Detailed analysis of tachycardia cycle length aids diagnosis of the mechanism and location of atrial tachycardias.

AIMS: Although the mechanism of an atrial tachycardia (AT) can usually be elucidated using modern high-resolution mapping systems, it would be helpful if the AT mechanism and circuit could be predicted before initiating mapping. OBJECTIVE: We examined if the information gathered from the cycle length (CL) of the tachycardia can help predict the AT-mechanism and its localization. METHODS: One hundred and thirty-eight activation maps of ATs including eight focal-ATs, 94 macroreentrant-ATs, and 36 localized-ATs in 95 patients were retrospectively reviewed. Maximal CL (MCL) and minimal CL (mCL) over a minute period were measured via a decapolar catheter in the coronary sinus. CL-variation and beat-by-beat CL-alternation were examined. Additionally, the CL-respiration correlation was analysed by the RhythmiaTM system. : Both MCL and mCL were significantly shorter in macroreentrant-ATs [MCL = 288 (253-348) ms, P = 0.0001; mCL = 283 (243-341) ms, P = 0.0012], and also shorter in localized-ATs [MCL = 314 (261-349) ms, P = 0.0016; mCL = 295 (248-340) ms, P = 0.0047] compared to focal-ATs [MCL = 506 (421-555) ms, mCL = 427 (347-508) ms]. An absolute CL-variation (MCL-mCL) < 24 ms significantly differentiated re-entrant ATs from focal-ATs with a sensitivity = 96.9%, specificity = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 66.7%. The beat-by-beat CL-alternation was observed in 10/138 (7.2%), all of which showed the re-entrant mechanism, meaning that beat-by-beat CL-alternation was the strong sign of re-entrant mechanism (PPV = 100%). Although the CL-respiration correlation was observed in 28/138 (20.3%) of ATs, this was predominantly in right-atrium (RA)-ATs (24/41, 85.7%), rather than left atrium (LA)-ATs (4/97, 4.1%). A positive CL-respiration correlation highly predicted RA-ATs (PPV = 85.7%), and negative CL-respiration correlation probably suggested LA-ATs (NPV = 84.5%). CONCLUSION: Detailed analysis of the tachycardia CL helps predict the AT-mechanism and the active AT chamber before an initial mapping.

Confirmation of the achievement of linear lesions using "activation vectors" based on omnipolar technology.

BACKGROUND: Although differential pacing conventionally has been used to confirm the achievement of block across linear lesion sets, high-resolution mapping demonstrates that pseudo-block is observed in 20%-30% of cases. OBJECTIVES: The purpose of this study was to examine the reliability and versatility of a method using "activation vectors" based on omnipolar technology to confirm the block line. METHODS: Linear ablation was performed during pacing, with the HD Grid catheter (Abbott) placed beside the linear lesion opposite the pacing site. The endpoint of complete linear lesion was complete inversion of the activation vectors to the opposite direction. When inversion of the activation vectors was not observed after 10 minutes of radiofrequency (RF) application, high-resolution mapping was performed to assess whether complete block was achieved. RESULTS: In 33 patients, 24 cavotricuspid isthmus lines, 11 mitral isthmus (MI) lines, 16 posterior lines, and 2 intercaval lines were performed using this method. Of the total of 53 lines, 10 (18.9%) required intermediate evaluation of the block line with high-resolution mapping because of the absence of inversion of activation vectors despite 10 minutes of RF application, resulting in incomplete block with endocardial gaps or epicardial conductions. Additional RF applications finally achieved inversion in direction of activation vectors in the 10 lines. In total, the present method can diagnose achievement of complete block line with 100% accuracy, whereas conventional differential pacing misdiagnosed incomplete block with epicardial conduction in posterior lines in 3 cases and in MI lines in 2 cases. CONCLUSION: Confirmation of complete linear lesions using "activation vectors" based on omnipolar technology is a reliable and versatile method.

Alcohol Consumption Is Associated With Postablation Recurrence but Not Changes in Atrial Substrate in Patients With Atrial Fibrillation: Insight from a High-Density Mapping Study.

