Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial.

Background and aims: Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet. Methods: The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72). Results: All patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to -0.5) vs. -0.4 (-0.6 to -0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to -0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to -1.3) vs. -0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (-0.9 ± 0.25 vs. -0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI4mm regression (odds ratio = 4.41, 95%CI = 1.19-16.30, p = 0.02). Conclusions: In statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.

BNP level predicts bleeding event in patients with heart failure after percutaneous coronary intervention.

OBJECTIVE: This study aimed to investigate the association between heart failure (HF) severity measured based on brain natriuretic peptide (BNP) levels and future bleeding events after percutaneous coronary intervention (PCI). BACKGROUND: The Academic Research Consortium for High Bleeding Risk presents a bleeding risk assessment for antithrombotic therapy in patients after PCI. HF is a risk factor for bleeding in Japanese patients. METHODS: Using an electronic medical record-based database with seven tertiary hospitals in Japan, this retrospective study included 7160 patients who underwent PCI between April 2014 and March 2020 and who completed a 3-year follow-up and were divided into three groups: no HF, HF with high BNP level and HF with low BNP level. The primary outcome was bleeding events according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. The secondary outcome was major adverse cardiovascular events (MACE). Furthermore, thrombogenicity was measured using the Total Thrombus-Formation Analysis System (T-TAS) in 536 consecutive patients undergoing PCI between August 2013 and March 2017 at Kumamoto University Hospital. RESULTS: Multivariate Cox regression showed that HF with high BNP level was significantly associated with bleeding events, MACE and all-cause death. In the T-TAS measurement, the thrombogenicity was lower in patients with HF with high BNP levels than in those without HF and with HF with low BNP levels. CONCLUSIONS: HF with high BNP level is associated with future bleeding events, suggesting that bleeding risk might differ depending on HF severity.

The effect of continuous glucose monitoring-guided glycemic control on progression of coronary atherosclerosis in type 2 diabetic patients with coronary artery disease: The OPTIMAL randomized clinical trial.

BACKGROUND: Continuous glucose monitoring (CGM) improves glycemic fluctuation and reduces hypoglycemic risk. Whether CGM-guided glycemic control favorably modulates coronary atherosclerosis in patients with type 2 diabetes (T2DM) remains unknown. METHODS: The OPTIMAL trial was a prospective, randomized, single-center trial in which 94 T2DM patients with CAD were randomized to CGM- or HbA1c-guided glycemic control for 48 weeks (jRCT1052180152). The primary endpoint was the nominal change in total atheroma volume (TAV) measured by serial IVUS. The secondary efficacy measure was the nominal change in maxLCBI4mm on near-infrared spectroscopy imaging. RESULTS: Among the 94 randomized patients, 82 had evaluable images at 48 weeks. Compared to HbA1c-guided glycemic control, CGM-guided control achieved a greater reduction in %coefficient of variation [-0.1 % (-1.8 to 1.6) vs. -3.3 % (-5.1 to -1.5), p = 0.01] and a greater increase in the duration with glucose between 70 and 180 mg/dL [-1.5 % (-6.0 to 2.9) vs. 6.7 % (1.9 to 11.5), p = 0.02]. TAV increased by 0.11 ± 1.9 mm3 in the HbA1c-guided group and decreased by -3.29 ± 2.00 mm3 in the CGM-guided group [difference = -3.4 mm3 (95%CI: -8.9 to 2.0 mm3), p = 0.22]. MaxLCBI4mm, increased by 90.1 ± 25.6 in the HbA1c-guided group and by 50.6 ± 25.6 in the CGM-guided group (difference = -45.6 (95%CI: -118.1 to 26.7) p = 0.21]. A post-hoc exploratory analysis showed a greater regression of maxLCBI4mm in the CGM-guided group [difference = 20.4 % (95%CI:1.3 to 39.5 %), p = 0.03]. CONCLUSIONS: CGM-guided control for 48 weeks did not slow disease progression in T2DM patients with CAD. A greater regression of lipidic plaque under CGM-guided glycemic control in the post-hoc analysis requires further investigation.

Impact of heart failure severity and major bleeding events after percutaneous coronary intervention on subsequent major adverse cardiac events.

