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Introduction: Visually-guided laser balloon ablation (VGLA) currently requires careful manual rotation of the laser to create overlapping lesions. A novel semi-automated VGLA may reduce ablation times and lesion gaps. We aimed to compare semi-automated (SA) VGLA to that of manual (MN) VGLA., Methods: Acute: Nine swine underwent right superior pulmonary vein isolation (PVI) using either SA (n = 3, 13-18 W), MN (n = 3, 8.5-12 W), or radiofrequency (RF, n = 3, 25-40 W) and were killed acutely. Chronic: 16 swine, underwent PVI using either SA (n = 8, 15 W) or MN (n = 8, 10 W), and were survived for 1 month before being killed. All hearts were then submitted for pathological evaluation., Results: Acute: PVI was successful in all 9/9 swine with lesion counts significantly lower in the SA arm (5.3 ± 5.9, 33.7 ± 10.0, and 28.0 ± 4.4 in SA, MN, and RF arms; p = .007 for SA and MN). At necropsy, circumferentiality and transmurality were 98% and 94% in SA, 98% and 80% in MN, and 100% and 100% in RF arms. A single steam pop was noted on sectioning in the SA arm swine and occurred in the high dose (18 W) strategy. Chronic: PVI was acutely successful in 16/16 swine with no difference in PVI durability rates (62.5% vs. 75.0%), lesion transmurality (95.8 ± 17.4% vs.91.9 ± 25.9%), and circumferentiality (95.8 ± 6.6% vs. 94.8 ± 6.3%) between SA and MN arms. Catheter use time and lesion counts were lower in the SA arm compared to the MN arm (11.5 ± 12.7 vs. 21.8 ± 3.8 min, p = .046 and 4.8 ± 3.83 vs. 35.4 ± 4.4, p < .001)., Conclusion: Motor-assisted semi-automated laser balloon ablation can improve upon procedural efficiency by reducing ablation time., (© 2022 Wiley Periodicals LLC.)

Background: Immune checkpoint inhibitors (ICIs) are a central part of cancer therapy; however, cardiac complications, such as myocarditis, have the potential for significant morbidity and mortality. Within this population, the clinical significance of longitudinal strain (LS) remains unknown., Objectives: This study sought to define the changes in LS in ICI-treated patients, and their associations with high-sensitivity troponin I (hsTnI) and myocarditis., Methods: We conducted a retrospective cohort study of patients who received ICIs at our hospital from April 2017 to September 2021. All patients underwent echocardiography and blood sampling at standardized time intervals. We measured the changes in global and regional LS before and after ICI administration. Age- and sex-adjusted Cox regression analysis was used to evaluate the association between LS and elevations in hsTnI and myocarditis., Results: In a cohort of 129 patients with a median follow-up period of 170 (IQR: 62-365) days; 6 and 18 patients had myocarditis and hsTnI elevation, respectively. In an age- and sex-adjusted Cox proportional hazards model, an early relative worsening of ≥10% in the basal and mid LS and ≥15% in global LS was associated with hsTnI elevation. Relative reductions in LS were not significantly associated with myocarditis; however, 4 of the 6 patients with myocarditis had relative reduction of ≥10% in the basal LS., Conclusions: An early worsening in the global and regional LS was associated with increased hsTnI in patients receiving ICIs. Assessment of LS early after ICI administration should be further studied as a strategy for risk stratification of ICI-treated patients., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

The fitness landscape represents the complex relationship between genotype or phenotype and fitness under a given environment, the structure of which allows the explanation and prediction of evolutionary trajectories. Although previous studies have constructed fitness landscapes by comprehensively studying the mutations in specific genes, the high dimensionality of genotypic changes prevents us from developing a fitness landscape capable of predicting evolution for the whole cell. Herein, we address this problem by inferring the phenotype-based fitness landscape for antibiotic resistance evolution by quantifying the multidimensional phenotypic changes, i.e., time-series data of resistance for eight different drugs. We show that different peaks of the landscape correspond to different drug resistance mechanisms, thus supporting the validity of the inferred phenotype-fitness landscape. We further discuss how inferred phenotype-fitness landscapes could contribute to the prediction and control of evolution. This approach bridges the gap between phenotypic/genotypic changes and fitness while contributing to a better understanding of drug resistance evolution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Iwasawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The indications for immune checkpoint inhibitors (ICIs) are expanding in cancer drug therapy, and while cardiac events associated with ICIs are often fatal, there are few reports regarding cardiac complications associated with long-term ICI therapy. We aimed to study cardiac complications in patients undergoing long-term ICI therapy. From the database of our local cardio-oncology unit, we enrolled patients with cancer undergoing ICI therapy for more than 6 months and for whom cardiologists continuously performed routine follow-ups. We defined the primary endpoint as discontinuation of ICI due to cardiac events. We also analyzed changes in cardiac biomarkers and echocardiographic parameters. We retrospectively analyzed 55 consecutive patients (43 males, mean age: 65 ± 11 years) treated with ICI therapy in our hospital between January 2017 and June 2021. None of the patients discontinued ICI therapy due to cardiac events more than 6 months after treatment was initiated. Among the participants, we observed four patients with elevated serum troponin I levels, seven patients with decreased global longitudinal strain values, and two patients with elevated plasma brain natriuretic peptide levels. No patient required drug intervention for these cardiac events; furthermore, there were no cases of clinically diagnosed myocarditis. In the present study, there were no cardiac events causing ICI discontinuation in patients undergo ICI therapy for more than 6 months., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is a specific first-line treatment for patients with HER2-positive cancers. Cardiac dysfunction is among the most problematic adverse events associated with trastuzumab. Although regular echocardiographic screening is recommended for early detection of cardiac damage, few reports have investigated the validity of echocardiographic screening in chemotherapy. Therefore, the aim of this study was to determine whether a GLS-guided management approach could reduce cardiotoxicity and discontinuation of trastuzumab chemotherapy. Methods and Results: To evaluate the usefulness of global longitudinal strain (GLS)-guided cardioprotective interventions, we retrospectively analyzed 67 patients treated with trastuzumab who underwent structured echocardiographic assessments before and after 1, 3, and 6 courses of trastuzumab administration. If a >15% relative decrease in GLS was identified, cardioprotective agents were administered. Thirty (44.8%) patients had breast cancer; the remaining patients had salivary gland cancer. The median observation period for the intervention group was 304 days from the initial evaluation. Nineteen (28.4%) patients exhibited a >15% relative decrease in GLS, and consequently received cardioprotective agents. The incidence of trastuzumab discontinuation for cardiogenic reasons was significantly lower among patients receiving GLS-guided interventions than among those not receiving the intervention (2.4% vs. 24.0%; P=0.009). The incidence of a subsequent decline in left ventricular ejection fraction was lower among patients receiving the intervention than among those not receiving the intervention (4.8% vs. 24.0%; P=0.04). Conclusions: GLS-guided cardioprotective intervention significantly decreased the incidence of trastuzumab discontinuation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Atrial fibrillation is a clinically important arrhythmia. There are some reports on machine learning models for AF diagnosis using electrocardiogram data. However, few reports have proposed an eXplainable Artificial Intelligence (XAI) model to enable physicians to easily understand the machine learning model's diagnosis results.We developed and validated an XAI-enabled atrial fibrillation diagnosis model based on a convolutional neural network (CNN) algorithm. We used Holter electrocardiogram monitoring data and the gradient-weighted class activation mapping (Grad-CAM) method.Electrocardiogram data recorded from patients between January 4, 2016, and October 31, 2019, totaling 57,273 electrocardiogram waveform slots of 30 seconds each with diagnostic information annotated by cardiologists, were used for training our proposed model. Performance metrics of our AI model for AF diagnosis are as follows: sensitivity, 97.1% (95% CI: 0.969-0.972); specificity, 94.5% (95% CI: 0.943-0.946); accuracy, 95.3% (95% CI: 0.952-0.955); positive predictive value, 89.3% (95% CI: 0.892-0.897); and F-value, 93.1% (95% CI: 0.929-0.933). The area under the receiver operating characteristic curve for AF detection using our model was 0.988 (95% CI: 0.987-0.988). Furthermore, using the XAI method, 94.5 ± 3.5% of the areas identified as regions of interest using our machine learning model were identified as characteristic sites for AF diagnosis by cardiologists.AF was accurately diagnosed and favorably explained with Holter ECG waveforms using our proposed CNN-based XAI model. Our study presents another step toward realizing a viable XAI-based detection model for AF diagnoses for use by physicians.

