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.

Comparison of clinical outcomes and left ventricular remodeling after ST-elevation myocardial infarction between patients with and without diabetes mellitus.

Left ventricular remodeling (LVR) after ST-elevation myocardial infarction (STEMI) is generally thought to be an adaptive but compromising phenomenon particularly in patients with diabetes mellitus (DM). However, whether the extent of LVR is associated with poor prognostic outcome with or without DM after STEMI in the modern era of reperfusion therapy has not been elucidated. This was a single-center retrospective observational study. Altogether, 243 patients who were diagnosed as having STEMI between January 2016 and March 2019, and examined with echocardiography at baseline (at the time of index admission) and mid-term (from 6 to 11 months after index admission) follow-up were included and divided into the DM (n = 98) and non-DM groups (n = 145). The primary outcome was major adverse cardiovascular events (MACEs) defined as the composite of all-cause death, heart failure (HF) hospitalization, and non-fatal myocardial infarction. The median follow-up duration was 621 days (interquartile range: 304-963 days). The DM group was significantly increased the rate of MACEs (P = 0.020) and HF hospitalization (P = 0.037) compared with the non-DM group, despite of less LVR. Multivariate Cox regression analyses revealed that the patients with DM after STEMI were significantly associated with MACEs (Hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.20-6.47, P = 0.017) and HF hospitalization (HR 3.62, 95% CI 1.19-11.02, P = 0.023) after controlling known clinical risk factors. LVR were also significantly associated with MACEs (HR 2.44, 95% CI 1.03-5.78, P = 0.044) and HF hospitalization (HR 3.76, 95% CI 1.15-12.32, P = 0.029). The patients with both DM and LVR had worse clinical outcomes including MACEs and HF hospitalization, suggesting that it is particularly critical to minimize LVR after STEMI in patients with DM.

Novel Acute Myocardial Infarction Risk Stratification (nARS) System Reduces the Length of Hospitalization for Acute Myocardial Infarction.

BACKGROUND: The novel Acute Myocardial Infarction (AMI) Risk Stratification (nARS) system was recently developed based on original criteria. The use of nARS may reduce the length of hospitalization. Methods and Results: We allocated 560 AMI patients into the pre-nARS group (before adopting nARS) or the nARS group. Patients in the nARS group were subdivided into the low (L), intermediate (I), and high (H) risk groups, whereas patients in the pre-nARS group were subdivided into the equivalent L (eL), equivalent I (eI), or equivalent H (eH) risk groups based on the nARS criteria. Length of coronary care unit (CCU) stay was significantly shorter in the nARS group (2.8±3.5 days) compared with the pre-nARS group (4.4±5.4 days; P<0.001). Length of hospital stay was also shorter in the nARS group (9.4±8.9 days) compared with the pre-nARS group (13.4±12.8 days; P<0.001). Length of CCU stay was significantly shorter in the L (1.1±1.0 days), I (2.8±3.5 days), and H (5.0±4.8 days) risk groups compared with corresponding eL (2.2±1.1 days), eI (4.4±5.4 days), and eH (7.1±7.8 days) risk groups. CONCLUSIONS: Length of CCU and hospital stay were significantly shorter in the nARS group compared with the pre-nARS group. The use of nARS may save medical resources in the treatment of AMI in the regional health-care system.

Comparison of clinical outcomes between sufficient versus insufficient diagonal branch flow in anterior acute myocardial infarction.

In primary percutaneous coronary intervention (PCI), revascularization to the main branch is considered to be more important than that to the side branch. The purpose of the present study was to compare in-hospital clinical outcomes between sufficient and insufficient diagonal flow in patients with anterior ST-elevation acute myocardial infarction. A total of 229 left anterior descending artery (LAD)-AMI with final Thrombolysis in Myocardial Infarction (TIMI)-3 LAD flow were included, and divided into the sufficient diagonal flow group (TIMI-3 diagonal flow: n = 170) and the insufficient diagonal flow group (TIMI ≤ 2 diagonal flow: n = 59). The primary endpoint was the incidence of mechanical complication. The secondary endpoints were incidences of in-hospital death, heart failure at discharge, and left ventricular thrombus. There were no significant differences in the primary endpoint (the sufficient diagonal flow group: 1.2%, the insufficient diagonal flow group: 0%, P = 0.403). In-hospital death was more frequently observed in the insufficient diagonal flow group (8.5%) than the sufficient diagonal flow group (2.9%) without reaching statistical significance (P = 0.073). The incidence of heart failure at discharge, and thrombus in left ventricular were not different between the two groups. In conclusion, in-hospital outcomes were not significantly different between the sufficient and insufficient diagonal flow groups. We may not stick to the diagonal flow in LAD-STEMI, as long as the LAD flow is maintained by PCI.