Background: Heart failure (HF) is associated with a high bleeding risk after percutaneous coronary intervention (PCI). Additionally, major bleeding events increase the risk of subsequent major adverse cardiac events (MACE). However, whether brain natriuretic peptide (BNP) levels and major bleeding events following PCI are associated with MACE and all-cause death remains unknown. This study aimed to investigate the impact of HF severity or bleeding on subsequent MACE and all-cause death. Methods: The Clinical Deep Data Accumulation System (CLIDAS), a multicenter database involving seven hospitals in Japan, was developed to collect data from electronic medical records. This retrospective analysis included 7160 patients who underwent PCI between April 2014 and March 2020 and completed a three-year follow-up. Patients were divided according to the presence of HF with high BNP (HFhBNP) (>100 pg/ml) and major bleeding events within 30 days post-PCI (30-day bleeding): HFhBNP with bleeding (n = 14), HFhBNP without bleeding (n = 370), non-HFhBNP with bleeding (n = 74), and non-HFhBNP without bleeding (n = 6702). Results: In patients without 30-day bleeding, HFhBNP was a risk factor for MACE (hazard ratio, 2.19; 95% confidence interval, 1.56-3.07) and all-cause death (hazard ratio, 1.60; 95% confidence interval, 1.60-2.23). Among HFhBNP patients, MACE incidence was higher in patients with 30-day bleeding than in those without bleeding, but the difference was not significant (p = 0.075). The incidence of all-cause death was higher in patients with bleeding (p = 0.001). Conclusions: HF with high BNP and bleeding events in the early stage after PCI might be associated with subsequent MACE and all-cause death.

Distal Radial Approach in Coronary Angiography Using a Transdermal Nitroglycerin Patch: Double-Blinded Randomized Trial.

Nitroglycerin dilates the radial artery and prevents spasm, which increases the success rate of sheath cannulation through the conventional transradial approach. However, the effects of nitroglycerin on distal radial approach (DRA) procedures are not known. The aim of this study is to elucidate whether a transdermal nitroglycerin patch improves the rate of successful DRA cannulation. A total of 92 patients scheduled for coronary angiography by means of DRA randomly received (1:1) a transdermal nitroglycerin patch preintegrated with the covering material or only the covering material on their upper arm on the side of the puncture. The diameter of the distal radial artery was evaluated with ultrasound at baseline and after application. DRA procedures were performed in a double-blind fashion. The primary outcome was the rate of successful palpation-guided distal radial artery cannulation with the first puncture. The nitroglycerin group had larger distal radial artery diameter after patch application than that of the no-treatment group (mean, 3.21 mm vs 2.71 mm, p <0.001), but not at baseline (mean, 2.64 mm vs 2.64 mm, p = 0.965).The nitroglycerin group had a significantly higher success rate of DRA cannulation with the first puncture than that of the no-treatment group (59% vs 24%, p = 0.001; odds ratio 4.5, 95% confidence interval 1.9 to 11.0). The nitroglycerin group required fewer punctures than did the no-treatment group (median, 1 vs 3, p = 0.019). There were no significant differences in the occurrence of hypotension between the 2 groups. No patients experienced radial artery occlusion. In conclusion, transdermal nitroglycerin patch application safely facilitates DRA cannulation. Trial Registration: Japan Registry of Clinical Trials, https://jrct.niph.go.jp/ (identifier: jRCTs051210128).

Characterization of plaque phenotypes exhibiting an elevated pericoronary adipose tissue attenuation: insights from the REASSURE-NIRS registry.

