Pulsed Field Ablation for the Treatment of Atrial Fibrillation: PULSED AF Pivotal Trial.

BACKGROUND: Pulsed field ablation uses electrical pulses to cause nonthermal irreversible electroporation and induce cardiac cell death. Pulsed field ablation may have effectiveness comparable to traditional catheter ablation while preventing thermally mediated complications. METHODS: The PULSED AF pivotal study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) was a prospective, global, multicenter, nonrandomized, paired single-arm study in which patients with paroxysmal (n=150) or persistent (n=150) symptomatic atrial fibrillation (AF) refractory to class I or III antiarrhythmic drugs were treated with pulsed field ablation. All patients were monitored for 1 year using weekly and symptomatic transtelephonic monitoring; 3-, 6-, and 12-month ECGs; and 6- and 12-month 24-hour Holter monitoring. The primary effectiveness end point was freedom from a composite of acute procedural failure, arrhythmia recurrence, or antiarrhythmic escalation through 12 months, excluding a 3-month blanking period to allow recovery from the procedure. The primary safety end point was freedom from a composite of serious procedure- and device-related adverse events. Kaplan-Meier methods were used to evaluate the primary end points. RESULTS: Pulsed field ablation was shown to be effective at 1 year in 66.2% (95% CI, 57.9 to 73.2) of patients with paroxysmal AF and 55.1% (95% CI, 46.7 to 62.7) of patients with persistent AF. The primary safety end point occurred in 1 patient (0.7%; 95% CI, 0.1 to 4.6) in both the paroxysmal and persistent AF cohorts. CONCLUSIONS: PULSED AF demonstrated a low rate of primary safety adverse events (0.7%) and provided effectiveness consistent with established ablation technologies using a novel irreversible electroporation energy to treat patients with AF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04198701.

Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer.

PURPOSE: Here, we investigated the potential predictive and elucidating efficacy of cell-free DNA (cfDNA) changes on clinical outcomes and biological effects, respectively, after short-term palbociclib and fulvestrant treatment for patients with hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer (ABC). METHODS: In this secondary analysis of the Japan Breast Cancer Research Group-M07 (FUTURE) trial, blood cfDNA was obtained before palbociclib treatment and on day 15 of cycle one (28-day cycle). Target enrichment was performed using next-generation sequencing; progression-free survival (PFS) was compared based on cfDNA changes between baseline and day 15 of cycle one after combination therapy. RESULTS: Fifty-six patients (112 paired blood samples) were examined. The median follow-up time was 8.9 months. PIK3CA (30.4%, 17/56), FOXA1 (30.4%, 17/56), and ESR1 (28.6%, 16/56) were most frequently mutated at baseline. The number of mutated genes was significantly decreased on day 15 compared with that at baseline (paired t test: P value = 0.025). No significant difference was observed in PFS (decrease group, 7.9 m vs the others, 9.3 m; log-rank P value = 0.75; hazard ratio, 1.13; 95% confidence interval, 0.53-2.41). Among patients without previous aromatase inhibitor treatment (n = 15), three (20%) had ESR1 mutations after progression to fulvestrant. CONCLUSION: No significant association was observed between changes in mutated genes after short-term palbociclib and fulvestrant treatment and disease progression; a significant reduction in cfDNA mutation level was observed on day 15 of cycle one. Clinical meanings of cfDNA should be investigated in the future trials.

Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.

BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC. METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy. RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis. CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.

Epicardial adipose tissue density predicts the presence of atrial fibrillation and its recurrence after catheter ablation: three-dimensional reconstructed image analysis.