Understanding the constraints that shape the evolution of antibiotic resistance is critical for predicting and controlling drug resistance. Despite its importance, however, a systematic investigation of evolutionary constraints is lacking. Here, we perform a high-throughput laboratory evolution of Escherichia coli under the addition of 95 antibacterial chemicals and quantified the transcriptome, resistance, and genomic profiles for the evolved strains. Utilizing machine learning techniques, we analyze the phenotype-genotype data and identified low dimensional phenotypic states among the evolved strains. Further analysis reveals the underlying biological processes responsible for these distinct states, leading to the identification of trade-off relationships associated with drug resistance. We also report a decelerated evolution of β-lactam resistance, a phenomenon experienced by certain strains under various stresses resulting in higher acquired resistance to β-lactams compared to strains directly selected by β-lactams. These findings bridge the genotypic, gene expression, and drug resistance gap, while contributing to a better understanding of evolutionary constraints for antibiotic resistance.

Introduction: Pulmonary vein isolation (PVI) using standard radiofrequency (RF) catheters is limited by incomplete contiguity and prolonged procedural times. A novel, 9-mm lattice-tip irrigated RF catheter can create wide lesions rapidly in swine atria., Methods: In five swine, temperature limited (75°C) irrigated RF for 5 seconds/ablation was selected, to isolate seven pulmonary veins (PVs; five right superior and two inferior commons) and create five right atrial lines. After 4 weeks, repeat mapping and additional ablation to create atrial isthmus lesions were performed. The chronic lesions were submitted for histology. This was compared with right superior PVI data using standard 3.5-mm irrigated tip ablation in six swine., Results: All targeted PVs (seven of seven, 100%) were acutely isolated. Durable isolation was observed in all six of six PVs treated with 5-second applications, but not in one PV inadvertently treated with 4-second applications. For the durably isolated PVs, the mean lesion count/PV and total RF time/PV was 16.3 ± 5.2 applications and 81.3 ± 25.9 seconds for the right superior and 14.5 ± 0.7 applications and 71.1 ± 5.5 seconds for the inferior common PV. Right atrial linear ablation was performed with a lesion count of 12 ± 2.3 applications and RF times of 59.5 ± 12.5 seconds. Cavotricuspid and mitral isthmus linear ablations were transmural along their entire length. All 53 of 53 (100%) sections were transmural on histology., Conclusion: Rapid and durable PVI and linear atrial ablation is feasible with this novel 9-mm lattice-tip catheter., (© 2020 Wiley Periodicals, Inc.)

Aims: Pulsed field ablation (PFA) is a novel, non-thermal modality that selectively ablates myocardium with ultra-short electrical impulses while sparing collateral tissues. In a proof-of-concept study, the safety and feasibility of ventricular PFA were assessed using a prototype steerable, endocardial catheter., Methods and Results: Under general anaesthesia, the left and right ventricles of four healthy swine were ablated using the 12-Fr deflectable PFA catheter and a deflectable sheath guided by electroanatomic mapping. Using the study catheter, electrograms were recorded for each site and pre-ablation and post-ablation pacing thresholds (at 2.0 ms pulse width) were recorded in two of four animals. After euthanasia at 35.5 days, the hearts were submitted for histology. The PFA applications (n = 39) resulted in significant electrogram reduction without ventricular arrhythmias. In ablation sites where it was measured, the pacing thresholds increased by >16.8 mA in the right ventricle (3 sites) and >16.1 mA in the left ventricle (7 sites), with non-capture at maximum amplitude (20 mA) observable in 8 of 10 sites. Gross measurements, available for 28 of 30 ablation sites, revealed average lesion dimensions to be 6.5 ± 1.7 mm deep by 22.6 ± 4.1 mm wide, with a maximum depth and width of 9.4 mm and 28.6 mm, respectively. In the PFA lesions, fibrous tissue homogeneously replaced myocytes with a narrow zone of surrounding myocytolysis and no overlying thrombus. When present, nerve fascicles and vasculature were preserved within surrounding fibrosis., Conclusion: We demonstrate that endocardial PFA can be focally delivered using this prototype catheter to create homogeneous, myocardium-specific lesions., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: During atrial fibrillation ablation, oesophageal heating typically prompts reduction or termination of radiofrequency energy delivery. We previously demonstrated oesophageal temperature rises are associated with posterior left atrial pulmonary vein reconnection (PVR) during redo procedures. In this study, we assessed whether mechanical oesophageal deviation (MED) during an index procedure minimizes posterior wall PVRs during redo procedures., Methods and Results: Patients in whom we performed a first-ever procedure followed by a clinically driven redo procedure were divided based on both the use of MED for oesophageal protection and the ablation catheter employed (force or non-force sensing) in the first procedure. The PVR sites were compared between MED using a force-sensing catheter (MEDForce), or no MED with a non-force (ControlNoForce) or force (ControlForce) sensing catheter. Despite similar clinical characteristics, the MEDForce redo procedure rate (9.2%, 26/282 patients) was significantly less than the ControlNoForce (17.2%, 126/734 patients; P = 0.002) and ControlForce (17.5%, 20/114 patients; P = 0.024) groups. During the redo procedure, the posterior PVR rate with MEDForce (2%, 1/50 PV pairs) was significantly less than with either ControlNoForce (17.7%, 44/249 PV pairs; P = 0.004) or ControlForce (22.5%, 9/40 PV pairs; P = 0.003), or aggregate Controls (18.3%, 53/289 PV pairs; P = 0.006). However, the anterior PVR rate with MEDForce (8%, 4/50 PV pairs) was not significantly different than Controls (aggregate Controls-3.5%, 10/289 PV pairs, P = 0.136; ControlNoForce-2.4%, 6/249 PV pairs, P = 0.067; ControlForce-10%, 4/40 PV pairs, P = 1.0)., Conclusion: Oesophageal deviation improves the durability of the posterior wall ablation lesion set during AF ablation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Pulsed field ablation (PFA) is a uniquely tissue-selective, nonthermal cardiac ablation modality. Delivery parameters such as the electrical waveform composition and device design are critical to PFA's efficacy and safety, particularly tissue specificity. In a series of preclinical studies, we sought to examine the electrophysiological and histological effects of PFA and compare the safety and feasibility of durable pulmonary vein and superior vena cava (SVC) isolation between radiofrequency ablation and PFA waveforms., Methods: A femoral venous approach was used to gain right and left atrial access under general anesthesia in healthy swine. Baseline potentials in right superior pulmonary and inferior common vein and in SVC were assessed. Bipolar PFA was performed with monophasic (PFA Mono ) and biphasic (PFA Bi ) waveforms in 7 and 7 swine sequentially and irrigated radiofrequency ablation in 3 swine. Vein potentials were then assessed acutely, and at ≈10 weeks; histology was obtained., Results: All targeted veins (n=46) were successfully isolated on the first attempt in all cohorts. The PFA Bi waveform induced significantly less skeletal muscle engagement. Pulmonary vein isolation durability was assessed in 28 veins: including the SVC, durability was significantly higher in the PFA Bi group (18/18 PFA Bi , 10/18 PFA Mono , 3/6 radiofrequency, P =0.002). Transmurality rates were similar across groups with evidence of nerve damage only with radiofrequency. Pulmonary vein narrowing was noted only in the radiofrequency cohort. The phrenic nerve was spared in all cohorts but at the expense of incomplete SVC encirclement with radiofrequency., Conclusions: In this chronic porcine study, PFA-based pulmonary vein and SVC isolation were safe and efficacious with demonstrable sparing of nerves and venous tissue. This preclinical study provided the scientific basis for the first-in-human endocardial PFA studies.