Comparison of Clinical Outcomes between the Ostial Versus Non-Ostial Culprit in Proximal Left Anterior Descending Artery Acute Myocardial Infarction.

Percutaneous coronary interventions to the proximal left anterior descending artery (pLAD)-acute myocardial infarction (AMI) are still challenging, especially in the ostial pLAD. Clinical outcomes of the ostial pLAD-AMI were not well investigated. The aim of the present study was to compare clinical outcomes of the ostial pLAD-AMI with those of the non-ostial pLAD-AMI. The primary endpoint was the major cardiovascular events (MACE), defined as the composite of cardiac death, AMI, stent thrombosis (ST), target lesion revascularization (TLR), and target vessel revascularization (TVR). Between January 2009 and March 2016, a total of 401 pLAD-AMI were included as the study population and were divided into 78 ostial pLAD-AMI (the ostial pLAD group), and 323 non-ostial pLAD-AMI (the non-ostial pLAD group). The median follow-up duration was 414 days. The MACE tended to be higher in the ostial pLAD group (8.0% at 30 days, 19.9% at 400 days) than in the non-ostial pLAD group (4.4% at 30 days, 12.9% at 400 days) without reaching statistical significance (P = 0.087). The prevalence of cardiac death was significantly higher in the ostial pLAD group (6.6% at 30 days, 9.5% at 400 days) as compared with the non-ostial pLAD group (3.1% at 30 days, 4.5% at 400 days) (P = 0.034). There were no significant differences in ST, AMI, TLR, or TVR. We concluded that, as compared with the non-ostial pLAD-AMI, the clinical outcomes of the ostial pLAD-AMI, especially cardiac death, tended to be worse, requiring special attention to the ostial pLAD-AMI.

The Comparison of Clinical Outcomes Between Inferior ST-Elevation Myocardial Infarction with Right Ventricular Infarction Versus Without Right Ventricular Infarction.

Right ventricular infarction (RVI) is a complication following inferior ST-elevation myocardial infarction (STEMI). The aim of the present study was to investigate the clinical outcomes of RVI in the contemporary primary percutaneous coronary intervention (PCI) era. The primary endpoint was in-hospital death, and the secondary endpoint was major adverse cardiac events (MACE), defined as the composite of cardiovascular death, re-hospitalization for heart failure, and non-fatal acute myocardial infarction (AMI). Event-free survival curves for MACE were constructed using the Kaplan-Meier method, and statistical differences between curves were assessed using the log-lank test. A total of 1354 patients with AMI were screened from January 2010 to December 2016. The final study population involved 315 patients with STEMI whose infarct related artery (IRA) was the right coronary artery (RCA). We categorized these 315 patients into the RVI group (n = 85) and the non-RVI group (n = 230). Median follow-up duration was 358 (IQR: 208-987) days. In-hospital deaths were more frequently observed in the RVI group (9.4%) than in the non-RVI group (3.0%) (P = 0.018). However, the incidence of MACE was not different between the groups (P = 0.537). In conclusion, in-hospital clinical outcomes were poorer in the RVI group than in the non-RVI group. However, mid-term MACE was not different between the two groups, suggesting the importance of aggressive acute treatment for STEMI patients with RVI.

Appetite Predicts Clinical Outcomes in High Risk Patients Undergoing Trans-Femoral TAVI.

