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Patients with epicardial coronary vasospastic angina (VSA) may be likely to have coronary microvascular dysfunction, although mixed results have been reported. The aim of this study was to evaluate coronary microvascular function in detail using novel invasive physiologic indices, such as resistive reserve ratio (RRR) and microvascular resistance reserve (MRR). A total of 45 patients undergoing intracoronary acetylcholine (ACh) provocation test and invasive coronary circulatory evaluation using a thermodilution method were prospectively included. VSA was diagnosed as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes by intracoronary injection of ACh. Coronary circulation was assessed with physiologic indices including fractional flow reserve, resting and hyperemic mean transit time (Tmn), coronary flow reserve (CFR), basal resistance index, index of microcirculatory resistance (IMR), RRR, and MRR. Of 45 patients, 23 (51.1%) were diagnosed as having VSA. Patients with positive ACh test had longer resting Tmn (slower coronary flow velocity), higher basal resistance index, and greater RRR and MRR than those without, while fractional flow reserve, CFR, and IMR did not differ significantly between the two groups. In conclusion, although conventional measures such as CFR and IMR failed to show significant differences, RRR and MRR, novel invasive coronary physiologic indices, provided counterintuitive insights that coronary microvascular dilation function was better preserved in patients with VSA than those without.

Patients with previous atherosclerotic cardiovascular disease (ASCVD) are typically managed by secondary prevention modalities; however, they may experience recurrent events. In acute myocardial infarction (MI), the prognostic effect of preexisting ASCVD on the short- and long-term outcomes remains uncertain. This retrospective, multicenter registry included 2,475 patients with acute MI who underwent percutaneous coronary intervention. Previous ASCVD was defined as a history of ischemic events in the coronary, cerebral, and peripheral arterial territories. Patients were divided into 2 groups according to preexisting ASCVD. The primary end point was major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular death, recurrent MI, and ischemic stroke during hospitalization and after discharge. The bleeding outcomes were also evaluated. Of the 2,475 patients, 475 (19.2%) had previous ASCVD. Patients with previous ASCVD were older and likely to have more co-morbidities than those without ASCVD. During hospitalization, the MACE rates were higher in the ASCVD group than in the non-ASCVD group (16.4% vs 9.6%, p <0.001). Similarly, during a median follow-up of 542 days after discharge, patients with previous ASCVD had an increased risk of MACEs than those without ASCVD (13.4% vs 5.6%, p <0.001). The multivariable analyses identified previous ASCVD as a factor that was significantly associated with MACEs after discharge. Major bleeding events occurred more frequently in the ASCVD group than in the non-ASCVD group. In conclusion, preexisting ASCVD was often observed in patients with acute MI and was particularly associated with long-term ischemic outcomes after discharge; thus, further clinical investigations are needed in this vulnerable patient subset.

Background Although glucose variability (GV) is reportedly associated with coronary plaque vulnerability, namely lipid-rich plaque, details are not fully understood. The aim of this study was to evaluate relations of GV after discharge to vulnerable plaque formation assessed by near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with and without diabetes. Methods A total of 40 patients undergoing percutaneous coronary intervention under NIRS-IVUS guidance were included, among whom 13 (33%) had diabetes and 20 (50%) presented with acute myocardial infarction (MI). GV was evaluated by a flush glucose monitoring system, primarily with mean amplitude of glycemic excursion (MAGE). Lipid-rich plaque was assessed by maximum lipid core burden index in 4 mm (maxLCBI 4mm ) in the target lesion using NIRS-IVUS. Results Mean MAGE and maxLCBI 4mm were 69.7 ± 25.6 mg/dl and 508.0 ± 294.9. Intra-day GV was not significantly associated with maxLCBI 4mm in the entire study population, while MAGE was correlated with maxLCBI 4mm in non-diabetic patients ( r  = 0.46, p  = 0.02). In patients with and without acute MI presentation, no significant relations were found between MAGE and maxLCBI 4mm . Conclusion GV was associated with lipid core plaque formation, especially in non-diabetic patients.

IntroductionHeart failure occasionally develops after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), despite procedural success. Most cases present with mildly reduced or preserved left ventricular ejection fraction (LVEF), underscoring the role of diastolic dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown benefits across the heart failure spectrum, independent of LVEF. The purpose of this randomised controlled trial is to determine whether adding a SGLT2 inhibitor to conventional medications improves LV diastolic function in patients with preserved LVEF after TAVI.Methods and analysisThis study is a prospective, single-centre, open-label, randomised, parallel-group, two-arm trial enrolling patients with mildly reduced or preserved LVEF (≥40%) undergoing TAVI for severe AS. Participants will be randomised in a 1:1 ratio to receive either conventional medications plus empagliflozin or conventional medications alone. In the empagliflozin group, participants will receive conventional medical therapy plus empagliflozin 10 mg orally once daily, initiated 4 weeks after TAVI. Empagliflozin treatment will continue throughout the study period. Participants in the control group will receive conventional medications without empagliflozin. The primary endpoint is the change in E/e’, assessed by echocardiography from treatment initiation at 4 weeks post TAVI (day 1) to day 168 (week 24). Each group will include 50 patients, totalling 100 patients.Ethics and disseminationEthical approval for this study has been obtained from the Chiba University Hospital Certified Clinical Research Review Board (CRB0111-25).Trial registration numberjRCT1031250190.

