Perivascular fat attenuation index measured by coronary computed tomography angiography as a tool for assessment of ischaemia-causing lesions: a case report.

BACKGROUND: It can be difficult to diagnose coronary artery disease in patients with acute coronary syndrome if coronary angiography does not identify stenosis. Coronary inflammation, which can contribute to the pathogenesis of coronary artery disease and acute coronary syndrome, can be quantified using the perivascular fat attenuation index. Furthermore, the perivascular fat attenuation index is a marker for all-cause mortality, cardiac-related mortality and impaired global coronary flow reserve. CASE PRESENTATION: Here we report a case of a patient presenting with symptoms of acute coronary syndrome. The patient had hypokinesis of the lateral-posterior wall of the left ventricle, decreased myocardial perfusion in the posterior wall myocardium and elevated myocardial troponin-T and creatine phosphokinase levels. However, coronary computed tomography angiography did not identify arterial stenosis. The patient did have an increased perivascular fat attenuation index, indicating coronary inflammation. Moreover, the fat attenuation index was higher around the left circumflex artery than around the right coronary artery or left anterior descending artery. Intravascular ultrasonography identified an intramural haematoma, leading to a diagnosis of type 3 spontaneous coronary artery dissection in the left circumflex artery. CONCLUSIONS: Perivascular fat attenuation index may be a useful tool to help identify and localise disease-causing lesions, and to direct further testing to confirm a diagnosis of spontaneous coronary artery dissection in acute coronary syndrome patients without significant arterial stenosis.

Spectral imaging with dual-layer spectral detector computed tomography for the detection of perfusion defects in acute coronary syndrome.

To evaluate the feasibility of spectral imaging with dual-layer spectral detector computed tomography (CT) for the diagnosis of acute coronary syndrome. We identified 30 consecutive patients who underwent cardiac CT using dual-layer spectral detector CT and were diagnosed with acute ischemic syndrome by an invasive coronary angiography. We reconstructed 120 kVp images and generated virtual monochromatic images (VMIs; 40-200 keV in 10 keV increments), iodine concentration maps, and effective atomic number (Z) maps. We calculated the contrast and contrast-to-noise ratio (CNR) between myocardial normal and hypo-perfusion and chose the VMIs with the best CNR for quantitative analysis. We compared the image noise, contrast, and CNR of 120 kVp images and the best VMIs, CT value, iodine concentration, and effective Z between myocardial normal and hypo-perfusion with the paired t test. As the X-ray energy decreased, venous attenuation, contrast, and CNR gradually increased. The 40 keV image yielded the best CNR. The contrast and CNR between myocardial normal and hypo-perfusion were significantly higher in 40 keV images than those in 120 kVp images. The iodine concentration and the effective Z were significantly higher in normal myocardium than those in hypo-perfused myocardium. Spectral imaging with dual-layer spectral detector CT is a feasible technique to detect the hypo-perfused area of acute ischemic syndrome.

Monotherapy With Prasugrel After Dual-Antiplatelet Therapy for Japanese Percutaneous Coronary Intervention Patients With High Bleeding Risk　- A Prospective Cohort Study (PENDULUM mono Study).

BACKGROUND: The risks of bleeding and cardiovascular events in high bleeding risk (HBR) Japanese patients undergoing percutaneous coronary intervention (PCI) while receiving single-antiplatelet therapy (SAPT) remains unknown. We aimed to evaluate the frequency of bleeding and cardiovascular events associated with prasugrel monotherapy after short-term dual-antiplatelet therapy (DAPT) in Japanese HBR patients after PCI.Methods and Results:The PENDULUM mono study was a multicenter, non-interventional, prospective registry (n=1,173). The primary endpoint was the cumulative incidence of clinically relevant bleeding (CRB; Bleeding Academic Research Consortium types 2, 3, and 5) from 1 to 12 months after PCI. Secondary endpoints included major adverse cardiac and cerebrovascular events (MACCE). The proportion of patients who received prasugrel monotherapy at 12 months after PCI was 79.7%, and no cases of stent thrombosis were observed among these patients. The cumulative incidence of CRB was 3.2% from 1 to 12 months after PCI; that of MACCE was 3.8%. Severe anemia, chronic kidney disease, oral anticoagulant use at discharge, and heart failure were significantly associated with CRB. CONCLUSIONS: Among HBR patients undergoing PCI who were not suitable for concomitant aspirin and were scheduled for prasugrel monotherapy, most patients were on prasugrel monotherapy after DAPT. Cumulative incidences of CRB and MACCE after periprocedural period were 3.2% and 3.8%, respectively, and no cases of stent thrombosis were reported. SAPT might be a suitable alternative to DAPT.

Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial.

Importance: Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. Objective: To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. Design, Setting, and Participants: Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. Interventions: Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. Results: Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, -1.34% [95% CI, -2.57% to -0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, -0.55% [95% CI, -1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, -1.13% [95% CI, -1.84% to -0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority). Conclusions and Relevance: Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02619760.

Assessment of Myocardial Viability in Chronic Myocardial Infarction Using the Dual-Energy Computed Tomography Myocardial Extracellular Volume Fractionation Technique: A Case Report.

Assessment of myocardial viability in patients with myocardial infarction is critical to identify residual ischemic tissue in areas of reduced function and to determine the need for revascularization. We present the case of an 80-year-old man with chest pain and a history of hypertension. Initial evaluation revealed abnormal electrocardiogram findings, and subsequent studies suggested chronic anteroseptal myocardial infarction with reduced cardiac function. Dual-energy cardiac computed tomography was performed to evaluate the coronary arteries and myocardium. Late iodine enhancement images obtained by dual-energy computed tomography showed mixed plaques and severe proximal left anterior descending artery stenosis. Conventional late iodine enhancement imaging was inconclusive, prompting extracellular volume fraction analysis using iodine density imaging. Extracellular volume fraction assessment indicated viable anterior myocardium, leading to successful coronary revascularization. Follow-up demonstrated improved wall motion and ejection fraction. Our study highlights the utility of late iodine enhancement with dual-energy computed tomography in assessing myocardial viability as a noninvasive alternative to magnetic resonance imaging, particularly in patients with contraindications to magnetic resonance imaging. This approach aids in treatment planning, evaluation of efficacy and determination of prognosis in cases of ischemic heart disease.

The 30-second chair stand test (CS30) as a predictor of exercise tolerance in elderly individuals (≥75 years) with stage A/B heart failure.

Background: In Japan, the number of very elderly individuals with heart failure (HF) is on the rise. One indicator of HF stage progression is a decrease in exercise tolerance (ET). While peak oxygen uptake (peak VO2) determined by cardiopulmonary exercise testing (CPX) is the gold standard for ET assessment, the wide-scale applicability of CPX is constrained owing to expensive equipment and challenges in this population. The 30-second chair stand test (CS30), a simple and quick alternative, is widely used among community-dwelling elderly individuals. The objective of this study was to investigate whether CS30 is a predictor of ET in elderly individuals with stage A/B HF. Methods: Of 748 outpatients aged 75 years and over who visited our center between March 2021 and December 2022, 493 patients (296 males and 197 females) were included in this study. CS30 was measured using a seat height of 40 cm, and peak VO2 was assessed using CPX. Results: The findings showed a statistically significant positive association between CS30 and peak VO2 for both males and females (males: ß = 0.255, 95 % CI = 0.102-0.407; females: ß = 0.282, 95 % CI = 0.043-0.521). Receiver operating characteristic (ROC) analyses showed moderate accuracy of CS30 in predicting low ET in both sexes (males AUC = 0.740, 95 % CI = 0.640-0.841, p < 0.001; females AUC = 0.725, 95 % CI = 0.644-0.807, p < 0.001). The cut-off values of CS30 were established as 18 times for males and 16 times for females. Conclusions: CS30 is a potentially convenient method for estimating current ET in older adults, providing a feasible alternative to CPX.

PCSK9 inhibition with orally administered NNC0385-0434 in hypercholesterolaemia: a randomised, double-blind, placebo-controlled and active-controlled phase 2 trial.

