Spontaneous coronary artery dissection (SCAD) is an increasingly recognized, non-atherosclerotic cause of acute coronary syndrome (ACS), predominantly affecting younger women without traditional cardiovascular risk factors. SCAD results from an intramural hematoma or intimal tear that compresses the coronary lumen, leading to myocardial ischemia. Diagnosis is critical, as management differs fundamentally from atherosclerotic ACS. Conservative therapy is preferred for hemodynamically stable patients due to high rates of spontaneous vessel healing; revascularization is reserved for ongoing ischemia, hemodynamic instability or left main/multivessel involvement. Long-term management focuses on reducing recurrence risk through β-blocker therapy, strict blood pressure control, and individualized cardiac rehabilitation. Although outcomes are generally favorable, recurrence occurs in up to 20% of patients. Ongoing research is needed to refine antiplatelet strategies, identify genetic and vascular risk factors, and optimize preventive care.

Background: Adequate endothelization after drug-eluting stent (DES) implantation is essential to reduce thrombotic risk. Adequate strut coverage (ASC) is defined as ≥40 μm on optical coherence tomography, but its functional significance remains uncertain. Coronary angioscopy can assess neointimal function by detecting thrombus and plaque color. This study evaluated functionally adequate endothelization and contributing factors after DES implantation.

Methods and Results: Post hoc analyses of the COLLABORATION 1 and 2 studies were performed using serial optical coherence tomography and coronary angioscopy 1 and 12 months after DES implantation. Four DES types were examined: durable polymer everolimus-eluting stent (DP-EES); sirolimus-eluting stent (SES); polymer-free biolimus-coated stent (PF-BCS); and dual-therapy sirolimus-eluting stent (DTS). PF-BCS and DTS were classified as “ingenious” DES, and DP-EES and SES were classified as “fundamental.” The correlation between the percentage of struts with ≥40 μm coverage (%ASC) and functional neointima (i.e., no thrombus and white plaque) was assessed. Among 150 patients (177 lesions), thrombus and yellow plaque were inversely correlated with %ASC at 12 months. Cut-off values of %ASC were 67% for thrombus prevention and 90% for plaque stabilization. Multivariable analysis identified the use of ingenious DES, prasugrel therapy, and hypertension as independent predictors of chronic adequate endothelization.

Conclusions: Functional protection against thrombus requires %ASC ≥67%, and plaque stabilization requires ≥90%. The use of ingenious DESs and prasugrel contributes to improved chronic adequate endothelization.

Background: Chronic kidney disease is associated with an increased incidence of stent thrombosis (ST) following drug-eluting stent (DES) implantation, but the clinical outcomes after DES-ST in hemodialysis (HD) patients compared with non-HD patients have not been fully elucidated.

Methods and Results: From the REAL-ST registry, we evaluated 655 patients with DES-ST, divided into 2 groups: HD group (n=59) and non-HD group (n=596). The primary endpoint was the cumulative 3-year incidence of all-cause death after the index ST event. Late ST was more prevalent in the HD group, whereas early and very late ST were common in the non-HD group. Following the index ST event, the HD group showed significantly higher 3-year incidences of all-cause death (48.2% vs. 22.9%, P=0.0005), cardiac death (33.4% vs.15.8%, P=0.003) and target lesion revascularization (TLR: 36.2% vs. 17.5%, P=0.0002) compared with the non-HD group. The cumulative 3-year incidence of recurrent ST did not differ significantly between groups (7.3% vs. 5.9%, P=0.88). After multivariable adjustment, HD remained significantly associated with an increased risk of all-cause death (adjusted hazard ratio [aHR], 1.95; 95% confidence interval [CI], 1.25–3.04; P=0.003), cardiac death (aHR, 1.75; 95% CI, 1.02–2.99; P=0.04) and TLR (aHR, 2.63; 95% CI, 1.52–4.57; P<0.001).

Conclusions: Compared with non-HD patients, HD patients experienced worse clinical outcomes following their index DES-ST event.

Background: The retrograde approach improves the procedural success rate of chronic total occlusion percutaneous coronary interventions (CTO-PCIs). However, it remains unclear whether the primary retrograde approach (PRA) offers benefits in terms of procedural success and burden/resource use in challenging cases. Therefore, we compared efficacy between the primary antegrade approach (PAA) and PRA in complex CTO-PCIs.

