Effect of pulmonary vein isolation on rotor/multiple wavelet dynamics in persistent atrial fibrillation, association with vagal response and implications for adjunctive ablation.

Persistent atrial fibrillation (PeAF) may develop arrhythmogenic substrates of rotors/multiple wavelets. However, the ways in which pulmonary vein isolation (PVI) affects the dynamics of rotor/multiple wavelets in PeAF patients remain elusive. Real-time phase-mapping (ExTRa mapping, EXT) in the whole left atrium (LA) was performed during PeAF before and after PVI (n = 111). The percentage of time in which rotor/multiple wavelets (phase singularities) was observed during each 5-s phase-mapping recording (non-passive activation ratio, %NP) was measured as an index of its burden. The mapping areas showing %NP ≥ 50% were defined as rotor/multiple-wavelet substrates (RSs). Before PVI, RSs were globally distributed in the LA. After PVI, %NP decreased (< 50%) in many RSs (PVI-modifiable RSs) but remained high (≥ 50%) in some RSs, especially localized in the anterior/septum/inferior regions (PVI-unmodifiable RSs, 2.3 ± 1.0 areas/patient). Before PVI, vagal response (VR) to high-frequency stimulation was observed in 23% of RSs, especially localized in the inferior region. VR disappearance after PVI was more frequently observed in PVI-modifiable RSs (79%) than in PVI-unmodifiable RSs (55%, p < 0.05), suggesting that PVI affects autonomic nerve activities and rotor/multiple wavelet dynamics. PVI-unmodifiable RSs were adjunctively ablated in 104 patients. The 1-year AT/AF-free survival rate was 70% in those with PVI alone (n = 115), and 86% in patients with the adjunctive ablation (log-rank test = 7.65, p < 0.01). PVI suppresses not only ectopic firing but also rotor/multiple wavelets partly via modification of autonomic nerve activities. The adjunctive ablation of PVI-unmodifiable RSs improved the outcome in PeAF patients and might be a novel ablation strategy beyond PVI.

Prognostic significance of the Holter-derived T-wave variability in patients with ventricular tachyarrhythmias complicating acute coronary syndrome-TWIST study.

BACKGROUND: We aimed to investigate the association between ventricular repolarization instability and sustained ventricular tachycardia and ventricular fibrillation (VT/VF) occurring within 48 h (acute-phase VT/VF) after the onset of acute coronary syndrome (ACS) and the prognostic role of repolarization instability and heart rate variability (HRV) after discharge from the hospital. METHODS: We studied 572 ACS patients with a left ventricular ejection fraction >35%. The ventricular repolarization instability was assessed by the beat-to-beat T-wave amplitude variability (TAV) using high-resolution 24-h Holter ECGs recorded at a median of 11 days from the date of admission. We calculated the HRV parameters including the deceleration capacity (DC) and non-Gaussian index calculated on a 25 s timescale (λ25s). The DC and λ25s were dichotomized based on previous studies' thresholds. RESULTS: Acute-phase VT/VF developed in 43 (7.5%) patients. In-hospital mortality was significantly higher among VT/VF patients (4.7% vs. 0.9%, p = .03). An adjusted logistic model showed that the maximum TAV (odds ratio 1.02, 95% confidence interval [CI] 1.00-1.29, p = .04) was associated with acute-phase VT/VF. During a median follow-up period of 2.1 years, 19 (3.3%) patients had cardiac deaths or resuscitated cardiac arrest. Acute-phase VT/VF (p = .12) and TAV (p = .72) were not significant predictors of survival. An age and sex-adjusted Cox model showed that the DC (p < .01), λ25s (p < .01), and emergency coronary intervention (p < .01) were independent predictors. CONCLUSION: T-wave amplitude variability was associated with acute-phase VT/VF, but the TAV was not predictive of survival post-discharge. The DC, λ25s, and emergency coronary intervention were independent predictors of survival.

Systematic Screening for Atrial Fibrillation in Patients at Moderate-to-High Risk of Stroke　- Potential to Increase the Atrial Fibrillation Detection Rate (SCAN-AF).

