Published papers

A 79 year-old male without structural heart disease suffered from drug refractory ventricular tachycardia (VT). VTs and premature ventricular complexes (PVCs) with the same morphology occurred incessantly with a concordant R pattern in chest leads and a tall R in Lead II, III, and aVF. The origin was expected to be near the left epicardial ventricular outflow tract (LVOT), which was termed the left ventricular summit area. Pace-mapping from the LVOT and the left coronary cusp (LCC) did not match well with the QRS morphology of the PVC. A good match was obtained from the distal great cardiac vein (GCV), and radiofrequency (RF) delivery eliminated the PVC and VT. However, the PVC recurred four times upon cessation of RF delivery. By placing an ablation catheter at the LCC, we obtained pace-mapping showing two different types of QRS morphologies; one was an rS pattern in V1, and the other was an R pattern in V1 with a longer stimulus to QRS interval, which was a nearly perfect match to the PVC. RF application to the LCC permanently eliminated PVCs and VTs. Several VTs from the epicardial LVOT can be cured by RF application from both the distal GCV and the LCC. © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).

We investigated electrophysiological and histological effect on canine anatomical isthmus in right atrium by photosensitization reaction (PR) of talaporfin sodium operated via a manipulative 7 Fr. laser catheter to establish a nonthermal tachyarrhythmia treatment. We continuously administrated talaporfin sodium via a left femoral vein to maintain photosensitizer concentration of 25-35 μg/ml in blood plasma, which is within the range of clinical use in human. Fifteen-minute after kickoff of the photosensitizer administration, a 663 nm laser was irradiated via the laser catheter for 30 s/point with irradiance of 10 W/cm2. After 17 times irradiations, a 23 ms delay of the electrical signal propagation along tricuspid annulus was observed. This result might demonstrate the acute electrical conduction delay induced by PR. The canine heart was extracted 10 days after PR and Azan staining specimen was histologically evaluated to investigate the myocardial damage by PR. The transmural fibrosis in anatomical isthmus was found. We demonstrated the PR-induced electrical conduction delay in acute phase in vivo using continuous photosensitizer dosed canine model, which maintain the clinical photosensitizer concentrat. © 2013 SPIE.

A 45-year-old male was admitted to our hospital after successful resuscitation of cardiac arrest. Ventricular fbrilla-tion (VF) had occurred during breakfast and was defbrillated by an automated external defbrillator operated by emergency medical service staff. On admission, his ECG demonstrated complete right bundle branch block as the sole abnormality. Intensive examination could not detect any structural disease leading to a diagnosis of idiopathic VF and implantation of an ICD. VF storm occurred one month after hospital discharge and beta-blocker, amiodarone, and sedative administration had no effect on VF. Likewise, catheter ablation for triggering premature ventricular beats failed to control the VF storm. The VF storm then subsided in the following weeks and the patient was discharged on amiodarone. A half month later VF storm recurred and the patient was admitted again. This time, isoproterenol infusion was effective in suppressing VF, and thereafter the patient was administered bepridil and followed up without recurrence of VF for 1.5 years. From these benefcial effects, the VF of the patient was suggested to share common arrhythmogenic characteristics to those of Brugada syndrome or J-wave associated VF.

An application of photodynamic therapy for myocardial ablation, which would induce myocardial electrical conduction block, is proposed. For the proposed application, an extracellular photosensitization reaction (PR) is performed while photosensitizer is distributed in myocardial interstitial space by employing a short drug-light interval. Because the myocardial necrosis depth must be accurately controlled to prevent surrounding tissue injury during the myocardial ablation procedure, the necrosis depth during PR needs to be predicted. The purpose of this study is to investigate the availability of predicting PR-induced myocardial necrosis depth (dnec) using a defined fluorescence-fall amount (FA), which is the calculated result of fluorescence intensity decrease from the start of the PR multiplied by irradiation duration and corresponds to photosensitizer consumption amount under an assumption that the photosensitizer consumption rate is faster than the photosensitizer supply rate. The correlation between FA and dnec was experimentally investigated in vivo using an open-chested canine heart model with 2.5 and 5.0 mg/kg of talaporfin sodium at an irradiance of 5-20 W/cm 2 for 5-20 s. The fluorescence measurement was performed at a wavelength of 710 nm during the PR to derive FA. One week after the PR, a uniform necrosis depth was measured histopathologically as dmnec. A logarithmic correlation between dmnec and FA was confirmed with R2=0.69-0.80 and a dmnec range of 0.2-7.1 mm. The defined FA might be useful for predicting dnec for the extracellular PR in myocardium when using talaporfin sodium. © 2013 Springer-Verlag.

