Left atrial reservoir strain is a marker of atrial fibrotic remodeling in patients undergoing cardiovascular surgery: Analysis of gene expression.

Left atrial strain (LAS) measured by two-dimensional speckle tracking echocardiography (2DSTE) is considered to be a marker of LA structural remodeling, but it remains unsettled. We investigated the potential usefulness and clinical relevance of LAS to detect atrial remodeling including fibrosis by analyzing gene expression in cardiovascular surgery patients. Preoperative 2DSTE was performed in 131 patients (92 patients with sinus rhythm [SR] patients including paroxysmal AF [PAF], 39 atrial fibrillation [AF]) undergoing cardiovascular surgery. Atrial samples were obtained from the left atrial appendages, and mRNA expression level was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) in 59 cases (24 PAF, 35 AF). Mean value of left atrial reservoir strain (mLASr) correlated with left atrial volume index (LAVI), and left atrial conduit strain (mLAScd). mLASr also correlated with left atrial contractile strain (mLASct) in SR patients including PAF. mLASr was significantly lower, and LAVI was higher, in the AF group, compared with SR patients including PAF. The expression of COL1A1 mRNA encoding collagen type I α1 significantly increased in AF patients (p = 0.031). mLASr negatively correlated with COL1A1 expression level, and multivariate regression analysis showed that mLASr was an independent predictor of atrial COL1A1 expression level, even after adjusting for age, sex, and BMI. But, neither mLAScd / mLASct nor LAVI (bp) correlated with COL1A1 gene expression. The expression level of COL1A1 mRNA strongly correlated with ECM-related genes (COL3A1, FN1). It also correlated ECM degradation-related genes (MMP2, TIMP1, and TIMP2), pro-fibrogenic cytokines (TGFB1 encoding TGFß1, END1, PDGFD, CTGF), oxidant stress-related genes (NOX2, NOX4), ACE, inflammation-related genes (NLRP, IL1B, MCP-1), and apoptosis (BAX). Among the fibrosis-related genes examined, univariable regression analysis showed that log (COL1A1) was associated with log (TGFB1) (adjusted R2 = 0.685, p<0.001), log (NOX4) (adjusted R2 = 0.622, p<0.001), log (NOX2) (adjusted R2 = 0.611, p<0.001), suggesting that TGFB1 and NOX4 was the potent independent determinants of COL1A1 expression level. mLASr negatively correlated with the ECM-related genes, and fibrosis-related gene expression level including TGFB1, NOX2, and NLRP3 in PAF patients. PAF patients with low mLASr had higher expression of the fibrosis-related gene expression, compared with those with high mLASr. These results suggest that LASr correlates with atrial COL1A1 gene expression associated with fibrosis-related gene expression. Patients with low LASr exhibit increased atrial fibrosis-related gene expression, even those with PAF, highlighting the utility of LAS as a marker for LA fibrosis in cardiovascular surgery patients.

Narrow QRS ectopy with concealed connections from a para-Hisian origin to the proximal left fascicles.

INTRODUCTION: Catheter ablation of ectopy originating from the vicinity of the His bundle can be challenging. METHODS AND RESULTS: We report a case of a 33-year-old man with narrow QRS ectopy with preferential conduction from a para-Hisian origin to the proximal left fascicles, which was successfully eliminated by radiofrequency ablation in the right coronary cusp, guided by ultrahigh-resolution mapping of the His bundle, bundle branch, and fascicular electrograms. CONCLUSION: Some narrow QRS ectopy may originate from the vicinity of the conduction system, instead of the "true" conduction system, and have concealed connections from its origin to the conduction system.

Electrographic flow mapping of persistent atrial fibrillation: intra- and inter-procedure reproducibility in the absence of 'ground truth'.