Epicardial adipose tissue (EAT) induces inflammation in the atria and is associated with atrial fibrillation (AF). Several studies have examined the relationship between EAT volume (EAT-V) and density (EAT-D) and the presence of AF after catheter ablation. However, conclusions have been inconsistent. This study included 43 consecutive patients who underwent catheter ablation for AF and 30 control patients. EAT-V and EAT-D around the entire heart, entire atrium, left atrium (LA), and right atrium (RA) were measured in detail using reconstructed three-dimensional (3D) EAT images from dual-source computed tomography (CT). None of the measurements of EAT-V differed significantly between patients with AF and controls or between patients with recurrent AF and those without. On the other hand, all measurements of EAT-D were higher in patients with AF than in controls (entire atrium, p < 0.001; RA, p < 0.001; LA, p = 0.002). All EAT-D measurements were associated with the presence of AF. Among patients with AF who underwent ablation, all EAT-D measurements were higher in patients with recurrent AF than in those without. The difference was significant for EATRA-D (p = 0.032). All atrial EAT-D values predicted recurrent AF (EATRA-D: hazard ratio [HR], 1.208; 95% confidence interval [95% CI], 1.053-1.387; p = 0.007; EATLA-D: HR, 1.108; 95% CI 1.001-1.225; p = 0.047; EATatrial-D: HR, 1.174; 95% CI 1.040-1.325; p = 0.010). The most sensitive cutoffs for predicting recurrent AF were highly accurate for EATRA-D (area under the curve [AUC], 0.76; p < 0.01) and EATatrial-D (AUC = 0.75, p < 0.05), while the cutoff for EATLA-D had low accuracy (AUC, 0.65; p = 0.209). For predicting the presence of AF and recurrent AF after catheter ablation, 3D analysis of atrial EAT-D, rather than EAT-V, is useful.

Treatment with catheter ablation for patients with arrhythmia-induced cardiomyopathy caused by atrial fibrillation promises a good prognosis.

Clinical outcomes after catheter ablation in patients with reduced left ventricular (LV) ejection fraction (EF) and atrial fibrillation (AF) remain unclear. This study aimed to explore the clinical outcomes of patients with arrhythmia-induced cardiomyopathy (AIC) and the influence of pharmacological treatment on clinical outcomes in patients with AIC after the procedure. Ninety-six patients with AF with a reduced LVEF (LVEF < 50%, 66.7 ± 10.9 years; 72 males) underwent AF ablation. AIC was defined as patients whose LVEF recovered ≥ 50% after catheter ablation (n = 67) and patients whose LVEF remained reduced were defined as non-AIC (n = 29). During a median follow-up of 25 (13-40) months, Kaplan-Meier analysis demonstrated that patients with AIC were associated with less frequent cardiovascular death (p = 0.025) and hospitalization for worsening heart failure (p < 0.001) than those without AIC. Freedom from AF recurrence was similar between the two groups (p = 0.47). In multivariate analysis, the LV end-diastolic diameter (p = 0.0002) and the CHA2DS2-VASc scores (p = 0.0062) were independent predictors of AIC. Among the 67 patients with AIC, no significant differences in baseline characteristics, except for LV chamber size and cryoballoon use, were observed between patients with AIC with (n = 31) and without renin-angiotensin system (RAS) inhibitors (n = 36). In the Kaplan-Meier analysis, cardiovascular death, hospitalization for worsening heart failure, and AF recurrence after catheter ablation did not differ between patients treated with and without RAS inhibitors (all p > 0.05). Catheter ablation in patients with AIC due to AF is associated with a good post-procedural prognosis.IRB information The study was approved by the Research Ethics Committee of the University of Fukui (No. 20220151) and clinical trial registration (UMIN000050391).

Fulvestrant plus palbociclib in advanced or metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer after fulvestrant monotherapy: Japan Breast Cancer Research Group-M07 (FUTURE trial).