Electrophysiological Properties of the Superior Vena Cava and Venoatrial Junction Background Although the superior vena cava (SVC) has been well known to be one of the important foci triggering atrial fibrillation (AF), its electrophysiological characteristics have received little research attention. The aim of this study was to investigate the electrophysiological properties of the SVC and venoatrial junction (VAJ). Methods Twenty-five consecutive AF patients without structural heart disease undergoing electrical SVC isolation were included in this study. After pulmonary vein isolation, a circular decapolar catheter and 2 multipolar catheters were emplaced in the VAJ, right atrial appendage (RAA), and SVC, respectively. Burst pacing and single extrastimulus were applied from the RAA and SVC. The atrial and caval potentials on the circular catheter in the VAJ were investigated. Results Intracaval conduction delay and various degrees of conduction block over the VAJ were observed with burst pacing from both the RAA and SVC. A single extrastimulus from the RAA and SVC with a basic cycle length of 600 milliseconds prolonged the conduction time via the VAJ by 81 ± 49.7 milliseconds and 61 ± 58.7 milliseconds, respectively. The atrial and caval electrograms at the VAJ, which were separated from each other by pacing applications, facilitated mapping of the earliest activation site at the VAJ. Conclusions Intracaval conduction delay and decremental conduction property via the VAJ were demonstrated using pacing maneuvers. Pacing applications from the RAA or SVC can help distinguish the atrial and caval potentials and can facilitate mapping of the optimal ablation sites to isolate the SVC. © 2014 Wiley Periodicals, Inc.

Background: We investigated various serum inflammatory markers to predict ablation responders who have no atrial fibrillation (AF) relapse after the initial ablation. Methods: Forty-four consecutive AF patients (age: 59 ± 8 years, paroxysmal: 31, CHADS2: 1.1 ± 1.1) who underwent an initial pulmonary vein isolation were investigated. Various serum inflammatory markers, such as adiponectin, ANP, BNP, 1CTP, F1+2, hs-CRP, IL-6, intact P1NP, MDA-LDL, MMP-2, TGF-β, TIMP-2, and TNF-α, were evaluated prior to ablation. AF relapse was defined as AF documented in telemonitoring electrocardiograms twice a day during 9.7 ± 2.4 months of follow-up with three months of a blanking-period. Results: A total of 29 patients (paroxysmal: 21) maintained sinus rhythm after the initial catheter ablation. These ablation responders had significantly lower MMP-2 (Sinus vs. Relapsed: 748 ± 132.7 vs. 841.2 ± 152.4 ng/mL, P=0.042) and TNF-α (1.1 ± 0.4 vs. 1.8 ± 1.7 pg/mL, P=0.046) levels prior to ablation. A BNP-adjusted Cox multivariate regression analysis revealed that the independent predictive factor for AF recurrence was high MMP-2 levels (>766 ng/mL) accompanied by high TNF-α levels (>1.2 pg/mL). Conclusions: The levels of MMP-2 and TNF-α might be useful for predicting initial AF catheter ablation responders. © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).

Background We performed contact force (CF) monitoring during pulmonary vein (PV) isolation to evaluate CF according to sheath type, catheter position, and inadequate ablation.Methods Thirty consecutive patients (paroxysmal atrial fibrillation, 23; CHADS2 score, 0.5 ± 0.7; age, 56 ± 10 years) who underwent PV isolation using a CF-sensing catheter were included. Data for operator-blinded CF, impedance, and duration of the "first touch" (first round of ablation in each PV) was collected. We compared the CF, maximum CF, force-time integral, average impedance, and impedance drop (Δ impedance) between different sheaths (Swartz™ vs. Agilis™) in 12 different catheter positions, and in inadequate first touches requiring additional ablation.Results A total of 1283 ablation points (Swartz™, 620 points; Agilis™, 663 points) were evaluated. The average CF was significantly higher in the Agilis™ group (17.8 ± 13.0 g) than the Swartz™ group (15.0 ± 12.4 g; P < 0.001), especially in the anterior, inferior-anterior, and inferior-posterior sections of the right PV, and the top of the roof, and calina of the left PV. The Δ impedance showed a mildly significant negative relationship with the average CF (r = - 0.206; P < 0.001) and with the force-time integral (r = - 0.279; P < 0.001). Compared to first touches, the average CF and Δ impedance were significantly smaller in inadequate first touches in the Swartz™ group, but not in the Agilis™ group.Conclusions CF for PV isolation was significantly different depending on the position of the catheter and the type of sheath.

