High plasma concentrations of vanin-1 in patients with coronary artery disease.

Vanin-1 is a pantetheinase that hydrolyzes pantetheine to pantothenic acid and cysteamine. Vanin-1 has become recognized to be associated with oxidative stress and inflammation. In animal models, vanin-1 was reported to accelerate atherosclerosis. However, no study has reported blood vanin-1 concentrations in patients with coronary artery disease (CAD). We investigated plasma vanin-1 concentrations in 388 patients undergoing elective coronary angiography for suspected CAD. Patients with acute coronary syndrome were excluded. Of the 388 study patients, CAD was found in 207 patients [1-vessel (1-VD), n = 88; 2-vessel (2-VD), n = 66; and 3-vessel disease (3-VD), n = 53]. Plasma vanin-1 concentrations were higher in patients with CAD than in those without CAD (median 0.59 vs. 0.46 ng/mL, P < 0.005). Vanin-1 concentrations in patients without CAD and those with 1-VD, 2-VD, and 3-VD were 0.46, 0.58, 0.57, and 0.61 ng/mL, respectively, and were highest in 3-VD (P < 0.05). A high vainin-1 concentration (> 0.48 ng/mL) was found in 46% of patients without CAD, 61% of 1-VD, 65% of 2-VD, and 66% of 3-VD (P < 0.01). Vanin-1 concentrations significantly correlated with the number of stenotic coronary segments (r = 0.14, P < 0.02). In the multivariate analysis, vanin-1 concentration was a significant factor associated with CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.63 (95%CI = 1.04-2.55) for the high vanin-1 concentration of > 0.48 ng/mL. Thus, plasma vanin-1 concentrations in patients with CAD were found to be high and to be associated with the presence and severity of CAD.

High plasma levels of endosialin and cardiovascular events in patients undergoing coronary angiography.

Endosialin, also known as tumor endothelial marker-1, is a transmembrane glycoprotein that plays a role in inflammation and tumor progression. Endosialin is upregulated in atherosclerotic lesions. To elucidate the association between blood endosialin levels and cardiovascular events, we measured plasma endosialin levels in 389 patients undergoing coronary angiography who were followed up for a mean follow-up of 6.4 ± 4.2 years for cardiovascular events (cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or need for coronary revascularization). Of the 389 patients, 223 had coronary artery disease (CAD). No significant difference was found in plasma endosialin levels between patients with and without CAD (median 0.92 vs. 0.92 ng/mL). During the follow-up, cardiovascular events occurred in 62 patients. Compared with patients without events, those with events had higher endosialin levels (1.12 vs. 0.89 ng/mL), and more often had endosialin level of > 1.1 ng/mL (53% vs. 31%) (P < 0.01). A Kaplan-Meier analysis showed lower event-free survival in patients with endosialin > 1.1 ng/mL than those with ≤ 1.1 ng/mL (P < 0.01). In a multivariate Cox regression analysis, endosialin > 1.1 ng/mL was an independent predictor of cardiovascular events (hazard ratio = 2.00; 95%CI = 1.21-3.32; P < 0.01). Thus, high plasma endosialin levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography.

Association between high plasma levels of legumain and cardiovascular events in patients undergoing coronary angiography.

Degradation of vascular extracellular matrix is important in atherosclerosis. Cysteine protease legumain is upregulated in atherosclerotic plaques. We recently reported that plasma legumain levels are high in patients with complex coronary lesions. This study investigated the association between legumain levels and cardiovascular events in 372 patients undergoing coronary angiography. Patients with acute coronary syndrome were excluded. Of the 372 patients, 225 had coronary artery disease (CAD). During a mean follow-up of 7.0 ± 4.3 years, cardiovascular events occured in 62 patients. Compared with 310 patients without events, 62 with events tended to have higher prevalence of complex lesions (15% vs. 10%). Notably, patients with events had higher legumain levels (median 5.51 vs. 4.90 ng/mL, P < 0.01) than those without events. A Kaplan-Meier analysis showed lower event-free survival in patients with legumain > 5.0 ng/mL than in those with ≤ 5.0 ng/mL (P < 0.01). In multivariate Cox regression analysis, legumain level was an independent predictor of cardiovascular events. The hazard ratio for legumain > 5.0 ng/mL for cardiovascular events was 2.18 (95%CI = 1.27-3.77, P < 0.01). Only among 225 patients with CAD, patients with events had higher legumain levels (5.49 vs. 4.73 ng/mL) than without events (P < 0.02). Legumain level was also a predictor of cardiovascular events in patients with CAD. Thus, high plasma legumain levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography and those with stable CAD.

Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Different Determinants of the Recurrence of Atrial Fibrillation and Adverse Clinical Events in the Mid-Term Period After Atrial Fibrillation Ablation.

BACKGROUND: It is unclear whether there are differences in the clinical factors between atrial fibrillation (AF) recurrence and adverse clinical events (AEs), including stroke/transient ischemic attack (TIA), major bleeding, and death, after AF ablation.Methods and Results:We examined the data from a retrospective multicenter Japanese registry conducted at 24 cardiovascular centers between 2011 and 2017. Of the 3,451 patients (74.1% men; 63.3±10.3 years) who underwent AF ablation, 1,046 (30.3%) had AF recurrence and 224 (6.5%) suffered AEs (51 strokes/TIAs, 71 major bleeding events, and 36 deaths) over a median follow-up of 20.7 months. After multivariate adjustment, female sex, persistent and long-lasting persistent AF (vs. paroxysmal AF), and stepwise increased left atrial diameter (LAd) quartiles were significantly associated with post-ablation recurrences. A multivariate analysis revealed that an age ≥75 years (vs. <65 years), body weight <50 kg, diabetes, vascular disease, left ventricular (LV) ejection fraction <40% (vs. ≥50%), Lad ≥44 mm (vs. <36 mm), and creatinine clearance <50 mL/min were independently associated with AE incidences, but not with recurrences. CONCLUSIONS: This study disclosed different determinants of post-ablation recurrence and AEs. Female sex, persistent AF, and enlarged LAd were determinants of post-ablation recurrence, whereas an old age, comorbidities, and LV and renal dysfunction rather than post-ablation recurrence were AEs determinants. These findings will help determine ablation indications and post-ablation management.

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

High Plasma Levels of Fortilin in Patients with Coronary Artery Disease.

Excessive apoptosis is known to be a common feature of atherosclerotic lesions. Fortilin is recognized to have potent antiapoptotic properties. An increased fortilin expression was demonstrated in atherosclerotic lesions, and fortilin knockout mice developed less atherosclerosis. However, no study has reported blood fortilin levels in patients with coronary artery disease (CAD). We investigated plasma fortilin levels in 384 patients undergoing coronary angiography. CAD severity was evaluated as the numbers of stenotic vessels and segments. CAD was found in 208 patients (one-vessel (1VD), n = 86; two-vessel (2VD), n = 68; and three-vessel disease (3VD), n = 54). Plasma C-reactive protein (CRP) levels were higher in patients with CAD than without CAD (median 0.60 vs. 0.45 mg/L, p < 0.01). Notably, fortilin levels were higher in patients with CAD than without CAD (75.1 vs. 69.7 pg/mL, p < 0.02). A stepwise increase in fortilin was found according to the number of stenotic vessels: 69.7 in CAD(−), 71.1 in 1VD, 75.7 in 2VD, and 84.7 pg/mL in 3VD (p < 0.01). Fortilin levels also correlated with the number of stenotic segments (r = 0.16) and CRP levels (r = 0.24) (p < 0.01). In a multivariate analysis, fortilin levels were independently associated with 3VD. The odds ratio for 3VD was 1.93 (95%CI = 1.01−3.71) for a high fortilin level (>70.0 pg/mL). Thus, plasma fortilin levels in patients with CAD, especially those with 3VD, were found to be high and to be associated with the severity of CAD.

Clinical outcomes of ablation versus non-ablation therapy for atrial fibrillation in Japan: analysis of pooled data from the AF Frontier Ablation Registry and SAKURA AF Registry.