BACKGROUND: Currently available injectable drugs that target proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce serum LDL cholesterol and improve cardiovascular outcomes. This phase 2 study assessed NNC0385-0434, an oral PCSK9 inhibitor, in individuals receiving oral lipid-lowering therapy. METHODS: In this randomised, double-blind, placebo-controlled and active-controlled trial, 42 research sites across seven countries (Belgium, Germany, Greece, Japan, the Netherlands, Poland, and the USA) recruited individuals with established atherosclerotic cardiovascular disease (aged ≥40 years) or at high risk of atherosclerotic cardiovascular disease (aged >50 years), who had LDL cholesterol concentration of at least 1·8 mmol/L and were receiving maximum tolerated statins and stable lipid-lowering therapy. The study randomly allocated participants (3:1) with an interactive web response system to receive either NNC0385-0434 (15 mg, 40 mg, or 100 mg) once a day co-formulated with the oral absorption enhancer sodium N-[8-(2-hydroxybenzoyl)amino] caprylate (500 mg); placebo; or open-label evolocumab (140 mg) every 2 weeks administered subcutaneously. Blinding was performed within each dose level. The primary endpoint was percentage change from baseline in LDL cholesterol measured by ß quantification at week 12. All randomly assigned participants received at least one dose of treatment and were included in both safety and efficacy analyses. The trial was registered on ClinicalTrials.gov, NCT04992065, and is completed. FINDINGS: Between Aug 16, 2021, and Jan 28, 2022, we randomly assigned 267 patients to one of the three NNC0385-0434 dose cohorts (n=53 per cohort), matching placebo (n=54), or open-label evolocumab (n=54). The study population comprised 82 (31%) women and 185 (69%) men; mean age was 64·3 years (SD 9·0). Baseline mean LDL cholesterol concentration was 2·7 mmol/L (SD 0·8). Treatment with NNC0385-0434 resulted in reductions in LDL cholesterol from baseline to week 12, of 32·0 percentage points (95% CI 20·9 to 43·0) in the 15 mg cohort, 44·9 percentage points (33·8 to 56·0) in the 40 mg cohort, and 61·8 percentage points (50·7 to 72·9) in the 100 mg cohort, compared with the placebo group (p<0·0001 for each). Patients treated with evolocumab had similar LDL cholesterol reductions (59·6% [SE 4·1] decrease from baseline) to patients receiving NNC0385-0434 100 mg (56·2% [4·0]). The estimated treatment difference between NNC0385-0434 100 mg and evolocumab 140 mg was 3·4 percentage points [95% CI -7·8 to 14·7]. The most frequently reported adverse event was COVID-19, which affected 31 (12%) of 267 patients, with similar numbers across treatment groups. Investigative sites reported gastrointestinal disorders as the most frequent treatment-related adverse event (26 patients and 35 events total in the three NNC0385 cohorts and one patient and one event each in the placebo and evolocumab cohorts). No deaths or treatment-related serious adverse events occurred. INTERPRETATION: This study showed excellent 12-week LDL cholesterol lowering efficacy and good patient tolerance of an oral PCSK9 inhibitor, NNC0835-0434, similar to an injectable drug. However, the sponsor chose to discontinue further development of NNC0835-0434 due to portfolio considerations. FUNDING: Novo Nordisk.

Clopidogrel vs Aspirin Monotherapy Beyond 1 Year After Percutaneous Coronary Intervention.

BACKGROUND: It remains unclear whether clopidogrel is better suited than aspirin as the long-term antiplatelet monotherapy following dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). OBJECTIVES: This study compared clopidogrel monotherapy following 1 month of DAPT (clopidogrel group) with aspirin monotherapy following 12 months of DAPT (aspirin group) after PCI for 5 years. METHODS: STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy 2) is a multicenter, open-label, adjudicator-blinded, randomized clinical trial conducted in Japan. Patients who underwent PCI with cobalt-chromium everolimus-eluting stents were randomized in a 1-to-1 fashion either to clopidogrel or aspirin groups. The primary endpoint was a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis) or major bleeding (TIMI major or minor bleeding). RESULTS: Among 3,005 study patients (age: 68.6 ± 10.7 years; women: 22.3%; acute coronary syndrome: 38.3%), 2,934 patients (97.6%) completed the 5-year follow-up (adherence to the study drugs at 395 days: 84.7% and 75.9%). The clopidogrel group compared with the aspirin group was noninferior but not superior for the primary endpoint (11.75% and 13.57%, respectively; HR: 0.85; 95% CI: 0.70-1.05; Pnoninferiority < 0.001; Psuperiority = 0.13), whereas it was superior for the cardiovascular outcomes (8.61% and 11.05%, respectively; HR: 0.77; 95% CI: 0.61-0.97; P = 0.03) and not superior for major bleeding (4.44% and 4.92%, respectively; HR: 0.89; 95% CI: 0.64-1.25; P = 0.51). By the 1-year landmark analysis, clopidogrel was numerically, but not significantly, superior to aspirin for cardiovascular events (6.79% and 8.68%, respectively; HR: 0.77; 95% CI: 0.59-1.01; P = 0.06) without difference in major bleeding (3.99% and 3.32%, respectively; HR: 1.23; 95% CI: 0.84-1.81; P = 0.31). CONCLUSIONS: Clopidogrel might be an attractive alternative to aspirin with a borderline ischemic benefit beyond 1 year after PCI.

