Antithrombotic therapy is crucial for older patients with coronary artery disease (CAD) and atrial fibrillation (AF) who are at a high risk of bleeding and thrombotic events. To examine the age-stratified effects of rivaroxaban monotherapy compared with those of rivaroxaban plus antiplatelet agent combination therapy. This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label randomized clinical trial. This was a multicenter study conducted in Japan from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD that did not require revascularization were enrolled. Participants were stratified into 4 groups by age (<70 years, 70-74 years, 75-79 years, and ≥80 years). Study data were analyzed from August 2024 to July 2025. Rivaroxaban monotherapy or rivaroxaban plus antiplatelet agent therapy. The primary efficacy end point was a major adverse cardiovascular event, defined as a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding. This study included a total of 2215 participants (mean [SD] age, 74.3 [8.2] years; 1751 male [79.1%]). The incidence of primary efficacy end points per patient-year for rivaroxaban monotherapy vs rivaroxaban plus antiplatelet agent therapy was 3.2% vs 4.3% (<70 years), 3.2% vs 2.8% (70-74 years), 3.8% vs 5.3% (75-79 years), and 6.2% vs 10.3% (≥80 years). The hazard ratios were 0.74 (95% CI, 0.40-1.37) for those younger than 70 years, 1.16 (95% CI, 0.55-2.45) for those aged 70 to 74 years, 0.72 (95% CI, 0.41-1.26) for those aged 75 to 79 years, and 0.61 (95% CI, 0.40-0.93) for those 80 years and older (P for interaction =.51). For the primary safety end points, the incidence was 0.5% vs 2.3% (<70 years), 2.2% vs 2.4% (70-74 years), 1.1% vs 2.1% (75-79 years), and 2.9% vs 4.3% (≥80 years). The hazard ratios were 0.23 (95% CI, 0.06-0.79) for those younger than 70 years, 0.91 (95% CI, 0.39-2.15) for those aged 70 to 74 years, 0.52 (95% CI, 0.19-1.42) for those aged 75 to 79 years, and 0.67 (95% CI, 0.35-1.27) for those 80 years and older (P for interaction =.33). Results of this post hoc analysis of the AFIRE randomized clinical trial reveal that rivaroxaban monotherapy reduced the risk of major cardiovascular events and major bleeding across the broad range of age in patients with AF and stable CAD. Possible age-related differences in trends, with more pronounced efficacy in older patients and more pronounced safety in younger patients, should be considered as hypothesis generating and require further research. ClinicalTrials.gov Identifier: NCT02642419.

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n = 207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with "cholesterol absorption". Statin usage also had a positive correlation with "cholesterol synthesis". Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

AIM:Several clinical trials using intravascular ultrasound (IVUS) evaluation have demonstrated that intensive lipid-lowering therapy by statin or a combination therapy with statin and ezetimibe results in significant regression of coronary plaque volume. However, it remains unclear whether adding ezetimibe to statin therapy affects coronary plaque composition and the molecular mechanisms of plaque regression. We conducted this prospective IVUS analysis in a subgroup from the CuVIC trial. METHODS:The CuVIC trial was a prospective randomized, open, blinded-endpoint trial conducted among 11 cardiovascular centers, where 260 patients with coronary artery disease who received coronary stenting were randomly allocated into either the statin group (S) or the combined statin and ezetimibe group (S＋E). We enrolled 79 patients (S group, 39 patients; S＋E group, 40 patients) in this substudy, for whom serial IVUS images of nonculprit lesion were available at both baseline and after 6-8 months of follow-up. RESULTS:After the treatment period, the S＋E group had significantly lower level of low-density lipoprotein cholesterol (LDL-C; 80.9±3.7 vs. 67.7±3.8 mg/dL, p=0.0143). Campesterol, a marker of cholesterol absorption, and oxysterols (β-epoxycholesterol, 4β-hydroxycholesterol, and 27-hydroxycholesterol) were also lower in the S＋E group. IVUS analyses revealed greater plaque regression in the S＋E group than in the S group (-6.14% vs. -1.18% for each group, p=0.042). It was noteworthy that the lowering of campesterol and 27-hydroxycholesterol, but not LDL-C, had a significant positive correlation with plaque regression. CONCLUSIONS:Compared with statin monotherapy, ezetimibe in combination with statin achieved significantly lower LDL-C, campesterol, and 27-hydroxycholesterol, which resulted in greater coronary plaque regression.