Transcatheter aortic valve implantation (TAVI) has been recognized as a standard therapy for severe aortic valve stenosis. However, since some patients who receive TAVI have poor outcomes, the predictors of clinical outcomes after TAVI are important. The aim of this study was to investigate the association between appetite and long-term clinical outcomes.We screened consecutive cases who received TAVI at our medical center between July 2014 and October 2018. A total of 139 patients who received transfemoral TAVI were included as the final study population. They were divided into a good appetite group (n = 105) and a less appetite group (n = 34) according to their dietary intake rate (> 90%: good appetite group, ≤ 90%: less appetite group). We defined the intake rate as the average for breakfast, lunch, and dinner on the day just before discharge. We defined two-year major adverse cardiovascular and cerebrovascular events (MACCE) as a composite of cardiovascular death, myocardial infarction, any coronary revascularization, history of hospitalization due to heart failure, and disabling acute cerebral infarction. Kaplan-Meier analyses and multivariate Cox regression analysis were performed.The median duration of the follow-up period was 372 (189-720) days. Kaplan-Meier curves showed that the less appetite group got MACCE more frequently (event free rate of the less appetite group: 76.5% versus the good appetite group: 94.3%, Log Rank P = 0.01). In multivariate Cox regression analysis, having less appetite was a significant predictor of two-year MACCE (HR 5.26, 95%CI 1.66-16.71, P < 0.01).In conclusion, among the patients who received transfemoral TAVI, appetite status just before discharge was significantly associated with long-term outcome.

Clinical characteristics associated with pacing-induced cardiac dysfunction: a high incidence of undiagnosed cardiac sarcoidosis before permanent pacemaker implantation.

Previous studies suggested that right ventricular pacing was associated with pacing-induced cardiac dysfunction (PICD). The purpose of this study was to investigate the clinical characteristics including the incidence of undiagnosed cardiac sarcoidosis (CS) in patients with atrioventricular block (AVB) who manifest PICD. We retrospectively investigated consecutive patients with permanent pacemaker (PPM) undergoing a first-generator replacement surgery with a new PPM or an upgrade procedure to a cardiac resynchronization therapy (CRT) device between December 1, 2011 and June 30, 2017. Patients with AVB showing normal echocardiographic findings before PPM implantation were included and divided into 2 groups: patients with post-PPM left ventricular ejection fraction (LVEF) < 40% and/or undergoing an upgrade procedure to CRT (PICD group) and patients with post-PPM LVEF ≥ 40% who underwent replacement surgery with a new PPM (no-PICD group). There were 15 and 41 patients in the PICD and no-PICD groups, respectively. A wider-paced QRS duration just after the PPM implantation and/or lower pre-PPM LVEF was observed in the PICD group. Furthermore, 46.7% of the PICD patients (7/15) satisfied the diagnostic criteria for CS according to the guideline of the Japanese Circulation Society, although no patients fulfilled these criteria before PPM implantation. In conclusion, a high incidence of CS was observed in patients with AVB who had PICD. However, none of these patients was diagnosed with CS before PPM implantation.

Clinical outcomes of left main crossover stenting for ostial left anterior descending artery acute myocardial infarction.

Percutaneous coronary interventions to ostial left anterior descending artery (LAD)-acute myocardial infarction (AMI) were challenging, especially in crossover stenting from left main trunk (LMT) to LAD. The clinical outcomes of ostial LAD-AMI that needed crossover stenting were not well investigated. The objective of this study was to compare the clinical outcomes of LMT crossover stenting with those of ostial LAD just proximal (jp) stenting. Between January 2009 and March 2016, 1499 patients were diagnosed as AMI in our institution. Among them, 76 ostial LAD-AMIs were included in this study, and divided into 30 LMT crossover stenting (the crossover group) and 46 jp stenting (the jp stenting group). The primary endpoint was major cardiovascular events (MACE) defined as the composite of cardiac death, acute myocardial infarction (AMI), stent thrombosis (ST), target lesion revascularization (TLR) and target vessel revascularization (TVR). The frequency of MACE was comparable between the 2 groups (16.7% in the crossover group and 21.7% in the jp stenting group, P = 0.587). Similarly, the frequency of cardiac death was comparable between the 2 groups (6.7% in the crossover group and 13.0% in the jp stenting group, P = 0.376). The frequencies of TLR (6.7% in the crossover group and 6.5% in the jp stenting group, P = 0.980) and TVR (10.0% in the crossover group and 8.7% in the jp stenting group, P = 0.848) were not significantly different between the 2 groups. In conclusion, the clinical outcomes of the crossover stenting were comparable to the jp stenting in the stenting strategy for ostial LAD-AMI. LMT-LAD crossover stenting would be the acceptable strategy for ostial LAD-AMI.