Whether ablation for atrial fibrillation (AF) is, in terms of clinical outcomes, beneficial for Japanese patients has not been clarified. Drawing data from 2 Japanese AF registries (AF Frontier Ablation Registry and SAKURA AF Registry), we compared the incidence of clinically relevant events (CREs), including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular events, and death, between patients who underwent ablation (n = 3451) and those who did not (n = 2930). We also compared propensity-score matched patients (n = 1414 in each group). In propensity-scored patients who underwent ablation and those who did not, mean follow-up times were 27.2 and 35.8 months, respectively. Annualized rates for stroke/TIA (1.04 vs. 1.06%), major bleeding (1.44 vs. 1.20%), cardiovascular events (2.15 vs. 2.49%) were similar (P = 0.96, 0.39, and 0.35, respectively), but annualized death rates were lower in the ablation group than in the non-ablation group (0.75 vs.1.28%, P = 0.028). After multivariate adjustment, the risk of CREs was statistically equivalent between the ablation and non-ablation groups (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.71-1.11), but it was significantly low among patients who underwent ablation for paroxysmal AF (HR 0.68 [vs. persistent AF], 95% CI 0.49-0.94) and had a CHA2DS2-VASc score < 3 (HR 0.66 [vs. CHA2DS2-VASc score ≥ 3], 95% CI 0.43-0.98]). The 2-year risk reduction achieved by ablation may be small among Japanese patients, but AF ablation may benefit those with paroxysmal AF and a CHA2DS2-VASc score < 3.

The Protective Role of Sestrin2 in Atherosclerotic and Cardiac Diseases.

Atherosclerotic disease, such as coronary artery disease (CAD), is known to be a chronic inflammatory disease, as well as an age-related disease. Excessive oxidative stress produced by reactive oxygen species (ROS) contributes to the pathogenesis of atherosclerosis. Sestrin2 is an anti-oxidant protein that is induced by various stresses such as hypoxia, DNA damage, and oxidative stress. Sestrin2 is also suggested to be associated with aging. Sestrin2 is expressed and secreted mainly by macrophages, endothelial cells, and cardiomyocytes. Sestrin2 plays an important role in suppressing the production and accumulation of ROS, thus protecting cells from oxidative damage. Since sestrin2 is reported to have anti-oxidant and anti-inflammatory properties, it may play a protective role against the progression of atherosclerosis and may be a potential therapeutic target for the amelioration of atherosclerosis. Regarding the association between blood sestrin2 levels and atherosclerotic disease, the blood sestrin2 levels in patients with CAD or carotid atherosclerosis were reported to be high. High blood sestrin2 levels in patients with such atherosclerotic disease may reflect a compensatory response to increased oxidative stress and may help protect against the progression of atherosclerosis. This review describes the protective role of sestrin2 against the progression of atherosclerotic and cardiac diseases.

Association between Plasma Follistatin-like Protein 1 Levels and the Presence and Severity of Coronary Artery Disease.

Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein known for its role in inflammation. However, plasma FSTL1 levels in patients with coronary artery disease (CAD) have not been fully elucidated. Thus, in this study, we investigated the plasma FSTL1 levels of 350 patients who underwent elective coronary angiography. The severity of CAD was represented as the numbers of > 50% stenotic vessels and segments and the severity score. CAD was detected in 196 patients, of whom 84 had 1-vessel disease (1-VD), 62 had 2-VD, and 50 had 3-VD. Plasma high-sensitivity C-reactive protein (hsCRP) levels were higher in patients with CAD than in those without CAD (median 0.56 versus 0.44 mg/L, P < 0.01). Notably, plasma FSTL1 levels were higher in patients with CAD than in those without CAD (median 4.05 versus 3.47 ng/mL, P < 0.02). A stepwise increase in FSTL1 levels was found depending on the number of > 50% stenotic vessels: 3.47 in CAD (-), 3.74 in 1-VD, 4.42 in 2-VD, and 4.65 ng/mL in 3-VD (P < 0.05). FSTL1 levels also correlated with the number of > 50% stenotic segments and the severity score (r = 0.14 and r = 0.15, respectively, P < 0.005) and hsCRP levels (r = 0.10, P < 0.05). In the multivariate analysis, FSTL1 levels were an independent factor associated with CAD. The odds ratio for CAD was 1.61 (95% CI = 1.01-2.58) for high FSTL1 level of > 3.6 ng/mL (P < 0.05). In conclusion, plasma FSTL1 levels in patients with CAD were found to be high and associated with the presence and severity of CAD, thus, suggesting that FSTL1 may play a role in the progression of coronary atherosclerosis.