AIMS: Validating mapping systems that identify atrial fibrillation (AF) sources (focal/rotational activity) is confounded by the absence of ground truth. A key concern of prior mapping technologies is spatiotemporal instability, manifesting as poor map reproducibility. Electrographic flow (EGF) employs a novel algorithm that visualizes atrial electrical wavefront propagation to identify putative AF sources. We analysed both intra- (3 min) and inter- (>3 months) procedure EGF map reproducibility. METHODS AND RESULTS: In 23 persistent AF patients, after pulmonary vein isolation (PVI), EGF maps were generated from 3 serial 1 min recordings using a 64-electrode basket mapping catheter (triplets) at right and left atrial locations. Source prevalence from map triplets was compared between recordings. Per protocol, 12 patients returned for 3-month remapping (1 non-inducible): index procedure post-PVI EGF maps were compared with initial EGF remapping at 3-month redo. Intra-procedure reproducibility: analysing 224 map triplets (111 right atrium, 113 left atrium) revealed a high degree of map consistency with minimal min-to-min shifts: 97 triplets (43%), exact match of leading sources on all 3 maps; 95 triplets (42%), leading source within 1 electrode space on 2 of 3 maps; and 32 triplets (14%), chaotic leading source pattern. Average deviation in source prevalence over 60 s was low (6.4%). Inter-procedure reproducibility: spatiotemporal stability of EGF mapping >3 months was seen in 16 of 18 (89%) sources mapped in 12 patients with (re)inducible AF. CONCLUSION: Electrographic flow mapping generates reproducible intra- and inter-procedural maps, providing rationale for randomized clinical trials targeting these putative AF sources.

Longitudinal Changes in Natriuretic Peptides and Reverse Cardiac Remodeling in Patients with Heart Failure Treated with Sacubitril/Valsartan Across the Left Ventricular Ejection Traction Spectrum.

Sacubitril/valsartan improves outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the relationship between longitudinal changes in natriuretic peptides and echocardiographic parameters in patients with HF treated with sacubitril/valsartan across the left ventricular ejection fraction (LVEF) range is not fully understood.In patients with HF treated with sacubitril/valsartan, comprehensive data on natriuretic peptides, including atrial natriuretic peptide (ANP), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), BNP, and echocardiography, were measured after 6 months of treatment. We assessed the change in natriuretic peptides and echocardiographic parameters in LVEF classification subgroups.Among 49 patients, the median ANP concentration increased from 55 pg/mL at baseline to 78 pg/mL (P < 0.001). The NT-proBNP concentration decreased from 250 pg/mL to 146 pg/mL (P < 0.001). No significant change was observed in the BNP concentration (P = 0.640). The trajectories of each natriuretic peptide in patients with LVEF > 40% (n = 22) were similar to those in individuals with LVEF ≤ 40% (n = 27). Regardless of LVEF classification, echocardiography at 6 months showed a significant improvement in LVEF, left ventricular end-diastolic volume, and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'). The reduction in natriuretic peptide concentration was related to LV reverse remodeling and decreased left and right atrial pressures assessed by E/e' and inferior vena cava diameter.Sacubitril/valsartan induced an increase in ANP, a reduction in NT-proBNP, and no change in plasma BNP, regardless of LVEF. It caused LV reverse remodeling, and the natriuretic peptide concentration changes were associated with structural and functional echocardiographic parameters.

Comprehensive Unloading Strategy for Rapid Heart Recovery Under Support With Impella.

The establishment of a strategy for rapid heart recovery in patients with cardiogenic shock is required. Impella is a percutaneous left ventricular (LV) assist device that maintains hemodynamic stability and also causes LV mechanical unloading. However, the timing at which Impella should be started and a systematic strategy after the start of Impella have not been established. We report a representative case of dilated cardiomyopathy requiring catecholamines and intra-aortic balloon pumping (IABP). The hemodynamics were unstable under IABP support, and withdrawal from IABP or catecholamines was considered impossible. However, the exchange of the IABP with Impella CP made it possible to suppress the heart rate with ivabradine, introduce intensive heart failure medication, and discontinue catecholamines. The patient was weaned from Impella 24 days after the start of the first Impella CP. Rapid heart recovery was achieved with favorable outcomes. We present a comprehensive strategy for rapid heart recovery using Impella in a patient with cardiogenic shock.

