Evaluation of an in vitro coronary stent thrombosis model for preclinical assessment.

Stent thrombosis remains an infrequent but significant complication following percutaneous coronary intervention. Preclinical models to rapidly screen and validate therapeutic compounds for efficacy are lacking. Herein, we describe a reproducible, high throughput and cost-effective method to evaluate candidate therapeutics and devices for either treatment or propensity to develop stent thrombosis in an in vitro bench-top model. Increasing degree of stent malapposition (0.00 mm, 0.10 mm, 0.25 mm and 0.50 mm) was associated with increasing thrombosis and luminal area occlusion (4.1 ± 0.5%, 6.3 ± 0.5%, 19.7 ± 4.5%, and 92.6 ± 7.4%, p < 0.0001, respectively). Differences in stent design in the form of bare-metal, drug-eluting, and bioresorbable vascular scaffolds demonstrated differences in stent thrombus burden (14.7 ± 3.8% vs. 20.5 ± 3.1% vs. 86.8 ± 5.3%, p < 0.01, respectively). Finally, thrombus burden was significantly reduced when healthy blood samples were incubated with Heparin, ASA/Ticagrelor (DAPT), and Heparin+DAPT compared to control (DMSO) at 4.1 ± 0.6%, 6.9 ± 1.7%, 4.5 ± 1.2%, and 12.1 ± 1.8%, respectively (p < 0.01). The reported model produces high throughput reproducible thrombosis results across a spectrum of antithrombotic agents, stent design, and degrees of apposition. Importantly, performance recapitulates clinical observations of antiplatelet/antithrombotic regimens as well as device and deployment characteristics. Accordingly, this model may serve as a screening tool for candidate therapies in preclinical evaluation.

Cost assessment of treatment of acute myocardial infarction and angiographically visible coronary thrombus.

AIM: Study was aimed to assess the real-world costs of manual thrombectomy (MT) in selected ST-segment elevation myocardial infarction patients with intracoronary thrombus (IT). METHODS: Study group (IT+) comprised 51 patients with MT applied and control group (IT-) comprised 56 patients without IT who underwent angioplasty alone. Costs comprised hospital care and cost of disposable materials used during primary angioplasty. RESULTS: Complex management of patients with IT is more expensive, though allows to achieve clinical outcomes comparable to low-risk ST-segment elevation myocardial infarction patients without IT. CONCLUSION: A complex pharmaco-interventional strategy, with glycoprotein IIB/IIIA inhibitor and MT, though more expensive, may prove cost-effective.

Abluminal Neointimal Healing by Optical Coherence Tomography Assessment After Drug-Eluting Stent Implantation on Organized Recanalized Thrombus.

Six-month PCI follow-up results of left anterior descending (LAD) and circumflex (CX) drug-eluting stent implantation are presented. Angiography showed patent LAD and CX stents. However, OCT revealed almost all abluminal cavities were completely filled, which the authors surmise was due to a neointimal healing process.

Optical coherence tomography assessment and quantification of intracoronary thrombus: Status and perspectives.

Coronary angiography is the "golden standard" imaging technique in interventional cardiology and it is still widely used to guide interventions. A major drawback of this technique, however, is that it is inaccurate in the evaluation and quantification of intracoronary thrombus burden, a critical prognosticator and predictor of intraprocedural complications in acute coronary syndromes. The introduction of optical coherence tomography (OCT) holds the promise of overcoming this important limitation, as near-infrared light is uniquely sensitive to hemoglobin, the pigment of red blood cells trapped in the thrombus. This narrative review will focus on the use of OCT for the assessment, evaluation and quantification of intracoronary thrombosis.

Mechanisms of atherothrombosis and vascular response to primary percutaneous coronary intervention in women versus men with acute myocardial infarction: results of the OCTAVIA study.