BACKGROUND Implementation of appropriate oral anticoagulant treatment for the prevention of stroke in very elderly patients with atrial fibrillation is challenging because of concerns regarding bleeding. METHODS We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven trial to compare a once-daily 15-mg dose of edoxaban with placebo in elderly Japanese patients (≥80 years of age) with nonvalvular atrial fibrillation who were not considered to be appropriate candidates for oral anticoagulant therapy at doses approved for stroke prevention. The primary efficacy end point was the composite of stroke or systemic embolism, and the primary safety end point was major bleeding according to the definition of the International Society on Thrombosis and Haemostasis. RESULTS A total of 984 patients were randomly assigned in a 1:1 ratio to receive a daily dose of 15 mg of edoxaban (492 patients) or placebo (492 patients). A total of 681 patients completed the trial, and 303 discontinued (158 withdrew, 135 died, and 10 had other reasons); the numbers of patients who discontinued the trial were similar in the two groups. The annualized rate of stroke or systemic embolism was 2.3% in the edoxaban group and 6.7% in the placebo group (hazard ratio, 0.34; 95% confidence interval [CI], 0.19 to 0.61; P<0.001), and the annualized rate of major bleeding was 3.3% in the edoxaban group and 1.8% in the placebo group (hazard ratio, 1.87; 95% CI, 0.90 to 3.89; P = 0.09). There were substantially more events of gastrointestinal bleeding in the edoxaban group than in the placebo group. There was no substantial between-group difference in death from any cause (9.9% in the edoxaban group and 10.2% in the placebo group; hazard ratio, 0.97; 95% CI, 0.69 to 1.36). CONCLUSIONS In very elderly Japanese patients with nonvalvular atrial fibrillation who were not appropriate candidates for standard doses of oral anticoagulants, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism and did not result in a significantly higher incidence of major bleeding than placebo. (Funded by Daiichi Sankyo; ELDERCARE-AF ClinicalTrials.gov number, NCT02801669.).

BackgroundLow-voltage zones (LVZs), as measured by electroanatomic mapping, are thought to be associated with fibrosis. We reported the efficacy of atrial fibrillation (AF) ablation aiming to homogenize left atrial (LA) LVZ. The purpose of this study was to evaluate the impact of LVZ extension outcomes after LVZ homogenization in patients with nonparoxysmal AF.MethodsThis prospective observational cohort study included 172 patients with nonparoxysmal AF undergoing their initial ablation. LVZ was defined as an area with bipolar electrograms <0.5 mV during sinus rhythm. LVZ extent was calculated as the percentage of LA surface area, and subsequently, LVZ was categorized into stages I (<5%), II (≥5% to <20%), III (≥20% to <30%), and IV (≥30%). Patients with LVZs underwent LVZ ablation aimed at homogenization of ≥80% of LVZs following pulmonary vein isolation. The primary endpoint was atrial tachyarrhythmia recurrence-free survival after a single procedure at 18 months off antiarrhythmic drugs. The association of %LVZ with recurrence-free survival was examined using Cox proportional hazard models.ResultsThe survival rates were 76%, 74%, 57%, and 28% in patients with stages I, II, III, and IV LVZ, respectively. The difference was significant between stages I and IV (log-rank, p < 0.001), while not significant between stages I vs. II and I vs. III (p = 0.843, p = 0.073, respectively). Cox proportional hazard model revealed that %LVZ was an independent predictor of recurrence-free survival (hazard ratio, 1.025 per 1% increase, p < 0.001; unadjusted model). The results were similar after demographic and clinical covariate adjustments and after excluding 12 patients who did not achieve homogenization of ≥80% of LVZ.ConclusionsThe extent of LVZ is an independent predictor for recurrence even after LVZ homogenization.

A 54-year-old man who developed sudden-onset palpitations presented to our hospital. The initial electrocardiogram showed sustained ventricular tachycardia (VT) at 218 beats/ min. Electrocardioversion successfully restored sinus rhythm (Picture 1). A transthoracic echocardiogram showed a wellcircumscribed and internal anechoic structure located in the pericardium (Picture 2). Magnetic resonance (MR) imaging and coronary MR angiography revealed a large saccular type right coronary aneurysm (Picture 3, 4). No late gadolinium enhancement was identified. The analysis of the QRS morphology and axis suggested mechanical compression from the epicardial side by the aneurysm is the central pathogenesis of VT. Surgical repair through ligation, incision and cryoablation, successfully prevented VT (Picture 5). A coronary aneurysm is typically asymptomatic, and few reports

