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BACKGROUND: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. OBJECTIVES: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. METHODS: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1, 021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length≥28mm], and minimum stent area >0.8× average reference lumen area [stent length

A decline in lung function is the basis of the definition of progressive fibrosing interstitial lung disease. This study aimed to evaluate the epidemiology and clinical relevance of lung function decline in sarcoidosis.This retrospective observational study was conducted at a general sarcoidosis clinic. Lung function decline was defined as a relative 24-month decline in the percentage of predicted forced vital capacity (%FVC) of ≥10% or the percentage of predicted diffusion capacity for carbon monoxide (%DLco) of ≥15%. The frequency of lung function decline and its associations with the subsequent 24-month change in lung function and survival time were analyzed.Of the 201 patients, 14 (7.0%) exhibited a 24-month decline in %FVC of ≥10% and 28 (16.6%) exhibited a 24-month decline in %DLco of ≥15%. A 24-month decline in lung function was not associated with a subsequent 24-month lung function decline. Eleven patients died during the median observational time of 148.3 months; 4 of the 11 deaths were associated with sarcoidosis. A 24-month decline in lung function was associated with worse survival even after the adjustment for composite physiological index (CPI) and pulmonary hypertension (PH): 24-month decline in %FVC ≥10%, hazard ratio (HR) adjusted for CPI = 21.8, HR adjusted for PH = 19.3 and 24-month decline in %DLco ≥15%, HR adjusted for PH = 6.74.A 24-month decline in lung function can be a risk factor for mortality in sarcoidosis irrespective of CPI and PH.

ExTRa Mapping™ has developed to visualize rotational activation as atrial fibrillation (AF) drivers. The current study was sought to evaluate the instability of AF drivers by ExTRa Mapping™.Variation of nonpassively activated ratio (%NP) among three-time repetitive recordings before and after pulmonary vein isolation (PVI) in left atrium was assessed in 26 persistent AF patients. The recoding time was set at 5 or 8 s for the respective patients. The outcome measures included %NP at each recording, mean value of the three-time recordings, and the instability index, which was defined as maximum difference per mean %NP × 100 (%).Total 683 sites 2049 recordings were assessed. Mean %NP was 33.3(23.3-42.7)%, and higher in sites with severe (≥50%) and patchy low voltage area than those without, but not in those with severe complex fractionated atrial electrogram area. There was significant correlation between actual and mean %NP (R = 0.86, P .001), but maximum difference among the repetitive recordings was 16(10-24)%. The instability index of %NP was 55.9(30.9-83.6)%, and significantly lower at the recordings of 8 s compared with 5 s (50.6[28.6-78.4]% vs. 60.4[35.0-90.0]%, P = .004). Furthermore, it was higher at sites with lower reliability of the recordings. After PVI, mean %NP significantly decreased (28.7[18.3-36.7]% vs. 37.7[28.7-45.7]%, P .001), but the instability index significantly increased compared with those before PVI (60.0[35.0-92.7]% vs. 48.9[29.1-75.0]%, P = .001).Rotational activation as AF drivers assessed by ExTRa Mapping™ is unstable, and repetitive and longer recording is required for the reliable assessment even after PVI.

It is still controversial whether catheter ablation for atrial fibrillation (AF) could improve clinical outcomes in general AF population. Among 4398 patients with diagnosis of AF in the outpatient department of Kyoto University Hospital between January 2005 and March 2015, we identified 537 pairs of patients who received first-time catheter ablation (ablation group) or conservative management (conservative group), matched for age, gender, AF duration, AF type, AF symptoms, and previous heart failure (HF). The primary outcome measure was a composite of cardiovascular death, HF hospitalization, ischemic stroke, or major bleeding. Most baseline characteristics were well balanced between the 2 groups, except for the higher prevalence of low body weight, history of malignancy, and severe chronic kidney disease in the conservative group. Median follow-up duration was 5.3 years. The cumulative 5-year incidence of the primary outcome measure was significantly lower in the ablation group than in the conservative group (5.2% versus 15.6%, log-rank P 0.001). Even after adjusting for the imbalances in the baseline characteristics, the lower risk of the ablation group relative to the conservative group for the primary outcome measure remained highly significant (HR 0.32, 95% CI 0.21-0.47, P 0.001). Ablation compared with conservative management was also associated with significantly lower risks for the individual components of the primary outcome. In this matched analysis in AF patients, ablation as compared with conservative management was associated with better long-term clinical outcomes, although we could not deny the possibility of selection bias and unmeasured confounding.

