A case of hyperchylomicronemia associated with GPIHBP1 autoantibodies and fluctuating thyroid autoimmune disease.

Recent studies have reported that patients with autoimmune hyperchylomicronemia caused by glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) autoantibodies are associated with rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Hashimoto's thyroiditis, Basedow's disease, and immune thrombocytopenia. We report a rare case of hyperchylomicronemia due to GPIHBP1 autoantibodies and fluctuating thyroid autoimmune disease. A 28-year-old woman, diagnosed with Hashimoto's thyroiditis at 26 years of age, started taking 50 µg/day of levothyroxine sodium. She had an episode of acute pancreatitis at 27 years of age; her serum triglyceride (TG) level was 1291 mg/dL at that time. The patient was referred to our hospital because her hyperchylomicronemia (hypertriglyceridemia) did not improve on treatment with pemafibrate and eicosapentaenoic acid (EPA). Serum total cholesterol and TG levels were 237 mg/dL and 2535 mg/dL, respectively, while plasma pre-heparin lipoprotein lipase (LPL) mass was 15 ng/mL (26.5-105.5 ng/mL). We diagnosed her as Basedow's disease based on autoimmune antibodies and ultrasound examination. Targeted exome sequencing revealed no pathogenic variants in the LPL or GPIHBP1 genes. The serum GPIHBP1 autoantibody level was 686.0 U/mL (<58.4 U/mL) and GPIHBP1 mass was 301.9 pg/mL (570.6-1625.6 pg/mL). The patient showed hyperchylomicronemia during periods of hypothyroidism and hyperthyroidism, whereas GPIHBP1 autoantibodies were positive during episode of hyperchylomicronemia but negative during periods of normal TG levels. Based on these findings, the patient was diagnosed with hyperchylomicronemia due to GPIHBP1 autoantibodies and treated with rituximab. GPIHBP1 autoantibodies remained undetectable and TG levels were controlled at approximately 200 mg/dL.

Radial versus femoral access in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: A propensity-matched analysis from real-world data of the K-ACTIVE registry.

BACKGROUND: The access site for primary percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (STEMI) recently shifted from femoral to radial. However, few real-world data on Japanese patients exist. METHODS: To elucidate the clinical selection and impact of the access site in STEMI patients, we analyzed a Japanese observational prospective multicenter registry of acute myocardial infarction (K-ACTIVE: Kanagawa ACuTe cardIoVascular rEgistry) in 2015 to 2021. Data were analyzed in the entire population and a propensity score-matched population adjusted for confounding factors. Major adverse cardiac event (MACE) was defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Bleeding Academic Research Consortium (BARC) type 3 or 5 was used to assess bleeding events. MACE plus BARC type 3 or 5 bleeding were considered composite events. Clinical outcomes were followed for 30 days. RESULTS: The 6802 STEMI patients included 4786 patients with radial access (70.3 %) and 2016 with femoral access (29.7 %). Femoral access tended to be selected for more severe conditions than radial access. The median door-to-device time in the radial access group was significantly shorter than the femoral access group in the entire population (75 min versus 79 min, p < 0.01). After propensity score matching (each group, n = 1208), the incidence of MACE tended to be lower in the radial access group [risk ratio (RR) 0.83, 95 % confidence interval (CI) 0.63-1.09, p = 0.17]. The incidence of BARC 3 or 5 bleeding was significantly less in the radial access group (RR 0.47, 95%CI 0.23-0.97, p = 0.04). The incidence of composite events was significantly less in the radial access group (RR 0.74, 95%CI 0.57-0.96, p = 0.02). CONCLUSION: In STEMI patients undergoing primary PCI, in comparison to femoral access, radial access reduced composite events in the entire population and the matched population, through a reduction in MACE and BARC 3 or 5 bleeding.

Second mRNA Vaccination of COVID-19 in a Patient Who Developed Pericarditis after the First Vaccination.

The coronavirus infection 2019 (COVID-19) pandemic has led to the development of mRNA vaccines with proven efficacy. However, it remains unclear whether patients who developed pericarditis after the first COVID-19 mRNA would be fit to receive the second vaccination. Herein, we present the case of a 64-year-old man who visited our emergency department with substernal chest discomfort that began 4 days after his first mRNA COVID-19 vaccination. Acute pericarditis was diagnosed based on symptoms and ST-segment elevation on an electrocardiogram. Chest pain improved 2 days after treatment.Since there are no guidelines on whether to administer an additional vaccination to a patient who developed pericarditis after the initial vaccination, we considered whether or not to administer the additional vaccination. We informed the patient about the risks and benefits and decided to administer the second dose. He did not experience any major adverse reactions. The indications for the second vaccination need to be thoroughly considered.