Aims: Subclinical brain damage due to microembolization could occur during catheter ablation procedures. We evaluated the microembolic signals (MESs) detected by transcranial Doppler during ablation of supraventricular tachycardias (SVTs) or idiopathic ventricular arrhythmias (VAs) with the use of different approaches., Methods and Results: This study included 36 patients (23 men, 49 ± 21 years) who underwent catheter ablation of SVTs (n = 27) or idiopathic VAs (n = 9). Left-sided ablation was performed by either a transaortic (Group 1, n = 11) or transseptal approach (Group 2, n = 9). A sole right-sided ablation was performed in the remaining 16 patients (Group 3). The MESs were counted throughout the procedure, and then analysed offline with a frequency analysis. The mean number of radiofrequency applications, total energy delivery time, total application energy, and total procedure time were 5.8 ± 5.0, 4.3 ± 3.3 min, 6625 ± 4633 J, and 81 ± 40 min, respectively, and there was no significant difference in the parameters between the three groups. The mean total number of MESs was 3.8 ± 3.1 in Group 1, 75 ± 58 in Group 2, and 0.3 ± 0.6 in Group 3 (P = 0.001). Few MESs were detectable during the radiofrequency energy deliveries in all groups. In Group 2, 19 ± 18 MESs were detected during the transseptal puncture period, and subsequently a relatively even distribution of emboli formation was observed. A frequency analysis suggested that 99, 91, and 100% of MESs were gaseous, in Group 1, Group 2, and Group 3, respectively. No neurological impairment was observed in any patients after the procedure., Conclusion: The retrograde aortic approach might potentially have a lower risk of subclinical brain damage than the transseptal approach during left-sided catheter ablation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Atrial fibrillation ablation is associated with substantial risks of silent cerebral events (SCEs) or silent cerebral lesions. We investigated which procedural processes during cryoballoon procedures carried a risk., Methods and Results: Forty paroxysmal atrial fibrillation patients underwent pulmonary vein isolation using second-generation cryoballoons with single 28-mm balloon 3-minute freeze techniques. Microembolic signals (MESs) were monitored by transcranial Doppler throughout all procedures. Brain magnetic resonance imaging was obtained pre- and post-procedure in 34 patients (85.0%). Of 158 pulmonary veins, 152 (96.2%) were isolated using cryoablation, and 6 required touch-up radiofrequency ablation. A mean of 5.0±1.2 cryoballoon applications was applied, and the left atrial dwell time was 76.7±22.4 minutes. The total MES counts/procedures were 522 (426-626). Left atrial access and Flexcath sheath insertion generated 25 (11-44) and 34 (24-53) MESs. Using radiofrequency ablation for transseptal access increased the MES count during transseptal punctures. During cryoapplications, MES counts were greatest during first applications (117 [81-157]), especially after balloon stretch/deflations (43 [21-81]). Pre- and post-pulmonary vein potential mapping with Lasso catheters generated 57 (21-88) and 61 (36-88) MESs. Reinsertion of once withdrawn cryoballoons and subsequent applications produced 205 (156-310) MESs. Touch-up ablation generated 32 (19-62) MESs, whereas electric cardioversion generated no MESs. SCEs and silent cerebral lesions were detected in 11 (32.3%) and 4 (11.7%) patients, respectively. The patients with SCEs were older than those without; however, there were no significant factors associated with SCEs., Conclusions: A significant number of MESs and SCE/silent cerebral lesion occurrences were observed during second-generation cryoballoon ablation procedures. MESs were recorded during a variety of steps throughout the procedure; however, the majority occurred during phases with a high probability of gaseous emboli., (© 2017 American Heart Association, Inc.)