OBJECTIVES: This study sought to assess in vivo sex differences in the pathophysiology of ST-segment elevation myocardial infarction (STEMI) and vascular response to primary percutaneous coronary intervention (PCI). BACKGROUND: There is no consensus on whether differences in the pathophysiology of STEMI and response to primary PCI between women and men reflect biological factors as opposed to differences in age. METHODS: In this prospective, multicenter study, 140 age-matched men and women with STEMI undergoing primary PCI with everolimus-eluting stent were investigated with intravascular optical coherence tomography, histopathology-immunohistochemistry of thrombus aspirates, and serum biomarkers. Primary endpoints were the percentages of culprit plaque rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow-up as determined by optical coherence tomography. RESULTS: Men and women had similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95% confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex differences in composition of aspirated thrombus and immune and inflammatory serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%; difference in medians: RR: 0.2%; 95% CI: -0.4% to 1.3%; p = 0.89) and amount of in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There were no sex differences in clinical outcome either at 30-day or 1-year follow-up. CONCLUSIONS: In patients presenting with STEMI undergoing primary PCI, no differences in culprit plaque morphology and factors associated with coronary thrombosis were observed between age-matched men and women. Women also showed similar vascular healing response to everolimus-eluting stents as men did. (Optical Coherence Tomography Assessment of Gender Diversity In Primary Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207).

The randomized physiologic assessment of thrombus aspiration in patients with acute ST-segment elevation myocardial infarction trial (PATA STEMI): study rationale and design.

INTRODUCTION: Routine thrombus aspiration is proposed to be superior to conventional primary percutaneous coronary intervention (PCI) in terms of improved myocardial perfusion, in patients with ST-segment elevation acute myocardial infarction (STEMI). However, myocardial perfusion after thrombus aspiration has not been evaluated by a quantitative, invasive method. We intend to determine whether manual thrombus aspiration in the infarct-related coronary artery increases myocardial perfusion assessed by index of microcirculatory resistance (IMR) compared with conventional primary PCI. STUDY DESIGN: PATA STEMI is a single-center, prospective, randomized trial with a planned inclusion of 128 patients with the first STEMI. Prior to coronary angiography, patients are randomly assigned to thrombus aspiration using the Eliminate aspiration catheter (Terumo Medical Supply, Japan) or to conventional primary PCI. After completion of primary PCI, IMR is determined both in infarct-related artery and in noninfarct-related arteries without critical stenoses. The primary end-point is a group mean value of IMR after thrombus aspiration compared with conventional primary PCI. Secondary end-points are myocardial perfusion grade, resolution of ST-segment elevation, enzymatic estimation of infarct size, left ventricular remodeling assessed by echocardiographic indices, and major adverse cardiac events rate at 1, 6, and 12 months. CONCLUSION: If manual thrombus aspiration significantly reduces microcirculatory resistance, thereby improving myocardial perfusion, it may become the routine strategy in primary PCI.

Assessment of plasma aminothiol levels and the association with recurrent atherothrombotic events in patients hospitalized for an acute coronary syndrome: a prospective study.

BACKGROUND: The aminothiols homocysteine and, to a lesser extent, cysteine have been associated with adverse cardiovascular outcome, whereas glutathione, as an antioxidant, may protect against atherosclerosis and thrombosis. Potentially, the combined assessment of these aminothiols may provide a more accurate association with future cardiovascular outcome. We evaluated the association between recurrent atherothrombotic events and the concentration of total plasma cysteine, homocysteine, and glutathione and their combination. METHODS: Respective aminothiols were measured by high-performance liquid chromatography in blood plasma of consecutive first-day survivors admitted for an acute coronary syndrome between April 2002 and January 2004. The combined score was calculated using the combination of the individual aminothiols. The end point was the composite of cardiovascular death, myocardial infarction, and/or stroke. RESULTS: A cohort of 375 consecutive patients (median age 66 years, 66% male) were followed for a median duration of 2.7 years. The end point occurred in 82 patients (22%). In univariate analyses, all aminothiols were significantly associated with the composite end point. After correction for possible confounders, only cysteine and glutathione remained significantly associated. The strongest association with the end point was observed for the combined score (adjusted hazard ratio, 1.40 per standard deviation increase; p=0.005). CONCLUSIONS: Although homocysteine is generally considered the aminothiol of interest with respect to cardiovascular disease, in our prospective study, only cysteine and glutathione appeared independently associated with recurrent atherothrombotic events. Moreover, we showed that an imbalance in the combination of aminothiols could be of more importance than investigating the individual metabolites.

