Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y₁₂inhibitor, has been the principal antiplatelet therapy after drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS) and chronic coronary disease. Particularly in patients with ACS, which presents a higher ischemic risk than chronic coronary artery disease, DAPT for up to 12 months is the recommended standard treatment. However, to decrease bleeding events related to the potency of P2Y₁₂inhibitors and a prolonged duration of DAPT, recent studies have suggested P2Y₁₂inhibitor monotherapy after short-term DAPT (1–3 months), which decreased the bleeding risk without an increased ischemic risk. In this article, we discuss the evidence related to the efficacy of a P2Y₁₂inhibitor as single-antiplatelet therapy after short-term DAPT compared with standard DAPT, with a focus on patients with ACS treated with DES.

Background: The optimal duration of dual antiplatelet therapy (DAPT) in patients with chronic kidney disease undergoing percutaneous coronary intervention (PCI), especially with third-generation drug-eluting stents (DES), remains unknown.

Methods and Results: We conducted a prespecified post hoc analysis of the HOST-IDEA trial, randomizing patients undergoing PCI with third-generation DES to 3- to 6-month or 12-month DAPT. In all, 1,997 patients were grouped by their estimated glomerular filtration rate (eGFR): high (>90 mL/min/1.73 m²), intermediate (60–90 mL/min/1.73 m²), and low (<60 mL/min/1.73 m²). The primary outcome was net adverse clinical events (NACE), a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding (Bleeding Academic Research Consortium Type 3 or 5) at 12 months. Secondary outcomes were target lesion failure (TLF) and major bleeding. The low eGFR group had the highest rates of NACE, TLF, and major bleeding compared with the other 2 groups (P<0.001). Rates of NACE were similar in the 3- to 6-month and 12-month DAPT in the high (2.9% vs. 3.2%; P=0.84), intermediate (2.1% vs. 2.8%, P=0.51), and low (8.9% vs. 9.1%; hazard ratio 0.99; P=0.97; P_interaction=0.88) eGFR groups. TLF and major bleeding events showed similar trends.

Conclusions: In patients undergoing PCI with third-generation DES, 3- to 6-month DAPT was comparable to 12-month DAPT for clinical outcomes regardless of renal function.

Background: Global coronary flow reserve (G-CFR) impairment represents coronary microvascular dysfunction (CMD) and correlates with poor prognosis. Hyperemic coronary flow is reduced in conventional CMD, but normal or mildly reduced with elevated resting flow in endogenous-type CMD (E-CMD). This retrospective study assessed the prognostic value of post-percutaneous coronary intervention (PCI) CMD, focusing on E-CMD.

Methods and Results: We included 320 chronic coronary syndrome (CCS) patients undergoing PCI and post-PCI phase contrast cine-cardiac magnetic resonance imaging (CMR). Major adverse cardiac and cerebrovascular events (MACCE) were evaluated, considering the presence of post-PCI CMD and E-CMD based on G-CFR and resting myocardial flow assessed by coronary sinus flow using CMR. CMD was defined as G-CFR <2.0 and classified as E-CMD or non-E-CMD. Post-PCI CMD was observed in 43.4% of patients, 63.3% exhibiting E-CMD. During a median 2.5-year follow-up, MACCE occurred in 26 (8.1%) patients, more often in those with CMD (11.5% vs. 5.5%; P=0.063). MACCE incidence was higher in E-CMD than non-E-CMD and non-CMD (14.8% vs. 5.9% and 5.5%, respectively; P=0.027). Kaplan-Meier analysis revealed worse prognosis in E-CMD (P=0.025). Cox proportional hazards modeling revealed that E-CMD independently predicted MACCE (hazard ratio 3.24; 95% confidence interval 1.47–7.14; P=0.004).

Conclusions: Post-PCI CMD, particularly E-CMD, was significantly associated with worse outcomes in CCS patients. Post-PCI CMD evaluation could guide therapeutic strategies for CCS patients.

Background: The clinical outcomes of percutaneous coronary intervention (PCI) using drug-coated balloons (DCB) for de novo coronary artery lesions with eruptive calcified nodules remain unclear.