Objectives: This study sought to compare a novel lesion dimension estimation approach to actual measurements of lesion dimensions on necropsy in porcine atria and ventricles., Background: An irrigated-tip, force-sensing radiofrequency catheter with 6 temperature (tip-tissue interface) sensors allows for assessment of lesion dimensions based on estimated tissue temperature. Lesion dimension assessment has not been attempted previously in atrial tissue., Methods: Ablations were performed using this catheter in all chambers. Irrigated radiofrequency was delivered using 20 to 50 W for durations that ranged from 15 to 90 s with contact force ranging from 5 to 45 g to replicate a wide spectrum of clinical conditions. All swine were then sacrificed and lesions were identified and photographed. Three independent observers made offline measurements, which were then averaged to obtain lesion width and depth for comparison with estimated dimensions based on interface tissue temperature., Results: In 9 swine, 54 atrial and 61 ventricular lesions were assessed. In the atria, the mean difference between the measured and estimated depth and width was 0.9 ± 0.74 mm and 1.2 ± 0.9 mm, respectively. Eighty percent of all lesions had a difference of ≤1.7 mm for depth and ≤1.74 mm for width. In the ventricle, the mean difference between the measured and estimated depth and width was 0.75 ± 0.6 mm and 1.66 ± 1.1 mm, respectively. Eighty percent of all lesions had a difference of ≤1.1 mm ventricular depth and ≤2.6 mm for width., Conclusions: Estimation of lesion dimensions can be achieved with clinically relevant accuracy using unique temperature signatures. These data have important implications for understanding the adequacy of lesion overlap and assessment of transmurality., (Copyright © 2017. Published by Elsevier Inc.)

Background: Saline irrigation improved the safety of radiofrequency (RF) ablation, but the thermal feedback for energy titration is absent., Objectives: To allow temperature-controlled irrigated ablation, a novel irrigated RF catheter was designed with a diamond-embedded tip (for rapid cooling) and 6 surface thermocouples to reflect tissue temperature. High-resolution electrograms (EGMs) from the split-tip electrode allowed rapid lesion assessment. The authors evaluated the preclinical and clinical performance of this catheter for pulmonary vein (PV) isolation., Methods: Using the DiamondTemp (DT) catheter, pigs (n = 6) underwent discrete atrial ablation in a temperature control mode (60°C/50 W) until there was ∼80% EGM amplitude reduction. In a single-center clinical feasibility study, 35 patients underwent PV isolation with the DT catheter (study group); patients were planned for PV remapping after 3 months, regardless of symptomatology. A control group included 35 patients who underwent PV isolation with a standard force-sensing catheter., Results: Porcine lesion histology revealed transmurality in 51 of 55 lesions (92.7%). In patients, all PVs were successfully isolated; no char or thrombus formation was observed. Compared with the control group, the study cohort had shorter mean RF application duration (26.3 ± 5.2 min vs. 89.2 ± 27.2 min; p < 0.001), shorter mean fluoroscopic time (11.2 ± 8.5 min vs. 19.5 ± 6.8 min; p < 0.001), and lower acute dormant PV reconduction (0 of 35 vs. 5 of 35; p = 0.024). At 3 months, 23 patients underwent remapping: 39 of 46 PV pairs (84.8%) remained durably isolated in 17 of these patients (73.9%)., Conclusions: This first-in-human series demonstrated that temperature-controlled irrigated ablation produced rapid, efficient, and durable PV isolation. (ACT DiamondTemp Temperature-Controlled and Contact Sensing RF Ablation Clinical Trial for Atrial Fibrillation [TRAC-AF]; NCT02821351)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although percutaneous left ventricular assist devices (pLVADs) facilitate mapping and ablation of hemodynamically unstable ventricular tachycardia (VT), there is limited data whether clinical outcomes are improved. We sought to retrospectively compare the outcomes of patients undergoing scar-related VT ablation with and without pLVAD support., Methods and Results: The study population comprised 194 patients (109 pLVAD and 85 non-pLVAD). The pLVAD group more often had dilated cardiomyopathy (33% versus 13%; P =0.001), New York Heart Association heart failure class ≥III (51% versus 25%; P <0.001), lower left ventricular ejection fractions (26±10% versus 39±16%; P <0.001), and electrical storm (49% versus 34%; P =0.04). Procedure times (422±112 versus 330±92 minutes; P <0.001), postablation VT inducibility (20% versus 7%; P =0.02), and length of subsequent hospitalization (median 6 versus 4 days; P =0.001) were all higher in the pLVAD group. During median follow-up of 215 days, the primary end point (recurrent VT, heart transplantation, or death) occurred in 36% of the pLVAD versus 26% of the non-pLVAD groups ( P =0.14). After propensity matching for differences between groups, no differences were seen between groups for both acute procedural outcomes and the primary end point., Conclusions: In this large single-center scar-related VT ablation experience, despite the worse clinical status of the patients selected for pLVAD support, clinical outcomes were better than expected and were similar to healthier patients not receiving hemodynamic support. Patients with dilated cardiomyopathy presenting with electrical storm, advanced heart failure, and severe left ventricular dysfunction most frequently received hemodynamic support during VT ablation., (© 2017 American Heart Association, Inc.)

Although making artificial micrometric swimmers has been made possible by using various propulsion mechanisms, guiding their motion in the presence of thermal fluctuations still remains a great challenge. Such a task is essential in biological systems, which present a number of intriguing solutions that are robust against noisy environmental conditions as well as variability in individual genetic makeup. Using synthetic Janus particles driven by an electric field, we present a feedback-based particle-guiding method quite analogous to the "run-and-tumbling" behavior of Escherichia coli but with a deterministic steering in the tumbling phase: the particle is set to the run state when its orientation vector aligns with the target, whereas the transition to the "steering" state is triggered when it exceeds a tolerance angle [Formula: see text] The active and deterministic reorientation of the particle is achieved by a characteristic rotational motion that can be switched on and off by modulating the ac frequency of the electric field, which is reported in this work. Relying on numerical simulations and analytical results, we show that this feedback algorithm can be optimized by tuning the tolerance angle [Formula: see text] The optimal resetting angle depends on signal to noise ratio in the steering state, and it is shown in the experiment. The proposed method is simple and robust for targeting, despite variability in self-propelling speeds and angular velocities of individual particles.

Background: The exact circuit responsible for the atrioventricular (AV) nodal reentrant tachycardia (AVNRT) is still unknown. We evaluated the optimal slow pathway ablation area in patients with and without 2:1 AV conduction during the slow-fast AVNRT., Methods: Among 207 consecutive patients with slow-fast AVNRT who underwent slow pathway ablation, 12 (5.8 %) patients who had 2:1 AV conduction during tachycardia (group A) were included. Fifty-nine patients without 2:1 AV conduction during tachycardia or a lower common pathway (group B) were included as a control group. We measured the fluoroscopic vertical distance on the 45° left anterior oblique view between the optimal slow pathway ablation area and His bundle electrogram (HBE) recording site (height AH) and between the coronary sinus ostium and HBE site (height CH). The horizontal distances (width AH, width CH) on the 30° right anterior view were also measured., Results: The tachycardia cycle length (300 ± 39 vs. 371 ± 71 ms, p = 0.001) and AH interval during tachycardia (259 ± 33 vs. 324 ± 69 ms, p = 0.001) were significantly shorter in group A than in group B. The height AH/height CH was significantly smaller in group A than in group B (0.62 ± 0.15 vs. 0.76 ± 0.27, p = 0.034) whereas height CH was similar between the two groups (22.8 ± 6.4 vs. 23.4 ± 7.5 mm, p = 0.84). The width CA and width CH were similar between the two groups. Slow pathway ablation was successfully achieved in all 71 patients without any complications. The number of applications tended to be greater in group A than in group b; however, the difference did not reach statistical significance (8.8 ± 8.0 vs. 5.2 ± 5.2, p = 0.147)., Conclusions: The optimal slow pathway ablation area was located at a more superior position in group A than in group b.