PURPOSE: The combination of cyclin-dependent kinase 4/6 inhibitors and endocrine therapy is a standard treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC); however, their toxicities and financial burden are major issues, especially for prolonged treatment. We investigated fulvestrant plus palbociclib in patients with HR-positive MBC resistant to fulvestrant monotherapy. METHODS: Patients who initially received fulvestrant as their first- or second-line endocrine therapy were assigned to group A. Patients with disease progression during fulvestrant monotherapy who subsequently received fulvestrant plus palbociclib were assigned to group B. The primary endpoint was progression-free survival (PFS1) in group B. We set the threshold median PFS of 5 months (null hypothesis). RESULTS: Between January 2018 and February 2020 we enrolled 167 patients in group A (January 2018-February 2020) from 55 institutions, of whom 72 subsequently received fulvestrant plus palbociclib and were enrolled in group B. The median follow-up was 23.8 and 8.9 months in groups A and B, respectively. The median PFS in group B (combination therapy) was 9.4 (90% confidence interval [CI]: 6.9-11.2) months (p < 0.001). This was 25.7 (90% CI: 21.2-30.3) months in group A (fulvestrant monotherapy). The TTF in group B was 7.2 (90% CI: 5.5-10.4) months. In the post-hoc analysis, the median PFS1 in group B among patients with longer-duration fulvestrant monotherapy (> 1 year) was longer than that of patients with shorter-duration monotherapy (≤ 1 year) (11.3 vs. 7.6 months). No new toxicities were observed. CONCLUSION: Our findings suggest that palbociclib plus fulvestrant after disease progression despite fulvestrant monotherapy is potentially safe and effective in patients with HR-positive/HER2-negative advanced MBC.

Management of patients with presumed germline pathogenic variant from tumor-only genomic sequencing: A retrospective analysis at a single facility.

Cancer treatment is increasingly evolving toward personalized medicine, which sequences numerous cancer-related genes and identifies therapeutic targets. On the other hand, patients with germline pathogenic variants (GPV) have been identified as secondary findings (SF) and oncologists have been urged to handle them. All SF disclosure considerations for patients are addressed and decided at the molecular tumor boards (MTB) in the facility. In this study, we retrospectively summarized the results of all cases in which comprehensive genomic profiling (CGP) test was conducted at our hospital, and discussed the possibility of presumed germline pathogenic variants (PGPV) at MTB. MTB recommended confirmatory testing for 64 patients. Informed consent was obtained from attending physicians for 53 of them, 30 patients requested testing, and 17 patients tested positive for a confirmatory test. Together with already known variants, 4.5 % of the total confirmed in this cohort. Variants verified in this study were BRCA1 (n = 12), BRCA2 (n = 6), MSH2 (n = 2), MSH6 (n = 2), WT1 (n = 2), TP53, MEN1, CHEK2, MLH1, TSC2, PTEN, RB1, and SMARCB1. There was no difference in the tumor's VAF between confirmed positive and negative cases for variants determined as PGPV by MTB. Current results demonstrate the actual number of cases until confirmatory germline test for patients with PGPV from tumor-only CGP test through the discussion at the MTB. The practical results at this single facility will serve as a guide for the management of the selection and distribution of SF in the genome analysis.

Peri-procedural anticoagulation in patients with end-stage kidney disease undergoing atrial fibrillation ablation: results from the multicentre end-stage kidney disease-atrial fibrillation ablation registry.

AIMS: The optimal anticoagulation regimen in patients with end-stage kidney disease (ESKD) undergoing atrial fibrillation (AF) catheter ablation is unknown. We sought to describe the real-world practice of peri-procedural anticoagulation management in patients with ESKD undergoing AF ablation. METHODS AND RESULTS: Patients with ESKD on haemodialysis undergoing catheter ablation for AF in 12 referral centres in Japan were included. The international normalized ratio (INR) before and 1 and 3 months after ablation was collected. Peri-procedural major haemorrhagic events as defined by the International Society on Thrombosis and Haemostasis, as well as thromboembolic events, were adjudicated. A total of 347 procedures in 307 patients (67 ±9 years, 40% female) were included. Overall, INR values were grossly subtherapeutic [1.58 (interquartile range: 1.20-2.00) before ablation, 1.54 (1.22-2.02) at 1 month, and 1.22 (1.01-1.71) at 3 months]. Thirty-five patients (10%) suffered major complications, the majority of which was major bleeding (19 patients; 5.4%), including 11 cardiac tamponade (3.2%). There were two peri-procedural deaths (0.6%), both related to bleeding events. A pre-procedural INR value of 2.0 or higher was the only independent predictor of major bleeding [odds ratio, 3.3 (1.2-8.7), P = 0.018]. No cerebral or systemic thromboembolism occurred. CONCLUSION: Despite most patients with ESKD undergoing AF ablation showing undertreatment with warfarin, major bleeding events are common while thromboembolic events are rare.

