Histopathological Features of Aspirated Thrombi after Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction

BACKGROUND: Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population. METHODOLOGY/PRINCIPAL FINDINGS: Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (<1 day), lytic (1-5 days), or organized (>5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus. CONCLUSIONS/SIGNIFICANCE: Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients

Clinical outcomes of complex real-world diabetic patients treated with amphilimus sirolimus-eluting stents or zotarolimus-eluting stents : A single-center registry

Objective: To assess clinical outcomes of Amphilimus Sirolimus-Eluting Stents (A-SES) as compared to Zotarolimus-Eluting Stents (ZES) in complex real-world diabetic patients. Background: Patients with diabetes mellitus represent one of the most challenging scenarios with high rates of restenosis and stent thrombosis in the current era of drug-eluting stents. Hence, we assessed the safety of A-SES versus ZES in complex diabetic patients. Methods: In this observational study, we analyzed all consecutive patients with diabetes mellitus referred to our center from November 2012 to November 2014. The primary outcome was target-lesion failure at 1-year follow-up. Results: A total of 165 consecutive diabetic patients underwent percutaneous coronary intervention with A-SES or ZES for stable coronary artery disease in our tertiary center. Using the Kaplan Meier method the cumulative incidence of target-lesion failure was 6.7% (5.9% A-SES versus 7.5% ZES, p = 0.19) at 1-year follow-up. Event-free survival at 1. year follow-up was similar (89.4% A-SES vs. 83.3% ZES, p = 0.29). Interestingly, we did not find any cases of definite-, and only one case of probable stent thrombosis in this high risk cohort. Conclusion: In this real-world registry, A-SES and ZES seems to be associated with promising 1-year clinical safety outcomes following PCI in a contemporary cohort of high-risk diabetic patients. Our results should be considered hypothesis generating, as the clinical safety of A-SES has to be confirmed in a large trial

Impact of strut thickness on late luminal loss after coronary artery stent placement

To determine the influence of coronary artery stent strut thickness on angiographic late luminal loss, 663 patients were included in a single-center observational cohort after receiving an ACS Multilink stent in a native coronary vessel. At 6- to 10-month follow-up, 287 patients treated with a thin-strut stent (50 mum) had significantly less late luminal loss than 376 patients treated with a thick-strut stent (greater than or equal to90 mum) (mean 0.92 +/- 0.59 vs 1.06 +/- 0.71 mm, p = 0.011); on multivariate regression analysis, strut thickness was found to be an independent predictor for late luminal loss. (C) 2004 by Excerpta Medica, In

Eosinophilic infiltration in restenotic tissue following coronary stent implantation

OBJECTIVES: The aim of our study was to compare the histopathological features of restenotic tissue after balloon angioplasty and after stent placement. We emphasized on specific types of inflammatory cells to evaluate the type of tissue immune response in both situations. METHODS: A total of 32 patients underwent elective directional coronary atherectomy; 16 patients had restenosis after balloon angioplasty, 16 patients had in-stent restenosis (ISR). Atherectomy specimens were stained with antibodies against T cells, eosinophils, smooth muscle cell actin, macrophages and with antibodies against T cell activation markers. Quantitative morphometric analysis was performed using image analysis software. RESULTS: In-stent restenotic tissue contained more smooth muscle cells (P < 0.001), anti-CD3 positive T cells (P < 0.001) and eosinophils (P = 0.012). Anti-CD40L positive activated T cells were more numerous in ISR lesions (P = 0.003) and were frequently clustered around stent imprints in the tissue. Five ISR specimens contained grossly visible stent fragments amidst the restenotic tissue. In all cases of balloon restenosis, T cells and eosinophils (if present) were concentrated around lipid rich tissue. CONCLUSIONS: Our study indicates involvement of inflammatory responses in both types of restenosis, with significantly more eosinophils encountered in case of in-stent restenosis. In contrast with clustering of inflammatory cells around stent struts after stent placement, the inflammatory cells in balloon restenosis were located in association with lipid rich tissue, suggesting different inflammatory triggers in balloon restenosis and in-stent restenosi

One-year clinical outcomes of patients treated with polymer-free amphilimus-eluting stents or zotarolimus-eluting stents : A propensity-score adjusted analysis

