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Background and aims Recent studies have shown that coronary thrombus histopathology is associated with impaired myocardial reperfusion and poor clinical outcome in patients with acute myocardial infarction (AMI). We sought to investigate the age of thrombi aspirated during percutaneous coronary intervention (PCI) in patients with AMI and evaluate the relationship between histopathologic findings and major adverse cardiac and cerebrovascular events (MACCEs) defined as all-cause death, stroke, or myocardial infarction within 6 months of PCI. Methods In this prospective 2-center observational study, coronary material was obtained during PCI from 305 patients with AMI within 24 h of symptom onset. Thrombi were morphologically classified as either only fresh or older (lytic changes or organization). Results MACCE occurred in 38 (12.5%) patients. Only fresh thrombi were observed in 114 (37%) of 305 patients; older thrombi were identified in 191 (63%). The rate of MACCE was significantly higher among patients with older thrombus ( p = 0.011). Multivariate analysis also showed the presence of older thrombus [odds ratio (OR) 3.03, 95% confidence interval (CI) 1.122–9.522] is an independent predictor of MACCE within 6 months of PCI, as well as age (OR 1.051, 95% CI 1.013–1.094) and creatine kinase concentration (OR 1.025, 95% CI 1.013–1.037). The prevalence of slow flow or distal embolization during PCI and peak creatine kinase concentration were significantly higher in the older thrombus group ( p < 0.05, respectively). Conclusions Older thrombus found in aspirated coronary material is associated with impaired myocardial reperfusion and is an independent predictor of mid-term MACCE in patients with AMI. [ABSTRACT FROM AUTHOR]

To investigate the role of pentraxin 3 (PTX3) in atherosclerotic disease progression and plaque destabilization, as well as in coronary restenosis after directional coronary atherectomy (DCA). PTX3 contents of early and advanced atherosclerotic lesions of the aorta obtained at autopsy were determined by ELISA and Western blot. Also, coronary plaques of patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP) obtained by DCA were analyzed by immunohistochemistry for PTX3. The effects of PTX3 on smooth muscle cells (SMCs) and thrombogenesis were investigated with cultured human coronary artery SMCs and a flow chamber system, respectively. Advanced atherosclerotic lesions contained a significantly larger amount of PTX3 than early lesions (ELISA: 9.96 ± 2.77 ng/100 mg tissue, n = 8 vs 0.24 ± 0.18 ng/100 mg tissue, n = 6, P = 0.0097). Also, ACS plaques contained a significantly larger amount of PTX3 than SAP plaques (PTX3 immunohistochemistry–positive area percentage: 2.88 ± 0.53 %, n = 22 vs 0.67 ± 0.27 %, n = 23, P = 0.0009). Curiously, the patients who would remain free of post-DCA restenosis (n = 19) had plaques with a significantly higher PTX3 immunohistochemistry–positive area percentage than those who would develop restenosis (n = 12) (2.32 ± 0.49 % vs 0.49 ± 0.17 %, P = 0.002). In the mechanistic part of the study, PTX3 inhibited SMC proliferation and migration. PTX3 also inhibited platelet thrombus formation in the condition simulating arterial blood flow. PTX3 is increased in advanced (vs early) atherosclerotic lesions and unstable (vs stable) coronary plaques. The inhibitory effects of PTX3 on SMCs and thrombogenesis suggest that intraplaque PTX3 might have atheroprotective effects. [Display omitted] • Intraplaque CRP is known to promote atherosclerosis, but pentraxin 3 may not. • Pentraxin 3 in plaque increases as atherosclerosis progresses. • Pentraxin 3 inhibited SMC proliferation and migration in vitro. • Flow chamber system study showed pentraxin 3 inhibits thrombus formation. • Intraplaque pentraxin 3 might have atheroprotective effects. [ABSTRACT FROM AUTHOR]