BACKGROUND: To determine the rate of undiagnosed atrial fibrillation (AF) we screened for AF using an oscillometric blood pressure (BP) monitor device followed by a single-lead handheld electrocardiogram (ECG), with confirmation by 12-lead ECG as the reference standard.Methods and Results: From October 2017 to August 2019, 1,148 patients were enrolled without known AF, who were aged ≥65 years with moderate-to-high stroke risk, at 71 centers in Japan. After exclusion of 7 patients with confirmed AF at the index visit, 1,141 patients were asked to use an oscillometric BP monitor twice daily for 2 weeks (max: 4 weeks) to detect an irregular pulse. The BP monitor detected an irregular pulse in 481 patients, of which 1 patient had confirmed AF. Thereafter, 480 patients were instructed to acquire ECGs twice daily for an additional 2 weeks (max: 4 weeks) using a single-lead handheld ECG device. The handheld ECG device detected irregular rhythm in 41 patients, of which 1 patient had confirmed AF. In total, undiagnosed AF was confirmed in 9 (0.8%) patients of the overall study cohort during the 24-week follow-up period. CONCLUSIONS: Sequential use of a BP monitor and handheld ECG for 4 weeks is a practical strategy for identifying undiagnosed AF in Japanese people at heightened risk of stroke.

Selvester QRS score predicts improvement of LVEF in atrial fibrillation patients with systolic heart failure.

BACKGROUND: Left-ventricular systolic dysfunction (LVSD) comorbid with atrial fibrillation is reversible, but recovery is limited in a subset of patients. The Selvester QRS (S-QRS) score is an electrocardiogram-based assessment that reportedly reflects myocardial scar/damage. We evaluated the predictability of S-QRS score for the recovery of left-ventricular ejection fraction (LVEF) in persistent AF (PeAF) patients with LVSD undergoing catheter ablation (CA). METHOD: CA was performed in 51 PeAF patients with reduced LVEF (<40%); S-QRS scores were measured after restoration of sinus rhythm. LVEF was re-evaluated at one year after CA; LVEF recovery was related to the S-QRS score. RESULTS: The median [interquartile range] S-QRS score was 1 point [0-2]. LVEF increased from 32% [28-37] at baseline to 56% [49-57] at 1 year after CA. Thirty-seven patients achieved normalization of LVEF (≥50%, Group A); 14 patients did not (Group B). Group A had significantly lower S-QRS scores than Group B (0 point [0-2] vs. 2 points [2-3], p < .05). In univariate/multivariate analyses, S-QRS score was an independent predictor of LVEF normalization. In the receiver operating characteristic curve, the cut-off value of S-QRS score was 2 points for prediction of the LVEF normalization (AUC = 0.79). Patients with low S-QRS score (<2 points) had greater LVEF improvement than those with high S-QRS score (≥2 points, ΔLVEF: 23% [17-28] vs. 17% [12-24], p < .05). CONCLUSION: S-QRS scoring noninvasively assesses the improvement of LVEF in PeAF patients with LVSD after CA. A high S-QRS score may indicate underlying myocardial scar/damage associated with unknown etiologies for LVSD other than PeAF.

Safety and feasibility of a telemonitoring-guided exercise program in patients receiving cardiac resynchronization therapy.

BACKGROUND: Telerehabilitation is an alternative clinic-based rehabilitation. A remote monitoring (RM) system attached to a cardiac rhythm device can collect physiological data and the device function. This study aimed to evaluate the safety and feasibility of telerehabilitation supervised by an RM in patients receiving cardiac resynchronization therapy (CRT). METHODS: A single group pre-post exercise program was implemented for 3 months in 18 CRT recipients. The exercise regimen consisted of walking a prescribed number of steps based on a 6-min walk distance (6MWD) achieved at baseline. The patients were asked to exercise 3 to 5 times per week for up to 30 min per session, wearing an accelerometer to document the number of steps taken. The safety was assessed by the heart failure hospitalizations and all-cause death. The feasibility was measured by the improvement in the quality of life (QOL) using the EuroQol 5 dimensions, and daily active time measured by the CRT, 6MWD, B-type natriuretic peptide (BNP) level, and left ventricular ejection fraction (LVEF). RESULTS: No patients had heart failure hospitalizations or died. No patients had any ventricular tachyarrhythmias. One patient needed to suspend the exercise due to signs of exacerbated heart failure by the RM. Compared to baseline, there were significant improvements in the QOL (-0.037, p < .05), active time (1.12%/day, p < .05), and 6MWD (11 m, p < .001), but not the BNP (-32.4 pg/ml, p = .07) or LVEF (0.28%, p = .55). CONCLUSIONS: Three months of RM-guided walking exercise in patients with CRT significantly increased the QOL, active time, and exercise capacity without any adverse effects.