Clinical Outcomes of Off-Label Underdosing of Direct Oral Anticoagulants After Ablation for Atrial Fibrillation.

Direct oral anticoagulants (DOACs) are sometimes prescribed at off-label under-doses for patients who have undergone ablation for atrial fibrillation (AF). This practice may be an attempt to balance the risk of bleeding against that of stroke or AF recurrence.We examined outcomes of 1163 patients who continued use of a DOAC after ablation. The patients were enrolled in a large (3530 patients) multicenter registry in Japan. The study patients were classified as 749 (64.4%) appropriate standard-dose DOAC users, 216 (18.6%) off-label under-dose DOAC users, and 198 (17.0%) appropriate low-dose DOAC users.Age and CHA2DS2-VASc scores differed significantly between DOAC dosing regimens, with patients given an appropriate standard-dose being significantly younger (63.3 ± 9.4 versus 64.8 ± 9.5 versus 73.2 ± 6.8 years, P < 0.0001) and lower (2.1 ± 1.5 versus 2.4 ± 1.6 versus 3.4 ± 1.4, P < 0.0001) than those given an off-label under-dose or an appropriate low-dose. During the median 19.0-month follow-up period, the AF recurrence rate was similar between the appropriate standard-dose and off-label under-dose groups but relatively low in the appropriate low-dose group (42.5% versus 41.2% versus 35.4%, P = 0.08). Annualized rates of thromboembolic events, major bleeding, and death from any cause were 0.47%, 0.70%, and 0.23% in the off-label under-dose group, while those rates were 0.74%, 0.73%, and 0.65% in the appropriate standard-dose, and 1.58%, 2.12%, and 1.57% in the appropriate low-dose groups.In conclusion, the clinical adverse event rates for patients on an off-label under-dose DOAC regimen after ablation, predicated on careful patient evaluations, was not high as seen with that of patients on a standard DOAC dosing regimen.

Current Status and Clinical Outcomes of Oral Anticoagulant Discontinuation After Ablation for Atrial Fibrillation in Japan　- Findings From the AF Frontier Ablation Registry.

BACKGROUND: The safety of discontinuing oral anticoagulant (OAC) after ablation for atrial fibrillation (AF) in Japanese patients has not been clarified.Methods and Results:A study based on the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) was conducted. Data were collected from 3,451 consecutive patients (74.1% men; age, 63.3±10.3 years) who had undergone AF ablation at any of 24 cardiovascular centers in Japan between August 2011 and July 2017. During a 20.7-month follow-up period, OAC therapy was discontinued in 1,836 (53.2%) patients; 51 patients (1.5%) suffered a stroke/transient ischemic attack (TIA), 71 (2.1%) suffered major bleeding, and 36 (1.0%) died. Patients in whom OAC therapy was discontinued were significantly younger than those in whom OACs were continued, and their CHA2DS2-VASc scores were significantly lower. The incidences of stroke/TIA, major bleeding, and death were significantly lower among these patients. Upon multivariate adjustment, stroke events were independently associated with relatively high baseline CHA2DS2-VASc scores but not with OAC status. CONCLUSIONS: Although the incidences of stroke/TIA, major bleeding, and death were relatively low among patients for whom OAC therapy was discontinued, stroke/TIA occurrence was strongly associated with a high baseline stroke risk rather than with OAC status. Thus, discontinuation of OAC therapy requires careful consideration, especially in patients with a high baseline stroke risk.

Associations between plasma nesfatin-1 levels and the presence and severity of coronary artery disease.