Purpose We developed the intracardiac echocardiography (ICE) technique to minimize radiation exposure and other recent technology during ablation procedure for atrial fibrillation (AF). The aim of this study was to validate the impact of the current strategy using the recent technology for AF ablation on outcomes after procedure. Methods We evaluated the safety and efficacy of the current strategy in consecutive set of patients undergoing first‐time ablation for AF (N = 233) compared with the conventional strategy in earlier consecutive set of patients (N = 223). The current strategy included the technique of ICE to reduce radiation exposure, Ablation Index®‐guided pulmonary veins isolation, and minimum substrate ablation targeting only for induced AF. Outcome measures were radiation exposure, procedure time, in‐hospital adverse outcomes, and event‐free survival from tachyarrhythmias. Results Puncture‐to‐ablation time was slightly, but significantly increased in the current strategy than in the conventional strategy (48.0 minutes vs 44.7 minutes, P = .002), although total procedure time was significantly decreased in the current strategy (143.9 minutes vs 156.9 minutes, P, The current strategy using the recent technology with intracardiac echocardiography, lesion index, and minimum substrate ablation was feasible and reduced procedure time and radiation exposure. However, the arrhythmia‐free survival could not be improved.

ObjectiveThe clinical significance of ECG abnormalities during atrial fibrillation (AF) rhythm is poorly understood. The aim of the current study was to explore the impact of inverted T wave on cardiac prognosis in patients with AF.MethodsThe current study enrolled 2709 patients with AF whose baseline ECG was available from a Japanese community-based prospective survey, the Fushimi AF Registry, and the impact of inverted T wave in baseline ECG at AF rhythm on the composite of cardiac death, myocardial infarction and hospitalisation due to heart failure was examined.ResultsIntraventricular conduction delay, ST segment depression and inverted T wave were observed in 15.8%, 24.7% and 41.4% of baseline ECG with a mean heart rate of 94.7 beats per minute. The median follow-up duration was 5.0 years. The incidence rate of the composite cardiac endpoint was significantly higher in patients with inverted T wave than those without (5.8% vs 3.3% per patient-year, log-rank pConclusionsInverted T wave was commonly observed in patients with AF and its presence during AF rhythm was associated with subsequent cardiac events.

There is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE).The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (60 kg).Patients with lower body weight were older (70.8 versus 60.9 years, P 0.001), and more often women (75% versus 38%, P 0.001), and more often had active cancer (27% versus 19%, P 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P 0.001, and 35.8% versus 19.8%, P 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16-2.12, P = 0.003, and HR 1.50, 95%CI: 1.24-1.81, P 0.001, respectively).In the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE.

Aims We sought to investigate the time course of cardiac disorders after catheter ablation for atrial fibrillation (AF) in patients with coexisting heart failure (HF) during long‐term follow‐up. Methods and results We analysed consecutive 280 patients undergoing first‐time catheter ablation for AF who had coexisting HF, which was defined as prior HF hospitalization, estimated right ventricular systolic pressure ≥45 mmHg, or B‐type natriuretic peptide (BNP) ≥200 pg/dL before the procedure. The primary endpoints were improvements in left ventricular ejection fraction (LVEF), E/e′, BNP, left atrial dimension (LAD), and mitral regurgitation (MR) at 1 year. The secondary endpoints were serial changes of LVEF, E/e′, BNP, LAD, and MR at 6 months, 1 year, and 5 years and cumulative incidence of HF hospitalization. During the mean follow‐up of 5.1 ± 3.0 years, 70.7% of patients were free from recurrent AF. Among patients with LVEF

The characteristics of atrial fibrillation (AF) drivers identified by CARTOFINDER have not been thoroughly evaluated. Therefore, the current study was sought to validate the reliability of AF drivers.The reliability of focal and rotational activation identified by CARTOFINDER during AF was assessed by the sequential recordings in each site before and after pulmonary vein isolation (PVI) in 27 persistent AF patients. The primary outcome measures were the reproducibility rate during the sequential recordings and the stability rate between pre- and post-PVI.Among 32,135 points in 509 sites, focal activation was identified in 1775 points (5.5%) with a repetition of 11 (6-26) times during the recording. Rotational activation was identified in 132 points (0.4%) with a repetition number of 21 (14-21) times. AF drivers had significantly higher voltage and shorter AF cycle length than non-AF driver sites. The reproducibility rate of focal activation during the sequential recordings was 57.8% and increased with the repetition number. The reproducibility rate of rotational activation was 37.4%. The prevalence and the reproducibility rate of focal activation in post-PVI were significantly lower than pre-PVI (5.3% versus 6.0%, P = 0.02; 53.4% versus 63.6%, P 0.001). The stability rate of focal activation between pre- and post-PVI was only 28.3% but increased with the repetition number. There was no stable rotational activation between pre- and post-PVI.The reproducibility of AF drivers, especially focal activation, identified by CARTOFINDER is relatively favorable, but the stability between pre- and post-PVI was poor. These results depended on the repetition number during the recording.

