Background: It is not known whether clopidogrel use in cytochrome P450 (CYP) 2C19 loss-of-function (LOF) carriers with high bleeding risk (HBR) contributes to adverse outcomes after percutaneous coronary intervention (PCI).

Methods and Results: This retrospective observational study included 618 consecutive patients with available CYP2C19 polymorphism information who underwent PCI between September 2014 and August 2021. Patients with HBR (319 [52%] met the Academic Research Consortium definition) were divided into 2 groups according to P2Y₁₂inhibitor action, namely decreased (i.e., clopidogrel in CYP2C19 LOF carriers) and retained (i.e., clopidogrel in CYP2C19 LOF non-carriers or prasugrel regardless of CYP2C19 polymorphisms), and clinical outcomes at 1 year were compared using inverse probability-weighted Cox proportional hazard regression. The primary ischemic outcome (a composite of cardiovascular death, myocardial infarction, or ischemic stroke) was significantly higher in the decreased than retained group (10.2% vs. 3.0%; adjusted hazard ratio [aHR] 2.78; 95% confidence interval [CI] 1.40–5.52; P=0.004). The primary bleeding outcome (Bleeding Academic Research Consortium 3 or 5) did not differ significantly between the decreased and retained groups (3.4% vs. 6.9%, respectively; aHR 0.48; 95% CI 0.22–1.01; P=0.054). There were no interactions between the treatment groups and HBR status in primary ischemic and bleeding outcomes.

Conclusions: Among patients with HBR, clopidogrel use in CYP2C19 LOF carriers was significantly associated with increased ischemic events after PCI.

Background: Because of revisions to insurance reimbursement costs, medical fees have changed for investigations and percutaneous coronary intervention (PCI) treatment of chronic coronary syndrome (CCS). In this retrospective study, we investigated these changes and their effects on mortality and cardiovascular events.

Methods and Results: We included 1,483 patients who underwent elective PCI for CCS between April 2010 and September 2019. The primary outcomes were changes in PCI procedure fees and all included hospitalization fees due to the biennial revisions of reimbursement costs across 5 time periods (~2 years each). Secondary outcomes were rates of survival and freedom from major adverse cerebral and cardiovascular events (MACCE) in each time period. Patient characteristics were generally unchanged over the study period; however, treatment procedures changed significantly, with changes in the approach site (from transfemoral to transradial access; P<0.0001) and final device (from bare-metal stents to drug-eluting stents; P<0.0001), and an increase in the use of imaging modalities (P<0.0001). Medical fee parameters (primary outcomes) decreased significantly from 2010 to 2019 (P<0.001): PCI procedure fees decreased by 25%, whereas all included hospitalization fees decreased by 20%. There were no significant differences in survival or freedom-from-MACCE rates between periods.

Conclusions: Because of revisions to reimbursement prices, there were rapid and significant decreases in PCI procedure and hospitalization fees for CCS. These changes had no effect on mortality or cardiovascular events.

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.

Background: Angiographic fractional flow reserve (angioFFR) is a novel artificial intelligence (AI)-based angiography-derived fractional flow reserve (FFR) application. We investigated the diagnostic accuracy of angioFFR to detect hemodynamically relevant coronary artery disease.

Methods and Results: Consecutive patients with 30–90% angiographic stenoses and invasive FFR measurements were included in this prospective, single-center study conducted between November 2018 and February 2020. Diagnostic accuracy was assessed using invasive FFR as the reference standard. In patients undergoing percutaneous coronary intervention, gradients of invasive FFR and angioFFR in the pre-senting segments were compared. We assessed 253 vessels (200 patients). The accuracy of angioFFR was 87.7% (95% confidence interval [CI] 83.1–91.5%), with a sensitivity of 76.8% (95% CI 67.1–84.9%), specificity of 94.3% (95% CI 89.5–97.4%), and area under the curve of 0.90 (95% CI 0.86–0.93%). AngioFFR was well correlated with invasive FFR (r=0.76; 95% CI 0.71–0.81; P<0.001). The agreement was 0.003 (limits of agreement: −0.13, 0.14). The FFR gradients of angioFFR and invasive FFR were comparable (n=51; mean [±SD] 0.22±0.10 vs. 0.22±0.11, respectively; P=0.87).

Conclusions: AI-based angioFFR showed good diagnostic accuracy for detecting hemodynamically relevant stenosis using invasive FFR as the reference standard. The gradients of invasive FFR and angioFFR in the pre-stenting segments were comparable.