Contrast-enhanced computed tomography in the venous rather than the arterial phase is essential for the evaluation of the right phrenic nerve.

BACKGROUND: Preprocedural detection of the running course of the right pericardiophrenic bundles (PBs) is considered to be useful in preventing phrenic nerve (PN) injury during catheter ablation for atrial fibrillation (AF). However, previous studies using the arterial phase of contrast-enhanced computed tomography (CT) reported a relatively low right PBs detection rate. METHODS: This study included 63 patients with AF who underwent catheter ablation and preoperative contrast-enhanced CT imaging of the venous and arterial phases (66.7 ± 10.2 years; 44 male). The venous phase of contrast-enhanced CT significantly improved the detection rate of PBs compared to the arterial phase (96.8% vs. 60.3%, p < .001), and PBs were detected in the venous phase only in 23 (36.7%) patients. No significant differences were observed between the right PBs detection rate using non-contrast CT versus the arterial phase of contrast-enhanced CT (p = .37). Patients without visualization of the right PBs during the arterial phase had a higher frequency of chronic heart failure (p = .0083), lower left ventricular ejection fraction (p = .021), and a higher CHADS2 score (p = .048) than those with visualization. In five patients whose right PBs could only be detected during the venous phase of contrast-enhanced CT, the reconstructed running course of the right PBs corresponded with the PN generated by electrical high-output pacing. CONCLUSION: Contrast-enhanced CT images of the venous phase, rather than the arterial phase, are useful in detecting the right PBs, especially in patients with heart failure or reduced left ventricular ejection fraction.

Prognostic value of 1,5-anhydro-D-glucitol incorporating syntax score in acute coronary syndrome.

The utility of adding information on 1,5-anhydro-D-glucitol (1,5-AG), a marker for postprandial hyperglycemia, to a pre-existing scoring system in acute coronary syndrome (ACS) patients is unknown. This retrospective cohort study included 266 ACS patients. The end point was major adverse cardiac and cerebral events (MACCE) through 5 years of follow-up. To evaluate incremental benefits of combining 1,5-AG with the syntax score, we applied time-dependent receiver operating curve (ROC) analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA). Temporal changes to the area under time-dependent ROC curves showed that addition of 1,5-AG parameters to syntax score did not provide any incremental value (area under the curve for syntax alone, 0.673 (95% confidence interval (CI), 0.599-0.747) vs. with 1,5-AG combined, 0.671 (95%CI 0.596-0.746; Delong p = 0.65). Incorporating 1,5-AG into syntax score yielded a significant NRI of 0.291 (95%CI 0.015-0.567) and IDI of 0.055 (95%CI 0.018-0.093), while DCA analysis showed the limited net benefit in combination with 1,5-AG and syntax score. 1,5-AG values exhibited significant discriminatory utility for detecting MACCE within the ACS population. However, 1,5-AG levels contributed limited utility beyond syntax score based on time-dependent ROC and DCA analyses.Trial registration: UMIN000023837.

Low troponin I levels predict the presence of arrhythmia-induced cardiomyopathy in patients with atrial fibrillation and left ventricular systolic dysfunction.

Successful atrial fibrillation (AF) ablation can improve reduced left ventricular ejection fraction (LVEF) with AF, which is defined as arrhythmia-induced cardiomyopathy (AIC). However, it is difficult to pre-procedurally predict the presence of AIC. We aimed to explore the pre-procedural predictors of AIC in patients with AF and reduced LVEF. This study included 60 patients with a reduced LVEF (LVEF < 50%; 69.1 ± 8.8 years; 45 men) who underwent successful AF ablation. Responders were defined as patients whose LVEF post-procedurally improved to the normal range (≥ 50%). Multivariate analysis revealed that the log-transformed pre-procedural troponin I (TnI) levels (odds ratio [OR] = 0.059; 95% confidence interval [CI] = 0.0052-0.42, p = 0.003) and age (OR = 0.91; 95% CI = 0.82-1.00, p = 0.044) were independent predictors of post-procedural LVEF recovery; further, low TnI levels (< 11.1 pg/ml) predicted LVEF recovery (sensitivity, 79.1%; specificity, 76.5%; positive predictive value, 89.5%; and negative predictive value, 59.1%). There were no significant differences in TnI levels between the baseline and 1 month after the procedure. However, four patients with high baseline TnI levels showed a > 50% reduction in the TnI levels post-procedurally, with three of these patients showing LVEF recovery. Low pre-procedural TnI levels can predict LVEF recovery after successful AF ablation in patients with reduced LVEF.