Ambulatory electrocardiographic markers predict serious cardiac events in patients with chronic kidney disease: The Japanese Noninvasive Electrocardiographic Risk Stratification of Sudden Cardiac Death in Chronic Kidney Disease (JANIES-CKD) study.

BACKGROUND: Noninvasive electrocardiographic markers (NIEMs) are promising arrhythmic risk stratification tools for assessing the risk of sudden cardiac death. However, little is known about their utility in patients with chronic kidney disease (CKD) and organic heart disease. This study aimed to determine whether NIEMs can predict cardiac events in patients with CKD and structural heart disease (CKD-SHD). METHODS: We prospectively analyzed 183 CKD-SHD patients (median age, 69 years [interquartile range, 61-77 years]) who underwent 24-h ambulatory electrocardiographic monitoring and assessed the worst values for ambulatory-based late potentials (w-LPs), heart rate turbulence, and nonsustained ventricular tachycardia (NSVT). The primary endpoint was the occurrence of documented lethal ventricular tachyarrhythmias (ventricular fibrillation or sustained ventricular tachycardia) or cardiac death. The secondary endpoint was admission for cardiovascular causes. RESULTS: Thirteen patients reached the primary endpoint during a follow-up period of 24 ± 11 months. Cox univariate regression analysis showed that existence of w-LPs (hazard ratio [HR] = 6.04, 95% confidence interval [CI]: 1.4-22.3, p = .007) and NSVT [HR = 8.72, 95% CI: 2.8-26.5: p < .001] was significantly associated with the primary endpoint. Kaplan-Meier analysis demonstrated that the combination of w-LPs and NSVT resulted in a lower event-free survival rate than did other NIEMs (p < .0001). No NIEM was useful in predicting the secondary endpoint, although the left ventricular mass index was correlated with the secondary endpoint. CONCLUSION: The combination of w-LPs and NSVT was a significant risk factor for lethal ventricular tachyarrhythmias and cardiac death in CKD-SHD patients.

Wall thickness-based adjustment of ablation index improves efficacy of pulmonary vein isolation in atrial fibrillation: Real-time assessment by intracardiac echocardiography.

BACKGROUND: Ablation index (AI) linearly correlates with lesion depth and may yield better therapeutic performance in pulmonary vein isolation (PVI) when tailored to a patient's wall thickness (WT) in the left atrium (LA). METHODS AND RESULTS: First study: In paroxysmal atrial fibrillation patients (PAF; n = 20), the average LA WT (mm) in each anatomical segment for PVI was measured by intracardiac echocardiography (ICE) placed in the LA; the optimal AI for creating 1-mm transmural lesion (AI/mm) was calculated. Second study: PAF (n = 80) patients were randomly assigned either to a force-time integral protocol (FTI; 400 g·s, n = 40) or a tailored-AI protocol (TAI; n = 40). In TAI, the LA WT in each segment was individually measured by ICE before starting ablation; a target AI was adjusted according to the individual WT in each segment (AI/mm × WT). The acute procedure outcomes and the 1-year AF-recurrence rate were compared between FTI and TAI. TAI had higher success rate of first-pass isolation (88% vs. 65%) and had lower incidence of residual PV-potentials/conduction-gaps after a circular ablation than FTI (15% vs. 45%). The procedure time to complete PVI decreased in TAI compared to FTI (52 vs. 83 min), being attributed to the increased radiofrequency power and the decreased radiofrequency application time in each point in TAI. TAI had a lower 1-year AF-recurrence rate than FTI. CONCLUSION: TAI increased acute procedure success, decreased time for PVI, and reduced the 1-year AF-recurrence rate, compared to FTI. Understanding the precise ablation target and tailoring AI would improve the efficacy of PVI.

Risk stratification after acute myocardial infarction by amplitude-frequency mapping of cyclic variation of heart rate.