Incidence, distribution, and electrogram characteristics of endocardial-epicardial connections identified by ultra-high-resolution mapping during a left atrial posterior wall isolation of atrial fibrillation.

PURPOSE: The left atrial posterior wall (LAPW) can be a target for atrial fibrillation (AF) catheter ablation but is sometimes difficult to completely isolate due to the presence of endocardial-epicardial connections. We aimed to investigate the incidence and distribution of epicardial residual connections (epi-RCs) and the electrogram characteristics at epi-RC sites during an initial LAPW isolation. METHODS: We retrospectively studied 102 AF patients who underwent LAPW mapping before and after a first-pass linear ablation along the superior and inferior LAPW (pre-ablation and post-ablation maps) using an ultra-high-resolution mapping system (Rhythmia, Boston Scientific). RESULTS: Epi-RCs were observed in 41 patients (40.2%) and were widely distributed in the middle LAPW area and surrounding it. The sites with epi-RCs had a higher bipolar voltage amplitude and greater number of fractionated components than those without (median, 1.09 mV vs. 0.83 mV and 3.9 vs. 3.4 on the pre-ablation map and 0.38 mV vs. 0.27 mV and 8.5 vs. 4.2 on the post-ablation map, respectively; P < 0.001). Receiver operating characteristic analyses demonstrated that the number of fractionated components on the post-ablation map had a larger area under the curve of 0.847 than the others, and the sensitivity and specificity for predicting epi-RCs were 95.4% and 62.1%, respectively, at an optimal cutoff of 5.0. CONCLUSIONS: Among the patients with epi-RCs after a first-pass LAPW linear ablation, areas with a greater number of fractionated components (> 5.0 on the post-ablation LAPW map) may have endocardial-epicardial connections and may be potential targets for touch-up ablation to eliminate the epi-RCs.

Noncontact Charge Density Mapping-Guided Ablation of Persistent Atrial Fibrillation With a Multiple Trigger-Based Mechanism.

We present a case of radiofrequency catheter ablation of persistent atrial fibrillation (AF) with a trigger-based mechanism, guided by novel noncontact charge density mapping, which resulted in the simultaneous achievement of the termination of AF and complete elimination of multiple triggers that induced repeated recurrences of AF immediately after cardioversion. (Level of Difficulty: Advanced.).

Different solubilizing ability of cyclodextrin derivatives for cholesterol in Niemann-Pick disease type C treatment.

BACKGROUND: Niemann-Pick disease type C (NPC) is a fatal neurodegenerative disorder caused by abnormal intracellular cholesterol trafficking. Cyclodextrins (CDs), the most promising therapeutic candidates for NPC, but with concerns about ototoxicity, are cyclic oligosaccharides with dual functions of unesterified cholesterol (UC) shuttle and sink that catalytically enhance the bidirectional flux and net efflux of UC, respectively, between the cell membrane and the extracellular acceptors. However, the properties of CDs that regulate these functions and how they could be used to improve treatments for NPC are unclear. METHODS: We estimated CD-UC complexation for nine CD derivatives derived from native α-, ß-, and γ-CD with different cavity sizes, using solubility and molecular docking analyses. The stoichiometry and complexation ability of the resulting complexes were investigated in relation to the therapeutic effectiveness and toxicity of each CD derivative in NPC experimental models. FINDINGS: We found that shuttle and sink activities of CDs are dependent on cavity size-dependent stoichiometry and substituent-associated stability of CD-UC complexation. The ability of CD derivatives to form 1:1 and 2:1 complexes with UC were correlated with their ability to normalize intracellular cholesterol trafficking serving as shuttle and with their cytotoxicity associated with cellular UC efflux acting as sink, respectively, in NPC model cells. Notably, the ability of CD derivatives to form an inclusion complex with UC was responsible for not only efficacy but ototoxicity, while a representative derivative without this ability negligibly affected auditory function, underscoring its preventability. CONCLUSIONS: Our findings highlight the importance of strategies for optimizing the molecular structure of CDs to overcome this functional dilemma in the treatment of NPC.