Background: Optimal freeze doses are unknown during cryothermal cavo-tricuspid isthmus (CTI) ablation. This study aimed to evaluate the feasibility of 2-minute freeze doses for CTI ablation., Methods: Forty-eight consecutive patients undergoing cryothermal CTI ablation following pulmonary vein isolation were enrolled. CTI ablation was performed with 2-minute freeze cycles and 8-mm tip cryocatheters., Results: Bidirectional CTI block was successfully achieved in 45(93.8%) patients with a median of 5.0[4.0-6.0] cryocatheter applications. The total procedure and fluoroscopic times were a median of 16.5[13.0-20.0] and 4.0[2.0-5.0]min, respectively. A crossover to radiofrequency was performed in 3 patients including 1 due to coronary spasms during the cryoapplication. The tip temperature when block was achieved was a median of -81.0[-73.3 - -84.0]°C. Application times from the start of the last application to achieving block were significantly longer in patients with acute conduction resumption than in those without (46.8±4.0 vs. 20.2±8.8s, p<0.0001), and the optimal cutoff point for predicting no acute resumption was 38.5s (sensitivity 100%, specificity 99.5%). Vasospastic angina occurred in 2 patients, during the procedure in 1 and after in another. Durability could be evaluated a median of 6.0[3.0-8.0] months after the procedure in 14 patients, and conduction resumption was observed in 8(57.1%). The majority of gaps were located at the inferior vena cava edge., Conclusions: Acute CTI block was obtained by 2-minute freeze cycles with short procedure and fluoroscopic times. Care should be taken to avoid coronary spasms during the peri-procedural period. Additional cryoapplications might be required to improve conduction block durability., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Monitoring luminal esophageal temperatures (LETs) helps predict esophageal thermal lesions (ETLs) after catheter ablation. This study aimed to evaluate esophagus-related complications after second-generation cryoballoon ablation under simultaneous LETs monitoring from 2 esophageal probes., Methods: Forty consecutive paroxysmal atrial fibrillation patients undergoing second-generation cryoballoon ablation under conscious sedation followed by esophagogastroscopy were prospectively included. Two temperature probes inserted bi-nasally (both non-deflectable in 13, non-deflectable and deflectable in 27 patients) were used for LET monitoring. Pulmonary vein isolation was performed with one 28-mm balloon using single 3-minute freeze techniques., Results: The lowest LETs significantly correlated between different probes; however, deflectable probe showed significantly lower nadir LETs than non-deflectable probes (14.6 ± 9.2 vs. 20.0 ± 10.6 ℃, P<0.0001). Esophagogastroscopy post-ablation demonstrated ETLs and gastroparesis in 8 (20%) and 7 (17.5%) patients (total 13 [32.5%]), respectively. The optimal cutoff for the lowest LET measured on any probe for predicting no ETLs was 12.8 ℃ (sensitivity 78.1%, specificity 100%). When using deflectable and non-deflectable catheters, the optimal cutoff point for the lowest LET for predicting no ETLs was 11.4 ℃ (sensitivity 70.0%, specificity 100%) and 19.4 ℃ (sensitivity 63.6%, specificity 100%), respectively. No ETLs were detected in 12 (30%) patients with the esophagus located between the left atrium and spine. All esophagus-related complications were asymptomatic and had healed on repeat esophagogastroscopy by a mean of 53 ± 25 days after the procedure., Conclusions: The lowest LET highly depended on the temperature probe location. However, if a different cutoff value was applied, LET monitoring, regardless of the probe type, and anatomical information might help predict ETLs during second-generation cryoballoon ablation., (© 2016 Wiley Periodicals, Inc.)