BACKGROUND: Blunted cyclic variation of heart rate (CVHR), measured as a decrease in CVHR amplitude (Acv), predicts mortality risk after acute myocardial infarction (AMI). However, Acv also can be reduced in mild sleep apnea with mild O2 desaturation. We investigated whether Acv's predictive power for post-AMI mortality could be improved by considering the effect of sleep apnea severity. METHODS: In 24-hr ECG in 265,291 participants of the Allostatic State Mapping by Ambulatory ECG Repository project, sleep apnea severity was estimated by the frequency of CVHR (Fcv) measured by an automated algorithm for auto-correlated wave detection by adaptive threshold (ACAT). The distribution of Acv on the Acv-Fcv relation map was modeled by percentile regression, and a function converting Acv into percentile value was developed. In the retrospective cohort of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study, consisting of 673 survivors and 44 non-survivors after AMI, the mortality predictive power of percentile Acv calculated by the function was compared with that of unadjusted Acv. RESULTS: Among the ALLSTAR ECG data, low Acv values appeared more likely when Fcv was low. The logistic regression analysis for mortality in the ENRICHD cohort showed c-statistics of 0.667 (SE, 0.041), 0.817 (0.035), and 0.843 (0.030) for Fcv, unadjusted Acv, and the percentile Acv, respectively. Compared with unadjusted Acv, the percentile Acv showed a significant net reclassification improvement of 0.90 (95% CI, 0.51-1.42). CONCLUSIONS: The predictive power of Acv for post-AMI mortality is improved by considering its relation to sleep apnea severity estimated by Fcv.

Ischemic Stroke Risk Assessment by Multiscale Entropy Analysis of Heart Rate Variability in Patients with Persistent Atrial Fibrillation.

It has been recognized that heart rate variability (HRV), defined as the fluctuation of ventricular response intervals in atrial fibrillation (AFib) patients, is not completely random, and its nonlinear characteristics, such as multiscale entropy (MSE), contain clinically significant information. We investigated the relationship between ischemic stroke risk and HRV with a large number of stroke-naïve AFib patients (628 patients), focusing on those who had never developed an ischemic/hemorrhagic stroke before the heart rate measurement. The CHA2DS2-VASc score was calculated from the baseline clinical characteristics, while the HRV analysis was made from the recording of morning, afternoon, and evening. Subsequently, we performed Kaplan-Meier method and cumulative incidence function with mortality as a competing risk to estimate the survival time function. We found that patients with sample entropy (SE(s)) ≥ 0.68 at 210 s had a significantly higher risk of an ischemic stroke occurrence in the morning recording. Meanwhile, the afternoon recording showed that those with SE(s) ≥ 0.76 at 240 s and SE(s) ≥ 0.78 at 270 s had a significantly lower risk of ischemic stroke occurrence. Therefore, SE(s) at 210 s (morning) and 240 s ≤ s ≤ 270 s (afternoon) demonstrated a statistically significant predictive value for ischemic stroke in stroke-naïve AFib patients.

Factors associated with silent cerebral events during atrial fibrillation ablation in patients on uninterrupted oral anticoagulation.

INTRODUCTION: Silent cerebral events (SCEs) are related to the potential thromboembolic risk in atrial fibrillation (AF) ablation. Periprocedural uninterrupted oral anticoagulation (OAC) reportedly reduced the risk of SCEs, but the incidence still remains. METHODS AND RESULTS: AF patients undergoing catheter ablation were eligible. All patients took non-vitamin K antagonist oral anticoagulants (NOACs; n = 248) or vitamin K antagonist (VKA; n = 37) for periprocedural OAC (>4 weeks) without interruption during the procedure. Brain magnetic resonance imaging was performed within 2 days after the procedure to detect SCEs. Clinical characteristics and procedure-related parameters were compared between patients with and without SCEs. SCEs were detected in 66 patients (23.1%; SCE[+]) but were not detected in 219 patients (SCE[-]). Age was higher in SCE[+] than in SCE[-] (66 ± 10 vs. 62 ± 12 years; p < .05). Persistent AF prevalence, CHADS2 /CHA2 DS2 -VASc scores, serum NT-ProBNP levels, left atrial dimension (LAD), and spontaneous echo contrast prevalence in transesophageal echocardiography significantly increased in SCE[+] versus SCE[-]. SCE[+] had lower baseline activated clotting time (ACT) before heparin injection and longer time to reach optimal ACT (>300 s) than SCE[-] (146 ± 27 vs. 156 ± 29 s and 44 ± 30 vs. 35 ± 25 min; p < .05, respectively). In multivariate analysis, age, LAD, baseline ACT, and time to reach the optimal ACT were predictors for SCEs. The average values of the ACT parameters were significantly different among NOACs/VKA. CONCLUSION: Age, LAD, and intraprocedural ACT kinetics significantly affect SCEs during AF ablation. Different anticoagulants have different impacts on ACT during the procedure, which should be considered when estimating the risk of SCEs.