Evaluation of coronavirus-2019-related arterial thrombosis in noncontrast spectral computed tomography with electron density imaging.

Thrombosis can be associated with coronavirus disease 2019 infection. Computed tomography is essential for the diagnosis of pneumonia in these patients and conventionally contrast agents are required for the assessment of thrombus. In this study, we report a patient with coronavirus disease 2019 who was diagnosed with thrombosis using spectral noncontrast computed tomography with electron density imaging. The patient was a 76-year-old man who presented with a 2-day history of lower-leg pain. Tachycardia and atrial fibrillation were identified, with elevated D-dimer, N-terminal pro-B-type natriuretic peptide, creatine kinase, and C-reactive protein levels. Polymerase chain reaction testing for severe acute respiratory syndrome coronavirus-2 was positive. Conventional computed tomography showed pulmonary changes consistent with coronavirus disease 2019 and no changes in the aorta, but spectral computed tomography with electron density imaging of noncontrast computed tomography showed a thrombus in the right external iliac artery. Spectral computed tomography with electron density imaging provides more data compared with conventional computed tomography and has the potential to depict thrombus without the use of contrast media.

SYNTAX Score and 1-Year Outcomes in the OPTIVUS-Complex PCI Study Multivessel Cohort.

BACKGROUND: The optimal revascularization strategy in patients with multivessel disease and intermediate SYNTAX score (SS) has not been fully elucidated. This study aimed to investigate the clinical outcomes of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) stratified by SS. METHODS: This was a substudy of the OPTIVUS-Complex PCI study Multivessel Cohort, which aimed to meet the prespecified criteria for optimal stent expansion after IVUS-guided PCI. A total of 1,005 patients were divided into 3 groups according to SS: low, ≤22; intermediate, 23 to 32; and high, ≥33. The primary end points were major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of death, myocardial infarction, stroke, or coronary revascularization. RESULTS: The cumulative 1-year incidence of the primary end point was significantly higher in patients with high SS than in those with intermediate or low SS (25.0%, 10.9%, and 9.5%, respectively; p = 0.003). This difference was mainly caused by the incidence of coronary revascularization. In the multivariable Cox proportional hazards models, the excess risk of patients with high versus low SS remained significant for the primary end point (hazard ratio 3.19, 95% confidence interval 1.65 to 6.16, p <0.001), whereas the excess risk of patients with intermediate versus low SS was no longer significant (hazard ratio 1.20, 95% confidence interval 0.72 to 2.01, p = 0.46). CONCLUSIONS: After IVUS-guided multivessel PCI, patients with intermediate SS had a similar 1-year risk of MACCE to that of patients with low SS, whereas patients with high SS had a higher 1-year risk of MACCE than those with low SS.

Clopidogrel Monotherapy After 1-Month DAPT in Patients With High Bleeding Risk or Complex PCI.

Background: High bleeding risk (HBR) and complex percutaneous coronary intervention (PCI) are major determinants for dual antiplatelet therapy (DAPT) duration. Objectives: The aim of this study was to evaluate the effects of HBR and complex PCI on short vs standard DAPT. Methods: Subgroup analyses were conducted on the basis of Academic Research Consortium-defined HBR and complex PCI in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Verulam's-Eluting Cobalt-Chromium Stent-2) Total Cohort, which randomly compared clopidogrel monotherapy after 1-month DAPT with 12-month DAPT with aspirin and clopidogrel after PCI. The primary endpoint was the composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (Thrombolysis In Myocardial Infarction [TIMI] major or minor) endpoints at 1 year. Results: Regardless of HBR (n = 1,893 [31.6%]) and complex PCI (n = 999 [16.7%]), the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (HBR, 5.01% vs 5.14%; non-HBR, 1.90% vs 2.02%; P interaction = 0.95) (complex PCI, 3.15% vs 4.07%; noncomplex PCI, 2.78% vs 2.82%; P interaction = 0.48) and for the cardiovascular endpoint (HBR, 4.35% vs 3.52%; and non-HBR, 1.56% vs 1.22%; P interaction = 0.90) (complex PCI, 2.53% vs 2.52%; noncomplex PCI, 2.38% vs 1.86%; P interaction = 0.53), while it was lower for the bleeding endpoint (HBR, 0.66% vs 2.27%; non-HBR, 0.43% vs 0.85%; P interaction = 0.36) (complex PCI, 0.63% vs 1.75%; noncomplex PCI, 0.48% vs 1.22%; P interaction = 0.90). The absolute difference in the bleeding between 1- and 12-month DAPT was numerically greater in patients with HBR than in those without HBR (-1.61% vs -0.42%). Conclusions: The effects of 1-month DAPT relative to 12-month DAPT were consistent regardless of HBR and complex PCI. The absolute benefit of 1-month DAPT over 12-month DAPT in reducing major bleeding was numerically greater in patients with HBR than in those without HBR. Complex PCI might not be an appropriate determinant for DAPT durations after PCI. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498).

