endoscopy were examined by using ready-made endoscopes. Methods: Anesthetized swines (26-61 kg; n = 6) were used for the experiment. Electrocardiogram, femoral artery blood pressure, and oxygen saturation by pulse oximetry were continuously monitored during the procedures. Guided by the fluoroscopy, sheaths were advanced to the pericardial space using the modified Seldinger technique from the subxyphoid space. Results: After insertion of an endoscope with a maximum diameter of 6.9 mm, hemodynamic parameters were stable during the procedure with atropine. Stable and acceptable endoscopic images were obtained. Minor operations can be performed with pericardial endoscopic-guided laparoscopic forceps with no complications. Conclusions: The endoscopic pericardial procedure is effective and feasible. This procedure can increase the possibility and efficacy of nonsurgical treatment for cardiac diseases. Copyright © 2011 by The American Association for Thoracic Surgery.