Whole Exome Sequencing Insufficient for a Definitive Diagnosis of a Patient with Compound Heterozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder, and a genetic analysis is important to make a definitive diagnosis. A comprehensive genetic analysis using next generation sequencing (NGS) and whole exome sequencing (WES) is feasible. However, the application of NGS in the assessment of genomic structural variations is generally limited, and a substantial number of control samples are needed for such assessments. Thus, NGS alone is unlikely to detect genomic structural variations in a "singleton." We present the case of a patient with compound HeFH (heterozygous FH), whose causative mutations in the LDLR gene could not be identified by WES, necessitating the application of the multiplex ligation-dependent probe amplification (MLPA) technique.

A Japanese Dose of Prasugrel versus a Standard Dose of Clopidogrel in Patients with Acute Myocardial Infarction from the K-ACTIVE Registry.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin plus P2Y12 inhibitor is used as a standard therapy for patients with acute myocardial infarction (AMI) treated with drug-eluting stents (DESs). In Japan, clopidogrel was the major P2Y12 inhibitor used for a decade until the new P2Y12 inhibitor, prasugrel, was introduced. Based on clinical studies considering Japanese features, the set dose for prasugrel was reduced to 20 mg as a loading dose (LD) and 3.75 mg as a maintenance dose (MD); these values are 60 and 10 mg, respectively, globally. Despite this dose discrepancy, little real-world clinical data regarding its efficacy and safety exist. METHODS: From the K-ACTIVE registry, based on the DAPT regimen, patients were divided into a prasugrel group and a clopidogrel group. The ischemic event was a composite of cardiovascular death, non-fatal MI, and non-fatal stroke. The bleeding event was type 3 or 5 bleeding based on the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: Substantially more patients were prescribed prasugrel (n = 2786) than clopidogrel (n = 890). Clopidogrel tended to be selected over prasugrel in older patients with numerous comorbidities. Before adjustments were made, the cumulative incidence of ischemic events at 1 year was significantly greater in the clopidogrel group than in the prasugrel group (p = 0.007), while the cumulative incidence of bleeding events at 1 year was comparable between the groups (p = 0.131). After adjustments were made for the age, sex, body weight, creatine level, type of AMI, history of MI, approach site, oral anticoagulation therapy, presence of multivessel disease, Killip classification, and presence of intra-aortic balloon pumping, both ischemic and bleeding events became comparable between the groups. CONCLUSION: A Japanese dose of prasugrel was commonly used in AMI patients in the real-world database. Both the prasugrel and clopidogrel groups showed comparable rates of 1 year ischemic and bleeding events.

Impact of atrial fibrillation and the clinical outcomes in patients with acute myocardial infarction from the K-ACTIVE registry.

BACKGROUND: The clinical incidence and impact of atrial fibrillation (AF) in Japanese acute myocardial infarction (AMI) patients is not fully understood. METHODS: To elucidate the clinical incidence and impact of AF on in-hospital mortality in AMI patients, we analyzed a Japanese observational prospective multicenter registry of acute myocardial infarction (K-ACTIVE: Kanagawa ACuTe cardIoVascular rEgistry), which spans 2015 to 2019. A major adverse cardiac event (MACE) was defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. For assessing bleeding events, Bleeding Academic Research Consortium (BARC) type 3 or 5 was used. MACE plus BARC type 3 or 5 bleeding were considered as composite events. The clinical outcomes were followed for 1 year. RESULTS: The total of 5059 patients included 531 patients with AF (10.5%) and 4528 patients with sinus rhythm (SR; 89.5%). AF patients were significantly older and tended to have more comorbidities than SR patients. Oral anticoagulation therapy (OAC) was used in 44% of AF patients while single antiplatelet therapy was selected for 52% of patients with OAC. Crude in-hospital mortality was significantly greater in AF patients than in SR patients (10.4%, 5.0%, respectively, p < 0.01). The multivariate analysis was adjusted for age, sex, diabetes, hypertension, hemodialysis, smoking, previous MI, body mass index, Killip classification, out of hospital cardiac arrest, and OAC. In-hospital mortality was still significantly greater in AF patients than in SR patients in the logistic regression analysis [adjusted odds ratio 2.02 (1.31-3.14)]. AF was an independent risk factor for MACE and composite events in the Cox proportional hazards model [adjusted risk ratio (ARR) 1.91 (1.36-2.69), p < 0.01; ARR 1.72 (1.25-2.36), p < 0.01]. In contrast, AF was not an independent risk factor for bleeding [ARR 1.71 (0.79-3.71), p = 0.18]. CONCLUSION: In Japanese AMI patients, AF was often observed and was associated with worse MACE but not worse bleeding.

