Background:Anticoagulation for patients with atrial fibrillation (AF) complicated by left atrial thrombi (LAT) is a frequent cause of bleeding complications, but risk factors remain unknown.

Methods and Results:Of 3,139 AF patients who underwent transesophageal echocardiography, 82 with LAT under anticoagulation were included in this study. Patients treated with combination antiplatelet and anticoagulant therapy (n=31) were compared with those receiving anticoagulant monotherapy (n=51) to investigate the effects of antiplatelet agents during anticoagulation on bleeding complications. Over a mean (±SD) follow-up of 878±486 days, bleeding events occurred more frequently in the combination therapy than monotherapy group (58% vs. 20%; P<0.001), but there was no significant difference in embolic events (6.5% vs. 3.9%; P=0.606). Kaplan-Meier analysis also showed a significantly higher rate of bleeding events in the combination therapy group, but no significant difference in the rate of embolic events. Inverse probability of treatment weighting revealed that combination therapy was independently associated with an increased risk of bleeding (hazard ratio [HR] 2.98, 95% confidence interval [CI] 1.14–7.89, P=0.026), but not with the risk of embolic events (HR 0.30, 95% CI 0.04–2.59, P=0.275). Net clinical benefit analysis was almost negative for combination therapy vs. monotherapy.

Conclusions:In patients with AF and LAT, combination therapy was significantly associated with an increased risk of bleeding events, but not with a reduced risk of embolic events.

Background:Obesity is reportedly associated with the incidence of atrial fibrillation (AF), but the patterns of age-specific associations between body mass index (BMI) and the risk of AF are unknown.

Methods and Results:We analyzed 10,921 Japanese men without AF from a cohort of employees undergoing annual health examinations. During a follow-up period of 5.0±3.8 years, the incidence of AF was 118 (2.18/1,000 person-years). Using a multivariable Cox regression analysis, high BMI was associated with a risk of AF (hazard ratio; 1.07 by 1 unit change of BMI, 95% confidence interval [CI] 1.00–1.13, P=0.05) overall, and the effect of BMI on AF incidence changed with age (P for interaction=0.08); with subjects aged <65 years with BMI <25 as the reference, HR 0.74 (95% CI 0.47–1.17) in subjects aged <65 years with BMI ≥25, HR 2.98 (95% CI 1.36–6.54) in subjects aged ≥65 years with BMI <25, and HR 6.50 (95% CI 2.58–16.38) in subjects aged ≥65 years with BMI ≥25. The 5-year probability of AF incidence in subjects aged <65 years was 0.87% with BMI <25 and 0.64% in those with BMI ≥25, and in subjects aged ≥65 years it was 2.58% with BMI <25 and 5.53% with BMI ≥25.

Conclusions:Our results indicated that the effect of BMI on AF incidence changes with age among Japanese men. Both physicians and cardiologists need to integrate advice on lifestyle measures, particularly for elderly obese men, into their daily medical routine.

Background:Remote monitoring of cardiac implantable electronic devices improves clinical outcomes, but data on the association between the transmission rate (TR) of the remote monitoring, calculated in percentage as the ratio between days of transmission and days of follow-up after remote monitoring introduction, and death in patients with a pacemaker are limited.

Methods and Results:In this single-center retrospective observational study, we investigated 180 patients with a newly implanted pacemaker capable of using a specific remote monitoring system with daily transmission (79.5±8.8 years, men 50.6%). The study endpoint was all-cause death. During the follow-up period (median 2.7 years), 33 all-cause deaths were reported, and the TR was significantly lower in the deceased patients than in the survivors (89.6±9.6% vs. 95.4±7.0%, P<0.001). The area under the receiver-operating characteristic curve for TR to predict all-cause death was 0.72 (95% confidence interval [CI] 0.62–0.81, P<0.001). A TR of 95% had sensitivity of 74.1% and specificity of 63.6% for predicting all-cause death. In the multivariate Cox regression analysis, TR <95% was selected as a predictor of all-cause death (hazard ratio 3.43, 95% CI 1.61–7.27, P=0.001).

Conclusions:Low TR is a predictor of all-cause death in patients with a pacemaker. Patients with TR ≥95% may experience a lower incidence of death, and should have a good prognosis.