Background The circadian pattern of ventricular fibrillation (VF) episodes in patients with idiopathic ventricular fibrillation (IVF) is poorly understood.Methods Excluding Brugada syndrome and other primary electrical diseases, the circadian pattern of VF occurrence was determined in 64 patients with IVF. The clinical and electrocardiographic characteristics were compared among patients with nocturnal (midnight to 6:00 AM) VF and nonnocturnal VF in relation to J waves. A J wave was defined as either notching or a slur at the QRS terminal >0.1 mV above the isoelectric line in contiguous leads.Results The overall distribution pattern of VF occurrence showed 2 peaks at approximately 6:00 AM and around 8:00 PM. Nocturnal VF was observed in 20 patients (31.3%), and J waves were present in 14 of these 20 individuals (70.0%), whereas J waves were less frequent in the 44 nonnocturnal patients with VF: 16 (36.4%) (P =.0117). Among patients with J waves, nocturnal VF was observed in 46.7% with a peak at approximately 4:00 AM. Nocturnal VF was less common in patients without J waves, occurring in only 17.6% (P =.0124). Both the type and location of J waves and the pattern of the ST segment were similar between the nocturnal and nonnocturnal VF groups. J waves were associated with a VF storm and long-term arrhythmia recurrence.Conclusion In IVF, the presence of J waves may characterize a higher nocturnal incidence of VF and a higher acute and chronic risk of recurrence.

Background: Electrical storms (ESs) in patients with Brugada syndrome (BrS) are rare though potentially lethal. Methods and Results: We studied 22 men with BrS and ES, defined as ≥3 episodes/d of ventricular fibrillation (VF) and compared their characteristics with those of 110 age-matched, control men with BrS without ES. BrS was diagnosed by a spontaneous or drug-induced type 1 pattern on the ECG in the absence of structural heart disease. Early repolarization (ER) was diagnosed by J waves, ie, >0.1 mV notches or slurs of the terminal portion of the QRS complex. The BrS ECG pattern was provoked with pilsicainide. A spontaneous type I ECG pattern, J waves, and horizontal/descending ST elevation were found, respectively, in 77%, 36%, and 88% of patients with ES, versus 28% (P<0.0001), 9% (P=0.003), and 60% (P=0.06) of controls. The J-wave amplitude was significantly higher in patients with than without ES (P=0.03). VF occurred during undisturbed sinus rhythm in 14 of 19 patients (74%), and ES were controlled by isoproterenol administration. All patients with ES received an implantable cardioverter defibrillator and over a 6.0±5.4 years followup, the prognosis of patients with ES was significantly worse than that of patients without ES. Bepridil was effective in preventing VF in 6 patients. Conclusions: A high prevalence of ER was found in a subgroup of patients with BrS associated with ES. ES appeared to be suppressed by isoproterenol or quinidine, whereas bepridil and quinidine were effective in the long-term prevention of VF in the highest-risk patients.

Background-Approaches for closing the left atrial appendage (LAA) have been developed for stroke prevention. However, the prevailing maneuvers require an open-chest surgery, intravascular access, or transseptal puncture. We evaluated the feasibility and safety of pericardial endoscopy-guided LAA ligation in a canine model. Methods and Results-We used a total of 8 canines and computed tomography was performed before the procedures. After a double percutaneous pericardiocentesis, a transurethral rigid endoscope was inserted into the pericardial space. The ENDOLOOP ligature was advanced to the ostium of the LAA by counter pulling the tip of the LAA with forceps. After confirming the positioning guided by transesophageal echocardiography, the ligature was securely tightened. Acute success was evaluated by transesophageal echocardiography and chronic success was evaluated by blood testing, computed tomography, and transesophageal echocardiography. The LAA ligation was safely achieved in all canines without major complications. One month after the ligation, the ligated LAA was replaced by fibrotic tissue, and both the transesophageal echocardiography and computed tomographic images revealed no residual shunt. There was only a localized adhesion of the pericardium, where the original LAA was located, without the need for antibiotic or steroid administration. The postprocedural internal surface of the ligated LAA was smooth by virtue of intimal growth. Blood tests showed a slight elevation of the inflammatory markers, but this normalized spontaneously. Conclusions-Pericardial endoscopy-guided LAA ligation could provide an alternative, minimally invasive, and feasible solution for LAA closure that does not require vascular access or a transseptal puncture.