Chronic systemic inflammatory diseases (CSIDs) such as rheumatoid arthritis (RA) are reportedly associated with an increased risk of ischemic cardiovascular events including acute myocardial infarction (MI). However, data are limited on clinical characteristics and ischemic and bleeding outcomes after acute MI in patients with CSIDs. This bi-center registry included a total of 1001 patients with acute MI undergoing percutaneous coronary intervention. CSIDs included inflammatory rheumatological conditions (RA, systemic lupus erythematosus, vasculitis, etc.) and organ-specific diseases (chronic hepatitis, psoriasis, inflammatory bowel disease, etc.). The primary endpoint was net adverse clinical events (NACE), a composite of ischemic (all-cause death, MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events, during hospitalization and after discharge. Of the 1001 patients, 58 (5.8%) had CSIDs. The proportion of women was higher in patients with CSIDs than those without (37.9% vs. 22.1%, p = 0.009). During the hospitalization, no significant differences in the primary endpoint of NACE were observed between patients with and without CSIDs (10.3% vs. 12.7%, p = 0.84). During the median follow-up of 42.6 months after discharge, patients with CSIDs had a higher risk of NACE (22.5% vs. 10.1%, p = 0.01) than those without, mainly driven by an increased risk of ischemic events (18.4% vs. 8.4%, p = 0.03). A small but significant proportion of patients with acute MI (5.8%) had CSIDs. While the incidence of in-hospital events was similar, patients with CSIDs had worse outcomes after discharge, suggesting that further clinical investigations and therapeutic approaches are needed in this patient subset.

Various types of blood pressure (BP) variability have been recognized as risk factors for future cardiovascular events. However, the prognostic impact of in-hospital BP variability in patients with symptomatic peripheral arterial disease (PAD) has not yet been thoroughly investigated. A total of 386 patients with PAD who underwent endovascular therapy in two hospitals were retrospectively included. BP variability was assessed by the coefficient of variation (CV) of systolic BP measured during hospitalization by trained nurses. The primary endpoint was a composite of major adverse cardiovascular events (cardiovascular death, acute coronary syndrome, stroke, and hospitalization for heart failure) and major adverse limb events (major amputation, acute limb ischemia, and surgical limb revascularization). The mean systolic BP and the CV of systolic BP during hospitalization were 130.8 ± 15.7 mmHg and 11.2 ± 4.1%, respectively. During the median follow-up period of 22 months, 80 patients (21%) reached the primary endpoint. Receiver operating characteristic curve analysis showed that the CV of systolic BP significantly predicted major adverse cardiovascular and limb events (area under the curve 0.60, best cutoff value 9.8, P = 0.01). Using the best cutoff value, patients with high BP variability (n = 242) had a higher risk of clinical events than those with low BP variability (n = 144) (26% vs. 12%, P < 0.001). Multivariable analysis indicated that the CV of systolic BP, age, hemodialysis, and atrial fibrillation were associated with the primary endpoint. In conclusion, greater in-hospital systolic BP variability was associated with major adverse cardiovascular and limb events in patients with symptomatic PAD undergoing endovascular therapy.

This study aims to compare 1-year outcomes after transcatheter aortic valve replacement (TAVR) between patients with moderate–severe MR and severe MR preoperatively using the Japan Transcatheter Valve Therapy (J-TVT) registry. Patients undergoing TAVR for aortic stenosis between August 2013 and December 2019 with preoperative mitral regurgitation of moderate–severe (group MR3) or severe (group MR4) were included. Patients with a history of valve surgery and dialysis patients were excluded. A total of 2017 patients were included, and 1-year follow-up data were obtained from the registry (follow-up rate 98.5%). Propensity-score matching between MR3 and MR4 groups was performed. All-cause mortality and the composite outcome of death and/or heart failure events were compared. Crude data showed that 1-year survival was significantly higher in the MR 3 (89.8%) than MR 4 (84.7%) groups, and freedom from 1-year mortality and heart failure events was also higher in the MR 3 (87.1%) than MR 4 (80.5%) groups ( p  = 0.0001). After propensity-score matching, 452 cases (226 cases each in MR 3 group and MR 4 group) were extracted. Cox regression model showed no statistical difference in the 1-year survival rate between MR 3 group (84.5%) and MR 4 group (85.5%) ( p  = 0.84), nor in freedom from 1-year death and/or heart failure events between MR 3 group (80.2%) and MR 4 group (81.6%) ( p  = 0.72). The 1-year survival rate and freedom from death and/or heart failure events were found to be similar between patients undergoing TAVR with MR grade 3 and MR grade 4.