The Relationship between Holter Electrocardiography and Atrial Fibrillation Diagnosis Using Real-World Data in Japan.

The relationship between Holter electrocardiography (ECG) and atrial fibrillation (AF) diagnosis in the real world has not been widely evaluated in Japan.This is a claims-based retrospective study using a health insurance claims database provided by DeSC Healthcare Corporation. We identified patients with at least one Holter for any purpose during the data period from April 2015 to November 2020 and without diagnosis of AF before the tests (n = 19,739). We obtained a whole picture of Holter and AF diagnosis after correcting for population distribution bias in the dataset. Based on this picture and the assumption that the patient had AF at the 1st Holter whose AF was detected for the first time at the second or subsequent Holter, we estimated the number of diagnosis with AF and overlooked AF by initial Holter. We conducted sensitivity analyses changing the definition of AF, the potential detection period, and the washout period (a period required to avoid including patients who have already been diagnosed with AF or who have already undergone several Holters) to confirm the validity of the base scenario.Among patients for analysis, 88.4% had only one Holter. The percentage of AF diagnosis by initial Holter was 7.6%. The percentage of AF overlooked by initial Holter was estimated to be 31.4% and this value did not change much by sensitivity analyses.It was estimated that approximately 30% of AF patients were overlooked by initial Holter, and reducing the overlooked rate will be a clinical challenge.

The R Wave Amplitude in Lead aVL Could Predict Successful Catheter Ablation of Ventricular Arrhythmias Originating below the His Bundle Region of the Right Ventricle.

Radiofrequency catheter ablation (RFCA) to treat ventricular arrhythmias (VAs) originating below the His bundle (HB) region of the right ventricular (RV) septum could impair the atrioventricular node conduction. This study aimed to clarify the parameters of the 12-lead electrocardiography that predict successful RFCA of VAs originating from this region. This study included 20 consecutive patients (13 men; mean age, 68 ± 7 years) with monomorphic VAs in whom the earliest ventricular activation during the VA was below the HB region of the RV septum. According to the ablation results, the patients were divided into two groups: successful ablation (S-group; n = 10) and failed ablation groups (F-group; n = 10). The electrocardiographic parameters during the VAs and RFCA results were assessed. The R wave amplitudes in leads aVL (P = 0.001) and I (P = 0.010) in the S-group were both smaller than those in the F-group. In addition, the S-group had smaller negative deflection amplitudes in leads III (P = 0.002) and aVF (P = 0.003) than the F-group. According to the receiver operating characteristic curve analysis, the most useful electrocardiographic parameter for predicting successful ablation was the R wave amplitude in lead aVL (area under the curve, 0.895; P < 0.001); a cutoff value of < 1.3 mV predicted a successful RFCA with the highest accuracy (sensitivity, 90%; specificity, 80%; positive predictive value, 82%; negative predictive value, 89%). The R wave amplitude in lead aVL was the most useful parameter for predicting a successful RFCA to treat VAs originating below the HB region of the RV septum.

Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS).