Background:Few studies have investigated the importance of glycemic control in patients with diabetes mellitus (DM) for reducing the incidence of late target lesion revascularization (TLR) after implantation of new-generation drug-eluting stents (DES).

Methods and Results:We retrospectively identified 1,568 patients who underwent new-generation DES implantation. Patients were divided into 3 groups based on diabetic status and glycemic control 1 year after the procedure: those without DM (non-DM group; n=1,058) and those with DM at follow-up with either good (HbA1c <7%; n=328) or poor (HbA1c ≥7%; n=182) control. The cumulative 5-year incidence of clinically driven late TLR after the index procedure was significantly higher in DM with poor control at follow-up than in those with good control at follow-up or non-DM (14%, 4.8%, and 2.9%, respectively; P<0.0001). Multivariate analysis revealed that poor control at follow-up was significantly associated with a higher risk of clinically driven late TLR compared with the non-DM group (hazard ratio [HR] 4.58, 95% confidence interval [CI] 2.50–8.16, P<0.0001). However, good control at follow-up group was not associated with a higher risk of clinically driven late TLR compared with the non-DM group (HR 1.35, 95% CI 0.68–2.56, P=0.38).

Conclusions:DM patients with poor glycemic control at follow-up had a significantly higher risk of clinically driven late TLR than non-DM patients.

Background:Oral anticoagulant (OAC) therapy reduces the risk of stroke in patients with atrial fibrillation (AF). This study elucidated the causes of death and related factors in elderly Japanese AF patients.

Methods and Results:Over a median (interquartile range [IQR]) follow-up period of 46 (20–76) months, there were 171 all-cause deaths (28% cardiovascular, 46% non-cardiovascular, and 26% unknown causes) among 389 AF patients (median [IQR] age 80 [74–85] years; CHAD₂DS₂-VASc score 5 [4–6]). Cox regression analysis indicated that diabetes was associated with an increase in all-cause death (hazard ratio [HR] 1.48; 95% confidence interval [CI] 1.02–2.13), whereas hypercholesterolemia (HR 0.53; 95% CI 0.35–0.79), pre-existing heart failure (HR 0.67; 95% CI 0.48–0.95), and OAC use (HR 0.62; 95% CI 0.44–0.88) were associated with reductions in all-cause death. Pre-existing heart failure was associated with both cardiovascular (HR 3.03; 95% CI 1.33–8.20) and non-cardiovascular (HR 0.44; 95% CI 0.30–0.65) deaths, in opposite directions. OAC use was associated with a reduction in cardiovascular death (HR 0.34, 95% CI 0.17–0.69). The predominance of non-cardiovascular death and death-related factors were equivalent regardless of when observations started (before 2009 or in 2009 and later).

Conclusions:The predominant cause of death in elderly Japanese AF patients was non-cardiovascular. Distinct clinical factors were associated with cardiovascular and non-cardiovascular death.

Background:The effect of the COVID-19 pandemic on the respiratory management strategy with regard to the use of non-invasive positive pressure ventilation (NPPV) and high-flow nasal cannula (HFNC) in patients with acute heart failure (AHF) in Japan is unclear.

Methods and Results:This cross-sectional study used a self-reported online questionnaire, with responses from 174 institutions across Japan. More than 60% of institutions responded that the treatment of AHF patients requiring respiratory management became fairly or very difficult during the COVID-19 pandemic than earlier, with institutions in alert areas considering such treatment significantly more difficult than those in non-alert areas (P=0.004). Overall, 61.7% and 58.8% of institutions changed their indications for NPPV and HFNC, respectively. Significantly more institutions in the alert area changed their practices for the use of NPPV and HFNC during the COVID-19 pandemic (P=0.004 and P=0.002, respectively). When there was insufficient time or information to determine whether AHF patients may have concomitant COVID-19, institutions in alert areas were significantly more likely to refrain from using NPPV and HFNC than institutions in non-alert areas.

Conclusions:The COVID-19 pandemic has compelled healthcare providers to change the respiratory management of AHF, especially in alert areas.

Background:Although management of obstructive sleep apnea (OSA) has been recommended to improve outcomes of catheter ablation (CA) in patients with symptomatic atrial fibrillation (AF), the most cost-effective way of preprocedural OSA screening is undetermined. This study assessed the cost-effectiveness of OSA management before CA for symptomatic AF.