Intra-septal radiofrequency ablation within the transseptal puncture hole targeting an interatrial connection during a bi-atrial tachycardia.

A 74-year-old man after multiple mitral valve surgeries underwent catheter ablation of a bi-atrial tachycardia (BiAT). Ultra-high resolution activation mapping exhibited a reentrant circuit propagating around the inferior to anterior mitral annulus and right atrial (RA) septum with two interatrial connections. At the transeptal puncture site, continuous fractionated electrograms were recorded during the BiAT, and entrainment pacing revealed a post-pacing interval similar to the tachycardia cycle length, which suggested that the interatrial conduction from the RA to the left atrium (LA) was located just at the transseptal puncture site. A radiofrequency application inside the transseptal puncture hole could successfully eliminate the BiAT. The ablation target for BiATs propagating around the mitral annulus and RA septum is generally the anatomical mitral isthmus (MI). Since the present case had multiple incisions on both the RA and LA septum due to mitral valve surgeries, there was the possibility of the occurrence of a BiAT including the RA and LA septum after performing an MI linear ablation. Therefore, the preferable ablation target for the BiAT in the present case appeared to be the interatrial connection. Ultra-high resolution detailed mapping not only on the atrial endocardium but also in the transseptal puncture hole may be useful for identifying a critical interatrial connection of BiAT circuits.

Efficacy of Low-Dose Isoproterenol Infusion for the Exclusion of a Left Atrial Appendage Thrombus in Patients With Dense Spontaneous Echo Contrast Caused by Atrial Fibrillation.

BACKGROUND: In patients with atrial fibrillation (AF) and severe blood stasis in the left atrial appendage (LAA), dense spontaneous echo contrast (SEC) disturbs the distinct visualization of the LAA interior, thus making thrombus diagnosis inconclusive. We aimed to prospectively assess the efficacy and safety of a protocol for a low-dose isoproterenol (ISP) infusion to reduce SEC to exclude an LAA thrombus.Methods and Results: We enrolled 17 patients with AF and dense SEC (Grade 4 or sludge). ISP was infused with gradually increasing doses of 0.01, 0.02, and 0.03 µg/kg/min at 3-min intervals. After increasing the dose to 0.03 µg/kg/min for 3 min, or when the LAA interior was visible, the infusion was terminated. We reassessed the SEC grade, presence of an LAA thrombus, LAA function, and left ventricular ejection fraction (LVEF) within 1 min of ISP termination. Compared with baseline, ISP significantly increased LAA flow velocity, the LAA emptying fraction, LAA wall velocities, and LVEF (all P<0.01). ISP administration significantly reduced the SEC grade (median) from 4 to 1 (P<0.001). The SEC grade decreased to ≤2 in 15 (88%) patients, and the LAA thrombus was excluded. There were no adverse events. CONCLUSIONS: Low-dose ISP infusion may be effective and safe to reduce SEC and exclude an LAA thrombus by improving LAA function and LVEF.

A Focal Ablation Catheter Toggling Between Radiofrequency and Pulsed Field Energy to Treat Atrial Fibrillation.