No standard options existed for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer that progresses after second-line trastuzumab emtansine therapy before 2020. The purpose of this study was to examine the efficacy of pertuzumab retreatment after disease progression following pertuzumab-containing therapy for HER2-positive locally advanced or metastatic breast cancer for the first time. This randomized, open-label, multicenter phase III trial was undertaken in 93 sites in Japan. Eligible patients with HER2-positive breast cancer who had received pertuzumab, trastuzumab, and chemotherapy as first- and/or second-line therapy were randomly assigned (1:1) to: (i) pertuzumab, trastuzumab, and physician's choice chemotherapy (PTC), or (ii) trastuzumab and physician's choice chemotherapy (TC). The primary end-point was investigator-assessed progression-free survival (PFS). Between August 1, 2015 and December 31, 2018, 219 patients were randomized to PTC (n = 110) or TC (n = 109). Median follow-up was 14.2 months (interquartile range, 9.0-22.2), and median PFS was 5.3 months (95% confidence interval [CI], 4.0-6.6) with PTC and 4.2 months (95% CI, 3.2-4.8) with TC (stratified hazard ratio 0.76 [95% CI upper limit 0.967]; p = 0.022). Progression-free survival was improved by adding pertuzumab in all prespecified subgroups. The PTC arm showed a trend towards better overall survival and duration of response, but similar objective response and health-related quality of life. The incidence of treatment-related adverse events was similar between groups except for diarrhea. Pertuzumab retreatment contributes to disease control for HER2-positive locally advanced or metastatic breast cancer previously treated with pertuzumab-containing regimens.

Safety and durability of cavo-tricuspid isthmus linear ablation in the current era: Single-center 9-year experience from 1078 procedures.

BACKGROUND: Cavo-tricuspid isthmus (CTI) linear ablation is performed not only for atrial flutter (AFL) but empirically during atrial fibrillation (AF) ablation in real-world practice.  PURPOSE: We sought to evaluate the safety and durability of the CTI ablation.  METHODS: This retrospective study included 1078 consecutive patients who underwent a CTI ablation. AFL was documented before or during the procedure in 249 (23.1%) patients, and an empirical CTI and AF ablation were performed in 829 (76.9%) patients.  RESULTS: CTI block was successfully created in 1051 (97.5%) patients with a 10.3 ± 6.6 min total radiofrequency time. Repeat procedures were performed for recurrent arrhythmias in 187 (17.3%) patients at a median of 11.0 (5.0-30.0) months postprocedure, and conduction resumption was identified in 68/174 (39.1%). Among those undergoing a CTI ablation with an AF ablation, the durability was significantly higher in those with than without documented AFL (78.1% vs. 58.2%, p = .031).  The total radiofrequency time was significantly shorter (9.0 ± 5.3 vs. 10.0 ± 6.4 [mins], p = .024) and durability significantly higher (78.1 vs. 58.7[%], p = .043) in the large-tip than irrigated-tip catheter group. Iatrogenic AFL was observed after the empiric CTI ablation in 11 (1.3%) patients. Procedure-related complications occurred in 15 (1.4%) patients. Eight patients experienced coronary artery spasms, including one with ventricular fibrillation following ST elevation on the ward. The other six patients experienced transient atrioventricular block and one experienced cardiac tamponade requiring drainage.  CONCLUSIONS: Despite a high acute CTI ablation success, the conduction block durability was relatively low after the empiric ablation. An empiric CTI ablation at the time of the AF ablation is not recommended.

Subclinical sinus node dysfunction in patients with atrial fibrillation-Insight from ultrahigh-resolution mapping of human sinoatrial exits.

BACKGROUND: Even a short duration of paroxysmal episodes of atrial fibrillation (AF) is associated with sinus node (SN) remodeling and a reduced SN reserve or dysfunction. The number of earliest atrial activation sites (EASs) during sinus rhythm decreases according to the decrease in the SN reserve. OBJECTIVE: We sought to evaluate the EASs during sinus rhythm using an ultrahigh-density mapping system. METHODS: This study included 35 patients (supraventricular tachycardia [SVT]/paroxysmal atrial fibrillation [PAF]/persistent atrial fibrillation [PsAF] = 5/21/9) who underwent ultrahigh-resolution endocardial mapping of the SN area at rest and during ß-stimulation. The number of EASs was determined by the Lumipoint™ algorithm. RESULTS: The number of EASs was greatest in SVT patients both at rest (SVT/PAF/PsAF = 1.4 ± 0.8/1.0 ± 0/1.0 ± 0, p = .04) and during ß-stimulation (SVT/PAF/PsAF = 2.6 ± 1.0/1.3 ± 0.6/1.0 ± 0, p < .01). The number significantly increased with ß-stimulation as compared to baseline in the PAF patients (p = .02), but not in the PsAF patients. The brain natriuretic peptide (BNP) level was significantly higher in AF than SVT patients (SVT/PAF/PsAF = 12.3 [10.1-14.5]/25.7 [14.8-36.0]/73.4 [57.6-140] pg/ml, p < .01). In the PAF patients, the BNP level was significantly higher in those with unicentric EASs than multicentric EASs during ß-stimulation (28.1 [19.1-46.5] vs. 13.1 [9.4-26.9] pg/ml, p = .03), and the optimal cutoff point for the BNP level predicting unicentric EASs was 21.8 pg/ml (sensitivity 82.6%; specificity 85.7%). CONCLUSIONS: AF patients have a smaller number of EASs and poorer response to ß-stimulation than non-AF patients. An elevated BNP level might predict subclinical SN dysfunction in patients with PAF.