Methods and Results:A Markov model was developed to assess the cost-effectiveness of 3 OSA detection strategies before CA: no screening; Type 3 portable monitor (PM)-guided screening; and polysomnography (PSG)-guided screening. The target population consisted of a hypothetical cohort of patients aged 65 years with symptomatic AF, with 50% prevalence of OSA. We used a 5-year horizon, with sensitivity analyses for significant variables and scenario analyses for lower and higher OSA prevalence (30% and 70%, respectively). In the base-case, both types of OSA screening were dominant (less costly and more effective) relative to no screening. Although PSG-guided management was more effective than PM-guided management, it was more costly and therefore did not show clear benefit. These findings were replicated in cohorts with lower and higher OSA risks.

Conclusions:OSA screening before CA is cost-effective in patients with symptomatic AF, with PM screening being the most cost-effective. Physicians should consider OSA management using this simple tool in the decision making for treatment of symptomatic AF.

Background:In surgical aortic valve replacement (SAVR), coronary arteries are routinely assessed by transesophageal echocardiography (TEE) to prevent undesirable complications. This study evaluated the capabilities and pitfalls of TEE assessment.

Methods and Results:Of 147 consecutive SAVR patients undergoing aortic stenosis, the TEE records for 130 patients, in which the procedures were conducted by a single examiner, were analyzed retrospectively regarding data acquisition and the accuracy of detecting an anomalous origin, high or low takeoff, ostial diameter, and short left main truncus (LMT). The left and right coronary arteries could be visualized in every patient. A left coronary ostium >5 mm was found in 33 patients (25.4%). TEE revealed an anomalous origin in 2 patients (1.5%) that had not been diagnosed, but missed it in another patient. High takeoff was noted in 11 patients (8.3%), often associated with aortic disease necessitating aortic repair. In one such patient, occlusion of the right coronary artery was detected, necessitating coronary revascularization. Short LMT was found in 15 patients (11.8%) but misdiagnosed due to artifact in 1. During selective cardioplegia, malperfusion of the left anterior descending artery due to deep cannula placement was detected.

Conclusions:TEE provides fairly accurate assessment in SAVR, including detection of undiagnosed pathologies or pitfalls related to coronary arteries, although misdiagnosis due to artifacts should be kept in mind.

Background:COVID-19 is fatal to patients with pulmonary hypertension (PH), so preventive actions are recommended. This study investigated the effectiveness of telemedicine and effects on quality of life (QOL) in the treatment of patients with PH.

Methods and Results:Japanese patients with PH (n=40) were recruited from one referral center. Patient self-reported anxiety worsened significantly and elderly patients in particular experienced detrimental lifestyle changes under COVID-19. Telemedicine worked well to decrease the frequency of going out.

Conclusions:Telemedicine is effective in reducing travel distances, and frequent remote interventions may be desirable for older, anxious patients.

Background:Despite the growing knowledge regarding optimal treatments for critical limb ischemia (CLI), there are still a considerable number of patients who have to undergo major limb amputation. Intramuscular injection of autologous adipose-derived regenerative cells (ADRCs) in these patients has shown therapeutic potential in improving tissue ischemia, in both preclinical and initial pilot studies. Here, we present a clinical protocol for ADRCs use in a multicenter trial.

Methods and Results:The TACT-ADRC multicenter trial is a prospective, interventional, single-arm, open-labeled study at 8 hospitals in Japan, investigating the safety and feasibility of intramuscular injections of ADRCs and testing the hypothesis that this treatment promotes neovascularization and improves major amputation-free survival rates in patients with CLI who have no other treatment option. 40 patients with CLI will be enrolled and followed up from November 2015 to November 2020. Freshly isolated autologous ADRCs will be injected into the target ischemic limbs. Survival rate, adverse events, major limb amputation, ulcer size, 6-min walking distance, numerical rating scale, ankle–brachial pressure index, skin perfusion pressure and digital subtraction angiography will be evaluated at baseline and during 6 months’ follow-up.

Conclusions:This trial will demonstrate whether implantation of autologous ADRCs is a safe and effective method for therapeutic angiogenesis, resulting in an improvement in major amputation-free survival rates in patients with CLI.