Methods and Results: This single-center retrospective cohort study included all patients undergoing coronary CTO-PCI attempted by experienced high-volume operators between January 2016 and July 2023. The difficulty of the antegrade approach was determined using the Japanese CTO score, and the feasibility of interventional collaterals was determined using the collateral channel score. In 698 patients undergoing CTO-PCI, the overall technical and initial guidewire success rates were 91.4% and 83.8%, respectively. Of 380 patients with a Japanese CTO score ≥3 and a collateral channel score ≥2, PAA and PRA were performed in 161 (42.4%) and 219 (57.6%) patients, respectively. Initial guidewire success was higher with PRA than PAA (88.1% vs. 78.9%; P=0.01), and bail-out success was higher for a retrograde than antegrade approach (91.2% vs. 56%; P=0.0019). PRA was associated with longer guidewire crossing time, longer fluoroscopy time, and greater contrast use.

Conclusions: In patients with challenging CTO, poor antegrade conditions, and feasible interventional collaterals, PRA achieved higher initial guidewire success at the expense of higher procedural burden/resource use.

Background: Because the prognostic value of lipoprotein(a) [Lp(a)] levels in Japanese patients remains unclear, we assessed their distribution and association with long-term outcomes in ST-segment elevation myocardial infarction (STEMI).

Methods and Results: In our retrospective analysis of 868 consecutive patients with STEMI, the median serum Lp(a) level was 15.75 mg/dL at admission, and the median follow-up was 736.5 days. Using restricted cubic spline analysis, we stratified patients into high (≥47.26 mg/dL) and low (<47.26 mg/dL) Lp(a) groups. The high Lp(a) group had a higher proportion of older and female patients, with lower body weight, estimated glomerular filtration rate, and stent use, and higher dyslipidemia prevalence than those in the low Lp(a) group. The 5-year cumulative incidence of the composite primary endpoint (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or any revascularization) was significantly higher in the high Lp(a) group, primarily because of a high rate of any revascularization. Patients with elevated Lp(a) levels demonstrated higher rates of any revascularization for both de novo and restenotic lesions than those with lower levels. After adjusting for confounders, a high Lp(a) level was identified as an independent predictor of the primary endpoint (hazard ratio:1.932; 95% confidence interval:1.255–2.974).

Conclusions: In Japanese patients with STEMI, elevated Lp(a) levels were independently associated with worse long-term outcomes.

Background: This study investigated whether small dense low-density lipoprotein cholesterol (sdLDL-C) can predict long-term coronary artery disease (CAD) events in patients with stable CAD without metabolic dyslipidemia.

Methods and Results: Directly measured sdLDL-C was evaluated in 396 male and 144 female patients with stable CAD who had high-density lipoprotein cholesterol (HDL-C) ≥40 mg/dL and triglyceride <150 mg/dL. CAD events, which were defined as sudden cardiac death, acute coronary syndrome onset, and/or a need for coronary revascularization, were monitored for 12 years. First-time CAD events were observed in 110 men and 44 women. Kaplan-Meier event-free survival curves showed that patients with sdLDL-C ≥32.5 mg/dL (top quartile) had an increased risk of CAD events (log-rank P=0.009). The multivariate-adjusted hazard ratio (HR) in the top sdLDL-C quartile was 1.632 (95% confidence interval 1.159–2.297) and remained significant in 354 patients treated with statins (HR 1.582; P=0.041), whereas the risk in the top quartiles of LDL-C, non-HDL-C, apolipoprotein B, and triglyceride was not significantly higher relative to lower quartiles. Receiver operating characteristic curve analyses indicated that risk increased at cut-off values of sdLDL-C ≥32.2 mg/dL (HR 1.566; P=0.011) and sdLDL-C/LDL-C ratio ≥0.316 (HR 1.569; P=0.018).

Conclusions: Although sdLDL is a feature of metabolic dyslipidemia, high sdLDL-C can predict long-term recurrence of CAD events even in patients without metabolic dyslipidemia.

Background: This study compared changes in percentage atheroma volume (PAV) using an end-diastolic (ED) intravascular ultrasound (IVUS) segmentation approach vs. the conventional 1-mm interval analysis in serial IVUS data from the PACMAN-AMI trial.

Methods and Results: IVUS data from the PACMAN-AMI study were analyzed by 2 core laboratories: one with 1-mm segmentation and the other with an ED-based approach. The same arterial segments were assessed at baseline and at the 52-week follow-up in patients receiving alirocumab or placebo. Changes in segment length, lumen, vessel, total atheroma volume (TAV), and PAV between baseline and follow-up were compared between methods. Biomarkers associated with atherosclerotic progression were measured and correlated with TAV and PAV changes. In all, 387 segments were analyzed. Agreement between conventional and ED volumetric analysis was excellent (intraclass coefficient >0.891, P<0.001). TAV and PAV were larger in both groups in the ED analysis than with the conventional approach; however, changes between treatment arms were similar for the conventional and ED analyses (TAV: 14.34 vs. 14.64 mm³, respectively [P=0.823]; PAV: 1.29% vs. 1.25%, respectively [P=0.911]). Biomarker correlations with TAV and PAV changes did not differ between approaches.