BACKGROUND: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution-technology in coronary stenting. We aimed to assess 1-year clinical outcomes of PF-AES as compared to latest-generation permanent polymer zotarolimus-eluting stents (PP-ZES) in a real-world all-comers setting. METHODS: A prospective registry of patients treated with either PF-AES or PP-ZES between 2014 and 2016 was conducted. The primary outcome was defined as major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcome was defined as target-lesion failure (TLF) at 1 year. To account for measured confounders, a propensity-score adjusted Cox proportional-hazard model was built to evaluate clinical outcomes. RESULTS: A total of 734 consecutive patients with 1,269 DES implantations were enrolled. The population was characterized by 28% diabetes, 24% ST-segment elevation myocardial infarction, and a high number of complex lesions (69%). The rate of MACCE was 11.5% for PF-AES and 13.6% for PP-ZES, plog-rank  = 0.11. TLF was numerically lower in PF-AES as compared to PP-ZES (5.4 vs. 6.1%, plog-rank  = 0.68). After propensity-score adjustment, PF-AES showed a trend toward a lower rate of MACCE and a favorable rate of TLF as compared to PP-ZES (HR 0.70; 95%CI 0.45 to 1.10, P = 0.12; and HR 0.88; 95%CI 0.47 to 1.65, P = 0.68, respectively). Rates of definite ST were low (0.8 vs. 0.3%, plog-rank  = 0.62). CONCLUSIONS: Our study suggests that implantation of PF-AES was safe and effective in real-world patients, with low-rates of MACCE and TLF at 1 year. Our data needs to be confirmed by a large trial to evaluate the clinical outcomes of this novel polymer-free, eluting-technology used in PF-AES

Clinical and Angiographic Predictors and Prognostic Value of Failed Thrombus Aspiration in Primary Percutaneous Coronary Intervention

Objectives This study sought to investigate which factors are associated with failure of thrombus aspiration (TA) and if this has prognostic implications. Background The pathophysiological mechanism and clinical benefit of TA during primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction is still in debate. Methods Between August 2001 and October 2007, TA was attempted in 1,399 patients. Failure of TA was defined as the inability to reach and/or cross the occlusion with the aspiration catheter for effective thrombus removal. In addition, we analyzed patients in which no material could be obtained. We examined baseline clinical and angiographic variables related to failure of TA or to the lack of aspirate. Follow-up on vital status was obtained at 1 year. Results In 144 (10.3%) patients, the aspiration catheter failed to cross the lesion. After multivariable adjustment, marked proximal tortuosity (odds ratio [OR]: 2.88, 95% confidence interval [CI]: 1.92 to 4.31, p <0.001), the presence of a calcified lesion (OR: 2.70, 95% CI: 1.77 to 4.13, p <0.001), and a bifurcation lesion (OR: 1.97, 95% CI: 1.15 to 3.37, p = 0.013) were independent predictors of failed TA. Age over 60 years and the circumflex as infarct-related artery were associated with the lack of aspirate. Mortality rates at 1 year were 6.2% in patients with failed TA and 6.4% with successful TA (hazard ratio: 0.98, 95% CI: 0.49 to 1.95, p = 0.95). Conclusions The presence of marked proximal tortuosity of the infarct-related artery, a calcified lesion, and a bifurcation lesion are independent predictors of failure of thrombus aspiration. We found that unsuccessful TA did not affect 1-year mortality. (J Am Coll Cardiol Intv 2011;4:634-42) (C) 2011 by the American College of Cardiology Foundatio

Persistent Symptoms and Health Needs of Women and Men With Non-Obstructed Coronary Arteries in the Years Following Coronary Angiography

Background: The prognosis of women and men with persistent anginal complaints and non-obstructed coronary arteries is impaired as compared with asymptomatic women and men. The increased healthcare burden in the hospital due to repeated coronary angiography in these women and men has been documented, yet little is known about the percentage of women and men who remain symptomatic and under care of the general practitioner in the years following a coronary angiographic outcome of non-obstructed coronary arteries. Methods: From the Utrecht Coronary Biobank study, including individuals who underwent a coronary angiography from 2011 to 2015 (N = 2,546, 27% women), we selected women and men with non-obstructed coronary arteries (N = 687, 39% women). This population was linked to the Julius General Practitioners Network (JGPN); a database with routine care data of general practitioners. For every individual with non-obstructed coronary arteries, we selected an asymptomatic non-referred age-, sex-, and general practitioner-matched individual from the JGPN. We compared the healthcare consumption of men and women with non-obstructed coronary arteries to these matched individuals. The McNemar's test was used for pairwise comparison, and sex differences were assessed using stratified analyses. Results: The prevalence of non-obstructed coronary arteries was higher in women as compared with men (39 vs. 23%). During a median follow-up of 7 years [IQR 6.4-8.0], 89% of the individuals with non-obstructed coronary arteries (91% women and 87% men) visited their general practitioner for one or more cardiovascular consultations. This was compared to 34% of the matched individuals (89 vs. 34%, p < 0.001). The consultations were most often for angina (equivalents) (57 vs. 11%, p < 0.001) and heart failure (10 vs. 2%, p = 0.015). In addition, they more often consulted the general practitioner for psychosocial complaints (31 vs. 15%, p = 0.005). Findings were similar for women and men. Conclusions: A coronary angiographic outcome of non-obstructed coronary arteries is more common in women than in men. In the years following the coronary angiography, the majority of the population remains symptomatic. Both women and men with non-obstructed coronary arteries had higher health needs for angina, heart failure, and psychosocial complaints than matched asymptomatic individuals

Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis - A pathological thrombectomy study in primary percutaneous coronary intervention