Objectives: This study aimed to evaluate the incidence and pre-procedural predictors of right phrenic nerve injury (PNI) in electromyography-guided, second-generation cryoballoon (CB) ablation., Background: Second-generation CBs perform better pulmonary vein isolation (PVI) than first-generation CBs; however, right PNI remains a concern., Methods: One hundred consecutive patients with paroxysmal atrial fibrillation who underwent cryoablation were prospectively enrolled. Contrast-enhanced cardiac multidetector computed tomography (MDCT) was obtained pre-procedurally. PVI was performed with one 28-mm second-generation balloon using a 3-min freeze technique under electromyography guidance., Results: In all, 377 of 392 (96.2%) PVs were isolated using a CB. In 9 (9.0%) patients, right PNI was observed during the ablation of the right superior PV (RSPV). All events occurred during freezing, except for 1 that occurred during thawing. Right peri-cardiophrenic bundles (RPCBs) were identified at the level of the RSPV on MDCT in 97 patients. In the logistic regression analysis, the distance from the RSPV ostium to the RPCBs (hazard ratio: 0.263; 95% confidence interval [CI]: 0.110 to 0.630; p = 0.003) was the sole predictor of PNI. The optimal cutoff point for the distance for predicting right PNI was 12.4 mm (sensitivity 96.6%, specificity 88.9%) with an area under the curve of 0.968 (95% CI: 0.922 to 1.000). The PNI resolved spontaneously within 1 day and 2 months in 6 and 2 patients, respectively, and at 8 months in the remaining patient, with delayed recognition of an electromyography decrease., Conclusions: Persistent right PNI is a rare complication during electromyography-guided, second-generation CB ablation. Electromyography should be monitored even during the thawing time. Pre-procedural MDCT might be useful for risk stratification of right PNI., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The mini electrodes (ME) placed on the tip of the ablation electrode provide more precise local signal. We evaluated whether ME catheter was effective for the ablation of cavotricuspid isthmus (CTI)-dependent atrial flutter., Methods and Results: Eighty-five consecutive patients (68 men; 62 ± 10 years) underwent CTI ablation either using a catheter equipped with ME on the 8 mm tip (ME catheter) in 25 patients (Group A), 8 mm dumbbell-shaped (DS) tip catheter (DS catheter) in 30 patients (Group B), or 8 mm tip cryothermal catheter (Cryo catheter) in 30 patients (Group C). In cases of failed isthmus block, the catheter was changed to the other catheter, but patients remained in the original group following intention-to-treat analysis. The endpoint was achieved in all patients after 13 ± 7 applications in Group A, 9 ± 4 applications in Group B, and 5 ± 2 applications in Group C (P < 0.001). The fluoroscopic and procedure times were significantly longer in Group A (9 ± 7 and 28 ± 17 min, P = 0.001, and P = 0.002, respectively) when compared with Groups B (6 ± 4 and 13 ± 6 min) and C (4 ± 3 and 14 ± 7 min). A crossover was performed in 14 (56%) Group A patients, and 3 (10%) Group C patients. The mean power delivered in Group A was significantly lower than in Group B (31.3 ± 9.1 vs. 38.6 ± 7.6 W, P = 0.015)., Conclusion: The ME catheter was found to be less effective than the Cryo catheter and a DS catheter for the CTI ablation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Radiofrequency applications around pulmonary vein (PV) ostia often induce vagal reflexes., Objective: This study aimed to evaluate the impact of the order of the targeted PV on the vagal response during second-generation cryoballoon ablation., Methods: Eighty-one consecutive paroxysmal atrial fibrillation (AF) patients undergoing cryoballoon ablation were prospectively enrolled. PV isolation was performed with one 28-mm second-generation balloon using a 3-minute freeze technique. In the first 39 patients, the left superior PV (LSPV) was initially targeted. In the second 42, the LSPV was targeted following the right PVs., Results: Baseline rhythms were sinus rhythm and AF in 34 and 5 patients in the first group, and 34 and 8 in the second group, respectively. In the first group, sinus bradycardia/arrest requiring back-up pacing occurred in 13 patients (38.2%) at a median of 41.0 (10.0-55.5) seconds after balloon deflation (90 [60-100] seconds post freezing), and pauses requiring pacing in 1 (20.0%) with AF. In the second group, no sinus bradycardia/arrest occurred throughout the procedure; however, atrioventricular block requiring back-up pacing occurred 21 seconds after balloon deflation in 1 patient in whom right superior PV (RSPV) ablation was performed for only 60 seconds owing to right phrenic nerve injury. The cycle length was similar at baseline and post PV isolation between the 2 groups, and significantly shorter during RSPV ablation (P < .0001) in both. In total, marked vagal responses were significantly higher in the first than second group (14/39 vs 1/42, P < .0001)., Conclusions: LSPV cryoballoon ablation often provoked marked vagal responses; however, preceding RSPV ablation markedly suppressed this response., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The post-second-generation cryoballoon (CB) ablation isolation area during the chronic phase has not been described. The aim of this study was to quantitatively evaluate the chronic-phase isolation area after 28-mm second-generation CB ablation and compare it to the estimated conventional radiofrequency circumferential pulmonary vein isolation (CPVI) line., Methods and Results: Thirty-two patients with paroxysmal atrial fibrillation underwent pulmonary vein (PV) isolation using second-generation CB. After a median of 6.0 (4.0-9.0) months, the PV isolation area was evaluated using high-resolution mapping (1-mm electrode, 2-mm interelectrode spacing; 527±99 points per map) and pacing techniques in all patients (17 with and 15 without arrhythmia recurrence beyond blanking period) and compared with estimated conventional radiofrequency CPVI area. PV reconnections were observed in 34 of 126 PVs (27.0%) among 21 of 32 patients (65.6%), which were eliminated by a median of 1.0 (1.0-3.0) focal radiofrequency application. The left- and right-sided PV antrum isolation area and nonablated posterior wall areas were 9.8±1.7, 8.1±2.3, and 17.0±6.1 cm(2), respectively. The cryoablated areas were significantly smaller than the estimated conventional radiofrequency CPVI areas in all but the right inferior PV. The difference was highest in the left superior PV. In 2 patients (6.3%), recurrent atrial fibrillation originated from the foci identified at the left superior PV antrum outside the CB isolation area but inside the estimated conventional radiofrequency CPVI line., Conclusions: Although the PV isolation areas during the chronic phase after the second-generation CB ablation were generally wide, they were significantly smaller than the area encircled by the CPVI line except at the right inferior PV antrum. Recurrent atrial fibrillation could originate from the left superior PV antrum and could be isolated by a CPVI but not by a CB., (© 2016 American Heart Association, Inc.)

Background: Right phrenic nerve injury (PNI) is a major concern during superior vena cava (SVC) isolation due to the anatomical close proximity. The functional and histological severity of PNI parallels the degree of the reduction in the compound motor action potential (CMAP) amplitude. This study aimed to evaluate the feasibility of monitoring CMAPs during SVC isolation to anticipate PNI during atrial fibrillation (AF) ablation., Methods: Thirty-nine paroxysmal AF patients were prospectively enrolled. Radiofrequency energy was delivered point-by-point for 30 seconds with 20 W until eliminating all SVC potentials after the pulmonary vein isolation. Right diaphragmatic CMAPs were obtained from modified surface electrodes by pacing from the right subclavian vein. Radiofrequency applications were applied without fluoroscopy under CMAP monitoring at sites with phrenic nerve capture by high output pacing., Results: Electrical SVC isolation was successfully achieved with a mean of 9.4 ± 3.3 applications in all patients. In 3 (7.5%) patients, the SVC was isolated without radiofrequency delivery at phrenic nerve capture sites. Among a total of 346 applications in the remaining 36 patients, 71 (20.5%) were delivered while monitoring CMAPs. In 1 (1.4%) application, the RF application was interrupted due to a decrease in the CMAP amplitude. However, no PNI was detected on fluoroscopy, and the decreased amplitude recovered spontaneously. The remaining 70 (98.6%) applications exhibited no significant changes in the CMAP amplitude throughout the applications (from 1.01 ± 0.47 to 0.98 ± 0.45 mV, P = 0.383)., Conclusions: Stable right diaphragmatic CMAPs could be obtained, and monitoring CMAPs might be useful for anticipating right PNI during SVC isolation., (© 2016 Wiley Periodicals, Inc.)

Background: Right phrenic nerve injury (PNI) is a major concern during superior vena cava (SVC) isolation. Phrenic nerve (PN) localization by high-output pacing is a standard technique for anticipating PNI. This study evaluated the impact of catheter contact force (CF) on SVC mapping and PN localization., Methods: Twenty-one atrial fibrillation patients undergoing cardiac enhanced computed tomography (CT) were prospectively enrolled. SVC geometries were created at the SVC-right atrium junction level with low (<10 × g) and high (>10 × g) CFs. The PN was localized by high-output pacing (10 V, 2 milliseconds) at the SVC and anterior right superior pulmonary vein (RSPV) with different CFs., Results: The SVC cross-sectional area was significantly greater when created with high (22.1 ± 4.9 × g) compared with low CFs (4.2 ± 1.3 × g) (5.3 ± 1.4 cm2 vs. 2.3 ± 0.7 cm2 , P < 0.0001). High CFs distorted the SVC and anterior RSPV by a mean of 4.8 ± 2.5 and 4.4 ± 1.7 mm, with minimal distortion at the anteroseptal SVC. The PN was more frequently captured with a high compared with low CF at the SVC (95.2% vs. 71.4%, P = 0.038) and RSPV (66.7% vs. 14.3%, P = 0.0005). The PN capture area was also wider with a high compared with low CF at the SVC (9.0 ± 4.1 mm vs. 4.5 ± 2.8 mm, P = 0.001). The PN location was at the anterolateral, lateral, and posterolateral SVC in 3 (14.3%), 13 (61.9%), and 5 (23.8%) patients, respectively, which was identical to that identified on CT. No PNs located >1.98 mm from the RSPV were captured by RSPV pacing., Conclusions: CF impacted the SVC mapping and PN localization. Cardiac CT identified the PN location, and the distance from the pacing site influenced PN capture., (© 2015 Wiley Periodicals, Inc.)