BACKGROUND: Because of its safety, "single-shot" pulsed field ablation (PFA) catheters have been developed for pulmonary vein isolation (PVI). However, most atrial fibrillation (AF) ablation procedures are performed with focal catheters to permit flexibility of lesion sets beyond PVI. OBJECTIVES: This study sought to determine the safety and efficacy of a focal ablation catheter able to toggle between radiofrequency ablation (RFA) or PFA to treat paroxysmal or persistent AF. METHODS: In a first-in-human study, a focal 9-mm lattice tip catheter was used for PFA posteriorly and either irrigated RFA (RF/PF) or PFA (PF/PF) anteriorly. Protocol-driven remapping was at ∼3 months postablation. The remapping data prompted PFA waveform evolution: PULSE1 (n = 76), PULSE2 (n = 47), and the optimized PULSE3 (n = 55). RESULTS: The study included 178 patients (paroxysmal/persistent AF = 70/108). Linear lesions, either PFA or RFA, included 78 mitral, 121 cavotricuspid isthmus, and 130 left atrial roof lines. All lesion sets (100%) were acutely successful. Invasive remapping of 122 patients revealed improvement of PVI durability with waveform evolution: PULSE1: 51%; PULSE2: 87%; and PULSE3: 97%. After 348 ± 652 days of follow-up, the 1-year Kaplan-Meier estimates for freedom from atrial arrhythmias were 78.3% ± 5.0% and 77.9% ± 4.1% for paroxysmal and persistent AF, respectively, and 84.8% ± 4.9% for the subset of persistent AF patients receiving the PULSE3 waveform. There was 1 primary adverse event-inflammatory pericardial effusion not requiring intervention. CONCLUSIONS: AF ablation with a focal RF/PF catheter allows efficient procedures, chronic lesion durability, and good freedom from atrial arrhythmias-for both paroxysmal and persistent AF. (Safety and Performance Assessment of the Sphere-9 Catheter and the Affera Mapping and RF/PF Ablation System to Treat Atrial Fibrillation; NCT04141007 and NCT04194307).

Reverse remodeling of the tricuspid valve complex by sinus rhythm restoration after catheter ablation.

BACKGROUND: Atrial fibrillation (AF) can cause right atrium enlargement and structural changes of the tricuspid valve annulus (TVA). The features of the structural changes and benefits obtained from rhythm-control therapy is unknown. OBJECTIVES: We investigated how the TVA changes and whether its size decreases after rhythm-control therapy. METHODS: Multi-detector row computed tomography (MDCT) was performed before and after catheter ablation for AF. TVA morphology and right atrium (RA) volume was evaluated by MDCT. The features of TVA morphology in patients with AF after rhythm-control therapy were analyzed. RESULTS: MDCT was performed in 89 patients with AF. The 3D perimeter was more correlated with diameter in the anteroseptal-posterolateral (AS-PL) direction than in the anterior-posterior direction. Seventy patients showed 3D perimeter reduction owing to rhythm-control therapy and the change was associated with the rate of change in the AS-PL diameter. Rate of change of the 3D perimeter was associated with that of the AS-PL diameter among TVA morphology and RA volume. We divided the subjects into three groups according to the tertiles of the TA perimeter. 3D perimeter in all groups was decreased after rhythm-control therapy. The AS-PL diameter in the 2nd and 3rd tertiles was decreased and increased TVA height in all groups. CONCLUSION: TVA in patients with AF was enlarged and flattened in the early phase, and rhythm-control therapy resulted in reverse remodeling of the TVA and in the reduction of right atrial volume. These results suggest that early AF intervention can lead to the restoration of the TVA structure.

Unusual QRS complexes associated with the simultaneous presence of a right-sided accessory pathway, fasciculoventricular pathway, and incomplete right bundle branch block.

A 52-year-old man presented with delta waves on a body surface electrocardiogram, which suggested the presence of a right-sided accessory pathway (AP). Patients with right-sided APs generally have an rS pattern in leads V1-2, while he had an rS in lead V1 but an Rs in lead V2, which could not rule out the possibility of the presence of a septal AP or fasciculoventricular pathway (FVP). On the other hand, patients with septal APs or FVPs generally have a QS pattern in lead V1 instead of an rS pattern. An electrophysiological study demonstrated that the simultaneous presence of a right-sided posterolateral AP and FVP with incomplete right bundle branch block (ICRBBB) generated those unusual QRS complexes. The FVP arose distal to the site with ICRBBB, and the ICRBBB delayed the initiation of the FVP conduction. The delayed QS and Rs waves in leads V1-2 generated by the FVP conduction with ICRBBB appeared to produce rS and Rs patterns in leads V1-2, respectively. A radiofrequency application along the posterolateral tricuspid annulus eliminated the right-sided AP conduction. If the localization of APs based on the QRS morphology is difficult, multiple APs or an FVP with a conduction system disturbance should be noted. Learning objective: Patients with right-sided posterolateral accessory pathways (APs) generally have an rS pattern in lead V2, while patients with fasciculoventricular pathways (FVPs) generally have a QS pattern in lead V1. The present case with a suspected right-sided posterolateral AP had unusual QRS complexes, an rS in lead V1, Rs in lead V2, and monophasic R in leads V3-6, which were associated with the simultaneous presence of a right-sided posterolateral AP, FVP, and incomplete right bundle branch block.