Inflammation has been considered to promote atheroma instability. Coronary computed tomography angiography (CCTA) visualizes pericoronary adipose tissue (PCAT) attenuation, which reflects coronary artery inflammation. While PCAT attenuation has been reported to predict future coronary events, plaque phenotypes exhibiting high PCAT attenuation remains to be fully elucidated. The current study aims to characterize coronary atheroma with a greater vascular inflammation. We retrospectively analyzed culprit lesions in 69 CAD patients receiving PCI from the REASSURE-NIRS registry (NCT04864171). Culprit lesions were evaluated by both CCTA and near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS) imaging prior to PCI. PCAT attenuation at proximal RCA (PCATRCA) and NIRS/IVUS-derived plaque measures were compared in patients with PCATRCA attenuation ≥ and < -78.3 HU (median). Lesions with PCATRCA attenuation ≥ -78.3 HU exhibited a greater frequency of maxLCBI4mm ≥ 400 (66% vs. 26%, p < 0.01), plaque burden ≥ 70% (94% vs. 74%, p = 0.02) and spotty calcification (49% vs. 6%, p < 0.01). Whereas positive remodeling (63% vs. 41%, p = 0.07) did not differ between two groups. On multivariable analysis, maxLCBI4mm ≥ 400 (OR = 4.07; 95%CI 1.12-14.74, p = 0.03), plaque burden ≥ 70% (OR = 7.87; 95%CI 1.01-61.26, p = 0.04), and spotty calcification (OR = 14.33; 95%CI 2.37-86.73, p < 0.01) independently predicted high PCATRCA attenuation. Of note, while the presence of only one plaque feature did not necessarily elevate PCATRCA attenuation (p = 0.22), lesions harboring two or more features were significantly associated with higher PCATRCA attenuation. More vulnerable plaque phenotypes were observed in patients with high PCATRCA attenuation. Our findings suggest PCATRCA attenuation as the presence of profound disease substrate, which potentially benefits from anti-inflammatory agents.

Calcified plaque harboring lipidic materials associates with no-reflow phenomenon after PCI in stable CAD.

Calcified atheroma has been viewed conventionally as stable lesion which less likely increases no-reflow phenomenon. Given that lipidic materials triggers the formation of calcification, lipidic materials could exist within calcified lesion, which may cause no-reflow phenomenon after PCI. The REASSURE-NIRS registry (NCT04864171) employed near-infrared spectroscopy and intravascular ultrasound imaging to evaluate maximum 4-mm lipid-core burden index (maxLCBI4mm) at target lesions containing small (maximum calcification arc < 180°: n = 272) and large calcification (maximum calcification arc ≥ 180°: n = 189) in stable CAD patients. The associations of maxLCBI4mm with corrected TIMI frame count (CTFC) and no-reflow phenomenon after PCI were analyzed in patients with target lesions containing small and large calcification, respectively. No-reflow phenomenon occurred in 8.0% of study population. Receiver-operating characteristics curve analyses revealed that optimal cut-off values of maxLCBI4mm for predicting no-reflow phenomenon were 585 at small calcification (AUC = 0.72, p < 0.001) and 679 at large calcification (AUC = 0.76, p = 0.001). Target lesions containing small calcification with maxLCBI4mm ≥ 585 more likely exhibited a greater CTFC (p < 0.001). In those with large calcification, 55.6% of them had maxLCBI4mm ≥ 400 [vs. 56.2% (small calcification), p = 0.82]. Furthermore, a higher CTFC (p < 0.001) was observed in association with maxLCBI4mm ≥ 679 at large calcification. On multivariable analysis, maxLCBI4mm at large calcification still independently predicted no-reflow phenomenon (OR = 1.60, 95%CI = 1.32-1.94, p < 0.001). MaxLCBI4mm at target lesions exhibiting large calcification elevated a risk of no-reflow phenomenon after PCI. Calcified plaque containing lipidic materials is not necessarily stable lesion, but could be active and high-risk one causing no-reflow phenomenon.

Feasibility of rotational atherectomy in patients with acute coronary syndrome: favorable in-hospital outcomes and clinical importance of complexed coronary atherosclerosis.

The feasibility of rotational atherectomy (RA) during percutaneous coronary intervention (PCI) in patients who present with acute coronary syndrome (ACS) remains fully unsettled. We retrospectively evaluated 198 consecutive patients who underwent RA during PCI from 2009 to 2020. All patients underwent intracoronary imaging (intravascular ultrasound 96.5%, optical coherence tomography 9.1%, both 5.6%) during PCI. Patients who underwent RA during PCI were divided into two groups: ACS (n = 49; unstable angina pectoris, n = 27; non-ST-elevation myocardial infarction, n = 18, and ST-elevation myocardial infarction, n = 4) and chronic coronary syndrome (CCS) (n = 149). The RA procedural success rate was comparable between in the ACS and CCS groups (93.9 vs. 89.9%, P = 0.41). No significant differences were observed in procedural complications and in-hospital death between the groups. The incidence of major adverse cardiovascular event (MACE) after 2 years was significantly higher in ACS group compared with CCS group (38.7 vs. 17.4%, log-rank P = 0.002). Multivariable Cox regression analysis identified SYNTAX score or CABG SYNTAX score > 22 (hazard ratio (HR) 2.66, 95% confidence interval (CI) 1.40-5.06, P = 0.002) and mechanical circulatory support during the procedure (HR 2.61, 95% CI 1.21-5.59, P = 0.013) as predictors of MACE at 2 years, but not ACS on index admission (HR 1.58, 95% CI 0.84-2.99, P = 0.151). RA procedure is feasible as a bail-out strategy for ACS lesions. However, more complexed coronary atherosclerosis and mechanical circulatory support during RA procedure, but no ACS lesions were associated with worse mid-term clinical outcomes.

