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The presence of macrophages within the plaque is a defining hallmark of atherosclerosis. Macrophages are exposed to various microenvironments such as oxidized lipids and cytokines which effect their phenotypic differentiation and activation. Classically, macrophages have been divided into two groups: M1 and M2 macrophages induced by T-helper 1 and T-helper 2 cytokines, respectively. However, for a decade, greater phenotypic heterogeneity and plasticity of these cells have since been reported in various models. In addition to M1 and M2 macrophage phenotypes, the concept of additional macrophage phenotypes such as M (Hb), Mox, and M4 has emerged. Understanding the mechanisms and functions of distinct phenotype of macrophages can lead to determination of their potential role in atherosclerotic plaque pathogenesis. However, there are still many unresolved controversies regarding their phenotype and function with respect to atherosclerosis. Here, we summarize and focus on the differential subtypes of macrophages in atherosclerotic plaques and their differing functional roles based upon microenvironments such as lipid, intraplaque hemorrhage, and plaque regression.

Implantation of drug-eluting stents (DES) is the dominant treatment strategy for patients with symptomatic coronary artery disease. However, the first-generation DES had substantial drawbacks, including delayed healing, local hypersensitivity reactions and neoatherosclerosis, which all led to a steady increase in major adverse cardiovascular events over time. Subsequently, newer-generation DES were introduced with thinner struts, different scaffold designs (to improve deliverability while maintaining radial strength), different durable and biodegradable polymers — and in some cases no polymer (to improve vascular biocompatibility) — and new antiproliferative drug types and doses. Currently, >30 different DES are commercially available in Europe, with fewer available in the USA but with many new entrants coming onto the US market in the next few years. Never before have cardiologists been faced with so many choices of stent, each with its own unique design. In this Review, we detail preclinical and pathology studies for each stent design, examining thromboresistance, speed of neointimal coverage and completeness of healing, including endothelialization. We conclude by discussing how these design characteristics might affect the potential for shortening the minimum duration of dual antiplatelet therapy needed after coronary intervention.

INTRODUCTION: Bioprosthetic valve failure after mitral valve replacement is a well-recognized phenomenon, with pannus overgrowth being one notable cause. The standard treatments include redo surgical mitral valve replacement and the less invasive transcatheter treatment, mitral valve-in-valve. However, the feasibility and safety of performing mitral valve-in-valve when pannus overgrowth has reduced the valvular opening to a mere pinhole remains uncertain.CASE PRESENTATION: A 76-year-old woman, who had previously undergone mitral valve replacement, was admitted for congestive heart failure. Severe mitral stenosis and severe mitral regurgitation were diagnosed using transthoracic echocardiography. During redo mitral valve replacement, we observed that the prosthetic valve leaflets on the left atrial side were almost entirely covered with pannus tissue, leaving only a central pinhole for blood flow. Macroscopic and microscopic examination of the bioprosthesis revealed accordion-like leaflet deformation on the ventricular side.CONCLUSIONS: Although the transcatheter valve-in-valve procedure is recognized as a less invasive treatment option for degenerated biological valves, in certain cases such as ours, open surgery becomes imperative as the most appropriate treatment.

Post-operative pulmonary venous stenosis is a poor prognostic factor in single-ventricle haemodynamics. Implantation of a drug-eluting stent is a therapeutic option. However, due to their small size, they inevitably become inadequate as the patient grows. We present the first case, to the best of our knowledge, of the replacement of a small-diameter stent with a large-diameter stent during Fontan surgery.

The technology of percutaneous coronary intervention (PCI) is constantly being refined in order to overcome the shortcomings of present day technologies. Even though current generation metallic drug-eluting stents (DES) perform very well in the short-term, concerns still exist about their long-term efficacy. Late clinical complications including late stent thrombosis (ST), restenosis, and neoatherosclerosis still exist and many of these events may be attributed to either the metallic platform and/or the drug and polymer left behind in the arterial wall. To overcome this limitation, the concept of totally bioresorbable vascular scaffolds (BRS) was invented with the idea that by eliminating long-term exposure of the vessel wall to the metal backbone, drug, and polymer, late outcomes would improve. The Absorb-bioabsorbable vascular scaffold (Absorb-BVS) represented the most advanced attempt to make such a device, with thicker struts, greater vessel surface area coverage and less radial force versus contemporary DES. Unfortunately, almost one year after its initial approval by the U.S. Food and Drug Administration, this scaffold was withdrawn from the market due to declining devise utilization driven by the concerns about scaffold thrombosis (ScT) seen in both early and late time points. Additionally, the specific causes of ScT have not yet been fully elucidated. In this review, we discuss the platform, vascular response, and clinical data of past and current metallic coronary stents with the Absorb-BVS and newer generation BRS, concentrating on their material/design and the mechanisms of thrombotic complications from the pre-clinical, pathologic, and clinical viewpoints.