Filling defect (FD) in left atrial appendage (LAA) is commonly observed in contrast computed tomography (CT) among patients with atrial fibrillation (AF), although its prognostic impact has not been well explored. We enrolled 1,019 consecutive patients who underwent AF ablation with baseline contrast CT images. FD in LAA was graded into 3 groups: grade 0 for complete filling (79.7%), grade 1 for incomplete filling (12.6%), and grade 2 for complete FD (7.8%). We evaluated the impact of the FD grade on the long-term clinical outcomes during the mean follow-up of 4.4 ± 2.0 years. Patients with grade 2 FD had higher prevalence of nonparoxysmal AF, higher brain natriuretic peptide level, and larger left atrial volume than those with grade 0 or 1 FD. The 5-year cumulative incidence of recurrent atrial tachyarrhythmias was higher in patients with grade 2 FD than those with grade 0 or 1 FD (74.0% vs 38.8% and 62.1%, log-rank plt;0.001). The 5-year cumulative incidence of major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, heart failure hospitalization, and ischemic stroke, was also significantly higher in patients with grade 2 FD (19.4% vs 5.6% and 9.5%, log-rank plt;0.001). Follow-up CT images acquired in 87.1% of patients at median interval of 98 days showed significantly decreased FD (grade 1 in 4.5% and grade 2 in 2.1%, plt;0.001). The residual grade 2 FD at follow-up was associated with significantly higher risk for subsequent MACEs. In conclusion, among patients with AF receiving catheter ablation, severe FD in LAA in contrast CT was associated with higher incidence of arrhythmia recurrence and MACEs during follow-up.

Background: Rapid and accurate diagnosis of acute coronary syndrome (ACS) is critical to prevent the fatal complication accompanied with the delay of the treatment. However, the diagnosis of non-ST-segment elevation ACS (NSTE-ACS), especially shortly after the onset, is not straightforward because even high-sensitivity cardiac troponin (hs-cTn) is sometimes not elevated at that phase. We previously reported in a retrospective study that serum nardilysin is a potential biomarker for the early detection of NSTE-ACS. Here, we present the results of the Nardi-ACS study, a multicenter prospective study conducted at six centers in Japan to clarify the significance of nardilysin for the early detection of ACS. Methods and Results: We analyzed serum nardilysin and hs-cTnI (Architect; Abbott) in the sequential 2 independent cohorts; phase I primary cohort (435 patients with chest pain who consecutively visited to the emergency room (ER)) and phase II validation cohort (486 patients with a strong suspicion of ACS who underwent coronary angiography). The frequency of non-ACS, STEMI and NSTE-ACS was 64.4, 22.5, and 13.1 (%) in the phase I, and 14.0, 60.0, and 25.9 (%) in the phase II cohort, respectively. The cutoff value of serum nardilysin was set at 1350.9 pg/ml (mean +2SD) obtained in 246 healthy volunteers, while the cutoff of hs-cTnI was set at 52 pg/ml. The initial blood test in the phase I cohort revealed that nardilysin was significantly elevated in ACS patients, compared to non-ACS patients (p Conclusion: Nardilysin could be a potential biomarker for the early diagnosis of troponin-negative NSTE-ACS.

Basal interventricular septum (IVS) thinning on transthoracic echocardiography (TTE) is highly specific to cardiac sarcoidosis. Although basal IVS thinning is listed as one of the five major diagnostic criteria for cardiac sarcoidosis, its association with long-term cardiac function has not been investigated. This study aimed to evaluate the epidemiology and clinical relevance of basal IVS thinning in a clinic-based cohort of patients with sarcoidosis.This retrospective observational study was conducted at a general sarcoidosis clinic. The incidence of basal IVS thinning and associations with variables at baseline and a delayed onset of left ventricular (LV) dysfunction (LV ejection fraction [LVEF] 50%) were analyzed.Of the 1009 patients, 23 (2.3%) had basal IVS thinning. Basal IVS thinning was associated with cardiac pacemaker (PM) implantation at baseline (adjusted odds ratio = 20.5; 95% confidence interval [CI] = 7.9-53.2; P 0.01). Of the 768 patients with an LVEF of ≥50% at baseline who underwent one or more longitudinal TTEs after baseline, 36 (4.7%) developed LV dysfunction over a median observation period of 88.9 months. Basal IVS thinning and PM implantation at baseline were the independent predictors of a delayed onset of LV dysfunction (basal IVS thinning, adjusted hazard ratio [HR] = 3.7; 95% CI = 1.5-9.6; PM implantation, adjusted HR = 15.7; 95% CI = 7.4-33.3).Basal IVS thinning in patients with sarcoidosis can predict a delayed onset of LV dysfunction even when the LV function is preserved at the time of detection.