Background: The saphenous vein (SV) is used as an essential conduit in coronary artery bypass grafting (CABG), but the long-term patency of SV grafts is a crucial issue. The use of the novel “no-touch” technique of harvesting the SV together with its surrounding tissue has been reported to result in good long-term graft patency of SV grafts. We recently showed that perivascular adipose tissue (PVAT) surrounding the SV (SV-PVAT) had lower levels of metaflammation and consecutive adipose tissue remodeling than did PVAT surrounding the coronary artery. However, the difference between SV-PVAT and subcutaneous adipose tissue (SCAT) remains unclear.

Methods and Results: Fat pads were sampled from 55 patients (38 men, 17 women; mean [±SD] age 71±8 years) with coronary artery disease who underwent elective CABG. Adipocyte size was significantly larger in SV-PVAT than SCAT. The extent of fibrosis was smaller in SV-PVAT than SCAT. There were no significant differences between SCAT and SV-PVAT in macrophage infiltration area, quantified by antibodies for CD68, CD11c, and CD206, or in gene expression levels of metaflammation-related markers. Expression patterns of adipocyte developmental and pattern-forming genes differed between SCAT and SV-PVAT.

Conclusions: The properties of SV-PVAT are close to, but not the same as, those of SCAT, possibly resulting from inherent differences in adipocytes. SV-PVAT has healthy expansion with less fibrosis in fat than SCAT.

Background: Plaque characteristics associated with effective intravascular lithotripsy (IVL) treatment of calcification have not been investigated. This study identified calcified plaque characteristics that favor the use of IVL.

Methods and Results: Optical coherence tomography (OCT) was performed in 16 calcified lesions in 16 patients treated with IVL and coronary stenting. Cross-sectional OCT images in 262 segments matched across pre-IVL, post-IVL, and post-stenting time points were analyzed. After IVL, 66 (25%) segments had calcium fracture. In multivariable analysis, calcium arc (odds ratio [OR] 1.22; 95% confidence interval [CI] 1.13–1.32; P<0.0001), superficial calcification (OR 6.98; 95% CI 0.07–55.57; P=0.0182), minimum calcium thickness (OR 0.66; 95% CI 0.51–0.86; P=0.0013), and nodular calcification (OR 0.24; 95% CI 0.08–0.70; P=0.0056) were associated with calcium fracture. After stenting, stent area was larger for segments with fracture (8.0 [6.9–10.6] vs. 7.1 [5.2–8.9] mm²; P=0.004).

Conclusions: Post-IVL calcium fracture is more likely in calcified lesions with lower thickness, a larger calcium arc, superficial calcification, and non-nodular calcification, leading to a larger stent area.

Background: Recently, the function of high-density lipoprotein (HDL), rather than the HDL cholesterol (HDL-C) level, has been attracting more attention in risk prediction for coronary artery disease (CAD).

Methods and Results: Patients with clinically diagnosed familial hypercholesterolemia (FH; n=108; male/female, 51/57) were assessed cross-sectionally. Serum cholesterol uptake capacity (CUC) levels were determined using our original cell-free assay. Linear regression was used to determine associations between CUC and clinical variables, including low-density lipoprotein cholesterol and the carotid plaque score. Multivariable logistic regression analysis was used to test factors associated with the presence of CAD. Among the 108 FH patients, 30 had CAD. CUC levels were significantly lower among patients with than without CAD (median [interquartile range] 119 [92–139] vs. 142 [121–165] arbitrary units [AU]; P=0.0004). In addition, CUC was significantly lower in patients with Achilles tendon thickness ≥9.0 mm than in those without Achilles tendon thickening (133 [110–157] vs. 142 [123–174] AU; P=0.047). Serum CUC levels were negatively correlated with the carotid plaque score (Spearman’s r=0.37; P=0.00018). Serum CUC levels were significantly associated with CAD, after adjusting for other clinical variables (odds ratio=0.86, 95% CI=0.76–0.96, P=0.033), whereas HDL-C was not.

Conclusions: HDL function, assessed by serum CUC level, rather than HDL-C level, adds risk stratification information among FH patients.

Background: Whether the magnitude and predictors of improvement in exercise capacity after cardiac rehabilitation (CR) are the same between young-old (YO) and octogenarian (OCT) patients with acute myocardial infarction (AMI) is unknown.