Provocation and Localization of Arrhythmogenic Triggers from Persistent Left Superior Vena Cava in Patients with Atrial Fibrillation.

BACKGROUND: Although pulmonary vein isolation (PVI) is an established procedure for atrial fibrillation (AF), non-PV foci play a crucial role in AF recurrence. Persistent left superior vena cava (PLSVC) has been reported as critical non-PV foci. However, the effectiveness of provocation of AF triggers from PLSVC remains unclear. This study was designed to validate the usefulness of provoking AF triggers from PLSVC. METHODS: This multicenter retrospective study included 37 patients with AF and PLSVC. To provoke triggers, AF was cardioverted, and re-initiation of AF was monitored under high-dose isoproterenol infusion. The patients were divided into two groups: those whose PLSVC had arrhythmogenic triggers initiating AF (Group A) and those whose PLSVC did not have triggers (Group B). Group A underwent isolation of PLSVC after PVI. Group B received PVI only. RESULTS: Group A had 14 patients, whereas Group B had 23 patients. After a 3-year follow-up, no difference in the success rate for maintaining sinus rhythm was observed between the two groups. Group A was significantly younger and had lower CHADS2-VASc scores than Group B. CONCLUSIONS: The provocation of arrhythmogenic triggers from PLSVC was effective for the ablation strategy. PLSVC electrical isolation would not be necessary if arrhythmogenic triggers are not provoked.

Metabolic reprograming of cancer as a therapeutic target.

Our understanding of metabolic reprogramming in cancer has tremendously improved along with the technical progression of metabolomic analysis. Metabolic changes in cancer cells proved much more complicated than the classical Warburg effect. Previous studies have approached metabolic changes as therapeutic and/or chemopreventive targets. Recently, several clinical trials have reported anti-cancer agents associated with metabolism. However, whether cancer cells are dependent on metabolic reprogramming or favor suitable conditions remains nebulous. Both scenarios are possibly intertwined. Identification of downstream molecules and the understanding of mechanisms underlying reprogrammed metabolism can improve the effectiveness of cancer therapy. Here, we review several examples of the metabolic reprogramming of cancer cells and the therapies targeting the metabolism-related molecules as well as discuss practical approaches to improve the next generation of cancer therapies focused on the metabolic reprogramming of cancer.

Fine-tuned cholesterol solubilizer, mono-6-O-α-D-maltosyl-γ-cyclodextrin, ameliorates experimental Niemann-Pick disease type C without hearing loss.

Niemann-Pick disease type C (NPC) is a fatal disorder with abnormal intracellular cholesterol trafficking resulting in neurodegeneration and hepatosplenomegaly. A cyclic heptasaccharide with different degrees of substitution of 2-hydroxypropyl groups, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), acts as a strong cholesterol solubilizer and is under investigation for treating this disease in clinical trials, but its physicochemical properties and ototoxicity remain a concern. Here, we evaluated the potential of mono-6-O-α-maltosyl-γ-CD (G2-γ-CD), a single-maltose-branched cyclic octasaccharide with a larger cavity than HP-ß-CD, for treating NPC. We identified that G2-γ-CD ameliorated NPC manifestations in model mice and showed lower ototoxicity in mice than HP-ß-CD. To investigate the molecular mechanisms of action behind the differential ototoxicity of these CDs, we performed cholesterol solubility analysis, proton nuclear magnetic resonance spectroscopy, and molecular modeling, and estimated that the cholesterol inclusion mode of G2-γ-CD maintained solely the 1:1 inclusion complex, whereas that of HP-ß-CD shifted to the highly-soluble 2:1 complex at higher concentrations. We predicted the associations of these differential complexations of CDs with cholesterol with the profile of disease attenuation and of the auditory cell toxicity using specific cell models. We proposed that G2-γ-CD can serve as a fine-tuned cholesterol solubilizer for treating NPC, being highly biocompatible and physicochemically suitable for clinical application.