The comparison of clinical outcomes in patients with acute myocardial infarction and advanced chronic kidney disease on chronic hemodialysis versus off hemodialysis.

Acute myocardial infarction (AMI) is more frequently observed in patients with chronic kidney disease (CKD) than in patients without CKD. Initial treatment strategy for AMI includes primary percutaneous coronary intervention (PCI), which requires substantial amount of contrast media. We hypothesized that the clinical outcomes are comparable or worse in patients with AMI and advanced CKD off chronic hemodialysis as compared to patients with AMI and advanced CKD on chronic hemodialysis. The purpose of this study was to compare the clinical outcomes of patients with AMI and advanced CKD on hemodialysis versus off hemodialysis. A total of 148 patients with estimated glomerular filtration rate < 30 ml/min/1.73 m2 on admission were included and were divided into the HD group (n = 68) and non-HD group (n = 80). The length of hospitalization was significantly less in the HD group (15.7 ± 14.8 days) than in the non-HD group (22.4 ± 21.3 days) (P = 0.01). In-hospital death was significantly less in the HD group (10.3%) than in the non-HD group (25.0%) (P = 0.02). While the non-HD group was not significantly associated with in-hospital death after controlling clinical covariates, the non-HD group (odd ratio 2.89, 95% confidence interval 1.03-8.12, P = 0.04) was significantly associated with long hospitalization even after controlling clinical covariates. In conclusion, as compared to advanced CKD on chronic hemodialysis, advanced CKD off hemodialysis had higher morbidity and mortality in patients with AMI. Advanced CKD off hemodialysis was closely associated with long hospitalization even after controlling clinical factors.

Veno-Arterial Extracorporeal Membrane Oxygenation with Conventional Anticoagulation Can Be a Best Solution for Shock Due to Massive PE.

While most of pulmonary thromboembolism (PE) cases can be managed by thrombolytic and anticoagulation therapy, massive PE remains a life-threatening disease. Although surgical embolectomy can be a curative therapy for massive PE, peri-operative mortality for hemodynamically collapsed PE is extremely high. We present a case of hemodynamically collapsed massive PE. We avoided either thrombolytic therapy or surgical embolectomy, because the patient had recent cerebral contusion. Therefore, we managed the patient with the combination of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and conventional anticoagulation, which dramatically improved the patient's hemodynamics. In conclusion, the combination of V-A ECMO and conventional anticoagulation may be the preferred first line therapy for the patients with cardiogenic shock following massive PE.

Lower 1,5-anhydroglucitol is associated with adverse clinical events after percutaneous coronary intervention.

Diabetes mellitus and impaired glucose tolerance are well-known risk factors for coronary artery disease (CAD) and adverse clinical events after percutaneous coronary intervention (PCI). Postprandial hyperglycemia is an important risk factor for CAD and serum 1,5-anhydroglucitol (1,5-AG) reflects postprandial hyperglycemia more robustly than hemoglobin (Hb)A1c. We aimed to clarify the relationship between serum 1,5-AG level and adverse clinical events after PCI. We enrolled 141 patients after PCI with follow-up coronary angiography. We evaluated associations between glycemic biomarkers including HbA1c and 1,5-AG and cardiovascular events during follow-up. Median serum 1,5-AG level was significantly lower in patients with any coronary revascularization and target lesion revascularization (TLR) [13.4 µg/ml (first quartile, third quartile 9.80, 18.3) vs. 18.7 (12.8, 24.2), p = 0.005; 13.4 µg/ml (10.2, 16.4) vs. 18.7 (12.9, 24.2), p = 0.001, respectively]. Multivariate logistic analysis showed lower 1,5-AG was independently associated with any coronary revascularization and TLR (odds ratio 0.93, 95 % confidence interval 0.86-0.99, p = 0.04; 0.90, 0.81-0.99, p = 0.044, respectively), whereas higher HbA1c was not. Postprandial hyperglycemia and lower 1,5-AG are important risk factors for adverse clinical events after PCI.

Determinants of In-Hospital Death in Acute Myocardial Infarction With Triple Vessel Disease.