Background: The mechanism underlying the associations of sleep-disordered breathing (SDB) with stroke and atrial fibrillation (AF) is not well established. We explored the relationship between nocturnal intermittent hypoxia, a marker of SDB, and left atrial (LA)/LA appendage (LAA) function among AF patients. Methods: We evaluated 134 consecutive AF candidates for catheter ablation (age, 59.6 ± 9.4 years; body mass index [BMI], 24.8 ± 3.2; Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score, 1.2 ± 1.1, paroxysmal AF, n= 83) using nocturnal pulse oximetry, a noninvasive screening method for nocturnal intermittent hypoxia. Based on 3% oxygen desaturation index (3% ODI), patients were divided into nocturnal intermittent hypoxia (3% ODI > 15; n= 32) and control groups (3% ODI ≤ 15; n= 102). Results: The nocturnal intermittent hypoxia group demonstrated significantly higher weight, BMI, Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS2) and CHA2DS2-VASc scores, serum hemoglobin A1c and plasma brain natriuretic peptide levels, LA size, and prevalence of hypertension, vascular disease, and sick sinus syndrome. Echocardiographically, nocturnal intermittent hypoxia was associated with a higher grade of spontaneous echo contrast and low LAA flow velocity. Multiple regression analysis adjusted for type of AF, CHA2DS2-VASc score, BMI, plasma brain natriuretic peptide level, LA size, and rhythm on echocardiography revealed that 3% ODI was a factor independently associated with LAA flow velocity (β=-0.184; 95% confidence interval,-0.818 to-0.006). Conclusions: Nocturnal intermittent hypoxia was an independent determinant for low LAA flow velocity in patients with AF, suggesting that the connection between SDB and LAA function might underlie the association of AF with stroke.

Background: Automatic measurement becomes a preference, and indeed a necessity, when analyzing 1000 s of ECGs in the setting of either drug-inducing QT prolongation screening or genome-wide association studies of QT interval. The problem is that individual manufacturers apply different computerized algorithms to measure QT interval. We conducted a comparative study to assess the outcomes with different automated measurements of QT interval between ECG machine manufacturers and validated the related heart rate correction methods.Methods and Results: Herein, we directly compared these different commercial systems using 10,529 Fukuda Denshi ECGs and 72,754 Nihon Kohden ECGs taken in healthy Japanese volunteers. Log-transformed data revealed an equal optimal heart rate correction formula of QT interval for Fukuda Denshi and Nihon Kohden, in the form of QTc = QT/RR-0.347. However, with the raw data, the optimal heart rate correction formula of QT interval was in the form of QTc = QT+0.1566(1- RR) for Fukuda Denshi and QTc = QT+0.1526(1-RR) for Nihon Kohden. After optimization of heart rate correction of QT interval by the linear regression model using either log-transformed data or raw data, QTc interval was ,10 ms longer in Nihon Kohden ECGs than in those recorded on Fukuda Denshi machines. Indeed, regression analysis revealed that differences in the ECG machine used had up to a two-fold larger impact on QT variation than gender difference. Such an impact is likely to be of considerable importance when ECGs for a given individual are recorded on different machines in the setting of multi-institutional joint research.Conclusions: We recommend that ECG machines of the same manufacturer should be used to measure QT and RR intervals in the setting of multi-institutional joint research. It is desirable to unify the computer algorithm for automatic QT and RR measurements from an ECG.

Implantable cardioverter-defibrillators (ICDs) improve the survival of patients with ischemic or non-ischemic cardiomyopathy and a reduced ejection fraction. However, the efficacy of ICD therapy in patients with right ventricular outflow tract ventricular tachycardia (RVOT-VT) and early stage arrhythmogenic right ventricular dysplasia / cardiomyopathy (ARVD/C) has not been well clarified. Although the prognosis of RVOT-VT is generally good, malignant forms of RVOT-VT resulting in polymorphic VT have been reported by several investigators. Radiofrequency catheter ablation is still effective in such patients, and thus an ICD implantation is usually not required. On the other hand, according to the current guidelines in patients with ARVD/C, an ICD implantation is recommended for secondary prevention when the patients develop sustained VT or VF. An ICD implantation may also be considered for primary prevention in high-risk patients: extensive disease, family history of sudden cardiac death, or undiagnosed syncope. Since an ICD implantation in the early stage of ARVD/C is controversial, physicians should well consider its risks and benefits. Early intervention with ICD therapy in ARVD/C patients may reduce the arrhythmic death rate but increases the device related complications especially in younger patients.