Activated clotting time (ACT) kinetics under uninterrupted oral anticoagulants (OACs) has not been fully evaluated. The present study is sought to validate ACT kinetics including stability under uninterrupted use of OACs during an ablation procedure in daily clinical practice. We prospectively enrolled consecutive 554 patients with atrial fibrillation who underwent catheter ablation procedure under uninterrupted OACs. We evaluated ACT kinetics at an interval of 15 minutes during the procedure and periprocedural complications among 5 OACs (dabigatran [N = 46], rivaroxaban [N = 125], apixaban [N = 129], edoxaban [N = 184], and warfarin [N = 70]). Compared with the dabigatran group, time to achieve target ACT was significantly longer in the rivaroxaban and apixaban groups, but not in the edoxaban and warfarin groups (8.7 vs 11.7 minutes, P.001; 13.3 minutes, P.001; 8.8 minutes, P = .64; 10.3 minutes, P = .19, respectively). Heparin dose to achieve target ACT was comparable except for the warfarin group, whereas, compared with the dabigatran group, time in therapeutic range of ACT within the first hour was comparable in the rivaroxaban and apixaban group but significantly lower in the edoxaban and warfarin groups (73.7 % vs 63.0%, P = .06; 67.0 %, P = .16; 59.2 %, P = .001; 58.2%, P = .004, respectively). In multiple regression analysis, low body weight, rivaroxaban, apixaban, and morning session had significant associations with time and heparin dose to achieve target ACT, and there were positive associations of dabigatran and apixaban with time in therapeutic range of ACT within the first hour. The incidence of periprocedural complications did not significantly differ among the 5 groups. Under uninterrupted OAC use in daily clinical practice, dabigatran showed faster achievement of target ACT and higher stability of ACT than other OACs.

Background The impact of delays in the treatment with radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) has not been well evaluated. The aim of this study was to investigate the impact of diagnosis-to-ablation time (DAT) on the long-term clinical outcomes after AF-RFCA. Methods We enrolled 1206 consecutive patients undergoing first-time RFCA for AF. The study population was divided into 2 groups based on DAT: short ( 3 years) (N = 531) DAT groups. Results Mean follow-up duration was 5.0 ± 2.5 years. The 5-year event-free rates from recurrent atrial tachyarrhythmias after the first and second RFCAs were significantly higher in short DAT group than in long DAT group (60.2% versus 48.3%, log-rank P Conclusions In the management of AF, early RFCA was associated with significantly lower arrhythmia recurrence compared with delayed RFCA, leading to reduced cardiovascular hospitalization, especially in heart failure patients.

BACKGROUND Electroanatomic voltage mapping (EAVM) of the left atrium (LA) with multielectrodes is usually acquired during sinus rhythm (SR), and the feasibility of EAVM during atrial fibrillation (AF) rhythm is unclear. METHODS We performed EAVM of LA during both SR and AF rhythm in 44 patients undergoing catheter ablation for AF and validated the optimal cutoff value of low-voltage area (LVA) during AF rhythm for detecting LVA defined as bipolar voltages ≤0.5 mV during SR. RESULTS In each session, mean 829 and 552 points were acquired by multielectrodes during SR and AF rhythm, respectively. Mean proportion of LVA was 4.9% among LA surface area of 276.2 cm2 . Differences of LVA proportions between SR and AF rhythm were 5.8% (P