Conclusions: ED- and 1-mm-based analyses demonstrated comparable treatment effects of alirocumab on plaque regression in PACMAN-AMI. These findings support the use of the less time-consuming 1-mm segmentation method in serial IVUS studies.

Background: Intracoronary imaging-derived physiologic indices enable vessel-level assessment of coronary flow impairment by integrating obstructive plaque burden. However, accurately evaluating hyperemic flow remains challenging due to the difficulty of simultaneously incorporating both vascular geometry and plaque composition.

Methods and Results: We aimed to develop and validate a deep learning algorithm using optical coherence tomography (OCT) to predict continuous, lesion-specific changes in fractional flow reserve (∆FFR) along coronary segments. Model performance was evaluated using Pearson’s correlation, a confusion matrix, and a receiver operating characteristic (ROC) curve, with invasive wire-based FFR as the reference. The model was trained and tested on 157 OCT pullbacks from 86 patients, demonstrating enhanced predictive performance by incorporating anatomical and compositional OCT features compared to conventional feature-based machine learning approaches. Predicted ∆FFR_OCTvalues correlated strongly with wire-based ∆FFR (R=0.932, P<0.001), achieving an accuracy of 0.952 for detecting physiologically significant lesions and an area under the curve of 0.953 in the ROC analysis. The model accurately localized segmental pressure gradients, effectively distinguishing focal from diffuse disease patterns.

Conclusions: This novel deep learning-based algorithm enabled lesion-specific, pressure wire-free physiologic assessment from a single OCT pullback. By integrating anatomical and compositional data, it supported improved diagnostic accuracy and personalized treatment for coronary artery disease.

Background: Acute coronary syndrome (ACS) patients remain at risk from non-culprit lesions. This study used serial optical coherence tomography (OCT) to explore metabolic profiles and morphological evolution (vulnerability progression or regression) of non-culprit lesions in ACS patients.

Methods and Results: This study included 406 ACS patients with 1,054 non-culprit lesions who underwent OCT at baseline and at the 1-year follow-up (median 368 days). Non-culprit plaques were classified as lipid rich (thin- [TCFA] or thick [ThCFA]-cap fibroatheroma [fibrous cap thickness <65 and ≥65 μm, respectively]), fibrous, or calcified. Patients were stratified into vulnerability progression (≥1 plaque progressing from non-TCFA to TCFA), regression (≥1 plaque regressing from TCFA to non-TCFA), or no-change groups. Vulnerability progression occurred in 10 patients (11 lesions), all from ThCFA to TCFA. Vulnerability regression occurred in 96 patients (118 lesions), mainly from TCFA to ThCFA (109 lesions). Patients with progression were older (mean age 64.4 vs. 53.1 years; P=0.005) and had higher rates of diabetes (80.0% vs. 34.4%; P<0.001) and hypertension (70.0% vs. 56.3%; P=0.046). Regression was accompanied by an increase in layered plaques (+17%) and calcium deposition (+9%), associated with greater reductions in low-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B. Changes in lipid arc and fibrous cap thickness were positively correlated with on-treatment low-density lipoprotein cholesterol levels.

Conclusions: Serial OCT identified divergent non-culprit lesion trajectories closely associated with lipid lowering. Intensive lipid-lowering therapy is critical for high-risk patients, and OCT enables objective evaluation of plaque stabilization.

Background: The optimal treatment for functionally insignificant intermediate stenosis in non-infarct-related artery (IRA) after acute myocardial infarction (AMI) remains controversial. We identified high-risk non-IRAs using quantitative flow ratio (QFR)-derived physiological indices and evaluated their prognostic and therapeutic implications.