Sex Differences in the Density of Lipidic Plaque Materials: Insights From the REASSURE-NIRS MultiCenter Registry.

BACKGROUND: Intravascular imaging has shown better response of coronary atheroma to statin-mediated lowering of low-density lipoprotein cholesterol in women. However, its detailed mechanism remains to be determined yet. Modifiability of coronary atheroma under lipid-lowering therapies is partly driven by lipidic plaque component. Given a smaller plaque volume in women, lipidic plaque features including their density may differ between sex. Therefore, the current study sought to characterize sex-related differences in the density of lipidic plaque. METHODS: We analyzed 1429 coronary lesions (culprit/nonculprit lesions=825/604) in 758 coronary artery disease patients (men/women=608/150) from the REASSURE-NIRS multicenter registry (Revelation of Pathophysiological Phenotypes of Vulnerable Lipid-Rich Plaque on Near-Infrared Spectroscopy). Total atheroma volume at 4-mm segment, maximum 4-mm-lipid-core burden index, and lipid plaque density index (=maximum 4-mm-lipid-core burden index/total atheroma volume at 4-mm segment) on near-infrared spectroscopy/intravascular ultrasound imaging at culprit and nonculprit lesions were compared in men and women. RESULTS: Statin and high-intensity statin were used in 72.4 (P=0.81) and 22.9% (P=0.32) of study subjects, respectively. Women exhibited a smaller adjusted total atheroma volume at 4-mm segment (culprit lesions: 50.3±0.4 versus 54.2±0.3mm3, P<0.001, nonculprit lesions: 31.5±3.0 versus 44.4±2.1mm3, P<0.001), whereas their adjusted maximum 4-mm-lipid-core burden index did not differ between sex (culprit lesions: 544.7±29.9 versus 501.7±19.1, P=0.11, nonculprit lesions: 288.8±26.7 versus 272.7±18.9, P=0.51). Furthermore, a greater adjusted lipid plaque density index was observed in women (culprit lesions: 18.2±0.9 versus 9.8±0.6, P<0.001, nonculprit lesions: 23.0±2.0 versus 7.8±1.4, P<0.001). These adjustments of total atheroma volume at 4-mm segment, maximum 4-mm-lipid-core burden index, and lipid plaque density index included age, body mass index, hypertension, dyslipidemia, diabetes, smoking, a history of myocardial infarction and chronic kidney disease, low-density lipoprotein cholesterol level, statin and ezetimibe use, vessel volume, and hospital unit. The aforementioned plaque features consistently existed in both acute coronary syndrome and stable coronary artery disease subjects. CONCLUSIONS: Women harbored greater condensed lipidic plaque features, accompanied by smaller atheroma volume. These observations indicate potentially better modifiable disease in women, which underscores the need to intensify their lipid-lowering therapies for further improving their outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov/; Unique identifier: NCT04864171.

In-hospital adverse events and recurrence in hospitalized patients with acute pericarditis.