Background Atrial fibrosis is hallmark of structural remodeling in atrial fibrillation (AF), but the inflammatory mechanism remains unclear. The purpose of the present study was to identify the specific inflammatory biomarkers to atrial fibrosis evaluated by atrial low voltage (LV) in AF patients for clarification of the mechanism. Methods Forty inflammatory biomarkers were quantified in 16 consecutive AF patients measured left atrial low voltage during catheter ablation. Results Median %LV area was 17%. In Pearson's correlation analysis, interleukin (IL)-17A and interferon (IFN)-γ was the most significant positive and negative correlation with %LV (R=0.35 and 0.43, P10% as a reference standard) was 0.88. IL-17A/IFN-γ ratio was significantly higher in patients with significant LV than those without (1.41 versus 0.97, P=0.01), Furthermore, the sensitivity, specificity, and accuracy for detecting significant LV were 60%, 100%, and 75.0% at the cutoff value of 1.3. The event free survival from recurrent atrial tachyarrhythmias was not significantly different between patients with and without IL-17A/IFN-γ ratio >1.3 (83.3% versus 80.0% at 1-year, P=0.81). Conclusions Among inflammatory biomarkers, IL-17A/IFN-γ ratio was a significant predictor for the severity of left atrial low voltage n AF patients. Further study is needed to reveal the association between IL-17A and IFN-γ for development of fibrosis in AF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI GrantNumber JP19K17594

Background The patients with implantable cardiac defibrillator (ICD) or cardiac resynchronization therapy device (CRT) have high risk of cardiac events, and lower physical activity has been thought to be associated with higher rate of cardiac events. On the other hand, cardiovascular implantable electronic devices can monitor physical activity through a built-in accelerometer. This study aimed to analyze long-term outcomes by device-based monitoring of physical activity in patients with ICD or CRT. Methods We retrospectively reviewed 89 patients with ICD/CRT, (56 males, 66.5 years old; ICD 45, CRT-D 42, CRT-P 2) who survived longer than 6 months after implantation in our institution. We analyzed physical activity by devices at 6th month and divided to 2 groups; In Low activity group (group L; n=38), their physical activity (moving time above 70 steps/min walk level) is less than 2 hours/day, and in Normal activity group (group N; n=51), physical activity is more than 2 hours/day. We evaluated their background characteristics in each group, physical activity at 12th month, and composite outcomes of hospitalization due to worsening of heart failure (HF) and death of any cause. Results Mean follow-up period was 57.4 months (median 40 months). In group L, they had higher age (71.1 y.o. vs. 63.2 y.o.; p=0.0003), higher rate of low EF (76.3% vs. 54.9%; p=0.035), and lower rate of attendance to outpatient cardiac rehabilitation program (10.5% vs 27.5%; p=0.043) compared with group N. 85.7% of patients in group L stayed in low physical activity at 12th month, and 87.8% of patient in group N stayed in normal physical activity. Composite outcomes of HF hospitalization and death occurred significantly higher in group L (Log-rank p Conclusions Lower level of device-monitored physical activity was associated with higher mortality and higher rate of HF hospitalization in patients with ICD or CRT. Most of the patient in lower physical activity could not improve their activity from 6th month to 12th month. Early and continuous intervention is necessary especially for high risk patients such as high age or low EF. Figure 1 Funding Acknowledgement Type of funding source: None

The incidence of subsequent need for permanent pacemaker implantation (PMI) after radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in real world patients with and without pre-existing bradycardia has not yet been fully evaluated. Methods and Results: A total of 1,131 consecutive patients undergoing first-time RFCA for AF who had no previous or planned device implantation, were enrolled in the present study. Of 799 paroxysmal AF (PAF) patients, 121 (15.1%) had sinus node dysfunction (SND). Of 332 non-PAF patients, 73 (22.0%) had slow ventricular response (VR), defined as heart rate80 beats/min at rest without any rate-control drugs. The 5-year cumulative incidence of PMI after RFCA in PAF patients with and without SND was 14.8% and 1.7%, respectively (P0.001). The 5-year cumulative incidence of PMI after RFCA in non-PAF patients with and without slow VR was 14.8% and 4.7%, respectively (P0.001). SND and female gender in PAF patients, as well as slow VR and age ≥75 years in non-PAF patients, were independent and additive predictors of PMI. The 5-year cumulative incidence of PMI was 26.3% in female PAF patients with SND and 33.3% in elderly non-PAF patients with slow VR.PMI was avoided in85% of patients undergoing RFCA for PAF with pre-existing SND, although care should be taken for female patients. Decision-making regarding RFCA for non-PAF patients with slow VR, especially in the elderly, should be cautious.