Nesfatin-1 is a recently identified anorexigenic peptide mainly secreted from the brain and adipose tissue. Although nesfatin-1 may have pro-inflammatory and apoptotic properties, the association between plasma nesfatin-1 levels and coronary artery disease (CAD) has not been clarified yet. We investigated plasma nesfatin-1 levels in 302 patients undergoing elective coronary angiography. Of the 302 study patients, CAD was present in 172 (57%), of whom 67 had 1-vessel, 49 had 2-vessel, and 56 had 3-vessel disease. Compared with 130 patients without CAD, 172 with CAD had higher plasma nesfatin-1 levels (median 0.21 vs. 0.17 ng/mL, P < 0.01). A stepwise increase in nesfatin-1 levels was found depending on the number of > 50% stenotic coronary vessels: 0.17 in CAD(-), 0.20 in 1-vessel, 0.21 in 2-vessel, and 0.22 ng/mL in 3-vessel disease (P < 0.05). A high nesfatin-1 level (> 0.19 ng/mL) was found in 43% of patients with CAD(-), 55% of those with 1-vessel, 55% of those with 2-vessel, and 68% of those with 3-vessel disease (P < 0.05). Nesfatin-1 levels significantly correlated with the number of > 50% stenotic coronary segments (r = 0.14, P < 0.02). In multivariate analysis, plasma nesfatin-1 levels were a significant factor for CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.71 (95% CI 1.01-2.91) for high nesfatin-1 level of > 0.19 ng/mL (P < 0.05). Thus, plasma nesfatin-1 levels were found to be high in patients with CAD and were associated with CAD independent of atherosclerotic risk factors, suggesting that high nesfatin-1 levels in patients with CAD may play a role in the development of coronary atherosclerosis.

The Protective Role of Heme Oxygenase-1 in Atherosclerotic Diseases.

Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate ferrous iron, carbon monoxide (CO), and biliverdin, which is subsequently converted to bilirubin. These products have anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-thrombotic properties. Although HO-1 is expressed at low levels in most tissues under basal conditions, it is highly inducible in response to various pathophysiological stresses/stimuli. HO-1 induction is thus thought to be an adaptive defense system that functions to protect cells and tissues against injury in many disease settings. In atherosclerosis, HO-1 may play a protective role against the progression of atherosclerosis, mainly due to the degradation of pro-oxidant heme, the generation of anti-oxidants biliverdin and bilirubin and the production of vasodilator CO. In animal models, a lack of HO-1 was shown to accelerate atherosclerosis, whereas HO-1 induction reduced atherosclerosis. It was also reported that HO-1 induction improved the cardiac function and postinfarction survival in animal models of heart failure or myocardial infarction. Recently, we and others examined blood HO-1 levels in patients with atherosclerotic diseases, e.g., coronary artery disease (CAD) and peripheral artery disease (PAD). Taken together, these findings to date support the notion that HO-1 plays a protective role against the progression of atherosclerotic diseases. This review summarizes the roles of HO-1 in atherosclerosis and focuses on the clinical studies that examined the relationships between HO-1 levels and atherosclerotic diseases.

Plasma Heme Oxygenase-1 Levels and Carotid Atherosclerosis.

Background and Purpose- Heme oxygenase-1 (HO-1) catalyzes the oxidation of heme to generate carbon monoxide, biliverdin, and iron. Because these products have antiatherogenic properties, HO-1 may play a protective role against atherosclerosis. However, plasma HO-1 levels in patients with carotid atherosclerosis have not been reported. Methods- We investigated plasma HO-1 levels by ELISA in 136 subjects (age, 66±9 years) undergoing carotid ultrasonography. Results- Of the 136 study subjects, carotid plaque was found in 61 subjects (45%). Compared with 75 subjects without plaque, 61 with plaque were older and predominantly male ( P<0.05). Plasma HO-1 levels were higher in subjects with plaque than in those without plaque (median, 0.56 versus 0.44 ng/mL; P<0.05). The percentage of subjects with HO-1 level >0.50 ng/mL was higher in subjects with plaque than without plaque (66% versus 44%; P<0.025). In multivariate analysis, HO-1 level was a significant factor for carotid plaque independent of atherosclerotic risk factors. Odds ratio for plaque was 2.33 (95% CI, 1.15-4.75) for HO-1 level >0.50 ng/mL. Conclusions- Plasma HO-1 levels were high in subjects with carotid plaques, probably reflecting a protective response against carotid atherosclerosis.