Aortic calcification is associated with coronary artery calcification and is a potential surrogate marker for ischemic heart disease risk: A cross-sectional study.

Coronary artery calcification, an established marker of atherosclerotic plaque burden associated with increased risk of coronary artery disease, is routinely evaluated using electron beam computerized tomography or multidetector computed tomography (CT). However, aortic calcification, which is also a risk factor for adverse cardiac events, is not frequently assessed, despite being easily detected via standard chest radiography. We therefore sought to clarify the association between aortic calcification and significant coronary artery calcification to determine the feasibility of performing chest radiography to evaluate the risk of future cardiovascular events. Data from 682 consecutive patients who underwent cardiac CT scanning at our institution from May to September 2012 were included in this cross-sectional analysis. Electrocardiographic-gated CT was used to qualitatively evaluate calcification in 6 aortic segments. Cardiac contrast-ehnanced CT was performed to identify significant calcification of the coronary artery. Calcification was quantified by calculating the Agatston score, and the relationship between significant coronary artery calcification and calcification at each aortic site was evaluated. Among the aortic sites, calcification was most commonly observed in the aortic arch (77.4% of patients). Significant coronary artery calcification was observed in 267 patients (39.1%). Calcification in the ascending aorta, aortic arch, descending aorta, abdominal aorta, and aortic valve were significantly associated with the presence of coronary artery calcification after adjustment for cardiovascular risk factors and statin use (odds ratios [95% confidence intervals] 4.21 [2.55, 6.93], 1.65 [1.01, 2.69], 2.14 [1.36, 3.36], 2.87 [1.83, 4.50], and 3.32 [2.02, 5.46], respectively). Mitral valve calcification was weakly but nonsignificantly associated with coronary artery calcification (odds ratio 1.84 [95% confidence interval 0.94, 3.62]). Calcification of each aortic segment assessed was significantly associated with Agatston score ≥ 100. Aortic calcification was associated with coronary artery calcification. Calcification of the aortic arch, which can be readily detected by routine chest radiography, may be associated with coronary artery calcification and its assessment should therefore be considered to identify patients at increased risk of cardiovascular events. Further studies are warranted to confirm these findings.

Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure.

Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration: Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL: https://www.umin.ac.jp/ctr/index.htm .

Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction.

AIMS: Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). CONCLUSIONS: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Percutaneous Coronary Intervention: From the STOPDAPT-2 Total Cohort.

BACKGROUND: The benefit of clopidogrel monotherapy after 1-month dual antiplatelet therapy (DAPT) compared with 12-month DAPT with aspirin and clopidogrel was demonstrated in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2), but not in the STOPDAPT-2 acute coronary syndrome (ACS); however, both trials were underpowered based on the actual event rates. METHODS: We obtained the prespecified pooled population of 5997 patients as the STOPDAPT-2 total cohort (STOPDAPT-2: N=3009/STOPDAPT-2 ACS: N=2988; ACS: N=4136/chronic coronary syndrome [CCS]: N=1861), comprising 2993 patients assigned to 1-month DAPT followed by clopidogrel monotherapy, and 3004 patients assigned to 12-month DAPT with aspirin and clopidogrel after percutaneous coronary intervention. The primary end point was the composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or any stroke) or bleeding (Thrombolysis in Myocardial Infarction major/minor) end points at 1 year. RESULTS: One-month DAPT was noninferior to 12-month DAPT for the primary end point (2.84% versus 3.04%; hazard ratio [HR], 0.94 [95% CI, 0.70-1.27]; Pnoninferiority=0.001; Psuperiority=0.68). There was no significant risk-difference for the cardiovascular end point between the 1- and 12-month DAPT groups (2.40% versus 1.97%; HR, 1.24 [95% CI, 0.88-1.75]; Pnoninferiority=0.14; Psuperiority=0.23). There was a lower risk of the bleeding end point with 1-month DAPT relative to 12-month DAPT (0.50% versus 1.31%; HR, 0.38 [95% CI, 0.21-0.70]; Psuperiority=0.002). One-month DAPT relative to 12-month DAPT was associated with a lower risk for major bleeding regardless of ACS or CCS (ACS: HR, 0.46 [95% CI, 0.23-0.94]; P=0.03, and CCS: HR, 0.26 [95% CI, 0.09-0.79]; P=0.02; Pinteraction=0.40), while it was associated with a numerical increase in cardiovascular events in ACS patients, but not in CCS patients, although not statistically significant and without interaction (ACS: HR, 1.50 [95% CI, 0.99-2.27]; P=0.053, and CCS: HR, 0.74 [95% CI, 0.38-1.45]; P=0.39; Pinteraction=0.08). CONCLUSIONS: Clopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT with aspirin and clopidogrel had a benefit in reducing major bleeding events without being associated with increase in cardiovascular events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT02619760, NCT03462498.