Background The association between alcohol consumption, atrial substrate, and outcomes after atrial fibrillation (AF) ablation remains controversial. This study evaluated the impacts of drinking on left atrial substrate and AF recurrence after ablation. Methods and Results We prospectively enrolled 110 patients with AF without structural heart disease (64±12 years) from 2 institutions. High-density left atrial electroanatomic mapping was performed using a high-density grid multipolar catheter. We investigated the impact of alcohol consumption on left atrial voltage, left atrial conduction velocity, and AF ablation outcome. Patients were classified as abstainers (<1 drink/wk), mild drinkers (1-7 drinks/wk), or moderate-heavy drinkers (>7 drinks/wk). High-density mapping (mean 2287±600 points/patient) was performed on 49 abstainers, 27 mild drinkers, and 34 moderate-heavy drinkers. Low-voltage zone and slow-conduction zone were identified in 39 (35%) and 54 (49%) patients, respectively. There was no significant difference in the proportions of low-voltage zone and slow-conduction zone among the 3 groups. The success rate after a single ablation was significantly lower in drinkers than in abstainers (79.3% versus 95.9% at 12 months; mean follow-up, 18±8 months; P=0.013). The success rate after a single or multiple ablations was not significantly different among abstainers and drinkers. In multivariate analysis, alcohol consumption (P=0.02) and the presence of a low-voltage zone (P=0.032) and slow-conduction zone (P=0.02) were associated with AF recurrence after a single ablation, while low-voltage zone (P=0.023) and slow-conduction zone (P=0.024) were associated with AF recurrence after a single or multiple ablations. Conclusions Alcohol consumption was associated with AF recurrence after a single ablation but not changes in atrial substrate.

Endocardial contact mapping of the left atrial appendage in persistent atrial fibrillation.

INTRODUCTION: Isolation of the left atrial appendage (LAA) is often performed in persistent atrial fibrillation (AF). Propagation patterns in the LAA during AF remain to be elucidated. We sought to characterize propagation patterns in the LAA during AF in persistent AF. METHODS: Persistent AF patients undergoing catheter ablation were studied. Pulmonary vein isolation (PVI) was performed during continuous AF. If AF was not terminated by PVI, bi-atrial mapping was performed using a multi-electrode catheter during AF. Maps were collected at each site for 30 seconds and analyzed offline with a novel software, CARTOFINDER. This software made automatic determinations of whether activation was focal or rotational. The left atrium (LA) was divided into five regions, of which the LAA was one, and the right atrium (RA) into three. RESULTS: Eighty patients were studied (62 ± 10 years, 65 males). On average, 9.6 ± 2.2 and 4.1 ± 1.2 maps were created in the LA and RA, respectively. The LAA was mapped in 70 patients, resulting in 85 maps. In the LAA, activation was identified as focal more often than rotational (64 [91%] vs 10 [14%] patients, P < .001), seven patients displayed both. The number of focal activation events was greatest in the LAA (28.5 events/30 seconds [interquartile range, 15-54]) of the eight atrial regions. During focal activation, sites designated as earliest activation frequently covered a wide area, rather than being localized to a discrete site (5.4 ± 3.1 electrodes). CONCLUSIONS: The results of this study suggest that focal activation is a major mechanism underlying the arrhythmogenicity of the LAA in persistent AF.

Cryofreezing catheter ablation of adenosine triphosphate sensitive atrial tachycardia.

INTRODUCTION: Adenosine triphosphate (ATP) sensitive atrial tachycardia (AT) has been treated by radiofrequency catheter ablation. Cryofreezing energy has emerged as a novel energy source for catheter ablation. The aim of this study was to investigate the efficacy and safety of cryofreezing ablation for ATP-sensitive AT. METHODS AND RESULTS: A total of six patients with ATP-sensitive ATs were included in this study. A single atrial extrastimulation was able to initiate and terminate these ATs in all six patients. The electrophysiological findings satisfied the diagnostic criteria of ATP-sensitive AT. The ablation catheter was located at the earliest activation site of atrial excitation during the AT, and cryofreezing energy was delivered through a cryoablation catheter to perform cryomapping at temperature of -30 or -80°C. When cryomapping successfully terminated the ATs, cryoablation at a temperature of -80°C was subsequently performed. The earliest atrial activation during AT was recorded at the Koch's triangle area associated with a distinct intra-atrial activation sequence from that recorded during ventricular pacing. Cryoablation was performed at successful cryomapping sites and resulted in the complete elimination of the AT in all six patients without affecting the bidirectional atrioventricular (AV) nodal conduction. CONCLUSION: Cryofreezing energy was safe and effective in treating ATP-sensitive ATs even in patients with its origins located in the vicinity of the AV node.