Compared to acute myocardial infarction (AMI) with single vessel disease (SVD) or double vessel disease (DVD), AMI with triple vessel disease (TVD) is associated with higher mortality. The aim of this study was to identify the determinants of in-hospital death in AMI with TVD. We identified AMI patients with TVD in our tertiary medical center between January 2009 and December 2014. Baseline patient characteristics including laboratory data, echocardiograms, and coronary angiograms were collected from our hospital records. We divided our study population into a survivor group and non-survivor group. Multivariate stepwise logistic regression analysis was performed to identify the determinants of in-hospital death. A total of 138 AMI patients with TVD were identified and included as the final study population. Fifteen patients died during the hospitalization (mortality rate, 10.9%). Mean systolic blood pressure (134 ± 27 mmHg) was significantly greater in the survivor group compared with the non-survivor group (114 ± 31 mmHg) (P = 0.02). The prevalence of shock on admission was significantly less in the survivor group (15.4%) than in the non-survivor group (66.7%) (P < 0.001). Multivariate stepwise logistic regression analysis revealed that shock status on admission (OR 11.50, 95% CI 3.21-41.14, P < 0.001), the left anterior descending artery (LAD) as the infarct related artery (IRA) (OR 3.83, 95% CI 1.04-14.09, P = 0.04), and serum albumin on admission (OR 0.26, 95% CI 0.08-0.84, P = 0.02) were significantly associated with in-hospital death. In conclusion, shock status on admission, the LAD as the IRA, and a low serum albumin level were the determinants of in-hospital death in AMI patients with TVD.

Relationship between the number of drugs used during percutaneous coronary intervention and adverse events in patients with chronic coronary syndrome: Analysis of CLIDAS database.

Background: Polypharmacy is associated with an increased risk of adverse events due to the higher number of drugs used. This is particularly notable in patients with chronic coronary syndrome (CCS), who are known to use a large number of drugs. Therefore, we investigated polypharmacy in patients with CCS, using CLIDAS, a multicenter database of patients who underwent percutaneous coronary intervention. Method and results: Between 2017 and 2020, 1411 CCS patients (71.5 ± 10.5 years old; 77.3 % male) were enrolled. The relationship between cardiovascular events occurring during the median follow-up of 514 days and the number of drugs at the time of PCI was investigated. The median number of drugs prescribed was nine. Major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke, heart failure, transient ischemic attack, or unstable angina, occurred in 123 patients, and all-cause mortality occurred in 68 patients. For each additional drug, the adjusted hazard ratios for MACE and all-cause mortality increased by 2.069 (p = 0.003) and 1.102 (p = 0.010). The adjusted hazard ratios for MACE and all-cause mortality were significantly higher in the group using nine or more drugs compared to the group using eight or fewer drugs (1.646 and 2.253, both p < 0.001). Conclusion: This study showed that an increase in the number of drugs used for CCS may be associated with MACE and all-cause mortality. In patients with CCS, it might be beneficial to minimize the number of medications as much as possible, while managing comorbidities and using guideline-recommended drugs.

Change in pulse pressure and cardiovascular outcomes after percutaneous coronary intervention: The CLIDAS study.

Background: Limited data exist on the prognostic value of changes in pulse pressure (PP, the difference between systolic and diastolic blood pressure) during hospitalization for patients with coronary artery disease who have undergone percutaneous coronary intervention (PCI). Methods: In the Clinical Deep Data Accumulation System (CLIDAS), we studied 8,708 patients who underwent PCI. We aimed to examine the association between discharge PP and cardiovascular outcomes. PP was measured before PCI and at discharge. Patients were divided into five groups (quintiles) based on the change in PPQ1 (-18.0 ± 9.9 mmHg), Q2 (-3.8 ± 2.6), Q3 (reference; 3.7 ± 2.0), Q4 (11.3 ± 2.6), and Q5 (27.5 ± 11.2). We then analyzed the relationship between PP change and outcomes. Results: The mean patient age was 70 ± 11 years, with 6,851 (78 %) men and 3,786 (43 %) having acute coronary syndrome. U-shaped relationships were observed for the incidence rates of major adverse cardiac or cerebrovascular events (MACCE, a composite endpoint of cardiovascular death, myocardial infarction, and stroke), revascularization, and hospitalization for heart failure (HF). After adjusting for confounding factors, higher PP at discharge was associated with an increased risk of MACCE (adjusted hazard ratio 1.41; 95 %CI, 1.06-1.87 in Q5 [73.9 ± 9.3 mmHg]). Evaluating PP change revealed a U-shaped association with MACCE (1.50; 1.11-2.02 in Q1 and 1.47; 0.98-2.20 in Q5). Additionally, Q5 had a higher risk for hospitalization for HF (1.37; 1.00-1.88). Conclusions: Our findings demonstrate a U-shaped association between changes in PP and cardiovascular outcomes. This data suggests the significance of blood pressure control during hospitalization for patients who have undergone PCI.