Longitudinal effect of myocardial fat deposition on left ventricular diastolic function: a retrospective cohort study.

There is a known correlation between myocardial steatosis and heart function, but it is unclear how left ventricular diastolic function worsens over time in the myocardial steatosis setting. We sought to investigate whether intramyocardial fat deposition affects diastolic function over time. This was a retrospective analysis of patients who had undergone 1-3 echocardiography assessments between April 2011 and April 2017. Patients were divided into two groups: those with the presence of myocardial fat deposition in the left ventricular myocardium (assessed by having tissue within any 10-mm2 region with computed tomography values between - 190 and - 30 Hounsfield units; + MF), and those with absence of deposition not meeting the threshold (- MF). The rates of change of the standard early diastolic mitral annulus velocity (e') and the transmitral early peak velocity (E)/e' ratio at the second and third echocardiograph assessments were calculated relative to baseline. In total, 125 patients were eligible (+ MF, n = 39; - MF, n = 86) for inclusion. Compared with the - MF group, e' was significantly lower and E/e' was significantly higher in the + MF group at each scan timepoint, even when adjusted for body mass index and sex. A significant average decrease in e' and increase in E/e' was also observed in the + MF group across all scans compared with the - MF group. Myocardial steatosis was associated with an acceleration of decreased left ventricular diastolic function over time.

Influence of CYP2C19 genotypes for the effect of 1-month dual antiplatelet therapy followed by clopidogrel monotherapy relative to 12-month dual antiplatelet therapy on clinical outcomes after percutaneous coronary intervention: a genetic substudy from the STOPDAPT-2.

The ultra-short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy might be promising after percutaneous coronary intervention (PCI). However, CYP2C19 loss-of-function (LOF) alleles have been reported to diminish the effect of clopidogrel, and clopidogrel monotherapy has a concern about the increased ischemic risk for patients with such alleles. STOPDAPT-2 is the multicenter prospective open-label, but adjudicator-blinded randomized control study comparing 1-month DAPT followed by clopidogrel monotherapy with the standard 12-month DAPT after PCI with cobalt-chromium everolimus-eluting stents. Among the participants of STOPDAPT-2, selected patients participated in a substudy of the CYP2C19 gene test. Patients with two CYP2C19*2 or *3 alleles were defined as the poor metabolizer (PM), one allele as the intermediate metabolizer (IM), and no allele as the extensive metabolizer (EM). The primary endpoint was the composite of cardiovascular and bleeding events, as defined in STOPDAPT-2. Among 750 (24.9%) patients with known CYP2C19 genotypes, 129 (17.2%) were PM, 367 (49.0%) were IM, and 254 (33.9%) were EM. The hazard ratios of 1-month DAPT relative to 12-month DAPT for the primary endpoint in PM, IM, and EM strata were 0.66 (95% CI 0.11-3.94), 1.94 (95% CI 0.60-6.31), and 0.21 (95% CI 0.02-1.78), respectively (P interaction = 0.17), and those for cardiovascular composite endpoint were 1.00 (95% CI 0.14-7.10), 6.10 (95% CI 0.75-49.55), and 0.26 (95% CI 0.03-2.34), respectively (P interaction = 0.12). In conclusion, for the selected patients in STOPDAPT-2 trial, CYP2C19 LOF alleles had no significant, consistent interaction with the effect of 1-month DAPT relative to 12-month DAPT for clinical outcomes, although the study was overtly underpowered. TRIAL REGISTRY: STOPDAPT-2 ClinicalTrials.gov number, NCT02619760.