Methods and Results: We retrospectively assessed QFR-derived physiology in 240 non-IRAs (189 deferred [Defer group], 51 treated [percutaneous coronary intervention (PCI) group]) with diameter stenosis ≥40% and QFR ≥0.8 in 205 AMI patients treated between January 2014 and December 2023. In the Defer group, physiological indices associated with target vessel failure (TVF) were identified, and their discriminative performance and optimal cut-off values were determined using time-dependent receiver operating characteristic curve analysis with the Youden index. Adding QFR pressure pullback gradient (PPG) to QFR significantly enhanced time-dependent risk reclassification, as reflected by net reclassification improvement (P=0.039) and integrated discrimination improvement (P=0.023). After stratification using Youden-derived 3-year optimal cut-off values of 0.88 for QFR and 0.78 for QFR-PPG, deferred non-IRAs with high-risk physiology (QFR <0.88 and QFR-PPG <0.78) had a significantly higher 3-year TVF rate than those without high-risk physiology (42.1% vs. 9.9%; P<0.001). Among high-risk non-IRAs, the TVF rate was significantly higher in the Defer than PCI group, whereas it was similar among non-IRAs without high-risk physiology (P for interaction=0.040).

Conclusions: QFR-derived physiology, including QFR and QFR-PPG, can stratify high-risk non-IRAs and guide optimal treatment in patients with AMI.

Background: No studies have compared aspirin to P2Y₁₂inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients with diabetes.

Methods and Results: We conducted a prespecified diabetes subgroup analysis of the 1-year STOPDAPT-3 trial; patients were randomized at the time of index PCI, and outcomes from 30 days to 1 year were assessed using a 30-day landmark analysis comparing 1-month DAPT followed by aspirin monotherapy (aspirin group) to 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). The effect of aspirin relative to clopidogrel was not significant for the coprimary cardiovascular endpoint (composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) regardless of diabetes (aspirin/clopidogrel 5.3/5.6 vs. 3.9/3.7 per 100 person-years for diabetes vs. non-diabetes, respectively; hazard ratios [HRs] 0.96 [95% confidence interval {CI} 0.67–1.37] and 1.06 [95% CI 0.72–1.55], respectively; P_interaction=0.71), but there was a significant interaction between diabetes and the effect of aspirin relative to clopidogrel for the coprimary bleeding endpoint (Bleeding Academic Research Consortium 3 or 5; aspirin/clopidogrel 2.8/1.8 vs. 1.3/2.0 per 100 person-years diabetes vs. non-diabetes, respectively; HR 1.54 [95% CI 0.88–2.71] vs. 0.65 [95% CI 0.36–1.17], respectively; P_interaction=0.04).

Conclusions: From 30 days to 1 year after PCI, cardiovascular outcomes were similar between aspirin and clopidogrel regardless of diabetes. A nominal bleeding interaction was observed; given the exploratory and underpowered subgroup analyses, this finding should be interpreted cautiously.

Background: Although the COVID-19 pandemic has impacted the management of acute coronary syndrome (ACS), the prognostic implications for ACS patients with concurrent COVID-19 undergoing percutaneous coronary intervention (PCI) remain to be determined, particularly in large nationwide cohorts. This study investigated the association between concomitant COVID-19 and clinical outcomes in patients undergoing emergent PCI for ACS.

Methods and Results: This retrospective cohort study utilized data from the Japanese Percutaneous Coronary Intervention (J-PCI) nationwide registry, encompassing all patients presenting with ACS who underwent primary or emergent PCI between January 2021 and December 2023. Multivariable logistic regression models were employed to ascertain the independent association between COVID-19 positivity and in-hospital all-cause and cardiovascular mortality. The analysis included 279,662 ACS patients, of whom 1,812 (0.65%) tested positive for COVID-19. After multivariable adjustment, COVID-19 remained an independent predictor of in-hospital all-cause mortality (adjusted odds ratio [aOR] 1.46; 95% confidence interval [CI] 1.21–1.77). The association between COVID-19 and cardiovascular mortality was significant in univariable analysis but not after multivariable adjustment (aOR 1.22; 95% CI 0.98–1.52).

Conclusions: In this nationwide cohort, concomitant COVID-19 was independently associated with higher in-hospital all-cause mortality among patients with ACS undergoing PCI. These findings highlight the need for heightened surveillance and consideration of tailored therapeutic strategies in this high-risk population.

Background: Type 2 diabetes (T2D) substantially increases coronary artery disease (CAD) risk, with residual risk unexplained by conventional factors. Immunometabolic dysregulation, particularly in monocytes, is implicated, but causal cell type-resolved evidence is limited.

Methods and Results: We integrated peripheral blood mononuclear cells’ bulk and single-cell transcriptomes, identifying 1,799 differentially expressed genes enriched in immune and metabolic pathways. Two-sample Mendelian randomization identified 10 genes showing genetically predicted associations with both T2D and CAD. Among these, ADM, PGD, and ATG7 showed consistent genetically predicted associations with higher CAD risk. Single-cell analyses localized these genes to monocyte subsets and revealed enhanced intercellular communication with vascular cells. The genes also showed good discriminatory performance for CAD in T2D (AUCs 0.741–0.837).