Methods and Results: We studied 284 YO (age range 65–69 years; mean [±SD] 67±1 years) and 65 OCT (age range ≥80 years; mean [±SD] 83±2 years) patients who participated in a post-AMI CR program. After 3 months of CR, peak oxygen uptake (PV̇O₂) measured during cardiopulmonary exercise testing improved significantly in both age groups (P<0.01), although the percentage increase in PV̇O₂(%∆PV̇O₂) was significantly smaller in the OCT than YO group (5.4±13.7% vs. 10.0±12.8%; P<0.01). Multiple regression analysis demonstrated that independent predictors of %∆PV̇O₂were the number of outpatient CR (OPCR) sessions attended (P=0.015), left ventricular ejection fraction (P=0.028), and baseline PV̇O₂(P=0.0007) in the YO group; and the number of sessions attended (P=0.018), atrial fibrillation (P=0.042), and the presence of nutritional risk (Geriatric Nutritional Risk Index ≤98; P=0.036) in the OCT group.

Conclusions: The predictors of improvement in exercise capacity after CR differed between the YO and OCT patients with AMI. To obtain a greater improvement in PV̇O₂in CR, frequent OPCR session attendance may be necessary in both groups; in addition, particularly in OCT patients, better nutritional status may be important.

Background: MicroRNA (miR)-143 and miR-145 are non-coding RNAs present in smooth muscle cells and the heart. However, their behavior and physiological role in patients with acute myocardial infarction (AMI) have not been clarified.

Methods and Results: Plasma miR-143 and miR-145 concentrations were measured on Day 0 (on admission) and on Day 7 in AMI patients who could be followed up for 6 months (n=25). The control group consisted of subjects without significant coronary stenosis (n=20). Blood samples were collected from the antecubital vein, and plasma miR-143 and miR-145 concentrations were measured by quantitative reverse transcription-polymerase chain reaction. In AMI patients (n=25), left ventricular ejection fraction (LVEF) was measured by echocardiography in the acute and chronic (6 months) phases. On Day 7, plasma miR-143 and miR-145 concentrations were significantly higher in AMI patients than in the control group and on Day 0 in AMI patients. Plasma miR-143 and miR-145 concentrations increased significantly from Day 0 to Day 7. The increase in plasma miR-143 concentrations (∆miR-143) in the acute phase was positively correlated with the increase in LVEF in the chronic phase. Among many factors, only ∆miR-143 was favorably correlated with left ventricle (LV) functional recovery in the chronic phase.

Conclusions: An increase in plasma miR-143 concentrations in the acute phase may be a biomarker predicting recovery of LV function in the chronic phase in AMI patients.

Background: This study evaluated the safety and effectiveness of alirocumab in Japanese patients with familial hypercholesterolemia (FH) or non-FH in a real-world clinical setting.

Methods and Results: This post-marketing surveillance study had a 2-year standard observation period. The study included Japanese patients with hypercholesterolemia who were treatment naïve to alirocumab, had a high risk of developing cardiovascular events, and had an insufficient response to, or were unsuitable for, treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Alirocumab was administered at a dose of 75 or 150 mg via subcutaneous injection every 2 or 4 weeks. Overall, 1,177 and 1,038 patients were included in the safety and effectiveness analysis populations, respectively. The incidence of adverse drug reactions (ADRs) was 3.4% (40/1,177). The time to ADR occurrence was within 4 weeks in half the patients experiencing ADRs (n=20). There were no meaningful differences in the ADRs experienced in the FH and non-FH groups. The mean (±SE) percentage changes in low-density lipoprotein cholesterol from baseline to last observation carried forward were −46.9±2.1% and −42.7±2.0% in the non-FH and FH groups, respectively. Total cholesterol, triglycerides, apolipoprotein B/E, and lipoprotein(a) concentrations were decreased at Week 4 and maintained until Week 104 in the overall population.

Conclusions: Alirocumab was well tolerated and showed effectiveness in Japanese patients with hypercholesterolemia in a real-world clinical setting.

Background: Robot-assisted valve surgery represents the latest development in the field of minimally invasive approaches. Robotic assistance may provide greater visualization, enhanced dexterity, and greater precision than traditional mini-thoracotomy aortic valve replacement.

Methods and Results: Aortic valve replacement operations using the da Vinci Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) were performed on 2 patients, 1 with severe aortic insufficiency and the other with aortic stenosis. Both patients had an uneventful postoperative course and were discharged without any adverse events.

Conclusions: Robot-assisted assisted aortic valve replacement appears feasible and safe in limited cases.

Background: P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS).

Methods and Results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis.

Conclusions: This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This “aspirin-free” strategy may be a safe alternative to traditional DAPT following PCI.