Achievement of guideline-recommended target blood pressure is associated with reducing the risk of hemorrhagic and ischemic stroke in Japanese coronary artery disease patients -the CLIDAS study.

The Japanese Society of Hypertension have established a blood pressure (BP) target of 130/80 mmHg for patients with coronary artery disease (CAD). We evaluated the data of 8793 CAD patients in the Clinical Deep Data Accumulation System database who underwent cardiac catheterization at six university hospitals and the National Cerebral and Cardiovascular Center (average age 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). Patients were divided into two groups based on whether or not they achieved the guideline-recommended BP of <130/80 mmHg. We analyzed the relationship between BP classification and major adverse cardiac and cerebral event (MACCE) separately in two groups: those with ACS and those with chronic coronary syndrome (CCS). During an average follow-up period of 33 months, 710 MACCEs occurred. A BP below 130/80 mmHg was associated with fewer MACCEs in both the overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-1.00, p = 0.048) and the ACS group (HR 0.67, 95%CI 0.51-0.88, p = 0.003). In particular, stroke events were also lower among those with a BP below 130/80 mmHg in both the overall (HR 0.69, 95%CI 0.53-0.90, p = 0.006) and ACS groups (HR 0.44, 95%CI 0.30-0.67, p < 0.001). In conclusion, the achievement of BP guidelines was associated with improved outcomes in CAD patients, particularly in reducing stroke risk among those with ACS.

Corrigendum to "Impact of heart failure severity and major bleeding events after percutaneous coronary intervention on subsequent major adverse cardiac events" [Int. J. Cardiol. Cardiovasc. Risk and Prev. 2023 Jun 25:18:200193].

[This corrects the article DOI: 10.1016/j.ijcrp.2023.200193.].

Teneligliptin, a DPP-4 Inhibitor, Improves Vascular Endothelial Function via Divergent Actions Including Changes in Circulating Endothelial Progenitor Cells.

Purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endothelial progenitor cells (EPCs) in peripheral blood circulation. However, the underlying mechanisms and effects on vascular endothelial function remain unclear. We evaluated whether the DPP-4 inhibitor teneligliptin increases circulating EPCs by inhibiting stromal-derived factor-1α (SDF-1α) and improves flow-mediated vascular dilatation (FMD) in type 2 diabetes mellitus patients with acute coronary syndrome (ACS) or its risk factors. Patients and Methods: This single-center, open-label, prospective, randomized controlled trial evaluated 17 patients (hemoglobin A1c ≤7.5% and peak creatinine phosphokinase <2000 IU/mL) with ACS or a history of ACS or multiple cardiovascular risk factors. Metabolic variables of glucose and lipids, circulating EPCs, plasma DPP-4 activity, and SDF-1α levels, and FMD were evaluated at baseline and 28 ± 4 weeks after enrollment. Patients were randomly assigned to either the teneligliptin (n = 8) or control (n = 9) groups. Results: The DPP-4 activity (∆-509.5 ± 105.7 vs ∆32.8 ± 53.4 µU/mL) and SDF-1α levels (∆-695.6 ± 443.2 vs ∆11.1 ± 193.7 pg/mL) were significantly decreased after 28 weeks in the teneligliptin group than those in the control group. The number of EPCs showed an increasing trend in the teneligliptin treated group; albeit this did not reach statistical significance. Glucose and lipid levels were not significantly different between the groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group when compared to the control group (∆3.8% ± 2.1% vs ∆-0.3% ± 2.9%, P=0.006). Conclusion: Teneligliptin improved FMD through a mechanism other than increasing the number of circulating EPCs.

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.

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.