Pioglitazone has superior antiatherosclerotic effects compared with other classes of antidiabetic agents, and there is substantial evidence that pioglitazone improves cardiovascular (CV) outcomes. However, there is also a potential risk of worsening heart failure (HF). Therefore, it is clinically important to determine whether pioglitazone is safe in patients with type 2 diabetes mellitus (T2DM) who require treatment for secondary prevention of CV disease, since they have an intrinsically higher risk of HF. This prospective, multicenter, open-label, randomized study investigated the effects of pioglitazone on cardiometabolic profiles and CV safety in T2DM patients undergoing elective percutaneous coronary intervention (PCI) using bare-metal stents or first-generation drug-eluting stents. A total of 94 eligible patients were randomly assigned to either a pioglitazone or conventional (control) group, and pioglitazone was started the day before PCI. Cardiometabolic profiles were evaluated before PCI and at primary follow-up coronary angiography (5-8 months). Pioglitazone treatment reduced HbA1c levels to a similar degree as conventional treatment (pioglitazone group 6.5 to 6.0%, P < 0.01; control group 6.5 to 5.9%, P < 0.001), without body weight gain. Levels of high-molecular weight adiponectin increased more in the pioglitazone group than the control group (P < 0.001), and the changes were irrespective of baseline glycemic control. Furthermore, pioglitazone significantly reduced plasma levels of natriuretic peptides and preserved cardiac systolic and diastolic function (assessed by echocardiography) without incident hospitalization for worsening HF. The incidence of clinical adverse events was also comparable between the groups. These results indicate that pioglitazone treatment before and after elective PCI may be tolerable and clinically safe and may improve cardiometabolic profiles in T2DM patients. [ABSTRACT FROM AUTHOR]

Current guidelines recommend direct oral anticoagulants (DOACs) and warfarin for patients with atrial fibrillation (AF) who have a bioprosthetic valve (BPV). However, the data related to elderly patients (aged ≥80 years) with BPV replacement and AF are limited. This post-hoc subgroup analysis of a BPV-AF Registry enrolled 752 patients with BPV replacement and AF. The primary net outcome was a composite of cardiac death, stroke, systemic embolism, major bleeding, and cardiovascular events. Among 752 patients, 429 (57%) patients were ≥ 80 and 323 (43%) were < 80 years old. The higher risk in patients aged ≥80 than <80 years was significant for the net outcome (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.31–3.17; P = 0.001). After adjustment for confounders, there was no statistically significant difference between warfarin (reference) and DOAC users in the risk of net outcomes (adjusted HR, 1.26; 95% CI, 0.71–2.24; P = 0.44), stroke and systemic embolism (adjusted HR, 2.01; 95% CI, 0.48–8.38; P = 0.34), and major bleeding (adjusted HR, 0.73; 95% CI, 0.11–4.98; P = 0.75) in patients aged ≥80 years old as well as those aged <80 years. Among 489 warfarin users, the cumulative incidence of net outcomes tended to be higher in patients aged ≥80 than <80 years (12.2% vs. 5.7% at 1 year, log-rank P = 0.002). Among 263 DOAC users, however, it was similar between patients aged ≥80 and < 80 years. The present study demonstrated that DOAC showed similar efficacy and safety compared with warfarin even in elderly patients aged ≥80 years with BPV replacement and AF. • The risk of net outcomes was similar between warfarin and DOACs among elderly patients with a BPV and AF. • Among warfarin users, the risk of net outcomes tended to be higher in patients aged ≥80 years. • Among DOAC users, the risk of net outcomes was similar between patients aged ≥80 and < 80 years. [ABSTRACT FROM AUTHOR]

Aim: To clarify whether there is any association between the extent of Chlamydia pneumoniae (C. pneumoniae) infection and plaque instability or post–directional coronary atherectomy (DCA) restenosis, we determined the frequency of C. pneumoniae infection and its localization in symptomatic coronary atherosclerotic plaques using specimens obtained from DCA. Methods and results: Immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) revealed the existence of C. pneumoniae in all 50 specimens of coronary atherosclerotic plaques obtained by DCA. C. pneumoniae –positive cell ratio determined with IHC or copy numbers of C. pneumoniae DNA detected by RT-PCR did not differ significantly between patients with stable angina pectoris and those with acute coronary syndrome (IHC: 16.4 ± 7.6% vs 18.0 ± 7.1%, P =.42; RT-PCR: no. of cases with high copy numbers 12/25 vs 10/25, P =.78), or between patients with subsequent post-DCA restenosis and those without (IHC: 17.1 ± 8.0% vs 18.0 ± 7.4%, P =.74; RT-PCR: 5/12 vs 10/21, P = 1.00). Conclusions: C. pneumoniae was highly prevalent in coronary atherosclerotic plaques of patients who underwent DCA. However, the extent of C. pneumoniae infection in coronary atherosclerotic plaques was not associated with plaque instability or post-DCA restenosis. [ABSTRACT FROM AUTHOR]