Background: Cardiac computed tomography (CT) provides accurate imaging of the pulmonary vein (PV) and left atrial (LA) anatomy. This study aimed to evaluate the prevalence and morphological characteristics of anatomical variants that could influence atrial fibrillation (AF) ablation procedures., Methods and Results: One thousand forty consecutive patients (62±10 years, 243 female, 644 paroxysmal AF) undergoing pre-procedural imaging with a 320-row CT and their first AF ablation procedure were analyzed. A total of 194 (18.7%) patients had anatomical variants. Left, right, and inferior common PVs were observed in 118, 5, and 6 patients, respectively. Three right and left PVs were observed in 44 and 4 patients, respectively. Three patients had remnants of PVs after lobectomies, and significant PV stenosis was observed in one. Supernumerary PVs that drained into the LA and diverticula were observed in eight patients. One patient had a string-like structure connecting the LA septum and posterior LA, and the others had membranous structures incompletely compartmentalizing the LA. Three patients had persistent left superior vena cavae, two strong deviations of the LA and PVs, and one dexiocardia. All patients underwent successful PV isolation during the index procedure., Conclusions: Patients referred for AF ablation often have anatomical variants, which could influence the procedure. This information might aid in planning procedural strategies, and reducing unexpected procedural complications in AF ablation., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Inflammation plays a prominent role in the etiology of the early recurrence of atrial fibrillation (ERAF). We prospectively compared the proportion of ERAF and time-course patterns of biomarkers between radiofrequency (RF) and cryoballoon (CB) ablation., Methods and results: We enrolled 82 consecutive paroxysmal AF patients undergoing pulmonary vein (PV) isolation, performed with either a 28-mm 2nd-generation CB and 3-min freeze technique or point-by-point RF ablation. Each group had 41 patients. In the RF group, all PVs were successfully isolated with 28.9 ± 6.5 min of RF delivery. In the CB group, a mean of 5.3 ± 1.4 applications/patient was delivered. The proportion of ERAF was similar between the groups. The time-course patterns significantly differed between the groups for high-sensitivity C-reactive protein (hs-CRP) value (P=0.006) and myocardial injury markers (P<0.0001). Greater myocardial injury was observed in the CB than in the RF group (P<0.0001), whereas the peak hs-CRP value was comparable between the groups. The 2-day post-procedure hs-CRP value was the sole factor correlating with ERAF as identified by the multivariable analysis (hazard ratio 1.697; 95% confidence interval, 1.005-2.865; P=0.048) in the RF, but not the CB group., Conclusions: The proportion of ERAF was comparable after RF and 2nd-generation CB ablation. Despite CB ablation exhibiting greater myocardial injury than RF ablation, the inflammatory responses were comparable between the groups. The inflammatory response extent predicted ERAF post-RF ablation but not post-CB ablation.

Background: Radiofrequency ablation of the right superior pulmonary vein (RSPV) can lead to inadvertent superior vena cava (SVC) isolation due to the close anatomical proximity. This study aimed to evaluate the impact of PV isolation on SVC potentials with a second-generation cryoballoon., Methods: Thirty-one consecutive paroxysmal atrial fibrillation patients who underwent PV isolation exclusively with a 28 mm second-generation cryoballoon and single 3-minute freeze technique were prospectively enrolled. The produced SVC potential conduction delay during the RSPV isolation was prospectively evaluated using circular mapping catheters placed in the SVC throughout the cryoballoon procedure., Results: Stable SVC potentials were recorded in 28 (90.3%) patients. The produced SVC potential conduction delay during the RSPV isolation was a median of 6.0 (0.5-7.6) milliseconds, and >5.0 milliseconds in 16 (57.1%) patients. Among them, the delay had shortened by >5.0 milliseconds in 7 (43.8%) patients within 5 minutes after the RSPV application. The distance between the RSPV ostium and SVC was the sole parameter correlated with the produced delay (R = 0.77, P < 0.0001). For the association between the distance and a produced delay of >5 milliseconds, the area under the curve was 0.896 (95% confidential interval = 0.775-1.000). The optimal cutoff point for the distance predicting the occurrence of the conduction delay (>5 milliseconds) was 2.5 mm (sensitivity 83.3%, specificity 81.2%)., Conclusions: RSPV isolation with a second-generation cryoballoon could produce an SVC potential conduction delay. The anatomical distance between the RSPV and SVC significantly correlated with the impact., (© 2015 Wiley Periodicals, Inc.)