Overexpression of KCNJ2 in induced pluripotent stem cell-derived cardiomyocytes for the assessment of QT-prolonging drugs.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes hold great potentials to predict pro-arrhythmic risks in preclinical cardiac safety screening, although the hiPSC cardiomyocytes exhibit rather immature functional and structural characteristics, including spontaneous activity. Our physiological characterization and mathematical simulation showed that low expression of the inward-rectifier potassium (IK1) channel is a determinant of spontaneous activity. To understand impact of the low IK1 expression on the pharmacological properties, we tested if transduction of hiPSC-derived cardiomyocytes with KCNJ2, which encodes the IK1 channel, alters pharmacological response to cardiac repolarization processes. The transduction of KCNJ2 resulted in quiescent hiPSC-derived cardiomyocytes, which need pacing to elicit action potentials. Significant prolongation of paced action potential duration in KCNJ2-transduced hiPSC-derived cardiomyocytes was stably measured at 0.1 µM E-4031, although the same concentration of E-4031 ablated firing of non-treated hiPSC-derived cardiomyocytes. These results in single cells were confirmed by mathematical simulations. Using the hiPSC-derived cardiac sheets with KCNJ2-transduction, we also investigated effects of a range of drugs on field potential duration recorded at 1 Hz. The KCNJ2 overexpression in hiPSC-derived cardiomyocytes may contribute to evaluate a part of QT-prolonging drugs at toxicological concentrations with high accuracy.

The Relationship between the Profiles of SVC and Sustainability of SVC Fibrillation Induced by Provocative Electrical Stimulation.

BACKGROUND: Superior vena cava (SVC) can be a focus of atrial fibrillation (AF). However, distinctive features that identify SVC arrhythmogenicity remain unclear. Sustainability of fibrillation within the SVC might help with identifying SVC arrhythmogenicity. The purpose of this study was to investigate the relationship between the anatomical and electrical profiles of SVC and sustainability of SVC fibrillation induced by proactive electrical stimulation. METHODS: Consecutive 36 patients with paroxysmal or persistent AF who underwent repetitive pulmonary vein isolation (PVI) session were included in the study. After successful PVI, periodic rapid electrical stimuli were delivered to the SVC to induce SVC fibrillation. SVC fibrillation was defined as follows: (1) the local fibrillatory electrical activity persisted longer than 3 seconds, (2) the local fibrillatory activity penetrated through the atrium and maintained AF, and (3) the frequency of local activity was higher than that of any other atrial components such as coronary sinus and right atrial appendage. RESULTS: SVC fibrillation was induced in seven patients. The group with SVC fibrillation had significantly longer SVC sleeve and longer left atrial diameter compared with the group without SVC fibrillation. All patients with SVC fibrillation were free from AF recurrence after SVC isolation. CONCLUSIONS: The SVC sleeve longer than 30 mm had sustainability of SVC fibrillation induced by electrical stimulation. This finding advocates that arrhythmogenic substrate may exist in the SVC with long myocardial sleeve.

The radio frequency catheter ablation of inter-fascicular reentrant tachycardia: new insights into the electrophysiological and anatomical characteristics.

INTRODUCTION: Macro-reentrant ventricular tachycardias (VT) utilizing the bundle branches and Purkinje fibers have been reported as verapamil sensitive VT (idiopathic left VT), bundle branch reentrant VT (BBRT) and inter-fascicular reentrant tachycardia (inter-fascicular VT). However, diagnostic confusion exists with these VTs due to the difficulty in differentiating between them with conventional electrophysiological (EP) studies. The aim of this study was to clarify the EP and anatomical entity of inter-fascicular VT, and provide successful methods for the radio frequency catheter ablation (RFCA) of inter-fascicular VT. METHODS AND RESULTS: A total of nine patients were included in this study. All patients were diagnosed with idiopathic left VT in the first session, and underwent a second session after a failed RFCA. Detailed EP studies guided by a three-dimensional (3D) mapping system were performed to further analyze the VTs. All VTs were finally diagnosed as inter-fascicular VT. They were successfully cured with RFCA targeting the left anterior or posterior fascicle, which was regarded as a requisite part of the reentrant circuit of the inter-fascicular VT, using 3D and fluoroscopic images combined with a detailed EP investigation instead of the conventional RFCA method targeting Purkinje potentials for the RFCA of idiopathic left VT. CONCLUSIONS: Inter-fascicular VT could be misdiagnosed as idiopathic left VT due to the limitations of the conventional EP study. Failed RFCA in presumptive idiopathic left VT cases has to be carefully investigated by further analysis, and a tailored RFCA strategy targeting the requisite portions of the left fascicles in the inter-fascicular VT reentrant circuit will be required for the successful elimination of the inter-fascicular VT.