Previous studies have reported that a high neutrophil-to-lymphocyte ratio (NLR) is associated with disease severity and poor prognosis in COVID-19 patients. We aimed to investigate the clinical implications of NLR in patients with COVID-19 complicated with cardiovascular diseases and/or its risk factors (CVDRF). In total, 601 patients with known NLR values were selected from the CLAVIS-COVID registry for analysis. Patients were categorized into quartiles (Q1, Q2, Q3, and Q4) according to baseline NLR values, and demographic and clinical parameters were compared between the groups. Survival analysis was conducted using the Kaplan–Meier method. The diagnostic performance of the baseline and follow-up NLR values was tested using receiver operating characteristic (ROC) curve analysis. Finally, two-dimensional mapping of patient characteristics was conducted using t-stochastic neighborhood embedding (t-SNE). In-hospital mortality significantly increased with an increase in the baseline NLR quartile (Q1 6.3%, Q2 11.0%, Q3 20.5%; and Q4, 26.6%; p < 0.001). The cumulative mortality increased as the quartile of the baseline NLR increased. The paired log-rank test revealed significant differences in survival for Q1 vs. Q3 (p = 0.017), Q1 vs. Q4 (p < 0.001), Q2 vs. Q3 (p = 0.034), and Q2 vs. Q4 (p < 0.001). However, baseline NLR was not identified as an independent prognostic factor using a multivariate Cox proportional hazards regression model. The area under the curve for predicting in-hospital death based on baseline NLR was only 0.682, whereas that of follow-up NLR was 0.893. The two-dimensional patient map with t-SNE showed a cluster characterized by high mortality with high NLR at follow-up, but these did not necessarily overlap with the population with high NLR at baseline. NLR may have prognostic implications in hospitalized COVID-19 patients with CVDRF, but its significance depends on the timing of data collection.

The distal radial approach (dTRA) is increasingly recognized as a viable alternative to the conventional radial approach in coronary interventions. However, its utility in ST-elevation myocardial infarction (STEMI)—where rapid revascularization is critical—remains underexplored. To evaluate the feasibility and procedural characteristics of dTRA in STEMI patients undergoing primary percutaneous coronary intervention (PCI), using a prespecified subanalysis of the SPEEDY PCI study. Among 370 STEMI patients enrolled, 63 underwent PCI via dTRA and 307 via the conventional radial approach. A propensity score–matched analysis was performed using Killip class, GRACE score, and door-to-sheath time as covariates. After matching, the dTRA group had significantly shorter sheath-to-balloon (12.5 ± 11.5 vs. 19.7 ± 11.7 min, p  = 0.002) and door-to-balloon times (50.2 ± 25.9 vs. 62.3 ± 19.9 min, p  = 0.007). Procedural success and 30-day mortality rates were comparable between groups. dTRA appears feasible and safe for STEMI patients in high-volume centers. While shorter time metrics were observed, these may reflect institutional practices and operator experience rather than the access site alone.

Abstract Background Several side effects have been reported after mRNA COVID-19 vaccinations. Nonetheless, the risk of pulmonary hypertension (PH) is rarely reported. Most cases with acute PH following vaccination were due to macropulmonary embolism secondary to deep vein thrombosis. However, acute PH due to microthrombus formation after COVID-19 vaccination has not been reported before, although a microthrombus has been considered to lead to the dysfunction of multiple organs, particularly in patients infected with COVID-19. Case summary A 63-year-old woman without any past medical history presented to our hospital with facial and bilateral pedal oedema and progressive dyspnoea on exertion. Her symptoms began the day after her second COVID-19 vaccination and developed gradually, which prompted her to seek consultation in our hospital 6 weeks later. An echocardiogram revealed substantially elevated right heart pressure, and cardiac catheterization revealed high pulmonary artery pressure (mean PAP, 30 mmHg). Contrast-enhanced computed tomography and venous echography revealed no apparent thrombus, and ventilation/perfusion (V/Q) scintigraphy revealed no V/Q mismatch. However, elevated D-dimer indicated the presence of a coagulation–fibrinolysis system in her body; thus, heparin therapy was initiated intravenously on Day 3 for 4 days, followed by direct oral anticoagulants ended on Day 16. Her symptoms substantially improved as her D-dimer level decreased, and a follow-up cardiac catheterization on Day 14 revealed a decline in mean PAP (15 mmHg). Discussion Our case suggests that the presence of acute PH is likely due to microangiopathy. Further studies are required to reveal the relationship between immune responses and microthrombus formation after COVID-19 vaccination.