The high post-discharge mortality rate of acute myocardial infarction (AMI) survivors is concerning, indicating a need for reliable, easy-to-use risk prediction tools. We aimed to examine if a combined pre-procedural blood testing risk model predicts one-year mortality in AMI survivors. Overall, 1355 consecutive AMI patients who received primary coronary revascularization were divided into derivation (n = 949) and validation (n = 406) cohorts. A risk-score model of parameters from pre-procedural routine blood testing on admission was generated. In the derivation cohort, multivariable analysis demonstrated that hemoglobin < 11 g/dL (odds ratio (OR) 4.01), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (OR 3.75), albumin < 3.8 mg/dL (OR 3.37), and high-sensitivity troponin I > 2560 ng/L (OR 3.78) were significantly associated with one-year mortality after discharge. An increased risk score, assigned from 0 to 4 points according to the counts of selected variables, was significantly associated with higher one-year mortality in both cohorts (p < 0.001). Receiver-operating characteristics curve analyses of risk models demonstrated adequate discrimination between patients with and without one-year death (area under the curve (95% confidence interval) 0.850 (0.756–0.912) in the derivation cohort; 0.820 (0.664–0.913) in the validation cohort). Our laboratory risk-score model can be useful for predicting one-year mortality in AMI survivors. [ABSTRACT FROM AUTHOR]

Activation of the classical complement pathway plays a major role in regulating atherosclerosis progression, and it is believed to have both proatherogenic and atheroprotective effects. This study focused on C1q, the first protein in the classical pathway, and examined its potentialities of plaque progression and instability and its relationship with clinical outcomes. To assess the localization and quantity of C1q expression in various stages of atherosclerosis, immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) were performed using abdominal aortas from eight autopsy cases. C1q immunoreactivity in relation to plaque instability and clinical outcomes was also examined using directional coronary atherectomy (DCA) samples from 19 patients with acute coronary syndromes (ACS) and 18 patients with stable angina pectoris (SAP) and coronary aspirated specimens from 38 patients with acute myocardial infarction. C1q immunoreactivity was localized in the extracellular matrix, necrotic cores, macrophages and smooth muscle cells in atherosclerotic lesions. Western blotting and real-time PCR illustrated that C1q protein and mRNA expression was significantly higher in advanced lesions than in early lesions. Immunohistochemical analysis using DCA specimens revealed that C1q expression was significantly higher in ACS plaques than in SAP plaques. Finally, immunohistochemical analysis using thrombus aspiration specimens demonstrated that histopathological C1q in aspirated coronary materials could be an indicator of poor medical condition. Our results indicated that C1q is significantly involved in atherosclerosis progression and plaque instability, and it could be considered as one of the indicators of cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether N -benzyl- N -methyl-2-[7,8-dihydro-7-(2-[18F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide (18F-FEDAC), a probe for translocator protein (TSPO), can visualize atherosclerotic lesions in rabbits and whether TSPO is localized in human coronary plaques. 18F-FEDAC-PET of a rabbit model of atherosclerosis induced by a 0.5% cholesterol diet and balloon injury of the left carotid artery (n = 7) was performed eight weeks after the injury. The autoradiography intensity of 18F-FEDAC in carotid artery tissue sections was measured, and TSPO expression was evaluated immunohistochemically. TSPO expression was examined in human coronary arteries obtained from autopsy cases (n = 16), and in human coronary plaques (n = 12) aspirated from patients with acute myocardial infarction (AMI). 18F-FEDAC-PET visualized the atherosclerotic lesions in rabbits as high-uptake areas, and the standard uptake value was higher in injured arteries (0.574 ± 0.24) than in uninjured arteries (0.277 ± 0.13, p < 0.05) or myocardium (0.189 ± 0.07, p < 0.05). Immunostaining showed more macrophages and more TSPO expression in atherosclerotic lesions than in uninjured arteries. TSPO was localized in macrophages, and arterial autoradiography intensity was positively correlated with macrophage concentration (r = 0.64) and TSPO (r = 0.67). TSPO expression in human coronary arteries was higher in AMI cases than in non-cardiac death, or in the vulnerable plaques than in early or stable lesions, respectively. TSPO was localized in macrophages in all aspirated coronary plaques with thrombi. 18F-FEDAC-PET can visualize atherosclerotic lesions, and TSPO-expression may be a marker of high-risk coronary plaques. [Display omitted] • 18F-FEDAC is a tracer of 18-kDa translocator protein. • 18F-FEDAC-positron emission tomography visualizes a rabbit atherosclerotic artery. • Higher 18F-FEDAC radioactivity in rabbit atherosclerotic artery than in myocardium. • Translocator protein expression in macrophages in rabbit and human atherosclerosis. • Translocator protein overexpression in coronary vulnerable and thrombotic plaques. [ABSTRACT FROM AUTHOR]