BACKGROUND Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective non-interventional study of stroke prevention in patients with newly diagnosed non-valvular AF (NAVF) that is being conducted in 35 countries. Methods and Results: A total of 52,081 patients with a new diagnosis of NVAF were enrolled prospectively in GARFIELD-AF. Of these, 4859 (9.3%) were recruited in Japan (2010-2016). In cohort 1 (2010-2011), few patients were on non-vitamin K antagonist oral anticoagulants (NOAC) globally. From cohort 2 onwards (2011-2016), however, there was a rapid increase in NOAC use around the globe, especially in Japan. By the last year of enrolment (2015-2016), 67.9% of patients in Japan and 43.1% of patients globally were on NOAC±antiplatelet therapy (AP). In Japan and globally, 17.0% and 12.2% of patients, respectively, did not receive stroke prevention treatment. Few patients in Japan (5.7%) received AP only. Compared with the other countries, the unadjusted rates of all-cause mortality and major bleeding were low, while rates of stroke/systemic embolism were similar after 1 year of follow-up. CONCLUSIONS GARFIELD-AF continues to provide important information on the homogeneity and heterogeneity of baseline characteristics and treatment patterns in patients with newly diagnosed NVAF. This diversity reflects the differences in outcomes in Japan compared with the rest of the world.

BACKGROUND:Eosinophilic myocarditis is characterized by myocardial eosinophilic infiltration and is largely associated with hypereosinophilia. However, eosinophilic myocarditis with a normal peripheral eosinophilic count has been previously reported. Since the absence of eosinophilia poses a challenge for therapeutic management, we evaluated whether troponin I (TnI) levels can be used in the management of eosinophilic myocarditis where peripheral eosinophilia is absent.CASE SUMMARY:We report the case of a 77-year-old woman who developed cardiogenic shock due to acute necrotizing eosinophilic myocarditis, which required mechanical circulatory support. She did not have hypereosinophilia, but endomyocardial biopsy confirmed massive infiltration of eosinophils into the myocardium. We administered high-dose corticosteroids for 3 days and she dramatically improved. Along with this, the TnI level, which was elevated at the time of patient presentation, also decreased after steroid therapy. Troponin I level did not increase again without taking any oral prednisolone, and the follow-up biopsy after 6 months showed complete recovery of eosinophilic myocarditis.DISCUSSION:Troponin I-guided treatment is a useful tool in the management of eosinophilic myocarditis because it helps with therapeutic decisions, especially in the absence of eosinophilia.

BackgroundThe optimal methodology for sedation and anesthesia during atrial fibrillation (AF) ablation has not been well established. We assessed the feasibility of total intravenous anesthesia (TIVA) by cardiologists with support from anesthesiologists during AF ablation and quality of pulmonary vein isolation (PVI) and single procedure success rate at 12 months.MethodsTIVA was performed by cardiologists using IV propofol and fentanyl under controlled ventilation via i-gel™ without neuromuscular blocking drugs in 160 consecutive patients (80 nonparoxysmal) with no anticipated difficult airway or other severe diseases. Anesthesiologists were requested to be on standby during the procedure. The incidence of anesthesia-associated complications and ablation-associated complications were assessed. To evaluate the quality of PVI, the prevalence of acute adenosine triphosphate (ATP)-provoked PV reconnections and late PV reconnections among those requiring a redo procedure was analyzed.ResultsTIVA was successfully completed in 152 patients (95%). In five (3%), we requested help from anesthesiologists, and in three (2%), TIVA was abandoned. No major anesthesia-associated complications were observed. Ablation-associated complications were observed in seven patients (4%). ATP provocation test was performed in 141 patients, and no acute PV reconnections were observed in 134 (95%). Success rates at 12 months were 85% of patients off antiarrhythmic drugs. Twenty-one of 24 patients with recurrence underwent a redo session, and 18 (86%) had no PV reconnections.ConclusionsTIVA by cardiologists with support from anesthesiologists during AF ablation may be feasible. The success rate at 12 months was high, and prevalence of acute and late PV reconnection was very low.