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) update 2022.

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Interventional and Therapeutics (CVIT) society proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018. Updated guidelines for the management of AMI were published by the European Society of Cardiology (ESC) in 2017 and 2020. Major changes in the guidelines for STEMI patients included: (1) radial access and drug-eluting stents (DES) over bare-metal stents (BMS) were recommended as a Class I indication, (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. In 2020, updated guidelines for Non-ST-Elevation Myocardial Infarction (NSTEMI) patients, the followings were changed: (1) an early invasive strategy within 24 h is recommended in patients with NSTEMI as a Class I indication, (2) complete revascularization in NSTEMI patients without cardiogenic shock is considered as Class IIa recommendation, and (3) in patients with atrial fibrillation following a short period of triple antithrombotic therapy, dual antithrombotic therapy (e.g., DOAC and single oral antiplatelet agent preferably clopidogrel) is recommended, with discontinuation of the antiplatelet agent after 6 to 12 months. Furthermore, an aspirin-free strategy after PCI has been investigated in several trials those have started to show the safety and efficacy. The Task Force on Primary PCI of the CVIT group has now proposed the updated expert consensus document for the management of AMI focusing on procedural aspects of primary PCI in 2022 version.

The impact of pre-hospital 12-lead electrocardiogram and first contact by cardiologist in patients with ST-elevation myocardial infarction in Kanagawa, Japan.

Background pre-hospital 12-lead electrocardiogram (ECG) by emergency medical service (EMS) personnel at the site of first medical contact (FMC) and the physician of first contact both play important roles in managing patients with ST-elevation myocardial infarction (STEMI). However, in Japan, pre-hospital 12-lead ECG is not routinely performed by EMS personnel at the site of FMC and the physician of first contact is not always a cardiologist. Methods from October 2015 to October 2019, 2035 consecutive STEMI patients transported from the field by ambulance were analyzed from the K-ACTIVE registry. Based on the presence (+) or absence (-) of pre-hospital 12-lead ECG / first contact by cardiologist, patients were divided into 4 groups (+/+, +/-, -/+, -/-). Patient characteristics, FMC to door time, door to device time and in-hospital mortality were compared. Results the numbers of patients in each group were as follows (+/+, n = 987; +/-, n = 211; -/+, n = 610; -/-, n = 227). For patient characteristics, there were significant differences in the prevalence of dyslipidemia and the presence of chest pain. The FMC to door time was similar (median value, +/+, 24 min; +/-, 25 min; -/+, 24 min; -/-, 24 min; p = 0.23). The door to device time was the shortest in the +/+ group (median value, +/+, 65 min; +/-, 80 min; -/+, 69 min; -/-, 88 min; p < 0.0001). Crude in-hospital mortality was the highest in the -/- group (+/+, 3.9%; +/-, 2.4%; -/+, 5.8%; -/-, 11.9%; p < 0.0001). After adjustment for age and sex, the adjusted odds ratios for in-hospital mortality were as follows [odds ratio (with 95% confidence interval) +/+, 0.33 [0.19-0.57]; +/-, 0.19 [0.07-0.52]; -/+, 0.49 [0.29-0.86]; -/-, 1 [reference)]. Conclusion pre-hospital 12-lead ECG and the physician of first contact had a significant impact on the door to device time and in-hospital mortality. Continuous efforts should be made to improve acute management of STEMI.

Clinical significance of prehospital 12-lead electrocardiography in patients with ST-segment elevation myocardial infarction presenting with syncope: from a multicenter observational registry (K-ACTIVE study).