Asymptomatic disrupted plaques were characterized by small plaque erosion or rupture with a small mural thrombus, and plaque erosion was the predominant morphology in asymptomatic plaque disruption.4 However, the disrupted plaques in the present AMI case showed small plaque rupture, plaque fissure, and plaque ulceration in non-culprit lesions. Intraplaque hemorrhage is frequently observed in advanced coronary atherosclerotic plaques and is believed to arise from the disruption of microvessels in plaques and may predict plaque rupture.5 Intraplaque hemorrhage was observed in all disrupted plaques in this case and at the plaque rupture areas, which suggests that it is the result of plaque disruption. It is possible that high-risk patients have multiple unstable plaques and that some of them cause asymptomatic plaque disruption with intraplaque hemorrhage before AMI onset. [Extracted from the article]

Because of the low atrioventricular (AV) block risk during cryo-ablation, it has become possible to treat AV nodal reentrant tachycardia (AVNRT) during arrhythmia. This study aimed to investigate the clinical outcomes of performing cryo-ablation for AVNRT during arrhythmia. Twenty-three patients with AVNRT treated by cryo-ablation during arrhythmia were enrolled. Cryo-ablation was performed gradually from the bottom to above the paraseptal tricuspid annulus until AVNRT was terminated. If the slow pathway was not eliminated despite cryo-ablation terminating the AVNRT, additional cryo-ablation was performed at a higher site until the slow pathway elimination was achieved. AVNRT was terminated by cryo-ablation in all 23 patients. However, the slow pathway was only eliminated in 6 patients. Among the remaining 17 patients, the slow pathway could not be ablated because transient AV block occurred during cryo-ablation at a higher site in 8 patients; however, cryo-ablation at a higher site successfully eliminated the slow pathway in the other 9 patients. In these 9 patients, the distance from the bottom of tricuspid annulus to the site of slow pathway elimination was significantly longer than that from bottom of tricuspid annulus to the AVNRT termination site (20.1 ± 5.3 vs 14.7 ± 4.5 mm: p = 0.027). During follow-up, AVNRT recurrence was confirmed in 3 patients. In 1 of these 3 patients, even a slow pathway elimination was achieved by cryo-ablation at the AVNRT termination site. The AVNRT termination site may not be the ideal site for performing cryo-ablation. [ABSTRACT FROM AUTHOR]

Background: Mitral valve prolapse (MVP) is often identified in patients with atrial septal defect (ASD), which occasionally require surgical intervention at the time of ASD closure or even long after the surgery. Ventricular and valvular geometric characteristics in preoperative ASD patients were evaluated by three‐dimensional (3D) transesophageal echocardiography. Methods and Results: Mitral valve (MV) complex geometry was quantitatively measured by 3D transesophageal echocardiography in 11 ASD patients (Qp/Qs > 1.5) and 11 controls. The ASD group had a significantly larger indexed prolapse volume and height, with a larger anterior mitral leaflet than controls (0.53 [0.33–0.75] vs 0.057 [0.027–0.11] mL/m2, P =.0001; 2.89 [2.13–3.50] vs 0.92 [0.48–1.32] mm/m2, P <.0001; 391.3 [346.4–445.1] vs 295.3 (281.9–330.0) mm2/m2, P =.011, respectively). The right ventricular (RV)‐to‐left ventricular (LV) end‐systolic diameter ratio was larger in the ASD group than in the control group (1.34 [0.96–1.45] vs 0.85 [0.75–0.88], P =.004). The indexed inter‐papillary muscle distance (IPMD) was significantly shorter in the ASD group than in the control group (7.77 [6.55–8.24] vs 9.71 [8.64–10.8] mm/m2, P =.011). IPMD was significantly correlated with the RV‐LV end‐systolic diameter ratio (r = −.70, P =.017). Conclusions: Inward shift of the LV papillary muscle tips due to RV dilation may be a major mechanism of MV prolapse in ASD. At the same time, positive remodeling of the anterior leaflet was observed in the ASD group, which may compensate for the billowing leaflet geometry to maintain effective coaptation. Three‐dimensional assessment of the MV apparatus geometry will help to further understand perioperative mitral regurgitation in patients with ASD. [ABSTRACT FROM AUTHOR]