Gene Therapy for Cardiac Arrhythmias.

UNLABELLED: Morbidity and mortality caused by cardiac arrhythmias are a major issue in developed countries. Although conventional therapeutic options including pharmacological therapy, catheter ablation, and implantable devices have shown extensive advances to help reduce morbidity and mortality, a certain segment of these arrhythmias is still refractory to treatment. Therefore, gene therapy was explored as a potential additional or alternative therapy. Gene therapy trials have been developed for bradycardia, atrial fibrillation, and ventricular tachycardia. For the treatment of bradycardia, "biological pacemaker" attempts have been examined utilizing virus vectors to eliminate inward rectifier potassium current, or to overexpress the If current to convert quiescent myocytes into spontaneously active cells. These gene therapy attempts were soon followed by gene and cell hybrid therapies, and cell transplantation therapies utilizing pacemaker cells derived from stem cells. For the treatment of tachycardia, two major strategies were conceived: 1) to increase the effective refractory period, or 2) to recover the conduction velocity. The establishment of a selective and highly efficient gene transfer method would enable us to apply these concepts into the atrial fibrillation and ventricular tachycardia models. Both concepts resulted in an elimination or reduction of tachyarrhythmias in large animal models. Although these trials proved the concept of gene therapy as an adjuvant or alternative approach for the treatment of cardiac arrhythmias, the limitation of these studies is the long-term efficacy and safety. Consequently, an improvement in the gene delivery method is required to overcome these issues. KEY WORDS: Atrial fibrillation; Biological pacemaker; Gene therapy; Ion channel; Ventricular tachycardia.

Distribution of the origin of adenosine triphosphatesensitive atrial tachycardias with the earliest activation recorded in the His bundle catheter: are they limited to the immediate vicinity of the His bundle?

BACKGROUND: The aim of this study was to assess the spatial distribution of the origins of adenosine triphosphate (ATP) sensitive focal atrial tachycardias (AT) that have their earliest activation recorded in the His bundle (HB) catheter. METHODS AND RESULTS: Catheters were placed according to the standard fashion for an electrophysiologic study of supraventricular arrhythmia, namely, high right atrium, HB, coronary sinus, and right ventricle. The ATs with their earliest activation recorded in the HB catheter and that were terminated by rapid injection of ATP (4.3 ± 2.5mg), formed the study group (n=12). After catheter ablation of these ATs, the distances between the successful ablation site and the HB area were measured. Only one successful site was near the HB and the other sites were at the noncoronary sinus of Valsalva (n=6), tricuspid annulus (n=3), right atrial septum (n=1), and left atrial septum (n=1). The average distance between the HB catheter and successful site was 10.4 ± 8.8mm. In 5 of the 12 cases (the 3 tricuspid and 2 septal foci), the distances were greater than 10mm. CONCLUSIONS: When ablating ATP-sensitive AT with the earliest activation recorded in the HB catheter, it is important to perform detailed mapping not only around the HB.

Gene therapy for cardiac arrhythmias.

Myocardial gene transfer has become a routine tool to investigate the pathophysiology of cardiac diseases, although translation of gene transfer techniques into therapeutics has not come as quickly as many had hoped. In the field of cardiac arrhythmias, there is a great need for new therapeutic options. The current work reviews the use of gene transfer to evaluate cellular electrophysiology, the application of in vivo gene transfer to treat common arrhythmias, and the current problems in the field of cardiac gene therapy. Arrhythmia gene therapy is a field in its infancy, and future human applications are dependent on solutions to the problems discussed in this review.

Clinical implication of the double potentials at the cavotricuspid isthmus for radiofrequency catheter ablation of typical atrial flutter.

An 87-year-old man was referred to our institution to undergo radiofrequency catheter ablation for typical atrial flutter. A decapolar electrode catheter with an interelectrode spacing of 1mm positioned at the cavotricuspid isthmus (CTI) exhibited 2 discrete potentials. The first electrogram was recorded at a site close to the tricuspid annulus and the second at a site close to the inferior vena cava at the CTI. Entrainment study showed that the first component was crucial to maintain the artrial flutten; however, the second one was found to function as a bystander portion of the reentrant circuit. Radiofrequency energy application at the site where the first potential was inscribed could terminate the atrial flutter creating a complete bidirectional conduction block at the CTI.