Patients with acute myocardial infarction (AMI) presenting with syncope have poor clinical outcomes partly due to a delay in the diagnosis. Although the impact of prehospital 12-lead electrocardiography (PHECG) on the reduction of first medical contact (FMC)-to-device time and subsequent adverse clinical events in patients with AMI has been demonstrated, the impact of PHECG for the patients presenting with syncope remains to be elucidated. This study aimed to explore the impact of PHECG on 30-day mortality in patients with ST-segment elevation myocardial infarction (STEMI) presenting with syncope. From a cohort of multi-center registry [Kanagawa-ACuTe cardIoVascular rEgistry (K-ACTIVE)], a total of 90 consecutive patients with STEMI presenting with syncope were included. The 30-day mortality were compared between patients with PHECG (PHECG group, n = 25) and those without PHECG (non-PHECG group, n = 65). There was no significant difference in the baseline clinical characteristics between the 2 groups. FMC-to-device time was significantly shorter in the PHECG group than in the non-PHECG group (122 [86, 128] vs. 131 [102, 153] min, p = 0.03) due to the shorter door-to-device time. Thirty-day mortality was significantly lower in the PHECG group than in the non-PHECG group (16.0 vs. 44.6%, p = 0.03). In conclusion, PHECG was associated with shorter FMC-to-device time and lower 30-day mortality in patients with STEMI presenting with syncope.

A novel risk stratification system "Angiographic GRACE Score" for predicting in-hospital mortality of patients with acute myocardial infarction: Data from the K-ACTIVE Registry.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is the most accurate risk assessment system for acute myocardial infarction (AMI), which was proposed in Western countries. However, it is unclear whether GRACE score is applicable to the present Japanese patients with a high prevalence of emergent percutaneous coronary intervention (PCI) and vasospasm. This study aimed to clarify the usefulness of GRACE risk score for risk stratification of Japanese AMI patients treated with early PCI and to evaluate a novel risk stratification system, "angiographic GRACE score," which is the GRACE risk score adjusted by the information of the culprit coronary artery and its flow at pre- and post-PCI, to improve its predicting availability. METHODS: The subjects were 1817 AMI patients who underwent PCI within 24 h of onset between October 2015 and August 2017 and were registered in Kanagawa Acute Cardiovascular (K-ACTIVE) Registry via survey form. The association between the clinical parameters and in-hospital mortality was investigated. RESULTS: A total of 79 (4.3%) in-hospital deaths were identified. The C-statistics for the in-hospital mortality of the GRACE score was 0.86, which was higher than that of the other conventional risk factors, including age (0.65), systolic blood pressure (0.70), heart rate (0.62), Killip classification (0.77), and serum levels of creatinine (0.68) and peak creatine kinase (0.74). The angiographic GRACE score improved the C-statistics from 0.86 of the original GRACE score to 0.89 (p < 0.05). In the setting of the cut-off value at 200, in-hospital mortality in the patients with the angiographic GRACE score <200 was 0.6%, which was relatively lower than those with ≥200, 9.4%. CONCLUSIONS: The GRACE score is a useful predictor of in-hospital mortality among Japanese AMI patients in the PCI era. Moreover, the angiographic GRACE score could improve the predicting availability.

RenalGuard system to prevent contrast-induced acute kidney injury in Japanese patients with renal dysfunction; RESPECT KIDNEY study.

Increasing the urine flow rate (UFR) reduces the toxic effect of contrast media. Use of the RenalGuard system enables the achievement of a high UFR by maintaining intravascular volume and prevents the development of contrast-induced acute kidney injury (CI-AKI). However, the efficacy and safety of RenalGuard system have not yet been evaluated in Japan. This multicenter prospective study evaluated the efficacy and safety of the RenalGuard therapy in preventing CI-AKI development in 60 Japanese patients with renal dysfunction [estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2] undergoing catheter procedures. Baseline eGFR and Mehran's CIN (contrast-induced nephropathy) risk score were 35.1 ± 8.5 mL/min/1.73 m2 and 11.7 ± 4.3, respectively. Regardless of this high-risk profile, the incidence of CI-AKI was 8.6% (5/58) compared with the 26.1% incidence estimated by the CIN risk score. Moreover, two-sided 95% (Fisher's) exact confidence interval was 2.9-19.0 and its upper limit (i.e., 19.0) was less than the prespecified threshold incidence of 25.0. Univariate logistic regression analysis demonstrated that the UFR during catheter procedure was one of the most important factor associated with CI-AKI (odds ratio 0.99, confidence interval 0.98-1.00, p = 0.03). In conclusion, RenalGuard therapy may prevent CI-AKI development in Japanese patients with renal dysfunction. Further large-scale prospective multicenter studies are necessary to confirm our findings.