Plasma Soluble Endoglin Levels Are Inversely Associated With the Severity of Coronary Atherosclerosis-Brief Report.

OBJECTIVE: Transforming growth factor-ß inhibits migration and proliferation of endothelial and smooth muscle cells. Endoglin is a transmembrane receptor for transforming growth factor-ß1 and transforming growth factor-ß3. Endoglin is released into blood as a soluble form (soluble endoglin [sEng]), but plasma sEng levels in patients with coronary artery disease (CAD) have not been elucidated. APPROACH AND RESULTS: We measured plasma sEng levels in 244 patients undergoing coronary angiography. The severity of coronary atherosclerosis was evaluated as the numbers of >50% stenotic vessels and segments. CAD was found in 147 patients, of whom 55 had 1-vessel, 42 had 2-vessel, and 50 had 3-vessel disease. Compared with 97 patients without CAD, 147 with CAD had lower sEng levels (median 4.04 versus 4.37 ng/mL; P<0.005). A stepwise decrease in sEng levels was found based on the number of stenotic vessels: 4.37 in CAD(-), 4.23 in 1-vessel, 4.13 in 2-vessel, and 3.74 ng/mL in 3-vessel disease (P<0.005). sEng levels inversely correlated with the number of stenotic segments (r=-0.25; P<0.001). In multivariate analysis, sEng was an independent factor for 3-vessel disease and CAD. Odds ratios for CAD and 3-vessel disease were 0.97 (95% confidence interval, 0.95-0.99; P<0.02) and 0.96 (95% confidence interval, 0.93-0.99; P<0.01) for a 0.1 ng/mL increase in sEng levels, respectively. CONCLUSIONS: Plasma sEng levels were low in patients with CAD, especially 3-vessel disease, and were inversely associated with the severity of coronary atherosclerosis.

Identification of Left Atrial Appendage Thrombi in Patients With Persistent and Long-Standing Persistent Atrial Fibrillation Using Intra-Cardiac Echocardiography and Cardiac Computed Tomography.

BACKGROUND: Intracardiac echocardiography (ICE) and cardiac computed tomography (CCT), in addition to standard transesophageal echocardiography (TEE), have been used to identify left atrial (LA) thrombi prior to ablation for atrial fibrillation (AF). The clinical advantages of this, however, remain unclear. This study therefore investigated the advantages of additional pre-procedural LA appendage (LAA) thrombus evaluation using ICE and the clinical value of CCT in persistent and long-standing persistent AF.Methods and Results:We analyzed data from 108 consecutive patients with persistent and long-standing persistent AF who were scheduled to undergo AF ablation. TEE was performed within 24 h prior to ablation. ICE was performed for 97 patients in whom a thrombus was not detected on TEE. CCT was performed in 95 patients. Thrombus or sludge was detected on TEE in 11 patients (10.3%), for whom ablation was cancelled. Four additional patients were diagnosed with LAA thrombus on ICE. When TEE and ICE were used as the reference for thrombus detection, the sensitivity, specificity, positive predictive value, and negative predictive value of CCT for identifying contrast defects in the LAA were 100%, 81.0%, 40.7%, and 100%, respectively. CONCLUSIONS: ICE combined with TEE increased the detection rate of LAA thrombi in patients with persistent and long-standing persistent AF. Moreover, CCT had high sensitivity and negative predictive value for LAA thrombus detection.

Barriers Associated With Door-to-Balloon Delay in Contemporary Japanese Practice.