A Practical Method for Continuous Production of sp3-Rich Compounds from (Hetero)Aryl Halides and Redox-Active Esters.

A practically useful coupling reaction between aromatic halides and redox-active esters was realized by nickel catalysis through the use of a packed zinc bed column in continuous flow. Multiple reuse of the column showed a negligible decrease in efficiency, affording high space/time yields. A wide range of substrates, including a number of heteroaryl halides and polyfunctional materials were coupled in generally good yields. Longer-time and larger-scale experiments further demonstrates the robustness of the system.

Association between inflammation and skeletal muscle proteolysis, skeletal mass and strength in elderly heart failure patients and their prognostic implications.

BACKGROUND: Inflammation and skeletal muscle wasting often coexist in elderly populations, but few studies have examined their relationship in elderly heart failure (HF) patients. This study examined the relationship between inflammation and increased skeletal muscle proteolysis, reduced skeletal mass and strength, and their prognostic implications in elderly HF patients (> 65 years) using a random forest approach. METHODS: We prospectively enrolled consecutive elderly HF patients (n = 78) and age- and sex-matched control subjects (n = 83). We measured the interleukin (IL)-6, C-reactive protein (CRP), and B-type natriuretic peptide (BNP) levels, lower limb muscle mass and strength, and 6-min walk distance. The amount of muscle proteolysis was determined by urinary 3-methylhystidine, normalized by creatinine (3-MH/Cr). The composite endpoint was defined as all-cause death or hospitalizations due to worsening HF. RESULTS: Compared to controls, elderly HF patients had a significantly higher IL-6, CRP, BNP, and 3-MH/Cr, and exhibited a reduced lower limb muscle mass and strength. A correlation analysis demonstrated significant positive correlations between the inflammatory cytokine levels and 3-MH/Cr and BNP, and negative correlations with the lower limb muscle mass and strength, and 6-min walk distance. During a median follow-up of 2.4-years, 24 patients reached the endpoint. A random forest model revealed that inflammatory cytokines, skeletal muscle wasting, and the BNP had greater effects on the risk prediction. The algorithm achieved an area under the receiver operating characteristic curve of 0.887 (95% CI, 0.772-1.000). CONCLUSION: This study provided evidence of the association between inflammation and increased skeletal muscle proteolysis, reduced skeletal mass and strength, and their prognostic roles in elderly HF patients.

Clinical experience of idarucizumab use in cases of cardiac tamponade under uninterrupted anticoagulation of dabigatran during catheter ablation of atrial fibrillation.

Anticoagulants are prescribed for prevention of thromboembolic events (TE) of atrial fibrillation (AF), however, their effects have a negative impact on disastrous bleeding outcomes. Idarucizumab was developed to reverse the anticoagulation effects of dabigatran. This study aimed to retrospectively investigate the clinical efficacy and safety of idarucizumab in the setting of progressive emergent bleeding events associated with catheter ablation (CA). Dabigatran is given uninterruptedly as an anticoagulant in patients undergoing CA of AF. The capacity of idarucizumab to reverse the anticoagulant effects of dabigatran in patients with cardiac tamponade associated with CA was examined by measuring the activated partial thromboplastin time (aPTT), active clotting time (ACT), and prothrombin international normalizing ratio (PT-INR). The primary endpoint was effective hemostasis. This analysis included 21 patients receiving idarucizumab, given for restoration of hemostasis. In all 21 patients, hemostasis was restored at a median of 205.6 ± 14.8 min. Normal intraoperative cessation of bleeding was reported in 16 patients, and completion of hemostasis was also ascertained in the remaining four within 5 h. No TEs occurred within 72 h after the idarucizumab administration. Despite a significant reduction in the aPTT and ACT, no significant change was observed in PT-INR after administering idarucizumab. In emergency situations, idarucizumab was able to reverse dabigatran within a relatively short period without any serious adverse events.