Clinical whole exome sequencing in severe hypertriglyceridemia.

BACKGROUND: Little data exist regarding the clinical application of whole exome sequencing (WES) for the molecular diagnosis of severe hypertriglyceridemia (HTG). METHODS: WES was performed for 28 probands exhibiting severe HTG (≥1000 mg/dl) without any transient causes. We evaluated recessive and dominant inheritance models in known monogenic HTG genes, followed by disease-network gene prioritization and copy number variation (CNV) analyses to identify causative variants and a novel genetic mechanism for severe HTG. RESULTS: We identified possible causative variants for severe HTG, including three novel variants, in nine probands (32%). In the recessive inheritance model, we identified two homozygous subjects with lipoprotein lipase (LPL) deficiency and one subject harboring compound heterozygous variants in both LPL and APOA5 genes (hyperchylomicronemia). In the dominant inheritance model, we identified probands harboring deleterious heterozygous variants in LPL, glucokinase regulatory protein, and solute carrier family 25 member 40 genes, possibly associated with this extreme HTG phenotype. However, gene prioritization and CNV analyses did not validate the novel genes associated with severe HTG. CONCLUSIONS: In 28 probands with severe HTG, we identified potential causative variants within nine genes associated with rare Mendelian dyslipidemias. Clinical WES may be feasible for such extreme cases, potentially leading to appropriate therapies.

Assessment of factors associated with measurability of fractional flow reserve derived from coronary computed tomography angiography in type 2 diabetic patients with intermediate coronary artery stenosis.

Recently, fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFRCT) has been developed. However, FFRCT cannot be calculated for all patients from CCTA datasets. The purpose of the present study, therefore, was to evaluate the predictors that results in cases being inappropriate for FFRCT processing. This study was a sub-analysis of the TRACT trial, from which 50 patients were divided into 2 groups according to FFRCT measurability (measurable [group M] or not measurable [group N]) using CCTA examination at baseline. Thirty-nine (78%) patients comprised group M and 11 (22%) comprised group N. Heart rate at CCTA examination (72 beats/min vs. 63 beats/min; p = 0.007) and Agatston score (665 vs. 33; p = 0.002) in group N were significantly higher than those in group M. Multivariate logistic regression analyses revealed that heart rate at CCTA examination (OR 1.348 [95% CI 1.167-1.556]; p < 0.001) and Agatston score (OR 1.002 [95% CI 1.000-1.003]; p = 0.004) were significant, independent factors associated with non-measurability of FFRCT. The frequency of poor image quality was highest in patients with heart rate > 65 beats/min and Agatston score > 400 (p < 0.0001). In conclusions, high heart rate at the time of CCTA examination and higher Agatston score were associated with poor image quality that resulted in cases being inappropriate for FFRCT processing. Heart rate control at CCTA examination is necessary to acquire good-quality images required for computing FFRCT.

Plaque Volume and Morphology are Associated with Fractional Flow Reserve Derived from Coronary Computed Tomography Angiography.

AIM: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) accurately diagnoses ischemic lesions of intermediate stenosis severity. However, significant determinants of FFRCT have not been fully evaluated. METHODS: This was a sub-analysis of the Treatment of Alogliptin on Coronary Atherosclerosis Evaluated by Computed Tomography-Based Fractional Flow Reserve trial. Thirty-nine diabetic patients (117 vessels) with intermediate coronary artery stenosis [percent diameter stenosis (%DS) ＜70%] in whom FFRCT was measured were included in this study. CCTA-defined, vessel-based volumetric and morphological characteristics of plaques were examined to determine their ability to predict FFRCT. RESULTS: Patient-based, multivariate linear regression analysis showed that hemoglobinA1c, triglycerides, and the estimated glomerular filtration rate were significant independent factors associated with FFRCT. Vessel-based, univariate linear regression analysis showed that the total atheroma volume (r=－0.233, p=0.01) and the percentage atheroma volume (PAV) (r=－0.284, p=0.002) as well as %DS (r=－0.316, p=0.006) were significant determinants of FFRCT. Among the plaque components, significant negative correlations were observed between FFRCT and low- (r=－0.248, p=0.007) or intermediate-attenuation plaque volume (r=－0.186, p=0.045), whereas calcified plaque volume was not associated with FFRCT. In the left anterior descending coronary artery (LAD), the plaque volume of each component was associated with FFRCT. CONCLUSIONS: Plaque volume, PAV, and %DS were significant determinants of FFRCT. Plaque morphology, particularly in LAD, was associated with FFRCT in diabetic patients with intermediate coronary artery stenosis.