The appropriate stent platform for treating coronary bifurcation lesions (CBLs) remains controversial. Previous bench tests have demonstrated the superiority of a 2-link cell design to 3-link cell design for creating inter-strut dilation at the side branch ostium. This randomized multicenter prospective BEGIN trial compared the biodegradable polymer-based biolimus A9-eluting stent (2-link BES) with the durable polymer-based cobalt chromium everolimus-eluting stent (3-link EES) in 226 patients with de novo CBLs. Patients with true bifurcations, defined as > 50% stenosis in the main vessel and side branch (SB) and an SB diameter > 2.25 mm, were enrolled. Guide wire re-crossing to the distal cell (near the carina) in the jailed SB and final kissing inflation were recommended. The SB angiographic endpoint was < 50% stenosis diameter. Left-main CBLs (13.5% vs. 13.0%) and 2-stent technique (30.6% vs. 22.6%) rates were similar. The primary endpoints (minimum lumen diameter at the SB ostium measured at an independent core laboratory at the 8-month follow-up) were comparable (1.64 ± 0.50 mm vs. 1.63 ± 0.51 mm, p = 0.976). There was no significant difference in composite outcomes of cardiac death, myocardial infarction, or target vascular revascularization at 12 months (7.4% vs. 8.0%, p = 0.894). Two-link BES and 3-link EES showed similar 8-month angiographic and 1-year clinical outcomes for true CBLs. [ABSTRACT FROM AUTHOR]

Abstract Background Whether a dipeptidyl peptidase-4 (DPP-4) inhibitor can attenuate atherosclerosis is still controversial. Some clinical trials reported that DPP-4 inhibitors in diabetes patients without a previous history of cardiovascular (CV) events could reduce carotid intima-media thickness (IMT). However, in the PROLOGUE study, which enrolled diabetes patients both with and without previous CV events, sitagliptin failed to slow the progression of carotid IMT relative to conventional therapy. Aim and methods We hypothesized that the effect of DPP-4 inhibitors on carotid atherosclerosis might be different between the primary and secondary prevention groups. We performed a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in carotid IMT in subgroups with or without previous CV events. Results No significant difference in the IMT changes between the treatment groups was found in the secondary prevention subgroup (sitagliptin, N = 102; conventional, 111). However, in the primary prevention subgroup (sitagliptin, 120; conventional, 109), we found significant inhibitory effects of sitagliptin on mean and max internal carotid artery IMT [estimated group difference: −0.096 mm (95% CI −0.175 to −0.018, p = 0.017) and −0.162 mm (95% CI −0.272 to −0.052, p = 0.004), respectively], although there was no significant difference in the common carotid artery IMT. Conclusions Our data suggest that there is a favorable effect of DPP-4 inhibitor treatment on carotid atherosclerosis in diabetes patients without previous CV events. Highlights • Sitagliptin failed to delay IMT progression in T2DM patients with previous CVD. • Sitagliptin slowed ICA-IMT progression in T2DM patients without previous CVD. • Sitagliptin therapy prior to CV event may be favorable for carotid atherosclerosis. • The therapy in patients with previous CVD may be insufficient to attenuate it. [ABSTRACT FROM AUTHOR]

Key Clinical Message We present a case of postcardiac injury syndrome with pericardial effusion following cardiac resynchronization therapy implantation which was treated by only colchicine. Although treatment using colchicine is not as common as NSAIDs or steroids, colchicine seems to be an effective and safe treatment option for the syndrome. [ABSTRACT FROM AUTHOR]