BACKGROUND: Acute pericarditis occasionally requires invasive treatment, and may recur after discharge. However, there are no studies on acute pericarditis in Japan, and its clinical characteristics and prognosis are unknown. METHODS: This was a single-center, retrospective cohort study of clinical characteristics, invasive procedures, mortality, and recurrence in patients with acute pericarditis hospitalized from 2010 to 2022. The primary in-hospital outcome was adverse events (AEs), a composite of all-cause mortality and cardiac tamponade. The primary outcome in the long-term analysis was hospitalization for recurrent pericarditis. RESULTS: The median age of all 65 patients was 65.0 years [interquartile range (IQR), 48.0-76.0 years], and 49 (75.3 %) were male. The etiology of acute pericarditis was idiopathic in 55 patients (84.6 %), collagenous in 5 (7.6 %), bacterial in 1 (1.5 %), malignant in 3 (4.6 %), and related to previous open-heart surgery in 1 (1.5 %). Of the 8 patients (12.3 %) with in-hospital AE, 1 (1.5 %) died during hospitalization and 7 (10.8 %) developed cardiac tamponade. Patients with AE were less likely to have chest pain (p = 0.011) but were more likely to have symptoms lasting 72 h after treatment (p = 0.006), heart failure (p < 0.001), and higher levels of C-reactive protein (p = 0.040) and B-type natriuretic peptide (p = 0.032). All patients complicated with cardiac tamponade were treated with pericardial drainage or pericardiotomy. We analyzed 57 patients for recurrent pericarditis after excluding 8 patients: 1 with in-hospital death, 3 with malignant pericarditis, 1 with bacterial pericarditis, and 3 lost to follow-up. During a median follow-up of 2.5 years (IQR 1.3-3.0 years), 6 patients (10.5 %) had recurrences requiring hospitalization. The recurrence rate of pericarditis was not associated with colchicine treatment or aspirin dose or titration. CONCLUSIONS: In acute pericarditis requiring hospitalization, in-hospital AE and recurrence were each observed in >10 % of patients. Further large studies on treatment are warranted.

Sex Differences in Long-Term Outcomes in Patients With Chronic Coronary Syndrome After Percutaneous Coronary Intervention　- Insights From a Japanese Real-World Database Using a Storage System.

BACKGROUND: Several studies have reported some sex differences in patients with coronary artery diseases. However, the results regarding long-term outcomes in patients with chronic coronary syndrome (CCS) are inconsistent. Therefore, the present study investigated sex differences in long-term outcomes in patients with CCS after percutaneous coronary intervention (PCI).Methods and Results: This was a retrospective, multicenter cohort study. We enrolled patients with CCS who underwent PCI between April 2013 and March 2019 using the Clinical Deep Data Accumulation System (CLIDAS) database. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, or hospitalization for heart failure. In all, 5,555 patients with CCS after PCI were included in the analysis (4,354 (78.4%) men, 1,201 (21.6%) women). The median follow-up duration was 917 days (interquartile range 312-1,508 days). The incidence of MACE was not significantly different between the 2 groups (hazard ratio [HR] 1.20; 95% confidential interval [CI] 0.97-1.47; log-rank P=0.087). After performing multivariable Cox regression analyses on 4 different models, there were still no differences in the incidence of MACE between women and men. CONCLUSIONS: There were no significant sex differences in MACE in patients with CCS who underwent PCI and underwent multidisciplinary treatments.

Heart-Brain Team Approach of Acute Myocardial Infarction Complicating Acute Stroke: Characteristics of Guideline-Recommended Coronary Revascularization and Antithrombotic Therapy and Cardiovascular and Bleeding Outcomes.

Background Acute myocardial infarction (AMI) infrequently occurs after acute stroke. The Heart-brain team approach has a potential to appropriately manage this poststroke cardiovascular complication. However, clinical outcomes of AMI complicating acute stroke (AMI-CAS) with the heart-brain team approach have not been characterized. The current study investigated cardiovascular outcomes in patients with AMI-CAS managed by a heart-brain team. Methods and Results We retrospectively analyzed 2390 patients with AMI at our institute (January 1, 2007-September 30, 2020). AMI-CAS was defined as the occurrence of AMI within 14 days after acute stroke. Major adverse cerebral/cardiovascular events (cardiac-cause death, nonfatal myocardial infarction, and nonfatal stroke) and major bleeding events were compared in subjects with  AMI-CAS and those without acute stroke. AMI-CAS was identified in 1.6% of the subjects. Most AMI-CASs (37/39=94.9%) presented ischemic stroke. Median duration of AMI from the onset of acute stroke was 2 days. Patients with AMI-CAS less frequently received primary percutaneous coronary intervention (43.6% versus 84.7%; P<0.001) and dual-antiplatelet therapy (38.5% versus 85.7%; P<0.001), and 33.3% of them did not receive any antithrombotic agents (versus 1.3%; P<0.001). During the observational period (median, 2.4 years [interquartile range, 1.1-4.4 years]), patients with AMI-CAS exhibited a greater likelihood of experiencing major adverse cerebral/cardiovascular events (hazard ratio [HR], 3.47 [95% CI, 1.99-6.05]; P<0.001) and major bleeding events (HR, 3.30 [95% CI, 1.34-8.10]; P=0.009). These relationships still existed even after adjusting for clinical characteristics and medication use (major adverse cerebral/cardiovascular event: HR, 1.87 [95% CI, 1.02-3.42]; P=0.04; major bleeding: HR, 2.67 [95% CI, 1.03-6.93]; P=0.04). Conclusions Under the heart-brain team approach, AMI-CAS was still a challenging disease, reflected by less adoption of primary percutaneous coronary intervention and antithrombotic therapies, with substantially elevated cardiovascular and major bleeding risks. Our findings underscore the need for a further refined approach to mitigate their ischemic/bleeding risks.