Sex-Related Differences in In-Hospital Mortality in Japanese ST-Elevation Acute Myocardial Infarction Patients Presenting to Hospital in the 24 Hours After Symptom Onset　- Results From K-ACTIVE.

Background: Despite the drastic advances in clinical care for patients with acute ST-elevation myocardial infarction (STEMI), female STEMI patients have higher in-hospital mortality rates than male patients. This study assessed the influence of sex on in-hospital mortality in STEMI patients in Kanagawa Prefecture, Japan. Methods and Results: From October 2015 to June 2018, 2,491 consecutive STEMI patients (23.9% female) who presented to hospital in the 24 h after symptom onset were analyzed. The female patients were 9 years older and less frequently had diabetes, smoking and prior MI than male patients. Pre-hospital managements, including prehospital 12-lead electrocardiography, and symptom-to-door time were similar between the sexes. A door-to-device time ≤90 min was achieved in 61.3% of female cases and in 65.0% of male cases (P=0.13). Reperfusion therapy was provided to 94.6% of female and 97.6% of male patients (P<0.001). In-hospital mortality rate was not significantly different between female and male patients (6.6% vs. 7.8%, P=0.37). On multivariate logistic regression analysis, female sex itself was not associated with in-hospital mortality (OR, 1.52; 95% CI: 0.67-3.47, P=0.32). Conclusions: There was no sex discrepancy in the in-hospital mortality of STEMI patients in this study. Guideline-based treatment, such as advanced pre-hospital management and a high use of reperfusion therapy might have attenuated the sex-related differences in the in-hospital mortality.

Changes in coronary atherosclerosis, composition, and fractional flow reserve evaluated by coronary computed tomography angiography in patients with type 2 diabetes.

BACKGROUND: The use of coronary computed tomography angiography (CCTA) for noninvasive anatomic detection of coronary artery disease is increasing. Recently, fractional flow reserve (FFR) assessment using routinely acquired CCTA datasets (FFRCT) has been developed. However, there are no reports about changes in coronary atherosclerosis, composition, and FFRCT in patients with type 2 diabetes. METHODS: This prospective, multicenter, observational trial evaluated changes in coronary atherosclerosis after alogliptin therapy in patients with type 2 diabetes. Fifty-one patients with type 2 diabetes who underwent CCTA examination and having intermediate coronary artery stenosis were treated with 25 mg of alogliptin. After 48 weeks, CCTA examination was repeated. The primary endpoint was changes in FFRCT, and the secondary endpoint was changes in total atheroma volume (TAV) from the baseline to the 48-week follow-up. RESULTS: The FFRCT decreased from the baseline to follow-up, but not significantly. A significant increase in TAV (from 658.5 mm3 to 668.9 mm3, p = 0.048) was observed. Vessel volume tended to increase, whereas percentage atheroma volume and lumen volume did not change. A significant negative correlation was observed between percentage change in TAV and change in FFRCT (r = -0.185, p = 0.048). A significant increase in calcified plaques (p = 0.01) and a decrease in intermediate-attenuation plaques (p = 0.006) was observed. CONCLUSIONS: In Japanese patients with diabetes and intermediate coronary artery stenosis, alogliptin could not improve FFRCT or reduce atheroma volume, whereas the plaque composition changed. A progression of atheroma volume was associated with a reduction in FFRCT.

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018.

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI.

Penetration rate of the placement of a drug-eluting stent for the treatment of superficial femoral artery lesions in Japan.