The presence of late potentials after percutaneous coronary intervention for the treatment of acute coronary syndrome as a predictor for future significant cardiac events resulting in re-hospitalization.

INTRODUCTION: We previously reported that LP positive patients after percutaneous coronary intervention (PCI) had higher rate of re-hospitalization in the small-scale study (135 patients). In this study, we evaluated correlation between LP and later cardiac events leading to re-hospitalization more extensively in greater population. METHODS AND RESULTS: A 24-h high-resolution (HR) ambulatory electrocardiogram (ECG) was performed in 421 patients that received PCI for the treatment of acute coronary syndrome (ACS) within 30 days. Various baseline characteristics and post-PCI ECG parameters including LP were examined for correlation with later re-hospitalization. LP was evaluated based on 3 different conditions, i.e., the worst, mean and best values, from 24-h signal-averaged QRS wave data. During the post-PCI follow-up period (611 ±â€¯489.0 days), 90 patients were re-hospitalized due to cardiac events. Multivariate analysis identified only positive LP based on the worst value as an independent predictor for re-hospitalization with OR 2.26. Most of re-hospitalization cases (>75%) were predominantly attributed to ischemic events. LP positive population had significantly higher incidences of ischemic events as well as overall re-hospitalization compared to LP negative population. The predictive power of LP was decreased when it was combined with other variables. The receiver operating characteristic analysis determined the LP cut-off values consistent with the LP positive criteria previously reported and standardized. CONCLUSION: The presence of LP in the 24-h HR ambulatory ECG post-PCI was an independent predictor for a risk of re-hospitalization due to ischemic cardiac events in ACS patients.

Cardiac Arrest Associated with Both an Anomalous Left Coronary Artery and KCNE1 Polymorphism.

A 14-year-old boy collapsed suddenly after a basketball game and was transported to our hospital after recovering from ventricular fibrillation by an automated external defibrillator. He had experienced loss of consciousness twice and has been examined for suspected long-QT syndrome at another hospital. The 12-lead electrocardiogram on admission revealed a prolonged QTc interval of 480 milliseconds. After the patient recovered without any sequelae, computed tomography revealed an anomalous left coronary artery arising from the opposite sinus of Valsalva and coursing between the aorta and the pulmonary artery. Furthermore, genetic testing identified a KCNE1-D85N abnormality. An anomalous coronary artery is one of the major causes of sudden death in young people; therefore, surgical revascularization is recommended for left coronary arteries arising from the contralateral sinus and coursing between the aorta and the pulmonary artery, regardless of myocardial ischemia. Transient myocardial ischemia may have exaggerated the instability from the arrhythmic substrate, even though KCNE1-D85N abnormalities alone are not thought to cause fatal arrhythmias. Besides routine electrocardiography, further examinations, including imaging and genetic testing, can characterize the pathophysiology of fatal cardiac disease.

A Decision Tree-Based Survival Analysis of Patients with a History of Inappropriate Implantable Cardioverter-Defibrillator Therapy.

Implantable cardioverter-defibrillators (ICDs) improve survival in patients who are at risk of sudden death. However, inappropriate therapy is commonly given to ICD recipients, and this situation may be associated with an increased risk of death. This study aimed to construct a risk stratification scheme by using decision tree analysis in patients who received inappropriate ICD therapy.Mortality was calculated from a retrospective data analysis of a multicenter cohort involving 417 ICD recipients. Inappropriate therapy was defined as therapy for nonventricular arrhythmias, including sinus tachycardia, supraventricular tachycardia, atrial fibrillation/flutter, oversensing, and lead failure. Inappropriate therapy included antitachycardia pacing, cardioversion, and defibrillation. The prognostic factors were identified by a Cox proportional hazards regression analysis, and we constructed a decision tree.During an average follow-up of 5.2 years, 48 patients (12%) had all-cause death. A multivariate Cox hazard model revealed that the age (hazard ratio [HR] 1.06, P < 0.001), ln B-type natriuretic peptide (BNP) (HR 1.47, P = 0.02), nonsinus rhythm at implantation (HR 2.70, P < 0.05), and inappropriate therapy occurring during sedentary/awake conditions (HR 3.51, P = 0.001) correlated with an increased risk of mortality. An inappropriate therapy due to abnormal sensing (HR 0.16, P = 0.04) decreased the risk of mortality. Furthermore, a decision tree analysis stratified the patients well by using 4 covariates: BNP, activity at the time of inappropriate therapy, mechanism of inappropriate therapy, and baseline rhythm at ICD implantation (log-rank test, P < 0.0001).We identified the predictors of mortality in inappropriate ICD therapy recipients and constructed a risk stratification scheme by using decision tree analysis.