Background: The mechanisms leading to atrial fibrosis in patients with atrial fibrillation (AF), especially in relation to inflammation, remain unclear. Methods and Results: Forty biomarkers were measured in peripheral blood samples collected prior to catheter ablation, and the association with left atrial (LVZ) was evaluated in 16 consecutive patients. The median %LVZ was 17%. In Pearson’s correlation analysis, interleukin(IL)-17A and interferon(IFN)-γ showed the most significant positive and negative correlations with %LVZ (R = 0.35 and 0.43, P

A 70-year-old woman, who had received mechanical aortic and mitral valve replacement for rheumatic valvular disease and implanted cardiac defibrillator (ICD) implantation for ventricular arrhythmia, underwent radiofrequency catheter ablation for symptomatic atrial fibrillation (AF). During the

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P, See Editorial by Tribouilloy et al

BackgroundAtrial fibrillation (AF) and renal failure coexist and interact. However, scarce data about association between renal function and clinical outcomes in patients undergoing catheter ablation for AF are available. We sought to evaluate long-term renal function and clinical outcomes after AF ablation.MethodsWe enrolled 791 non-dialysis patients undergoing catheter ablation for AF, and evaluated the incidence of worsening renal function (WRF) after the procedure, defined as >30% decline in estimate glomerular filtration rate.ResultsMean follow-up duration was 5.1±2.5 years. Five hundreds and twenty-six patients (66.5%) were free from recurrent atrial arrhythmias without any antiarrhythmic drugs at the time of final follow-up. Cumulative incidence of WRF was 13.2% at 5-year after procedure, which was significantly higher in patients with recurrent AF compared to those without (21.6% versus 8.7%, P2at baseline. Patients with WRF had significantly higher 5-year incidences of all-cause death, cardiovascular death, heart failure hospitalization, ischemic stroke, and major bleeding compared to those without WRF. After adjustment of baseline differences in the multivariate Cox model, the excessive risks of WRF for all-cause death and heart failure hospitalization remained significant (adjusted HR 3.46, P = 0.002; adjusted HR 3.67, PConclusionsIn AF patients undergoing catheter ablation for AF, arrhythmia recurrence was associated with WRF during follow-up, which was a strong predictor of adverse clinical outcomes.

Left atrial contrast computed tomography (LA-CT) as well as transesophageal echocardiography (TEE) can exclude left atrial appendage (LAA) thrombus, but is sometimes unable to evaluate LAA due to incomplete LAA filling. The aim of the current study was to validate the utility of real-time approach of LA-CT with real-time surveillance of LAA-filling defect (FD). We enrolled consecutive 894 patients with LA-CT studies acquired for catheter ablation and compared the diagnostic accuracy in demonstrating LAA-FD between conventional protocol (N = 474) and novel protocol with real-time surveillance of LAA-FD immediately after the initial scanning and, when necessary, adding delayed scanning in the supine or prone position (N = 420). Primary endpoint was severity of LAA-FD classified into the 3 groups: “Grade-0” for complete filling of contrast, “Grade-1” for incomplete filling of contrast, and “Grade-2” for complete FD of contrast. The prevalence of Grade-1 and Grade-2 FD was 17.3% and 11.2% in conventional protocol, whereas there was no patient with Grade-2 FD, and only 1 patient with Grade-1 FD after the additional scanning in novel protocol. In 5 patients with suspected LAA thrombus both by TEE and Grade-2 FD in LA-CT by the conventional protocol, ablation procedure was canceled due to diagnosis of LAA thrombus. Conversely, 4 patients with suspected LAA thrombus by TEE in novel protocol group was proved to have intact LAA by LA-CT with and without additional scanning. This novel approach with real-time surveillance improved the diagnostic accuracy of LA-CT in detecting LAA-FD, suggesting potential superiority of LA-CT over TEE in excluding LAA thrombus.

Background Radiofrequency catheter ablation (RFCA) for persistent atrial fibrillation (AF) is still challenging even in RFCA-era for AF. The aim of this study was to assess the clinical utility of nifekalant, a pure potassium channel blocker,during RFCA for persistent AF. Methods and results We retrospectively enrolled 157 consecutive persistentAF patientsundergoing first RFCA procedure withcomplex fractionated atrial electrogram (CFAE)ablation after pulmonary veins isolation and compared outcomes between patientswith (NFK group: N=79) and without (No-NFK group: N=78)additional CFAE ablation using intravenous nifekalant (0.3mg/kg). Primary endpoint was 24-month atrial arrhythmia-free survival post ablation.The prevalence of AF terminationwas significantly higher in NFK group than No-NFK group (64.6% versus 7.7%, P