Experimental ischemia-reperfusion models have shown that 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, have cardioprotective effects. SAMIT (Statin Acute Myocardial Infarction Trial) is a multicenter prospective open randomized trial, designed to evaluate the effects of statin treatment from the earliest stage on cardioprotection in patients with acute myocardial infarction (AMI). Patients were randomly assigned to receive atorvastatin (initial dose of 40 mg at admission followed by the maintenance dose of 10 mg/day for 30 days) or not (control), and then immediately underwent percutaneous coronary intervention (PCI) for the culprit lesion. The primary endpoints were infarct size and left ventricular function. The secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE) and various biomarkers. There were no significant differences in baseline characteristics between 2 groups of the statin treatment group and the control group. The left ventricular ejection fraction increased at 6 months after the onset of AMI, compared with the baseline level in the atorvastatin group ( P < 0.05), while it did not change in the control group. Although there were no significant differences in the MACCE, the changes in the levels of angiopoietin-like protein 2 (ANGPTL2) ( P < 0.05), and glyceraldehyde-derived advanced glycation end-products, (TAGE) ( P < 0.01) were suppressed at 2 weeks in the atorvastatin group, compared with the control group. Statin therapy started early after the onset reduced the levels of ANGPTL2 and TAGE, and thus, might have cardioprotective effects in patients with AMI. [ABSTRACT FROM AUTHOR]

Abstract: To examine the presence of CD34-positive cells and intranuclear factors in acute coronary thrombi, we compared thrombi in patients with type 2 diabetes mellitus (DM, n = 21) and without DM (n = 29). Immunohistochemical staining revealed the constitutive presence of platelets, fibrin, erythrocytes, neutrophils, extracellular high-mobility group box 1 (HMGB-1), and histone H3 in all thrombi. There were significantly more oval or flat CD34-positive cells and significantly larger HMGB-1-positive areas in the thrombi from patients with DM. The flat CD34-positive cells expressed ecto-nucleoside triphosphate diphosphohydrolase (a platelet aggregation inhibitor). The number of CD34-positive cells was negatively correlated with the serum levels of glucose and hemoglobin A1c, whereas the HMGB-1-positive area was positively correlated with the levels of serum glucose. The paucity of CD34-positive cells and the high levels of HMGB-1 expression in acute coronary thrombi from patients with type 2 DM could facilitate thrombus formation. [Copyright &y& Elsevier]

It yet has not been clarified whether there is a late catch-up phenomenon in target lesion revascularization (TLR) after sirolimus-eluting stent (SES) compared to bare metal stent (BMS) implantation. In 12,824 patients enrolled in the j-Cypher Registry, incidences of early (within first year) and late (1 year to 3 years) TLR were compared between 17,050 lesions treated with SESs and 1,259 lesions treated with BMSs. Incidences of TLR in SES-treated lesions were 5.7% at 1 year, 8.1% at 2 years, and 10.0% at 3 years, whereas those in BMS-treated lesions were 14.2%, 15.5%, and 15.5%, respectively (p <0.0001, log-rank test). Incidences of late TLR were significantly higher with SESs compared to BMSs (2.6% vs 1.4% at 2 years and 4.5% vs 1.4% at 3 years, p = 0.0007, log-rank test). A multivariable logistic regression model identified 7 independent risk factors for late TLR at 3 years after SES implantation: hemodialysis, low estimated glomerular filtration rate, ostial right coronary artery, lesion length ≥30 mm, 2 stents for bifurcation, American Heart Association/American College of Cardiology type B2/C, and vessel size <2.5 mm. Of these, 5 factors were common to those for early TLR. In conclusion, a late catch-up phenomenon was observed as indicated by the increasing incidence of late TLR after SES, but not after BMS, implantation. Risk factors for late TLR were generally common to those for early TLR. [Copyright &y& Elsevier]

To determine whether the expression of CD39 in coronary atherosclerotic lesions is related to plaque instability and thrombus formation, we assessed directional coronary atherectomy (DCA) specimens from patients with stable and unstable angina pectoris. CD39 immunoreactivity was decreased in culprit lesions in patients with unstable angina pectoris compared with those with stable angina pectoris, and was reduced in DCA specimens with thrombus formation. These results suggest that CD39 expressed in atheromatous plaque plays an important role in preventing acute coronary syndromes. [Copyright &y& Elsevier]