Urinary catheterization prior to PCI worsens clinical outcomes in patients with acute myocardial infarction.

BACKGROUND: Indwelling urethral catheters (IUCs) are used to measure urine volume, keep patients on bed rest, or keep the groin area clean in patients with acute myocardial infarction (AMI). However, the association between IUC use and in-hospital urinary-related complications is unknown. METHODS: This was a single-center retrospective analysis of 303 patients admitted to our hospital in 2018-2020 who had AMI without cardiogenic shock. An IUC was inserted in the emergency room upon initiation of invasive catheter treatment and removed as soon as possible. The primary outcome was in-hospital adverse urinary event (IHAUE), which consisted of in-hospital urinary tract infection and in-hospital gross hematuria. RESULTS: Of 303 patients, 243 patients (80.2 %) underwent IUC insertion. A lower proportion of patients with IUCs were male (72 % vs. 85 %, p = 0.044). A higher proportion had Killip classification 2 or 3 (13 % vs. 0 %, p = 0.003) or ST-elevation myocardial infarction (65 % vs. 32 %, p < 0.001). IHAUEs occurred significantly more commonly in patients with IUCs than without IUCs (11 % vs. 2 %, p = 0.023). Kaplan-Meier analysis showed that IHAUEs occurred more frequently in patients with IUCs than patients without IUCs (log-rank test p = 0.033). Furthermore, IUC use longer than the median of 2 days was associated with a higher odds ratio (OR) for IHAUE when compared with those without IUC use (OR, 3.65; 95 % confidence interval, 1.28-10.4; p = 0.015). There were no significant differences in in-hospital mortality by IUC status. CONCLUSIONS: IUC use is associated with a higher risk of IHAUEs in patients with uncomplicated AMI. Routine IUC use might not be recommended.

Relationships Among Heart Rate, ß-Blocker Dosage, and Prognosis in Patients With Coronary Artery Disease in a Real-World Database Using a Multimodal Data Acquisition System.

BACKGROUND: The optimal heart rate (HR) and optimal dose of ß-blockers (BBs) in patients with coronary artery disease (CAD) have been unclear. We sought to clarify the relationships among HR, BB dose, and prognosis in patients with CAD using a multimodal data acquisition system.Methods and Results: We evaluated the data for 8,744 CAD patients who underwent cardiac catheterization from 6 university hospitals and the National Cerebral and Cardiovascular Center and who were registered using the Clinical Deep Data Accumulation System. Patients were divided into quartile groups based on their HR at discharge: Q1 (HR <60 beats/min), Q2 (HR 60-66 beats/min), Q3 (HR 67-74 beats/min), and Q4 (HR ≥75 beats/min). Among patients with acute coronary syndrome (ACS) and patients with chronic coronary syndrome (CCS), those in Q4 (HR ≥75 beats/min) had a significantly greater incidence of major adverse cardiac and cerebral events (MACCE) compared with those in Q1 (ACS patients: hazard ratio 1.65, P=0.001; CCS patients: hazard ratio 1.45, P=0.019). Regarding the use of BBs (n=4,964), low-dose administration was significantly associated with MACCE in the ACS group (hazard ratio 1.41, P=0.012), but not in patients with CCS after adjustment for covariates. CONCLUSIONS: HR ≥75 beats/min was associated with worse outcomes in patients with CCS or ACS.