Background and Aim Clinically unsuspected pulmonary embolism can be detected using coronary computed tomography (CT), but the clinical significance of unsuspected pulmonary embolism remains unclear. Methods Pulmonary embolism was assessed using consecutive coronary CT from March 2003 to June 2007 to assess 1077 patients. Coronary CT was performed using a 16-row multidetector CT (MDCT) scanner with ECG-gating. A radiologist and a cardiologist retrospectively assessed the images of pulmonary arteries to arrive at a consensus diagnosis. Results Unsuspected pulmonary embolism was detected in 32/1,077 (3.0%) patients. No significant difference was observed with regard to death and acute pulmonary embolism between patients with and without unsuspected pulmonary embolism at five years (6.7% vs. 4.1%, p = 0.61). Prior cardiac surgery within three months of diagnosis of pulmonary embolism was an independent risk factor for unsuspected pulmonary embolism, which was detected in 10/89 (11%) of such patients. The absence of anticoagulant therapy was a risk factor (p = 0.015) for unsuspected pulmonary embolism post–cardiac surgery. Although only one out of 10 patients received anticoagulant therapy, none of the 10 experienced critical events. Five of the 10 patients underwent repeated coronary CT, and the embolus disappeared regardless of its size and location in four of the five patients who did not receive anticoagulant therapy. Conclusions The prevalence of unsuspected pulmonary embolism detected using coronary CT was 3.0%. Prior cardiac surgery within three months of diagnosing pulmonary embolism was an independent risk factor for unsuspected pulmonary embolism. The long-term clinical outcomes of patients with unsuspected pulmonary embolism were favorable. doi: 10.1111/jocs.12512 (J Card Surg 2015;30:301–306)

The aim of this study was to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) in patients with severe aortic stenosis (AS).The prognostic impact of LVEF in severe AS remains controversial.Among 3,815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study population consisted of 3,794 patients after excluding 21 patients without LVEF data. Patients were divided into 4 groups according to LVEF at index echocardiography (50%, 50% to 59%, 60% to 69%, and ≥70%; conservative strategy: n = 388, n = 390, n = 1,025, and n = 800; initial aortic valve replacement strategy: n = 206, n = 170, n = 375, and n = 440). Echocardiographic data were site reported, and there was no echocardiography core laboratory.In the conservative group, the cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significantly higher in patients with LVEFs 50% and 50% to 59% than in those with LVEFs 60% to 69% and ≥70% (72.3%, 58.4%, 38.7%, and 35.0%, respectively, p 0.001), whereas in the initial aortic valve replacement group, the negative effect of low LVEF was markedly attenuated (20.2%, 20.3%, 17.7%, and 12.4%, respectively, p = 0.03). After adjusting for confounders, LVEF 50% (hazard ratio: 1.82; 95% confidence interval: 1.44 to 2.28; p 0.001) and 50% to 59% (hazard ratio: 1.77; 95% confidence interval: 1.42 to 2.20; p 0.001) but not 60% to 69% (hazard ratio: 1.14; 95% confidence interval: 0.94 to 1.39; p = 0.17) were independently associated with poorer outcomes compared with LVEF ≥70% (reference) in the conservative group. In the initial aortic valve replacement group, the adjusted risk for the primary outcome measure was not significantly different across the 4 LVEF groups.This study demonstrates that survival in patients with severe AS is impaired when LVEF is 60%, and these findings have implications for decision making with regard to the timing of surgical intervention.

Background There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis ( AS ). Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax AS ‐related events (aortic valve–related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P P =0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P =0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS ‐related events remained significant (hazard ratio, 1.39; 95% CI , 1.07–1.81; P =0.02, and hazard ratio, 1.53; 95% CI , 1.17–2.00; P =0.002, respectively). The effect size of group 3 relative to group 1 for AS ‐related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI , 1.01–2.52; P =0.047, and hazard ratio, 1.67; 95% CI , 1.16–2.40, P =0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS ‐related events (interaction, P =0.88). Conclusions In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS ‐related events. However, the cumulative 5‐year incidence of the AS ‐related events remained very high even in asymptomatic patients with less greater Vmax.

Objective Our objective was to evaluate the effectiveness of combination therapy consisting of low-dose corticosteroids with weekly methotrexate in patients with cardiac sarcoidosis in whom long-term therapy is required. Combination therapy was selected because long-term standard corticosteroid therapy tends to result in various adverse effects and the steroid-sparing effects of methotrexate have been reported. Methods This study was a small open-label study comparing long-term functional changes between patients who received combination therapy (5-15 mg/day of prednisolone and 6 mg/week of methotrexate) and patients who received corticosteroids alone. The comparative analysis was based on the following therapeutic indexes: ejection fraction (EF), left ventricular end-diastolic diameter (LVDd) on echocardiography, serum N-terminal fragment pro-brain natriuretic peptide (NT-proBNP) and cardiothoracic ratio (CTR) on plain chest radiographs. Patients Seventeen patients with cardiac sarcoidosis were examined in the sarcoidosis clinic. Cardiac sarcoidosis was diagnosed based on the Japanese diagnostic guidelines published in 2006. Results The EF was significantly stabilized in the combination therapy group but not in the corticosteroids alone group at three years after the first treatment. The CTR and NT-proBNP levels were significantly stabilized in the combination therapy group compared with those observed in the corticosteroids alone group at both three and five years after the first treatment. The LVDd values tended to be stable in the combination therapy group compared with those observed in the corticosteroids alone group. The combination therapy was associated with few adverse effects. Conclusion Weekly methotrexate therapy with daily small doses of corticosteroids stabilized the EF, CTR and NT-proBNP levels in the serum without eliciting adverse effects longitudinally.