To determine whether the inflammatory response is equally involved in the pathogenesis of restenosis after coronary stenting and directional coronary atherectomy, we assessed restenotic lesions with immunohistochemical methods. Levels of C-reactive protein and macrophages were greater in patients with in-stent restenosis than in those with restenosis after directional coronary atherectomy. This suggests that the inflammatory response is more involved in the pathogenesis of in-stent restenosis than in restenosis after directional coronary atherectomy. [Copyright &y& Elsevier]

Objective: Proadrenomedullin N-terminal 20 peptide (PAMP) processed from an adrenomedullin precursor is a potent hypotensive peptide. It was anticipated that a mature form of PAMP (m-PAMP) and an intermediate PAMP-gly existed together in the blood. To measure concentrations of PAMPs in human plasma directly, we have developed a highly sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay, ICT-EIA).Design and methods: PAMP was reacted simultaneously with 2,4-dinitrophenyl (DNP)-biotinyl-bovine serum albumin (BSA)-anti-PAMP Fab'' conjugate and anti-PAMP Fab''-β-d-galactosidase conjugate. The immune complex that was formed was initially trapped onto a polystyrene bead coated with anti-DNP IgG, and then transferred onto a second polystyrene bead coated with streptavidin. The resulting three-component complex was then assayed fluorometrically.Results: The detection limits of ICT-EIA for both m-PAMP and PAMP-gly were 0.1 pmol/l with as little as 10 μl of plasma, and were a hundred times higher than with conventional radioimmunoassay (RIA). Using ICT-EIA, we determined that the plasma concentrations of m-PAMP and PAMP-gly in 51 healthy volunteers were 0.51 ± 0.19 and 1.15 ± 0.38 pmol/l (mean ± SD), respectively. Both plasma m-PAMP and PAMP-gly concentrations in patients with a variety of diseases, including hypertension, heart failure, chronic renal failure, and hemodialysis, were significantly higher than those in healthy subjects. In addition, both plasma m-PAMP and PAMP-gly concentrations in patients with New York Heart Association (NYHA) class I–IV heart failure were increased in proportion to clinical severity.Conclusions: These sensitive and specific ICT-EIAs may be used as a powerful tool for investigating the cardiovascular system in patients with heart failure. [Copyright &y& Elsevier]

We investigated whether positive immunohistochemical staining of C-reactive protein (CRP) in initial culprit lesions is related to coronary plaque instability and whether it could affect the outcome of directional coronary atherectomy (DCA). The plasma level of CRP is a reliable marker of the risk of coronary events and restenosis after percutaneous coronary intervention. However, the influence of tissue CRP in atheromatous plaque on plaque vulnerability and restenosis remains unknown. Samples of DCA obtained from 12 patients with stable angina pectoris and 15 patients with unstable angina pectoris were immunohistochemically stained with a monoclonal antibody against CRP. We performed follow-up coronary angiography on 22 of 27 patients to evaluate the presence of restenosis after DCA. Immunoreactivity to CRP was localized to macrophages, smooth muscle cells, and necrotic areas. The ratio of CRP positive cells to total cells was significantly higher in DCA samples from patients with unstable (17.9 +/- 2.0%) than with stable angina (11.0 +/- 2.5%) (p <0.05). Follow-up coronary angiography showed that 12 of 22 patients developed restenosis after DCA. The ratio was also significantly higher in DCA specimens from patients with restenosis (19.3 +/- 2.8%) compared with those without restenosis (11.0 +/- 2.0%) (p <0.05). In addition, the ratio significantly correlated with late luminal loss (r = 0.428, p <0.05) and loss index (r = 0.636, p = 0.0011) after DCA. Immunoreactivity to CRP in coronary atheromatous plaque increases in culprit lesions of unstable angina, and it affects restenosis after DCA. These findings suggest that CRP in atheromatous plaque plays an important role in the pathogenesis of unstable angina and restenosis after coronary intervention. [ABSTRACT FROM AUTHOR]