Methods and Results: This retrospective study analyzed the long-term outcomes of 308 consecutive patients (389 lesions) treated with PCI using DCB under optical coherence tomography guidance for de novo coronary artery lesions between September 2018 and November 2020. Patients were classified into 2 groups: those with an eruptive calcified nodule in the culprit lesion (CN group) and those without (non-CN group). The primary endpoint was major adverse cardiovascular events (MACE), including clinically driven target lesion revascularization (TLR), myocardial infarction (MI), and cardiac death. The median follow-up period was 2.6 years (interquartile range 1.9–3.4 years). The CN group had significantly higher rates of MACE (hazard ratio [HR] 9.2; 95% confidence interval [CI] 4.1–20.2; P<0.0001), TLR (HR 5.0; 95% CI 1.7–15.1; P<0.01), MI (HR 30.5; 95% CI 5.0–184.8; P<0.001), and cardiac death (HR 25.1; 95% CI 8.7–72.6; P<0.0001) than the non-CN group. Results were similar even after adjusting for potential confounding factors using propensity score matching.

Conclusions: This study demonstrated that patients with eruptive calcified nodules who underwent PCI with DCB for de novo coronary artery lesions had worse long-term clinical outcomes than patients without such nodules.

Background: The optimal treatment strategy for patients with coronary chronic total occlusion (CTO) and left ventricular systolic dysfunction (LVSD) remains unclear. This study investigated the long-term outcomes of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy (MT) in this specific patient cohort.

Methods and Results: This retrospective cohort study included 987 consecutive patients with CTO and LVSD who met the inclusion criteria and underwent either CTO-PCI (n=277), CTO-CABG (n=222), or CTO-MT (n=488) between 2014 and 2020. The primary outcome was all-cause mortality during follow-up. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE) and their components, including cardiovascular mortality, myocardial infarction (MI), stroke, unplanned revascularization, and hospitalization for heart failure. During a median follow-up of 5.3 years, 232 (23.51%) patients died from any cause. In the unadjusted analysis, CTO-MT was associated with worse long-term survival prospects. After inverse probability of treatment weighting and variable adjustment, CTO-PCI and CTO-CABG demonstrated significant reductions in the long-term risks of all-cause and cardiovascular mortality. Notably, CTO-CABG was associated with the lowest long-term risks of MACCE, MI, unplanned revascularization, and hospitalization for heart failure.

Conclusions: For patients with CTO and LVSD, successful CTO revascularization significantly improved long-term survival compared with CTO-MT. CTO-CABG can be regarded as the optimal treatment modality for better long-term prognosis.

Background: The angiography-derived non-hyperemic pressure ratio (angioNHPR) is a novel index of NHPR based on artificial intelligence (AI) that does not require pressure wires. We investigated the diagnostic accuracy of angioNHPR for detecting hemodynamically relevant coronary artery disease.

Methods and Results: In this retrospective single-center study, angioNHPR was assessed using the invasive NHPR as the reference standard. An angioNHPR ≤0.89 was defined as indicative of physiologically significant stenosis. Two angiographic projections ≥30° difference in angulation were selected. The lumen and centerline were automatically segmented by the prototype software, allowing for the calculation of the angioNHPR. We assessed 222 vessels from 178 patients. The accuracy of angioNHPR was 76.6% (95% confidence interval [CI] 70.4–82.0), with sensitivity 66.2% (95% CI 54.0–77.0), specificity 81.5% (95% CI 74.3–87.3), positive predictive value 62.7% (95% CI 53.6–70.9), and negative predictive value 83.7% (95% CI 78.6–87.7). The angioNHPR showed good correlation with invasive NHPR (r=0.72; 95% CI 0.64–0.77; P<0.001), and the agreement between angioNHPR and invasive NHPR was −0.01 (limits of agreement: −0.13, 0.11). The area under the curve (AUC) of angioNHPR was 0.81 (95% CI 0.75–0.86), which was significantly higher than that of 2-dimensional quantitative coronary angiography (AUC 0.69; 95% CI 0.62–0.75; P=0.007).

Conclusions: AI-based angioNHPR demonstrates good diagnostic performance using invasive NHPR as the reference standard.

Background: There are limited data on the use of whole-exome sequencing (WES) to diagnose severe hypertriglyceridemia. Our aim was to identify candidate genes linked to triglyceride levels via a genome-wide association study (GWAS) and to recruit participants with severe hypertriglyceridemia for WES to assess allelic variants in the candidate genes.

Methods and Results: A GWAS was conducted involving 120,140 participants to identify lead loci associated with blood triglyceride levels. Following the identification of these lead loci, WES was performed on DNA samples from 29 participants with hypertriglyceridemia whose triglyceride levels exceeded 800 mg/dL to assess variations in the corresponding genes. In the GWAS of 120,140 participants, the apolipoprotein A5 (APOA5) locus on chromosome 11 showed the strongest association with blood triglyceride levels (lead single nucleotide polymorphism [SNP] rs2075291; P=3.07×10⁻¹⁰⁸), along with 5 independent SNPs (most significant P=7.84×10⁻¹⁶⁷). Other key loci included BUD13 homolog (BUD13; P=2.73×10⁻⁶²), glucokinase regulator (GCKR; P=2.63×10⁻²⁴), and lipoprotein lipase (LPL; P=1.50×10⁻¹¹). WES in 29 hypertriglyceridemia patients identified additional genes, including ALDH1A2, APOC1, LPL, RGS7, and SIK3, showing significant allele frequency variations and potential roles in lipid metabolism.