Differences in major limb outcomes by indication for lower extremity endovascular revascularization in patients receiving hemodialysis.

The incidence of lower extremity artery disease (LEAD) in patient receiving hemodialysis is remarkably higher than the general population. The treatment strategy and prognosis for LEAD patients differs depending on whether a patient has intermittent claudication (IC) or critical limb-threatening ischemia (CLTI). However, the distinction between the prognosis in HD-dependent patients with IC and CLTI has not been fully elucidated. This study is to determine whether indication of PAD has a distinct impact on major adverse cardiovascular and cerebrovascular events (MACCE) and limb events in patients receiving hemodialysis. The current study included 2321 prospectively enrolled patients from the Tokyo taMA peripheral vascular intervention research ComraDE registry (UMIN-CTR no. UMIN000015100) between September 2014 and December 2016. Out of the enrolled patients, 1644 were not receiving hemodialysis (non-HD patients) and 603 were receiving hemodialysis (HD patients). A composite of all-cause death, myocardial infarction, and stroke events defined as MACCE; while limb events were defined as a composite of unscheduled major amputation, unscheduled major lower limb surgery, acute limb ischemia, unscheduled endovascular treatment, and target lesion revascularization. Propensity score matching was applied among the non-HD and HD patients, in whole group, IC subgroup, and CLTI subgroup. Kaplan-Meier analysis was used for the analysis of outcomes for the whole group, IC subgroup, and the CLTI subgroup. CLTI accounted for 75.5% of the HD patients, whereas IC was 63.4% in the non-HD patients. The HD patients exhibited more frequent below-the-knee lesions than those in the non-HD patients in both IC (p = 0.01) and CLTI (p < 0.001) subgroups. Overall, HD patients exhibited a significantly higher rate of MACCE at 24 months. This trend was similar for limb events in whole group and CLTI subgroup. In contrast, no significant differences in outcomes for limb events were found in IC subgroup. Although, prognosis after EVT in HD patients were significantly worse than non-HD patients, comparable outcome with non-HD patients was observed in the patients treated for IC. Clinical trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR No. UMIN000015100).

Bypass failure of internal mammary artery caused by subclavian artery stenosis: its clinical characteristics and cardiovascular outcomes in patients receiving coronary artery bypass graft surgery.

Background: While internal mammary artery (IMA) has become a major conduit of coronary artery bypass graft (CABG) surgery, subclavian artery stenosis (SAS) could cause subsequent coronary events due to ischemia of myocardial territory supplied by IMA. Clinical characteristics and cardiovascular outcomes of SAS-related IMA failure (SAS-IMAF) remain to be fully determined yet. Therefore, the current study was designed to characterize SAS-IMAF in patients receiving CABG with IMA. Methods: This is a retrospective observational study which analyzed 380 patients who presented acute coronary syndrome/stable ischemic heart disease (ACS/SIHD) after CABG using IMA (2005.01.01-2020.10.31). SAS-IMAF was defined as the presence of myocardial ischemia/necrosis caused by SAS. Clinical characteristics and cardiovascular outcomes [major adverse cardiovascular events (MACE) = cardiac death + non-fatal myocardial infarction + non-fatal ischemic stroke], were compared in subjects with and without SAS-IMAF. Multivariate Cox proportional hazards model and propensity score-matched analyses were used to compare cardiovascular outcomes between those with and without SAS-IMAF. Results: SAS-IMAF was identified in 5.5% (21/380) of study subjects. Patients with SAS-IMAF are more likely had a history of hemodialysis (P<0.001), stroke (P<0.001) and lower extremity artery disease (P<0.001). Furthermore, SAS-IMAF patients more frequently presented ACS (P=0.002) and required mechanical support (P=0.02). Despite SAS as a culprit lesion causing ACS/SIHD, percutaneous coronary intervention was firstly selected in 47.6% (10/21) of them. Consequently, 33.3% (7/21) of SAS-IMAF patients required additional revascularization procedure (vs. 0.3%, P<0.001). During 4.9-year observational period, SAS-IMAF exhibited a 5.82-fold [95% confidence interval (CI): 2.31-14.65, P<0.001] increased risk of MACE. Multivariate Cox proportional hazards model [hazard ratio (HR) 4.04, 95% CI: 1.44-11.38, P=0.008] and propensity score-matched analyses (HR 2.67, 95% CI: 1.06-6.73, P=0.038) consistently demonstrated the association of SAS-IMAF with MACE. Conclusions: SAS-IMAF reflects a high-risk phenotype of polyvascular disease, underscoring meticulous evaluation of subclavian artery after CABG using IMA.