Local impedance measurements during contact force-guided cavotricuspid isthmus ablation for predicting an effective radiofrequency ablation.

Background: An ablation catheter capable of contact force (CF) and local impedance (LI) monitoring (IntellaNav StablePoint, Boston Scientific) has been recently launched. We evaluated the relationship between the CF and LI values during radiofrequency catheter ablation (RFCA) along the cavotricuspid isthmus (CTI). Methods: Fifty consecutive subjects who underwent a CTI-RFCA using IntellaNav StablePoint catheters were retrospectively studied. The initial CF and LI at the start of the RF applications and mean CF and minimum LI during the RF applications were measured. The absolute and percentage LI drops were calculated as the difference between the initial and minimum LIs and 100 × absolute LI drop/initial LI, respectively. Results: We analyzed 602 first-pass RF applications. A weak correlation was observed between the initial CF and LI (r = 0.13) and between the mean CF and LI drops (r = 0.22). The initial LI and absolute and percentage LI drops were greater at effective ablation sites than ineffective ablation sites (median, 151 vs. 138 Ω, 22 vs. 14 Ω, and 14.4% vs. 9.9%; p < .001), but the initial and mean CF did not differ. At optimal cutoffs of 21 Ω and 10.8% for the absolute and percentage LI drops according to the receiver-operating characteristic analysis, the sensitivity, and specificity for predicting an effective ablation were 57.4% and 88.9% and 80.0%, and 61.1%, respectively. Conclusions: The effective sites during the CF-guided CTI-RFCA had greater initial LI and LI drops than the ineffective sites. Absolute and percentage LI drops of 21 Ω and 10.8% may be appropriate targets for an effective ablation.

Antiphospholipid Syndrome Diagnosed as a Result of the Occurrence of an Ischemic Stroke After a Successful Catheter Ablation of Atrial Fibrillation and Continuous Direct Oral Anticoagulants.

We report a case of an ischemic stroke after a successful catheter ablation of atrial fibrillation (AF) and continuous oral anticoagulation therapy with direct oral anticoagulants (DOACs), which was the trigger for diagnosing antiphospholipid syndrome (APS). A 68-year-old woman underwent catheter ablation of persistent AF and continued oral anticoagulation with edoxaban at a dose of 30 mg once daily after the ablation procedure. An asymptomatic intracerebral hemorrhage was detected by brain computed tomography and magnetic resonance imaging one month post-ablation. Oral anticoagulation with dabigatran at 110 mg twice daily was continued thereafter due to a high stroke risk profile of a CHA2D2-VASc score of 3. Eight months after the procedure, the patient had multiple acute cerebral infarctions despite no apparent recurrence of atrial tachyarrhythmias and continuation of the DOAC. A blood examination revealed the presence of anti-cardiolipin-beta2-glycoproteion complex antibodies and lupus anticoagulants, and the patient was diagnosed with primary APS. The DOAC was changed to warfarin. The patient has remained free from any ischemic or hemorrhagic cerebral events for 11 months after the oral anticoagulants were changed. The ischemic stroke in the present case appeared to be associated with APS rather than AF. A diagnosis of APS may be extremely crucial in AF patients who have new-onset ischemic strokes under continuous administration of DOACs, because vitamin K antagonists are more effective for the prevention of APS-related ischemic strokes than DOACs.