Clopidogrel versus aspirin in patients with atherothrombosis: CAPRIE-based calculation of cost-effectiveness for Germany.

OBJECTIVES: To model the 2-year cost-effectiveness of secondary prevention with clopidogrel versus aspirin (acetylsalicylic acid) (ASS) in German patients with myocardial infarction (MI), ischaemic stroke (IS) or diagnosed with peripheral arterial disease (PAD), based on CAPRIE trial data and from the perspective of German third party payers (TPP). METHODS: An existing Markov model was adapted to Germany by using German cost data. The model was extended by using different datasets for cardiovascular event survival times (Framingham vs. Saskatchewan health databases) and in two separate scenarios. RESULTS: The treatment with clopidogrel leads to a reduction of 13.19 vascular events per 1000 patients, of which 2.21 are vascular deaths. The overall incremental costs for the 2-year management of atherothrombotic patients with clopidogrel instead of ASS are calculated to be about euro1 241 440 per 1000 patients. The number of life-years saved (LYS) has been calculated as the difference in the number of life-years lost due to vascular death or events with ASS versus clopidogrel: it is 86.35 LYS when analysis is based on Framingham data and 66.07 LYS with Saskatchewan-based survival data. The incremental costs per LYS are euro14 380 and euro18 790, respectively. Cost-effectiveness is sensitive to changes in survival data, discounting and daily costs of clopidogrel, but stable against substantial (+/- 25%) changes in all other cost data. CONCLUSION: The findings for Germany are in line with published results for Belgium (euro13 390 per LYS) and also with results for Italy (euro17 500 per LYS), both based on Saskatchewan data, and with a French analysis based on Framingham data (euro15 907 per LYS). Even if no officially accepted cost-effectiveness threshold exists for Germany at present, incremental cost-effectiveness results of less than euro20 000 per LYS for the treatment with clopidogrel can be assumed to be acceptable for German third party payers.

Left atrial appendage assessment by second harmonic transthoracic echocardiography after an acute ischemic neurologic event.

Although second harmonic (sh) imaging is widely available in most contemporary ultrasound systems, its accuracy to evaluate left atrial appendage (LAA) morphology and function remains poorly characterized. We conducted a cross-sectional survey of patients with acute ischemic neurologic conditions (n = 51) who underwent both transesophageal and transthoracic echocardiography (TTE) to explore the performance of sh in LAA assessment. Doppler and LAA area evaluation by sh TTE were feasible in most patients (98%). We observed positive and significant associations between sh TTE and transesophageal echocardiography assessment of LAA peak emptying velocities (r = 0.63, P < .001) and LAA maximum area (r = 0.73, P < .001). In addition, all patients (n = 7) with LAA thrombus or spontaneous contrast had peak emptying velocities less than 50 cm/s on sh TTE (negative predictive value of 100%). In multivariate analysis, LAA peak emptying velocity remained independently associated with LAA thrombus or contrast. In conclusion, sh TTE can provide valuable and clinically relevant information of LAA morphology and dynamics.

Assessment of plaque vulnerability by angioscopic classification of plaque color.

BACKGROUND: The disruption of yellow plaque and subsequent thrombosis is regarded as the mechanism of acute coronary syndrome. However, there are limited reports on the assessment of plaque vulnerability. Therefore, we tested whether the angioscopically determined yellow color intensity of plaque is associated with the prevalence of thrombosis on the plaque. METHODS: The angioscopic images of 843 patients who underwent catheterization and angioscopic examination from November 1999 to July 2003 for the diagnosis of coronary artery diseases were analyzed. Suspected culprit vessel was observed by angioscopy, and the yellow color intensity (1, light yellow; 2, yellow; 3, intensive yellow) of all yellow plaques (n = 1253) detected in the nonstenotic (diameter stenosis <50%) coronary segments was determined, as well as whether there was thrombosis on the plaques. RESULTS: The number of detected yellow plaques was 345, 721, and 187 for color grade 1, 2, and 3, respectively. The prevalence of thrombosis detected by angioscopy (15%, 26%, and 52% on the plaque of color grade 1, 2, and 3, respectively, P <.0001) was significantly higher on the plaque of higher yellow color grade. CONCLUSIONS: The yellow color intensity of plaque determined by angioscopy was strongly related with the prevalence of thrombosis on the plaque. The yellow color intensity may be a marker of plaque vulnerability.