Conclusions: Our study confirms the role of known genetic loci in triglyceride metabolism and hypertriglyceridemia while uncovering novel loci, offering new perspectives on lipid regulation and potential avenues for therapeutic advancements.

Background: An acute hyperglycemic status is reportedly associated with poor prognosis in patients with acute cardiovascular diseases. Although the stress hyperglycemia ratio (SHR) is used to evaluate the hyperglycemic condition on admission, relationships between SHR and clinical outcomes, particularly heart failure (HF), remain uncertain in acute myocardial infarction (AMI).

Methods and Results: This retrospective multicenter study included 2,386 patients with AMI undergoing percutaneous coronary intervention. SHR was calculated using blood glucose and HbA1c levels. Co-primary endpoints included HF-related events (death, worsening HF, and hospitalization for HF) and major adverse cardiovascular events (MACE; death, recurrent AMI, and ischemic stroke) during the index hospitalization and after discharge. The mean (±SD) SHR was 1.30±0.51; HF events and MACE occurred in 680 (28.5%) and 233 (9.8%) patients during hospitalization, respectively. SHR was independently associated with in-hospital HF events and MACE. Of 2,017 patients who survived to discharge, 195 (9.7%) and 214 (10.6%) experienced HF events and MACE, respectively, over a median follow-up of 536 days. The risk of HF events was higher in patients with a high (>1.45) SHR than in those with SHR ≤1.45; there was no significant difference in MACE rates after discharge between these 2 groups.

Conclusions: In AMI patients, SHR was predictive of in-hospital outcomes, including HF events and MACE, whereas after discharge a higher SHR was associated with higher HF risks, but not MACE.

Background: Reduced insulin secretion is linked to diabetes and cardiovascular disease (CVD), but its role in non-diabetic CVD patients is unclear. The homeostasis model assessment of β-cell function (HOMA-β) measures pancreatic β-cell function. This study investigated the association between HOMA-β and adverse cardiovascular events in non-diabetic CVD patients.

Methods and Results: This study included 1301 non-diabetic CVD patients who underwent cardiac catheterization at the University of Yamanashi Hospital. HOMA-β was calculated based on fasting blood glucose and insulin levels. Patients were followed for 3 years to track adverse events, such as all-cause death, myocardial infarction, angina pectoris requiring percutaneous coronary intervention, and heart failure. Receiver operating characteristic curve analysis established a HOMA-β cut-off value of ≤49.3%. Kaplan-Meier analysis indicated that patients with HOMA-β ≤49.3% had a significantly higher risk of adverse events (P <0.001), with a 2.65-fold increased risk (hazard ratio 2.65; 95% confidence interval 1.97–3.57). Adding HOMA-β to traditional risk factors such as age, sex, estimated glomerular filtration rate, and left ventricular ejection fraction significantly improved risk prediction, as demonstrated by net reclassification improvement and integrated discrimination improvement.

Conclusions: Decreased HOMA-β is a significant predictor of adverse cardiovascular events in CVD patients without diabetes. These findings suggest reduced insulin secretion contributes to worse outcomes, underscoring the importance of monitoring HOMA-β in this population.

Background: Although the efficacy of an implantable cardioverter defibrillator (ICD) in preventing sudden cardiac death is well established, the incidence and predictors of appropriate ICD therapy in Japanese ischemic heart disease (IHD) patients remain unclear.

Methods and Results: We retrospectively studied Japanese 141 IHD patients undergoing transvenous ICD or cardiac resynchronization therapy with a defibrillator (CRT-D) implantation for primary or secondary prevention at Hirosaki University Hospital. Over a mean (±SD) follow-up period of 5.5±2.8 years, the incidence of appropriate ICD therapy was similar in the primary and secondary prevention groups, although it was relatively more frequent in the first 2 years in the secondary prevention group. Four patients died due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), mainly due to post-shock pulseless electrical activity. Once patients had received their first appropriate ICD therapy, 49.2% received second appropriate ICD therapy within 6 months. Cox proportional hazard analysis revealed that sustained VT as an index life-threatening ventricular tachyarrhythmia before ICD/CRT-D implantation was an independent predictor of appropriate ICD therapy, but VF was not.