Background - Acute ST-elevation myocardial infarction (STEMI) is caused by sudden occlusive coronary thrombosis, after plaque disruption; however, a considerable time interval between plaque disturbance and the onset of symptoms has been suggested. We therefore studied the age of intracoronary thrombi, aspirated during angioplasty in patients with acute STEMI. Methods and Results - Percutaneous intracoronary thrombectomy during angioplasty was performed in 211 consecutive STEMI patients within 6 hours after onset of anginal symptoms. The aspirated material was histologically screened on thrombus and plaque components, and thrombus age was classified as fresh ( 5 days). In all patients, intracoronary-derived material was retrieved in the filter of the collection bottle. Thrombus was identified in 199 (95 %) of 211 patients. In 12 patients (5 %), only plaque components were identified, and in 85 patients (41 %), both thrombus and plaque material were aspirated. In 18 (9 %) of 199 patients, the thrombus was organized, and in 70 patients (35 %), the thrombus showed lytic changes, whereas in 98 (49 %), a completely fresh thrombus was found. In 14 (7 %) of 199 patients, the thrombus showed combined features of both fresh thrombus and organized thrombus. Conclusions - In at least 50 % of patients with acute STEMI, coronary thrombi were days or weeks old. This indicates that sudden coronary occlusion is often preceded by a variable period of plaque instability and thrombus formation, initiated days or weeks before onset of symptom

Toll-like receptor 4 gene polymorphisms show no association with the risk of clinical or angiographic restenosis after percutaneous coronary intervention

Objective Restenosis after percutaneous coronary intervention (PCI) remains an issue even in the drug-eluting stent era. Genetic polymorphisms may provide insight in the pathogenesis of restenosis and may help in the stratification of patients at risk for restenosis. The aim of this study was to examine whether polymorphisms at the toll-like receptor 4 (TLR4) locus, that are associated with impaired innate immune system and with an increased risk of cardiovascular events, were associated with clinical and/or angiographic restenosis after PCI. Methods The GENetic Determinants of Restenosis (GENDER) project was a prospective, multicenter study that enrolled 3146 consecutive patients after successful PCI. Frequencies of the TLR4 896A/G (Asp299Gly; rs4986790) and 1196C/T (Thr399Ile; rs4986791) polymorphisms and haplotypes were assessed. Patients were followed up for 1 year and in a subgroup of 406 patients angiographic follow-up was obtained. Results We included a total of 2682 patients that underwent successful PCI. There was no association between genotypes and the risk of target vessel revascularization at 1-year or late luminal loss at 6-months angiographic follow-up (P = 0.53 and 0.44, respectively). Absence of association with target lesion revascularization and late luminal loss was replicated in the GEnetic risk factors for In-Stent Hyperplasia study Amsterdam (GEISHA) cohort study of 674 patients and in a subgroup of 550 patients with angiographic follow-up available (P = 0.26, and 0.86, respectively). Moreover, in both the studies, no significant differences between haplotypes A/C and G/T were observed for target vessel revascularization at late luminal loss. Conclusion Although inflammation has been implicated in the pathophysiology of restenosis, the 896A/G and 1196C/T polymorphisms or haplotypes based on these polymorphisms at the TLR4 locus are not associated with an increased risk of target vessel revascularization or angiographic restenosis after PCI. These polymorphisms are not useful for pre-PCI identification of patients at risk for restenosis. Pharmacogenetics and Genomics 20: 544-552 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Coronary Death

OBJECTIVES: The aim of this study was to assess differences in thrombus healing between ruptured and eroded plaques, given the natural difference in lesion substrate and that thrombi might exist days to weeks before the presentation of sudden coronary death. BACKGROUND: Although the ability to distinguish ruptures and erosions remains a major clinical challenge, in-hospital patients dying with acute myocardial infarction establish that erosions account for 25% of all deaths, where women experience a higher incidence compared with men. METHODS: Coronary lesions with thrombi (ruptures, n = 65; erosions, n = 50) received in consultation from the Medical Examiner's Office from 111 sudden death victims were studied. Thrombus healing was classified as early ( 7 days). Morphometric analysis included vessel dimensions, necrotic core size, and macrophage density. RESULTS: Late-stage thrombi were identified in 79 of 115 (69%) culprit plaques. Women more frequently had erosion with a greater prevalence of late-stage thrombi (44 of 50, 88%) than ruptures (35 of 65, 54%, p < 0.0001). The internal elastic lamina area and percent stenosis were significantly smaller in erosions compared with ruptures (p < 0.0001 and p = 0.02), where plaque burden was greater (p = 0.008). Although macrophage infiltration in erosions was significantly less than ruptures (p = 0.03), there was no established relationship with thrombus organization. Other parameters of thrombus length and occlusive versus nonocclusive showed no association with healing. CONCLUSIONS: Approximately two-thirds of coronary thrombi in sudden coronary deaths are organizing, particularly in young individuals-especially women, who perhaps might require a different strategy of treatmen