BACKGROUND: Door-to-balloon (DTB) time ≤90 min is an important quality indicator in the management of ST-elevation myocardial infarction (STEMI), but a considerable number of patients still do not meet this goal, particularly in countries outside the USA and Europe.Methods and Results:We analyzed 2,428 STEMI patients who underwent primary PCI ≤12 h of symptom onset who were registered in an ongoing prospective multicenter database (JCD-KiCS registry), between 2008 and 2013. We analyzed both the time trend in DTB time within this cohort in the registry, and independent predictors of delayed DTB time >90 min. Median DTB time was 90 min (IQR, 68-115 min) during the study period and there were no significant changes with year. Predictors for delay in DTB time included peripheral artery disease, prior revascularization, off-hour arrival, age >75 years, heart failure at arrival, and use of IABP or VA-ECMO. Notably, high-volume PCI-capable institutions (PCI ≥200/year) were more adept at achieving shorter DTB time compared with low-volume institutions (PCI <200/year). CONCLUSIONS: Half of the present STEMI patients did not achieve DTB time ≤90 min. Targeting the elderly and patients with multiple comorbidities, and PCI performed in off-hours may aid in its improvement.

Degree of dyspnoea in patients with non-ST-elevation acute coronary syndrome: A report from Japanese multicenter registry.

BACKGROUND: Degree of dyspnoea is almost universally evaluated in the patients presenting with acute coronary syndrome (ACS), but its clinical implications has not been thoroughly investigated. We aimed to describe the relationship between the severity of dyspnoea and in-hospital outcomes in patients with non-ST elevation ACS (NSTE-ACS) complicated with acute heart failure (AHF). METHODS: Between 2009 and 2014, 3287 consecutive patients with NSTE-ACS were enrolled in the Japanese prospective multicenter PCI registry. Patients complicated with AHF were subclassified based on the self-reported dyspnoea severity: no dyspnoeic symptoms, dyspnoea during moderate activity, mild activity or at rest. The recorded outcomes included in-hospital death, major cardiovascular (ie, cardiac death, shock, stroke or major bleeding) and renal events (ie, contrast-induced acute kidney injury [CI-AKI] or AKI requiring dialysis). RESULTS: In total, 441 (13.4%) patients had AHF upon presentation, including 76 (17.2%) with dyspnoea during moderate activity, 160 (36.3%) with dyspnoea during mild activity, and 205 (46.5%) with dyspnoea at rest. In-hospital mortality as well as major cardiovascular and renal events increased as dyspnoea severity worsened. After multivariate adjustment, dyspnoea at rest was strongly associated with in-hospital mortality (odds ratio [OR] 5.79; 95% confidence interval [CI], 2.56-13.11; P<.001) as well as major cardiovascular (OR, 2.55; 95% CI, 1.46-4.48; P<.001) and renal events (OR, 3.32; 95% CI, 2.05-5.38; P<.001), when compared to the patients without dyspnoea. CONCLUSIONS: Among NSTE-ACS patients complicated with AHF, both cardiovascular and renal event rates were associated with presence of dyspnoea, and its incidence increased in parallel with dyspnoea severity.

Outcomes of Percutaneous Coronary Intervention Performed With or Without Preprocedural Dual Antiplatelet Therapy.

BACKGROUND: Preprocedural dual antiplatelet therapy (DAPT) in percutaneous coronary interventions (PCI) has been shown to improve outcomes; however, the efficacy of the procedure and its complications in Japanese patients remain largely unexplored, so we examined the risks and benefits of DAPT before PCI and its association with in-hospital outcomes. METHODS AND RESULTS: We analyzed data from patients who had undergone PCI at 12 centers within the metropolitan Tokyo area between September 2008 and September 2013.Our study group comprised 6,528 patients, of whom 2,079 (31.8%) were not administered preprocedural DAPT. Non-use of preprocedural DAPT was associated with death, postprocedural shock, or heart failure (odds ratio [OR]: 1.47, 95% confidence interval [CI]: 1.10-1.96, P=0.009), and postprocedural myocardial infarction (OR: 1.41, 95% CI: 1.18-1.69, P<0.001) after adjusting propensity scores for known predictors of in-hospital complications. Non-use of DAPT was not associated with procedure-related bleeding complications (OR: 0.98, 95% CI: 0.71-1.59, P=0.764). CONCLUSIONS: Approximately one-third of the patients who underwent PCI did not receive preprocedural DAPT despite guideline recommendations. Our results indicate that patients undergoing PCI with DAPT have a lower risk of postprocedural cardiac events without any increased bleeding risk. Further studies are needed to implement the use of DAPT in real-world PCI.