Conclusions: The incidence of appropriate ICD therapy was comparable in primary and secondary prevention among Japanese IHD patients. We need to recognize the high-risk period for second appropriate ICD therapy after the first therapy and sustained VT as index life-threatening ventricular tachyarrhythmia as a risk factor for appropriate ICD therapy.

Background: Fatal arrhythmic events (FAEs), such as sudden cardiac death (SCD) and fatal ventricular arrhythmias, are a devastating complication in patients with coronary artery disease (CAD). Therefore, in this study we aimed to assess the incidence of FAEs in more recent Japanese patients with CAD and to examine whether risk stratification of FAEs can still be feasible using the left ventricular ejection fraction (LVEF).

Methods and Results: In the CREDO Kyoto PCI/CABG registry cohorts-2 and -3, there were 25,843 patients with LVEF data who received a first coronary revascularization (LVEF ≤35% group: N=1,671, 35%<LVEF≤40% group: N=1,075, 40%<LVEF≤45% group: N=1,594, and LVEF >45%: N=21,503). FAEs were defined as a composite of SCD or hospitalization for serious ventricular arrhythmias. The cumulative 5-year incidence of FAEs was 2.4% and it increased with decreasing LVEF (LVEF ≤35%: 8.84%, 35%<LVEF≤40%: 6.99%, 40%<LVEF≤45%: 4.49%, and LVEF >45%: 1.67%, log-rank P<0.0001). The adjusted risk of FAEs also increased with decreasing LVEF.

Conclusions: LVEF is still a strong independent factor for predicting FAEs in patients with CAD in the PCI era. There was no obvious decrease in the incidence of FAEs between the 2 cohorts. The risk factors for FAEs through the 2 cohorts, other than low LVEF, included age ≥75 years, diabetes, heart failure, hemodialysis, atrial fibrillation, and anemia.

Background: Coronary artery calcification (CAC) detected through chest computed tomography (CT) strongly predicts cardiovascular events in asymptomatic individuals undergoing primary prevention. Few studies with limited sample sizes have investigated the predictive value of CAC for cardiovascular complications in COVID-19. This study examined the impact of CAC on cardiovascular complications using a large-scale COVID-19 database.

Methods and Results: This multicenter retrospective cohort study used data from the Japan COVID-19 Task Force database. After exclusion based on missing information, 1,109 patients with COVID-19 were included. The Agatston score was used to evaluate CAC, dividing the population into 3 groups based on calcification degree (no, moderate, and severe CAC). The primary outcome was cardiovascular complications; the secondary outcome was critical outcomes. The severe CAC group had a higher rate of cardiovascular complications than the other groups. Multivariable analysis, considering COVID-19 severity factors, identified severe CAC as independently associated with cardiovascular complications but not with critical outcomes. Subgroup analysis revealed that, in patients without hypertension, diabetes, cardiovascular disease, or chronic kidney disease, severe CAC was significantly correlated with cardiovascular complications, whereas this association was not observed in patients with these underlying conditions.

Conclusions: Patients with COVID-19 and severe CAC had increased cardiovascular complications, and identifying cardiovascular and pulmonary findings on chest CT is essential. Measuring CAC via non-electrocardiogram-gated CT helps predict patient risk.

Background: Few studies have investigated the clinical characteristics and in-hospital outcomes of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) using real-world databases in the coronary intervention era.

Methods and Results: We conducted a retrospective analysis of 22,236 patients (mean [±SD] age 68±13 years, 23.4% female) enrolled in the Japan Acute Myocardial Infarction Registry (JAMIR) between 2011 and 2016. Based on urgent coronary angiography findings, 286 (1.3%) patients were diagnosed as MINOCA, and the remaining 21,950 (98.7%) as MI with obstructive coronary artery disease (MI-CAD). MINOCA patients were characterized by younger age, fewer coronary risk factors, lower rate of ST-elevation myocardial infarction, lower Killip classification, and lower peak creatinine phosphokinase levels than MI-CAD patients. In-hospital all-cause mortality did not differ between the MINOCA and MI-CAD groups (5.2% vs. 5.7%, respectively; P=0.82). Comparing cause-specific mortality, non-cardiac mortality was higher in the MINOCA than MI-CAD group (4.2% vs. 1.6%; P<0.01). Importantly, non-cardiac death was more prevalent among elderly (≥65 years) than younger (<65 years) patients in the MI-CAD group, whereas this trend was not observed in the MINOCA group.

Conclusions: Analysis of the real-world JAMIR database revealed a relatively high prevalence of non-cardiac death among MINOCA patients, underscoring the need for comprehensive management to improve disease prognosis, particularly in younger patients.