Aims: This study aimed to evaluate the electrocardiographic characteristics and predictors of successful ablation for ventricular arrhythmias (VAs) with superior axis originating in the ventricular septum., Methods and Results: This study included 385 consecutive patients with VAs undergoing radiofrequency ablation (RFA). Of these, 14 patients (3.7%) were identified who had VAs with superior axis that were mapped to and ablated at the left ventricular (LV) septum. These patients were classified into two groups, successful (n = 9, Success-RFA) and failed (n = 5, Fail-RFA) ablation. The QRS duration of the VAs was longer in the Success-RFA than the Fail-RFA [median (25%, 75% quartile), 140 (134, 149) vs. 128 (116, 132) ms; P = 0.007]. In the Success-RFA, the QRS morphology in lead V1 exhibited qR or rSR (r < 0.2 mV) pattern. In the Fail-RFA, QRS in lead V1 demonstrated an initial R-wave of ≥0.2 mV except for one patient who demonstrated a qR pattern. The initial R-wave amplitude of <0.2 mV in lead V1 identified successful ablation cases with 100% sensitivity and 80% specificity. The magnitude of the initial R-wave amplitude in lead V1 could be related to the originating site's depth within the septal tissue, which could also explain the RFA results., Conclusion: Four percent of VA patients had superior axis on electrocardiogram and foci that mapped to the LV septum, two-thirds of which were successfully ablated. The initial R-wave amplitude of <0.2 mV in lead V1 identified RFA success with high sensitivity and specificity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Adenosine triphosphate (ATP) testing reveals dormant pulmonary vein (PV) conduction after electrical PV isolation (PVI). This study aimed to evaluate the incidence of latent PV conduction after cryothermal PVI., Methods: Fifty-four consecutive paroxysmal atrial fibrillation patients undergoing cryothermal PVI were prospectively enrolled. PVI was performed with one 28-mm second-generation balloon using a 3-minute freeze technique, and touch-up lesions were created by focal cryothermal applications. ATP testing was performed following PVI with a 20-mm circular mapping catheter placed in each PV., Results: Of 217 PVs, 205 (94.5%) were isolated using a cryoballoon, and 12 required additional focal ablation. ATP testing was performed in 46 patients for 173 and 8 PVs, which were isolated by cryoballoons and focal ablation, respectively. No dormant PV conduction was provoked in any PVs, which were isolated by cryoballoons, whereas 4 (50.0%) out of 8 PVs requiring focal ablation had transient ATP-provoked reconnections (0 vs. 50.0%, P < 0.0001) with a median duration of 11.3 (10.7-17.1) seconds. The latent PV conduction site was identical to the residual conduction gap site after cryoballoon ablation in all. All latent conduction was successfully eliminated by 2 (2.0-9.5) additional focal applications. At a mean follow-up of 7.7 ± 1.6 months, 81.5% of the patients were arrhythmia free after a single procedure., Conclusions: No dormant PV conduction was provoked in PVs, which were isolated by 28-mm second-generation cryoballoons, but was provoked in 50% of PVs, which were isolated by focal cryoablation. These findings suggest that creating contiguous lesions is essential for eliminating dormant conduction in cryothermal ablation., (© 2015 Wiley Periodicals, Inc.)

Background: Left phrenic nerve injury (PNI) can occur during cryoballoon ablation of the left pulmonary veins (PVs). This study aimed to evaluate the feasibility of monitoring the bilateral phrenic nerve function during cryoballoon ablation of atrial fibrillation (AF)., Methods: Fifty consecutive paroxysmal AF patients undergoing cryoballoon ablation using one 28-mm second-generation balloon were prospectively enrolled. Bilateral diaphragmatic compound motor action potentials (CMAPs) were obtained from modified surface electrodes by pacing from the bilateral subclavian veins, and monitored during 3-minute cryoballoon applications at the ipsilateral PVs., Results: One hundred ninety of 202 PVs were successfully isolated exclusively using 28-mm cryoballoons. CMAPs could be obtained in all except 3 cases with catheter inaccessibility in the left subclavian vein. The left and right CMAP amplitudes were similar at baseline (1.04 ± 0.41 mV vs. 1.01 ± 0.43 mV, P = 0.49). Among 105 left and 132 right PV applications while monitoring CMAPs, 2 (1.9%) and 13 (9.8%) applications were interrupted for a decreased CMAP amplitude (P = 0.01). Among them, CMAPs decreased due to right PNI in 4 applications/patients and to catheter dislodgement in the remaining applications. PNI remained in 1 and recovered in the remaining 3 patients one day after the procedure. Applications without requiring interruptions exhibited no significant CMAP amplitude changes throughout the applications, and the time-course pattern was similar between the bilateral CMAPs (P = 0.292)., Conclusions: A stable bilateral diaphragmatic CMAP could be similarly obtained during cryoballoon applications in the vast majority of patients. Monitoring CMAPs might be useful to anticipate not only right but also left PNI during cryoballoon ablation., (© 2015 Wiley Periodicals, Inc.)

Objectives: The goal of this study was to systematically investigate the incidence and clinical significance of non-pulmonary vein (PV) foci revealed by adenosine/adenosine triphosphate (ATP) testing during atrial fibrillation (AF) ablation., Background: ATP is reported to provoke AF., Methods: A total of 464 patients with consecutive paroxysmal AF undergoing ATP testing after PV antrum isolation were included., Results: AF originating from non-PV foci was provoked in 26 (5.6%) total patients during first (n = 20) or repeat (n = 8) ablation procedures. Dormant PV conduction was also revealed by ATP testing in 6 patients. Non-PV foci were located in the superior vena cava (SVC) (i.e., the SVC group) and atria (i.e., the atria group) in 10 and 18 (9 each in the right and left atria) patients, respectively. In the multivariable analysis, being female was the sole independent predictor of ATP-provoked AF originating from non-PV foci (hazard ratio [HR]: 2.52 [95% confidence interval (CI): 1.069 to 5.929]; p = 0.034). After additional ablation targeting non-PV foci, freedom from recurrent AF after the last procedure was similar between the SVC group and patients without ATP-provoked AF but was significantly lower in the atria group than in others (p = 0.0008). Atria group membership (HR: 3.725 [95% CI: 1.692 to 8.199]; p = 0.001) and being female (HR: 1.538 [95% CI: 1.189 to 1.989]; p = 0.001) were significant independent predictors associated with recurrence after the last procedure in the multivariable Cox regression model., Conclusions: ATP provoked AF originating from non-PV foci under isoproterenol in 5.6% of patients undergoing paroxysmal AF ablation. ATP testing might be useful for identifying and eliminating AF originating from the SVC. The atria group was associated with a poor outcome after the last procedure despite efforts to eliminate non-PV foci., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The latest guidelines define "long-term success" as freedom from atrial arrhythmia recurrence more than 36 months after procedures without any antiarrhythmic drug therapy., Objective: The purpose of this study was to investigate the clinical outcomes and procedural findings in patients with recurrence beyond "long-term success.", Methods: Among patients who underwent pulmonary vein (PV) antrum isolation for drug-refractory symptomatic paroxysmal atrial fibrillation (AF), 37 in whom recurrent arrhythmias were observed during annual follow-up after "long-term success" and who underwent repeat procedures for recurrent arrhythmias were included in the study., Results: The time from the latest procedure to recurrence was a median of 61 ([25th, 75th percentiles]: [51-77.5]) months. Recurrent arrhythmia type was paroxysmal in 22 patients (59.5%) and persistent in 15 (40.5%). Recurrent arrhythmias were atrial tachycardia (AT) in 13 patients (35.1%), including 8 with AT unrelated to PVs. Repeat procedures were performed a median of 2.0 [1.0-4.0] months after identifying recurrent episodes. Recovered PV conduction was found in 29 patients (78.4%) and non-PV foci in 4 (10.8%). Freedom from recurrence 1 year after repeat procedures was 63.3%. Seven patients (18.9%) underwent further repeat procedures a median of 7.0 [2.0-28.0] months after repeat procedures and had no PV reconnections. In total, AF/AT unrelated to PVs was present in 24 patients (64.9%). In contrast, arrhythmias related to PVs were observed in 2 patients (5.4%) during a total of 46 repeat procedures after "long-term success.", Conclusion: Although PV reconnections were commonly found even after "long-term success," AF/AT unrelated to PVs was assumed to be present in the majority of this population., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)