IMPORTANCE: Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. OBJECTIVE: To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. INTERVENTIONS: Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. RESULTS: Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, −1.34% [95% CI, −2.57% to −0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P

There was limited data for incidence, timing, and predictor of myocardial damage after low-to-moderate dose of anthracycline-based chemotherapy (AC) in patients with breast cancer. Among the women with breast cancer, we prospectively assessed myocardial damage using high sensitive troponin I assay

Arteriovenous fistula has superior patency over other accesses, but vascular access intervention therapy (VAIVT) for stenosis or thrombosis still remain major reasons for hospital admission of dialysis patients. The aim of this study was to examine the usefulness of systematic evaluation of vascular access by color-Doppler ultrasound (CDUS). This study was a single-center observational design study. We planned screening CDUS to evaluate all vascular accesses once per year, and additionally, follow-up CDUS of post-interventional patients 1 month, 3 months and 6 months after their recent VAIVT. This systematic evaluation was started from September 2009. The observational period between September 2008 and August 2009 was defined as period A. The observational period between September 2009 and August 2010 was defined as period B. We compared the incidence of emergent VAIVT and X-ray exposure time during the period A to B. 131 patients with AV fistula were assigned. 13 patients were excluded due to death, hospital transfer or re-operation of their accesses. During period A, 57 VAIVTs were carried out, and 37 cases (65%) were emergent. During period B, 42 VAIVTs were carried out, and 11 cases (25%) were emergent. The incidence of emergent intervention therapy was lower during period B than period A (P < 0.001). The amount of X-ray exposure time per patient was decreased in patients who received VAIVT during both periods (P < 0.03). Systematic evaluation of vascular access by CDUS decreased the incidence of emergent VAIVT and X-ray exposure time.

Background Both adaptive servoventilation (ASV) and nocturnal oxygen therapy improve sleep disordered breathing (SDB), but their effects on cardiac parameters have not been compared systematically. Methods and results 43 patients with chronic heart failure (CHF; left ventricular ejection fraction (LVEF) ≤50%) with SDB were randomly assigned to undergo ASV (n=19, apnoea hypopnoea index (AHI)=34.2±12.1/h) or oxygen therapy (n=24, 36.9±9.9/h) for 3 months. More than 70% of SDB events in both groups were central apnoeas or hypopnoeas. Although nightly adherence was less for the ASV group than for the oxygen group (4.4±2.0 vs 6.2±1.8 h/day, p

Clinically unsuspected pulmonary embolism can be detected using coronary computed tomography (CT), but the clinical significance of unsuspected pulmonary embolism remains unclear.Pulmonary embolism was assessed using consecutive coronary CT from March 2003 to June 2007 to assess 1077 patients. Coronary CT was performed using a 16-row multidetector CT (MDCT) scanner with ECG-gating. A radiologist and a cardiologist retrospectively assessed the images of pulmonary arteries to arrive at a consensus diagnosis.Unsuspected pulmonary embolism was detected in 32/1,077 (3.0%) patients. No significant difference was observed with regard to death and acute pulmonary embolism between patients with and without unsuspected pulmonary embolism at five years (6.7% vs. 4.1%, p = 0.61). Prior cardiac surgery within three months of diagnosis of pulmonary embolism was an independent risk factor for unsuspected pulmonary embolism, which was detected in 10/89 (11%) of such patients. The absence of anticoagulant therapy was a risk factor (p = 0.015) for unsuspected pulmonary embolism post-cardiac surgery. Although only one out of 10 patients received anticoagulant therapy, none of the 10 experienced critical events. Five of the 10 patients underwent repeated coronary CT, and the embolus disappeared regardless of its size and location in four of the five patients who did not receive anticoagulant therapy.The prevalence of unsuspected pulmonary embolism detected using coronary CT was 3.0%. Prior cardiac surgery within three months of diagnosing pulmonary embolism was an independent risk factor for unsuspected pulmonary embolism. The long-term clinical outcomes of patients with unsuspected pulmonary embolism were favorable.