Objectives— We sought to investigate whether treatment with ezetimibe in combination with statins improves coronary endothelial function in target vessels in coronary artery disease patients after coronary stenting. Approach and Results— We conducted a multicenter, prospective, randomized, open-label, blinded-end point trial among 11 cardiovascular treatment centers. From 2011 to 2013, 260 coronary artery disease patients who underwent coronary stenting were randomly allocated to 2 arms (statin monotherapy, S versus ezetimibe [10 mg/d]+statin combinational therapy, E+S). We defined target vessel dysfunction as the primary composite outcome, which comprised target vessel failure during treatment and at the 6- to 8-month follow-up coronary angiography and coronary endothelial dysfunction determined via intracoronary acetylcholine testing performed in cases without target vessel failure at the follow-up coronary angiography. Coadministration of ezetimibe with statins further lowered low-density lipoprotein cholesterol levels (83±23 mg/dL in S versus 67±23 mg/dL in E+S; P <0.0001), with significant decreases in oxidized low-density lipoprotein and oxysterol levels. Among patients without target vessel failure, 46 out of 89 patients (52%) in the S arm and 34 out of 96 patients (35%) in the E+S arm were found to have coronary endothelial dysfunction ( P =0.0256), and the incidence of target vessel dysfunction at follow-up was significantly decreased in the E+S arm (69/112 (62%) in S versus 47/109 (43%) in E+S; P =0.0059). A post hoc analysis of post-treatment low-density lipoprotein cholesterol–matched subgroups revealed that the incidence of both target vessel dysfunction and coronary endothelial dysfunction significantly decreased in the E+S arm, with significant reductions in oxysterol levels. Conclusions— The CuVIC trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction after Coronary Stenting) has shown that ezetimibe with statins, compared with statin monotherapy, improves functional prognoses, ameliorating endothelial dysfunction in stented coronary arteries, and was associated with larger decreases in oxysterol levels.

Low Voltage‐Based Ablation for Atrial FibrillationBackgroundLow‐voltage zones (LVZs) represent fibrotic tissue and are substrates for atrial fibrillation (AF). We hypothesized that LVZ‐based substrate modification along with pulmonary vein isolation (PVI) would improve outcomes in persistent AF (PeAF) patients with LVZs, whereas PVI alone would work in patients without LVZs.Methods and ResultsVoltage mapping of the left atrium (LA) was performed during sinus rhythm in 101 PeAF patients in whom LVZ was defined as an area with bipolar electrograms <0.5 mV. Thirty‐nine patients had LVZs and underwent ablation of the entire LVZ area after PVI (LVZabl group). In the remaining 62 patients without LVZs, PVI alone was performed with no further substrate modifications (PVI group). An additional group of 16 consecutive PeAF patients with LVZ did not undergo any substrate modification after PVI and were used as a comparison group (LVZnon‐abl group) despite having similar size of LVZs to that in the LVZabl group. After a single session, 28 (72%) patients in the LVZabl group had no recurrence, whereas 49 (79%) patients in the PVI group had no recurrence during 18 ± 7 months of follow‐up (log‐rank, P = 0.400). In the LVZnon‐abl group, only 6 patients (38%) had no recurrence during 32 ± 7 months of follow‐up, even after a mean number of sessions of 1.8 (log‐rank, P < 0.001, compared with the LVZabl group).ConclusionsAdditional LVZ‐based substrate modification after PVI improved the outcome in PeAF patients with LVZs, whereas PVI alone worked in patients without LVZs, even in those with PeAF.

Both coronary perforation and aneurysms associated with sirolimus-eluting stent (SES) implantations are uncommon complications. We describe an unusual case of a coronary aneurysm associated with a coronary perforation after SES implantation. Although their pathogenesis has not yet been completely elucidated, some technical factors including the use of excessive pressure during the stent deployment, and sirolimus-induced vascular inflammatory reactions and poor healing response at the perforation site may be related to the shape of the aneurismal formation. Fortunately and interestingly, the size of the coronary aneurysm gradually decreased, and finally by 26 months a nearly complete resolution of the aneurysm had taken place. Furthermore, close follow-up by coronary 3-dimensional computed tomography (3DCT) could clearly demonstrate the natural course of this aneurysm. To the best of our knowledge, there have been no reports on the natural course of coronary aneurysm associated with a coronary perforation after SES(s) implantation for more than 2 years using coronary 3DCT as in this present case. The phenomenon of the spontaneous resolution of the coronary aneurysm after SES implantation may have clinical therapeutic implications.

A 63-year-old woman was admitted to hospital with the chief complaint of new onset chest discomfort and pretibial pitting edema. Transthoracic echocardiography revealed a large invasive tumor on the heart protruding into the right atrium and right ventricle, which obstructed the outflow tract. She underwent transvenous 9Fr, 9-MHz ultra intracardiac echocardiography (ICE) (EP Technologies, Boston Scientific Corporation, San Jose, CA, USA) guided biopsy, and a diagnosis of malignant lymphoma was established from the specimen obtained. ICE-guided cardiac tumor biopsy may be one of the most useful strategies for diagnosis of cardiac tumors. (Circ J 2009; 73: 381-383)