We investigated whether positive immunohistochemical staining of C-reactive protein (CRP) in initial culprit lesions is related to coronary plaque instability and whether it could affect the outcome of directional coronary atherectomy (DCA). The plasma level of CRP is a reliable marker of the risk of coronary events and restenosis after percutaneous coronary intervention. However, the influence of tissue CRP in atheromatous plaque on plaque vulnerability and restenosis remains unknown. Samples of DCA obtained from 12 patients with stable angina pectoris and 15 patients with unstable angina pectoris were immunohistochemically stained with a monoclonal antibody against CRP. We performed follow-up coronary angiography on 22 of 27 patients to evaluate the presence of restenosis after DCA. Immunoreactivity to CRP was localized to macrophages, smooth muscle cells, and necrotic areas. The ratio of CRP positive cells to total cells was significantly higher in DCA samples from patients with unstable (17.9 ± 2.0%) than with stable angina (11.0 ± 2.5%) (p <0.05). Follow-up coronary angiography showed that 12 of 22 patients developed restenosis after DCA. The ratio was also significantly higher in DCA specimens from patients with restenosis (19.3 ± 2.8%) compared with those without restenosis (11.0 ± 2.0%) (p <0.05). In addition, the ratio significantly correlated with late luminal loss (r = 0.428, p <0.05) and loss index (r = 0.636, p = 0.0011) after DCA. Immunoreactivity to CRP in coronary atheromatous plaque increases in culprit lesions of unstable angina, and it affects restenosis after DCA. These findings suggest that CRP in atheromatous plaque plays an important role in the pathogenesis of unstable angina and restenosis after coronary intervention. [Copyright &y& Elsevier]

In emergency clinical settings, it may be beneficial to use rapidly measured objective variables for the risk assessment for patient outcome. This study sought to develop an easy-to-measure and objective risk-score prediction model for in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). A total of 1027 consecutive STEMI patients were recruited and divided into derivation (n = 669) and validation (n = 358) cohorts. A risk-score model was created based on the combination of blood test parameters obtained immediately after admission. In the derivation cohort, multivariate analysis showed that the following 5 variables were significantly associated with in-hospital death: estimated glomerular filtration rate <45 mL/min/1.73 m2, platelet count <15 × 104/μL, albumin ≤3.5 g/dL, high-sensitivity troponin I >1.6 ng/mL, and blood sugar ≥200 mg/dL. The risk score was weighted for those variables according to their odds ratios. An incremental change in the scores was significantly associated with elevated in-hospital mortality (p < 0.001). Receiver operating characteristic curve analysis showed adequate discrimination between patients with and without in-hospital death (derivation cohort: area under the curve (AUC) 0.853; validation cohort: AUC 0.879), and there was no significant difference in the AUC values between the laboratory-based and Global Registry of Acute Coronary Events (GRACE) score (p = 0.721). Thus, our laboratory-based model might be helpful in objectively and accurately predicting in-hospital mortality in STEMI patients. [ABSTRACT FROM AUTHOR]

Abstract: Thrombus formation on disrupted atherosclerotic lesion is a key mechanism of cardiovascular events. Podoplanin (Aggrus), expressed on the surface of several tumor cells, is an endogenous ligand for C-type lectin-like receptor 2 (CLEC-2), and is involved in tumor cell-induced platelet aggregation and its malignant potency. Podoplanin, which is also expressed in lymphatic endothelial cells, facilitates blood/lymphatic vessel separation. However, podoplanin expression in atherosclerotic lesion has not been investigated. To clarify podoplanin expression in atherosclerotic lesion and to assess its importance for the onset of cardiovascular events, we examined podoplanin expression in abdominal aortas obtained from 31 autopsy cases. Immunohistochemical analysis indicated that podoplanin was localized to smooth muscle cells and macrophages. Moreover, podoplanin immunoreactivity was increased in advanced atherosclerotic lesions containing necrotic core, many macrophages and smooth muscle cells, compared with early lesions composed of smooth muscle cells and small numbers of macrophages. Furthermore, Western-blot and real time-PCR analyses showed that podoplanin expression was significantly enhanced in advanced atherosclerotic lesions, compared with early lesions. These results suggest that podoplanin contributes to thrombotic property of advanced stages of atherosclerosis and that it might be a novel molecular target for an anti-thrombus drug. [Copyright &y& Elsevier]