Left Atrial Appendage Thrombus Prior to Atrial Fibrillation Ablation in the Era of Direct Oral Anticoagulants.

BACKGROUND: In atrial fibrillation (AF) patients, the effect of direct oral anticoagulant (DOACs) therapy on the incidence of left atrial appendage thrombus (LAT) remains poorly investigated. This study examined the prevalence and risk factors of LAT in AF patients on DOACs undergoing catheter ablation, and sought an anticoagulation strategy for LAT. Methods and Results: In 407 AF patients on DOACs, transesophageal echocardiography (TEE) was performed 1 day before ablation. If patients had LAT, initial DOACs were switched to dabigatran (300 mg) or warfarin based on their renal function; TEE was repeated after treatment for ≥4 weeks. LAT was detected in 18 patients (4.4%). The prevalence of persistent AF and low-dose treatment/inappropriate dose reduction of DOACs, CHADS2/CHA2DS2-VASc scores, serum N-terminal pro-brain natriuretic peptide levels, and LA dimension/LA volume index significantly increased in patients with LAT vs. those without LAT. AF rhythm on TEE and spontaneous echo contrast also increased in patients with LAT; LA appendage flow velocity decreased. In the multivariate analysis, persistent AF and inappropriately reduced DOAC dose were risk factors for LAT. On repeat TEE, LAT had disappeared in 13 of 16 patients treated with dabigatran and in 2 of 2 patients treated with warfarin. CONCLUSIONS: DOACs still carry a finite risk of LAT in AF patients. Inappropriately reduced DOAC dose should be avoided to minimize the thromboembolic risk. Regular-dose dabigatran may have therapeutic efficacy against LAT.

Predicting acute kidney injury using urinary liver-type fatty-acid binding protein and serum N-terminal pro-B-type natriuretic peptide levels in patients treated at medical cardiac intensive care units.

BACKGROUND: The early prediction of acute kidney injury (AKI) can facilitate timely intervention and prevent complications. We aimed to understand the predictive value of urinary liver-type fatty-acid binding protein (L-FABP) levels on admission to medical (non-surgical) cardiac intensive care units (CICUs) for AKI, both independently and in combination with serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. METHODS: We prospectively investigated the predictive value of L-FABP and NT-proBNP for AKI in a large, heterogeneous cohort of patients treated in medical CICUs. Baseline urinary L-FABP and serum NT-proBNP were measured on admission. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. We studied 1273 patients (mean age, 68 years), among whom 46% had acute coronary syndromes, 38% had acute decompensated heart failure, 5% had arrhythmia, 3% had pulmonary hypertension, 2% had acute aortic syndrome, 2% had infective endocarditis, and 1% had Takotsubo cardiomyopathy. RESULTS: Urinary L-FABP levels correlated with serum NT-proBNP levels (r = 0.17, p < 0.0001). AKI occurred in 224 patients (17.6%), including 48 patients with stage 2 or 3 disease. Patients who developed AKI had higher one-week and 6-month mortality than those who did not develop AKI (p = 0.0002 and p = 0.003, respectively). In the multivariate logistic analysis, both L-FABP (p < 0.0001) and NT-proBNP (p = 0.006) were independently associated with the development of AKI. Adding L-FABP and NT-proBNP to a baseline model that included established risk factors further improved reclassification (p < 0.001) and discrimination (p < 0.01) beyond that of the baseline model or any single biomarker individually. CONCLUSIONS: Urinary L-FABP and serum NT-proBNP levels on admission are independent predictors of AKI, and when used in combination, improve early prediction of AKI in patients hospitalized at medical CICUs.