Conclusions: Multi-omics integration and genetic analyses supported a monocyte-centered immunometabolic framework involving ADM, PGD, and ATG7 that was consistent with elevated CAD risk in T2D, and generated testable hypotheses.

Background: Visceral fat (VF), particularly epicardial adipose tissue (EAT), plays a crucial role in the development of coronary artery disease (CAD). Cathelicidin (LL37) is an antimicrobial peptide involved in innate immunity and has been implicated in inflammatory processes. However, the relationship between VF accumulation, cathelicidin, and atherosclerosis remains unclear.

Methods and Results: Seventy-eight subjects without CAD were enrolled and classified by obesity type: normal-weight (normal; n=20), subcutaneous fat (SF; n=19), and VF (n=39). Plasma LL37 concentrations were compared across groups. LL37 expression in EAT was assessed in 9 patients undergoing open-heart surgery, stratified by CAD status. In animal experiments, angiotensin II-infused wild-type and Apoe^−/−mice fed a Western-type diet were treated with cathelicidin-related antimicrobial peptide (CRAMP) small interfering RNA (siRNA), scrambled siRNA, or vehicle. Atherosclerotic lesions were evaluated by enface Sudan IV staining. Plasma LL37 concentrations were higher in the VF than in the normal-weight and SF groups (median [IQR] 99.11 [91.70–129.86] vs. 58.63 [50.03–70.05] and 69.81 [54.64–87.39] ng/mL, respectively; P<0.001) and were correlated with VF area and EAT volume. LL37 expression in EAT was higher in patients with than without CAD (2.34 [2.06–3.90] % vs. 1.34 [0.81–1.49] %; P=0.034). Treatment with CRAMP siRNA significantly reduced atherosclerotic lesion area in Apoe^−/−mice without affecting blood pressure or lipid profiles.

Conclusions: LL37 is associated with VF accumulation and CAD. However, these findings are exploratory and warrant prospective validation to determine its potential utility as a biomarker.

Background: We aimed to clarify the impact of genetic testing on major adverse cardiovascular events (MACE) among patients with heterozygous familial hypercholesterolemia (HeFH) using data from the Hokuriku-plus FH Registry (UMIN000038210).

Methods and Results: In all, 431 patients were enrolled in the study, with a median follow-up of 3.9 years. The primary outcome was time to first MACE, defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, or non-fatal stroke. Using Cox proportional hazards regression models, we examined whether undergoing genetic testing was associated with a reduced risk of MACE. Among the 431 patients, sufficient data were available for 386 with HeFH, of whom 202 (52.3%) underwent genetic testing. Low-density lipoprotein cholesterol (LDL-C) levels at follow-up were significantly lower in group that underwent genetic testing than in the group that did not (median 102 vs. 130 mg/dL, respectively; P<0.001). During follow-up, 23 MACE occurred (18 in the non-testing group and 5 in the genetic testing group). Notably, undergoing genetic testing was significantly associated with a reduced risk of MACE, even after adjusting for LDL-C levels (hazard ratio 0.66; 95% confidence interval 0.20–0.92; P=0.033).

Conclusions: Genetic testing in patients with HeFH was associated with a reduced risk of MACE independent of LDL-C. Randomized controlled trials will be needed to clarify whether providing genetic testing can reduce MACE among patients with HeFH.

Background: Although Achilles tendon thickening (ATT) is associated with poor prognosis after percutaneous coronary intervention (PCI), its impact may differ between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS).

Methods and Results: We retrospectively analyzed 1,362 patients after PCI. ATT was present in 228 patients (16.7%) and associated with more 3-year major adverse cardiovascular events (MACE) (P<0.001). The association was pronounced in ACS patients (P=0.001), whereas in CCS patients, ATT showed a non-significant trend toward a higher incidence of MACE (P=0.066).

Conclusions: ATT may be a simple, non-invasive marker for risk stratification after PCI, particularly in ACS patients.

Background: The optimal timing for lactate sampling during acetylcholine (ACh) provocation to detect metabolic ischemia remains unclear.

Methods and Results: In 20 patients with suspected INOCA, blood samples from the coronary artery and coronary sinus were obtained at baseline, every minute for 5 min after ACh, and after nitroglycerin. Metabolic ischemia (negative lactate extraction ratio) occurred in 12 patients: 10 patients exhibited ischemia at 1 min, and 2 patients only at 2 min. No ischemia was observed beyond 3 min.

Conclusions: Sampling at both 1 and 2 min may reduce false-negative detection of metabolic ischemia during ACh provocation.