Stent placement for treating superficial femoral artery (SFA) lesions has been approved. The Zilver PTX stent, a drug-eluting stent (DES) for treating SFA lesions, has been available in Japan since 2012. However, the penetration rate of this DES has not yet been reported. This prospective multicenter registry study enrolled 314 patients (354 limbs) to be treated by stent placement in 2014 (UMIN000011551). The primary endpoint was the measurement of the penetration rate of the DES. The secondary endpoints were measuring the freedom from restenosis, freedom from target lesion revascularization (TLR), freedom from major adverse limb event (MALE), and the survival rate at 12 months postoperatively. Female patients comprised 28% participants. The mean age was 73.1 ± 9.2 years. A total of 56% patients had diabetes mellitus (DM), 36% patients were receiving hemodialysis, and 30% used cilostazol at baseline. The mean lesion length was 156 ± 101 mm, and the percentage of TASC II C/D lesions was 58%. Critical limb ischemia (CLI) was observed in 32% limbs. The penetration rates of the Zilver PTX stent were only 8%. The primary patency rate was similar between DES and bare-metal stents (BMS) at 12 months postoperatively (77 vs. 84%, p = 0.52). In this study, the rates of freedom from restenosis, freedom from TLR, freedom from MALE, and the survival rate at 12 months postoperatively were 83, 86, 85, and 89%, respectively. The penetration rate of a first-generation DES placement for treating SFA lesions is low in Japan. On the other hand, BMS is well utilized and its primary patency is acceptable.

Anti-inflammatory effect of factor-Xa inhibitors in Japanese patients with atrial fibrillation.

Activated factor-X (FXa) plays an important role not only in the coagulation cascade, but also in pro-inflammatory responses. However, few data exist regarding the anti-inflammatory effect of FXa inhibitors in clinical practice. The aim of this study was to evaluate the anti-inflammatory and anti-atherosclerotic effects of FXa inhibitors in Japanese patients with non-valvular atrial fibrillation (NVAF). Eighty-three patients with NVAF were treated with FXa inhibitors from March 2013 to March 2015 at our institution. Of these, 55 patients who were not pretreated with warfarin or dabigatran (rivarixaban in 23 patients and apixaban in 32) were included in this study. We measured various inflammatory and coagulation markers at baseline and at 6 months after treatment. Plasma concentrations of pentraxin 3 (PTX3) (from 2.45 ± 1.31 to 1.97 ± 1.00 ng/mL, p = 0.0009) and fibrin and fibrinogen degradation products (FDP) D-dimer (from 1.18 ± 0.70 to 0.74 ± 0.32 µg/mL, p < 0.0001) decreased, while those of TM (from 2.9 ± 0.8 to 3.2 ± 0.9 FU/mL, p = 0.003) increased significantly at 6 months. Interestingly, change of each marker denoted the same tendency in both rivaroxaban and apixaban. In conclusion, the present study suggests that FXa inhibitors have not only an anti-coagulant effect but also anti-inflammatory effects in patients with NVAF. Further large-scale prospective study is necessary to evaluate whether changes in these markers will be associated with a lower risk for future cardiovascular events.

Effects of alogliptin on fractional flow reserve evaluated by coronary computed tomography angiography in patients with type 2 diabetes: Rationale and design of the TRACT study.

BACKGROUND: Patients with type 2 diabetes are at high risk for developing coronary artery disease (CAD). Noninvasive anatomic assessment by coronary computed tomography angiography (CCTA) is being increasingly used for detecting or excluding CAD. Recently, fractional flow reserve (FFR) using routinely acquired CCTA datasets (FFRCT) has been developed. Although intensive glycemic control can reduce the risk of microvascular complications, intensive glucose control does not seem to be beneficial in preventing major cardiovascular events when compared with standard therapy. However, it has been reported that dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherogenic effects in an animal model. In addition, DPP-4 inhibitors attenuate the progression of carotid intima-media thickness in patients with type 2 diabetes. Therefore, this study will be performed to evaluate the effects of alogliptin, a DPP-4 inhibitor, on coronary atherosclerosis using FFRCT in patients with type 2 diabetes. METHODS AND DESIGN: This study will be a prospective, non-randomized, multicenter trial performed in Japan. Patients with type 2 diabetes who have intermediate coronary artery stenosis (diameter stenosis <70%) as evaluated by CCTA will be treated with 25mg/day of alogliptin. After 48 weeks' treatment, CCTA will be repeated. The primary endpoint will be changes in FFRCT, and the secondary endpoint will be the change in plaque volume from baseline to the 48-week follow-up. CONCLUSION: This study will be the first multicenter trial to evaluate the effects of alogliptin on coronary atherosclerosis using the newly developed FFRCT as the primary endpoint, and the findings will clarify the anti-atherogenic effects of alogliptin.