Clinical impact of cardiac magnetic resonance in patients with suspected coronary artery disease associated with chronic kidney disease (AQUAMARINE-CKD study): study protocol for a randomized controlled trial.

BACKGROUND: Although screening for coronary artery disease (CAD) using computed tomography coronary angiography in patients with stable chest pain has been reported to be beneficial, patients with chronic kidney disease (CKD) might have limited benefit due to complications of contrast agent nephropathy and decreased diagnostic accuracy as a result of coronary artery calcifications. Cardiac magnetic resonance (CMR) has emerged as a novel imaging modality for detecting coronary stenosis and high-risk coronary plaques without contrast media that is not affected by coronary artery calcification. However, the clinical use of this technology has not been robustly evaluated. METHODS: AQUAMARINE-CKD is an open parallel-group prospective multicenter randomized controlled trial of 524 patients with CKD at high risk for CAD estimated based on risk factor categories for a Japanese urban population (Suita score) recruited from 6 institutions. Participants will be randomized 1:1 to receive a CMR examination that includes non-contrast T1-weighted imaging and coronary magnetic angiography (CMR group) or standard examinations that include stress myocardial scintigraphy (control group). Randomization will be conducted using a web-based system. The primary outcome is a composite of cardiovascular events at 1 year after study examinations: all-cause death, death from CAD, nonfatal myocardial infarction, nonfatal ischemic stroke, and ischemia-driven unplanned coronary intervention (percutaneous coronary intervention or coronary bypass surgery). DISCUSSION: If the combination of T1-weighted imaging and coronary magnetic angiography contributes to the risk assessment of CAD in patients with CKD, this study will have major clinical implications for the management of patients with CKD at high risk for CAD. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) 1,052,210,075. Registered on September 10, 2021.

The Residual Lipid-Rich Coronary Atheroma Behind the Implanted Newer-Generation Drug-Eluting Stent and Future Stent-Related Event Risks.

BACKGROUND: Lipid-rich plaque is an important substrate that causes future coronary events. However, the clinical implications of underlying plaque characteristics in coronary lesions after newer-generation drug-eluting stent (DES) implantation remain unknown. METHODS: The current study analyzed 445 target lesions after newer-generation DES implantation in 416 patients with coronary artery disease (CAD) (chronic coronary syndrome/acute coronary syndrome = 264/181) from the REASSURE-NIRS multicentre registry. Near-infrared spectroscopy (NIRS) imaging was used to evaluate maximum lipid core burden index after stent implantation in target lesions (residual maxLCBI4mm). The primary and secondary outcomes were 3-year lesion-oriented clinical outcomes (LOCO): cardiac death, nonfatal target-lesion-related myocardial infarction (MI), or ischemia-driven target-lesion revascularization (ID-TLR) and patient-oriented clinical outcomes (POCO): all-cause death, nonfatal MI, or ID unplanned revascularization. Outcomes were compared by residual maxLCBI4mm tertile. RESULTS: Median residual maxLCBI4mm was 183; 16% of lesions had residual maxLCBI4mm > 400. Higher residual maxLCBI4mm was not associated with a greater likelihood of LOCO or POCO during the observational period (LOCO, log-rank P = 0.76; POCO, log-rank P = 0.84). Mixed-effects logistic regression demonstrated that residual maxLCBI4mm does not predict LOCO (odds ratio [OR], 1.000; 95% confidence interval [CI], 0.997-1.003; P = 0.95). There was no significant relationship between residual maxLCBI4mm and POCO (OR, 1.001; 95% CI, 0.999-1.002; P = 0.30). CONCLUSIONS: Residual maxLCBI4mm is not associated with LOCO or POCO in patients with CAD after newer-generation DES implantation. Our findings suggest that NIRS-derived underlying lipid-rich plaque is not associated with the risk of stent-related events and patient-based outcomes in patients with CAD who have received newer-generation DESs.