Relationship of body mass index to clinical outcomes after percutaneous coronary intervention.

BACKGROUND: Elevated body mass index (BMI) demonstrates lower all-cause and cardiovascular mortalities compared with normal-weight or lean patients in chronic diseases. This study investigated relationships between BMI and clinical outcomes following percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients, together with the sex-specific impacts of BMI on mortality. METHODS: We reviewed 1104 CAD patients who underwent PCI between 2006 and 2015. Patients were divided by BMI into three groups: lean, <18.5 kg/m2 ; normal, 18.5-24.9 kg/m2 ; and overweight/obese, ≥25 kg/m2 . The primary endpoint was all-cause mortality, and the secondary endpoint was 3-point major adverse cardiovascular events (MACE). RESULTS: Kaplan-Meier survival analysis demonstrated risks of all-cause death, and 3-point MACE were higher in lean patients compared with normal-weight and overweight/obese subjects (log-rank p < .001). Cox proportional hazard modelling showed overweight/obese was significantly associated with all-cause death (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.48-0.95; p = .03), and lean was significantly associated with 3-point MACE (HR 2.02, 95% CI 1.15-3.53; p = .01). Cox proportional hazard analysis with restricted cubic spline showed non-linear associations between BMI and both all-cause mortality and 3-point MACE (p for effect = .002 and = .003, respectively). No significant interaction was evident between sex and BMI for all-cause mortality (p for interaction = .104) or 3-point MACE (p for interaction =0.122). CONCLUSIONS: Lean category was associated with adverse outcomes among CAD patients. An obesity paradox regarding the independent association of elevated BMI with reduced mortality after PCI is evident in both males and females.

Mapping and ablation of left atrial roof-dependent tachycardias using an ultra-high resolution mapping system.

BACKGROUND: Left atrial roof-dependent tachycardias (LARTs) are common macroreentrant atrial tachycardias (ATs). We sought to characterize clinical LARTs using an ultra-high resolution mapping system. METHODS: This study included 22 consecutive LARTs in 21 patients who underwent AT mapping/ablation using Rhythmia systems. RESULTS: Three, 13, 4, and 2 LART patients were cardiac intervention naïve (Group-A), post-roof line ablation (Group-B), post-atrial fibrillation ablation without linear ablation (Group-C), and post-cardiac surgery (Group-D), respectively. The mean AT cycle length was 244 ± 43 ms. Coronary sinus activation was proximal-to-distal or distal-to-proximal in 16 (72.7%) ATs. The activation map revealed 13 (59.1%) clockwise and 9 (40.9%) counter-clockwise LARTs. A 12-lead synchronous isoelectric interval was observed in 10/19 (52.6%) LARTs. The slow conduction area was identified on the LA roof, anterior/septal wall, and posterior wall in 18, 6, and 2 ATs, respectively. Twenty concomitant ATs among 13 procedures were also eliminated, and peri-mitral AT coexisted in 7 of 9 non-group-B patients. In group-B, the conduction gap was predominantly located on the mid-roof. Sustained LARTs were terminated by a single application and linear ablation in 6 (27.3%) and 9 (40.9%), while converting to other ATs in 7 (31.8%) LARTs. Complete linear block was created without any complications in all, however, ablation at the mid-posterior wall was required to achieve block in 4 (18.2%) procedures. During 14.0 (6.5-28.5) months of follow-up, 17 (81.0%) and 19 (90.5%) patients were free from any atrial tachyarrhythmias after single and last procedures. CONCLUSIONS: The LART mechanisms were distinct in individual patients, and elimination of all concomitant ATs was required for the management.