ObjectivesPredictive algorithms to inform risk management decisions are needed for patients with COVID-19, although the traditional risk scores have not been adequately assessed in Asian patients. We aimed to evaluate the performance of a COVID-19-specific prediction model, the 4C (Coronavirus Clinical Characterisation Consortium) Mortality Score, along with other conventional critical care risk models in Japanese nationwide registry data.DesignRetrospective cohort study.Setting and participantsHospitalised patients with COVID-19 and cardiovascular disease or coronary risk factors from January to May 2020 in 49 hospitals in Japan.Main outcome measuresTwo different types of outcomes, in-hospital mortality and a composite outcome, defined as the need for invasive mechanical ventilation and mortality.ResultsThe risk scores for 693 patients were tested by predicting in-hospital mortality for all patients and composite endpoint among those not intubated at baseline (n=659). The number of events was 108 (15.6%) for mortality and 178 (27.0%) for composite endpoints. After missing values were multiply imputed, the performance of the 4C Mortality Score was assessed and compared with three prediction models that have shown good discriminatory ability (RISE UP score, A-DROP score and the Rapid Emergency Medicine Score (REMS)). The area under the receiver operating characteristic curve (AUC) for the 4C Mortality Score was 0.84 (95% CI 0.80 to 0.88) for in-hospital mortality and 0.78 (95% CI 0.74 to 0.81) for the composite endpoint. It showed greater discriminatory ability compared with other scores, except for the RISE UP score, for predicting in-hospital mortality (AUC: 0.82, 95% CI 0.78 to 0.86). Similarly, the 4C Mortality Score showed a positive net reclassification improvement index over the A-DROP and REMS for mortality and over all three scores for the composite endpoint. The 4C Mortality Score model showed good calibration, regardless of outcome.ConclusionsThe 4C Mortality Score performed well in an independent external COVID-19 cohort and may enable appropriate disposition of patients and allocation of medical resources.Trial registration number UMIN000040598.

Current drug-eluting stents have abluminal polymer coating; however, thrombus formation in these compared with that in uniformly coated stents remains controversial. We evaluated thrombus formation and early endothelialization after using abluminal biodegradable polymer-coated sirolimus- (BP-SES), and everolimus-eluting stents (BP-EES) versus a durable polymer-coated everolimus-eluting stent (DP-EES) in an in vivo setting. BP-SES, BP-EES, and DP-EES (n = 6 each) were implanted in coronary arteries of 12 mini-pigs that were then sacrificed after 7 and 10 days. Stents were stained with hematoxylin and eosin, and a combined Verhoeff and Masson trichrome stain. Areas of fibrin deposition were digitally detected and measured with off-line morphometric software. Stents were investigated for re-endothelialization by transmission electron microscopy. At 7 days, histological analysis revealed the lowest area of fibrin deposition in BP-SES (BP-SES vs. BP-EES vs. DP-EES; 0.10 ± 0.06 mm2 vs. 0.15 ± 0.07 mm2 vs. 0.19 ± 0.06 mm2, p = 0.0004). At 10 days, the area of fibrin deposition was significantly greater in DP-EES (0.13 ± 0.04 mm2 vs. 0.14 ± 0.05 mm2 vs. 0.19 ± 0.08 mm2, p = 0.007). Endothelial cells in BP-SES demonstrated a significantly greater number of tight junctions than those in DP-EES according to by transmission electron microscopy for both days (p<0.05). Various parameters, including an inflammatory reaction and neointimal formation, were comparable among the groups at 7 and 10 days. An abluminal biodegradable polymer-coated SES showed the least fibrin deposition and greatest endothelial cell recovery at an early stage following implantation in the coronary arteries of mini-pigs.