Triple antithrombotic therapy, including dual antiplatelet therapy and oral anticoagulant (OAC), is recommended for a short-term period after percutaneous coronary intervention (PCI) in patients requiring anticoagulation therapy. The purpose of this study was to compare in-hospital clinical outcomes between low-dose prasugrel (3.75 mg/day) and clopidogrel, as part of triple antithrombotic therapy, using a large database in Japan. Overall, 5,777 patients were eligible in this analysis. The patients were divided into 4 subgroups according to the type of P2Y12 inhibitor and OAC: clopidogrel/DOAC (n = 1,628), clopidogrel/VKA (n = 1,334), prasugrel/DOAC (n = 1,607), and prasugrel/VKA (n = 1,208). There was no significant difference in the incidence of death and gastrointestinal bleeding among the 4 subgroups. The prasugrel/DOAC group had significantly lower incidence of MI (OR 0.566, 95% CI 0.348-0.921). The incidence of ischemic stroke was significantly lower in the prasugrel/DOAC group (OR 0.701, 95% CI 0.502-0.979), and significantly higher in the clopidogrel/VKA group (OR 1.680, 95% CI 1.273-2.216). Need for blood transfusion was less frequent in the prasugrel/DOAC group (OR 0.729, 95% CI 0.598-0.890), and more frequent in both the clopidogrel/VKA group (OR 1.424, 95% CI 1.187-1.708) and the prasugrel/VKA group (OR 1.633, 95% CI 1.367-1.950). Combination of low-dose prasugrel and DOAC was associated with lower incidence of MI, ischemic stroke, and blood transfusion. Low-dose prasugrel may be feasible as part of triple therapy in patients undergoing PCI.

Background: Coronary computed tomography angiography (CTA) can be used to quantitatively and qualitatively evaluate the characteristics of perivascular adipose tissue (PVAT), including PVAT volume and perivascular fat attenuation index (FAI). Moreover, PVAT volume and perivascular FAI on CTA are reportedly high in patients with vasospastic angina (VSA); however, previous investigations have focused on the patient rather than vessel-level analyses. Therefore, this study aimed to assess the relationship between coronary vasospasm and PVAT or FAI by using coronary CTA at the vessel level. Methods: This retrospective study included 51 patients who underwent intracoronary acetylcholine (ACh) provocation testing for the VSA diagnosis and coronary CTA within a 6-month interval. A total of 125 coronary vessels were evaluated. PVAT and FAI on CTA were quantitatively evaluated. The primary interest of the present study was to determine the relationship between PVAT volume and FAI- and ACh-induced coronary vasospasms at the vessel level. Results: Of the 51 patients, 24 (47.1%) had a positive ACh provocation test (VSA), with 40 of 125 (32.0%) vessels having ACh-induced vasospasm. Obstructive epicardial coronary artery disease was observed in 12 vessels (9.6%). No significant differences in PVAT volume or FAI were identified between vessels with and without ACh-induced vasospasms. Similarly, PVAT volume and FAI did not differ significantly in the individual major coronary arteries between patients with and without positive ACh provocation test results. In contrast, FAI was significantly higher in vessels with obstructive coronary artery disease than in those without. Conclusions: In patients undergoing intracoronary ACh provocation tests and coronary CTA, no significant association was observed between ACh-induced coronary vasospasm and PVAT volume or FAI at the vessel level. However, FAI significantly increased in vessels with epicardial coronary disease.

ObjectivesWe aimed to investigate the regional variations in the number of interventions and surgeries for peripheral artery disease (PAD) and explore the major determinants of the variations.DesignCross-sectional study.SettingThe Japanese Ministry of Health, Labour and Welfare National Database and Diagnostic Procedure Combination database in 2018.DataThe rates of endovascular treatment (EVT), bypass surgery per 100 000 individuals in the population were calculated for all 47 prefectures in Japan. The total annual changes in the rates of EVT and bypass surgery in Japan from 2012 to 2019 were calculated.AnalysisA linear regression model was developed with rates of EVT and bypass surgery as dependent variables and regional medical supply in each prefecture as explanatory variables. These regional factors included the rate of percutaneous coronary intervention (PCI) for angina, the numbers of cardiovascular specialists, specialists in cardiac surgery, interventional radiology (IVR) training facilities and cardiovascular surgery training facilities, per 100 000, respectively.ResultsThere was a 5.7-fold difference (143 and 25 per 100 000 individuals aged ≥40 years) in the highest and lowest EVT rates. The highest and lowest rates of bypass surgery were 34 and <10 per 100 000 individuals aged ≥40 years in a prefecture, respectively. The rate of PCI contributed most significantly positive to the rate of EVT (p<0.001). However, the numbers of IVR and cardiovascular surgery training facilities had significant positive and negative relationships, respectively, with the rate of EVT. The numbers of specialists in cardiac surgery and cardiovascular specialists had significant positive (p=0.01) and negative (p=0.01) correlations, respectively, with the rate of bypass surgery.ConclusionsConsiderable regional variations in the rates of revascularisation for PAD were found. Unbalanced presence of medical resources, preference of suppliers and the training system had larger effects on the regional variation in Japan.