Cryoballoon left atrial roof ablation for persistent atrial fibrillation-Analysis with high-resolution mapping system.

BACKGROUND: Additional benefit of cryoballoon left atrial roof line ablation (CB-RA) beyond cryoballoon pulmonary vein isolation (CB-PVI) is suggested in patients with persistent atrial fibrillation (PsAF). We sought to investigate the feasibility of CB-RA for PsAF and to determine the ablation area. METHODS AND RESULTS: Fifty-three PsAF patients (67[58.5-75.5] years, 36 men, 11 longstanding PsAF) underwent CB-PVI. Subsequently, 44(83.0%) out of 53 patients underwent additional CB-RA. Voltage maps were created in all patients with a high-resolution mapping system. The total number and duration of CB-RAs were 3.9 ± 0.7 and 468 ± 84 s. LA roof areas were complete low voltage areas (LVAs) /scar in 37/44(84.1%) patients ("complete roof modification"). The normal LA posterior wall (LAPW) voltage area was 6.1(4.1-8.4) cm2 , and the %LAPW isolation area was 61.0(47.2-71.7)%. The %LAPW isolation area was significantly greater in CB-RA patients than those without (64.0[54.2-73.2] vs. 45.0[39.5-50.5]%, p = .041) despite significantly larger LAs in the former group. The %LAPW isolation area was significantly greater in patients with transverse LA diameters < 45 mm than those ≥ 45 mm (p < .0001). The single procedure 1-year AF freedom was 87.4% (22.5% on antiarrhythmic drug) and tended to be higher in CB-RA patients than those without. Among the 44 CB-RA patients, it was significantly higher in patients with a complete roof modification than those without (94.4% vs. 75.0%, p = .0049). One CB-RA patient experienced a delayed cardiac tamponade requiring drainage at 4-months post-procedure. CONCLUSIONS: CB-RA significantly expanded the LAPW isolation area, and a complete roof modification resulted in a high arrhythmia freedom in PsAF patients.

Relationships between sodium levels, haemodynamics and metalloproteinases in heart failure patients.

To estimate the associations between dysnatraemia and inflammatory marker [including interleukin-6 (IL-6)], and tissue remodelling marker [matrix metalloproteinase (MMP)-9 and tissue inhibitor of MMP (TIMP)-1], the pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure (PAP), and left ventricular end-diastolic pressure (EDP), and the prognostic relevance in patients with heart failure. The serum sodium level and circulating levels of IL-6, MMP-9, and TIMP-1 were measured in 173 heart failure patients. Dual heart catheterisation was performed to measure PCWP, mean PAP, and EDP. All-cause mortality was assessed during the follow-up period (mean 88 ± 49 months). Restricted cubic spline (RCS) regression showed a U-shaped association of serum sodium level with TIMP-1, with the lowest values in the 138-140 mmol/L range (P for effect = 0.042, P for non-linearity = 0.017). IL-6 and MMP-9 levels showed non-significant associations with serum sodium level. U-shaped associations of serum sodium level with PCWP (P for effect = 0.004, P for non-linearity = 0.001) and mean PAP (P for effect = 0.042, P for non-linearity = 0.017) were found with the RCS regression model. The random forest model revealed that TIMP-1, MMP-9, and IL-6 were important predictors for serum sodium levels. Restricted cubic spline Cox regressions demonstrated that TIMP-1 levels indicated a U-shaped, concaved, non-linear association with all-cause mortality (P for effect = 0.011, P for non-linearity = 0.022). Dysnatraemia is an index of TIMP-1 aggravation and elevated PCWP, mean PAP; hence, it is associated with worsening all-cause mortality.Clinical Trial Registration: UMIN000023840.