Current perspectives on reperfusion therapy for acute ST-segment elevation myocardial infarction: integrating pharmacologic and mechanical reperfusion strategies.

The therapeutic approach to patients with acute ST-segment elevation myocardial infarction (STEMI) has advanced rapidly over the past decade. Intravenous fibrinolytic therapy remains the most common form of reperfusion therapy worldwide, since fibrinolytics are associated with a dramatic reduction in mortality rates. However, primary percutaneous coronary intervention (PCI) is associated with improved outcomes and less bleeding complications compared with fibrinolytic therapy, but it is not widely available. Adjunctive therapies with intracoronary stents, glycoprotein (GP) IIb/IIIa inhibitors, and more potent antithrombin agents have shown great promise for the initial treatment of STEMI and have stimulated further investigation of combined pharmacological/mechanical reperfusion strategies that may be synergistic. Although the optimal combination of fibrinolytics, antiplatelet agents, antithrombins, and mechanical reperfusion at hospitals with and without primary PCI facilities remains elusive, results from recent studies suggest that such a combined approach may facilitate transfer of patients with STEMI from a referral hospital to an invasive hospital for definitive primary PCI after administration of a potent pharmacologic regimen designed to enhance early infarct-related artery reperfusion. Thus, as the reperfusion era continues to evolve, the ideal treatment strategy for patients with STEMI is being redefined to integrate pharmacologic and mechanical approaches to reperfusion.

Transesophageal echocardiography assessment of left atrial appendage function in untreated systemic hypertensive patients in sinus rhythm.

To assess left atrial appendage (LAA) function in hypertensive patients without treatment, transesophageal echocardiography (TEE) was performed in 46 hypertensive patients in sinus rhythm, aged 40 to 55 years, and in 16 control subjects (group I) without cardiovascular disease, aged 41 to 54 years. The hypertensive patients were divided into 2 groups according to left ventricular (LV) systolic function: group II, the group with normal LV systolic function (ejection fraction 0.63 +/- 0.08), and group III, the group with LV systolic dysfunction (ejection fraction 0.39 +/- 0.05). The LAA late emptying velocities (EVs) were significantly reduced in the hypertensive subgroups compared with the control group (P <.001), but no significant difference in the LAAEV was found between groups II and III. The LAAEV in the hypertensive patients had a significant negative correlation with diastolic blood pressure, systolic blood pressure, and left atrial (LA) diameter. The maximal LAA areas were significantly larger in the hypertensive subgroups than in the control group (P <.05). No significant difference in LAA maximal area existed between groups II and III. The maximal LAA area in the hypertensive patients had a significant positive correlation with diastolic blood pressure, systolic blood pressure, and LA diameter, but a significant negative correlation with LV ejection fraction. With TEE, LA spontaneous echocardiographic contrast (SEC) was present in 6 (43%) of 14 patients in group III (P <.01) and in 7 (22%) of 32 patients in group II (P <.05). No significant difference in the occurrence of LASEC was found between groups II and III. Left atrial appendage thrombi by TEE were observed in 4 (29%) of 14 patients in group III (P <.05) and in 4 (13%) of 32 patients in group II (P = not significant). No significant difference in the occurrence of LAA thrombus existed between groups II and III. In conclusion, in patients with untreated hypertension, marked elevation of afterload imposed on the left atrium may involve both the left atrium and the LAA, resulting in impairment of LAA function. This condition may worsen with subsequent occurrence of SEC and later, thrombus formation. Therefore assessment of LAA function may be important even in the hypertensive patient in sinus rhythm.

The role of intracoronary thrombus in unstable angina: angiographic assessment and thrombolytic therapy during ongoing anginal attacks.

Intracoronary thrombus is regarded as a potentially important factor in the etiology of unstable angina, but the incidence of intracoronary thrombus in unstable angina has not been clearly defined. To determine the occurrence of intracoronary thrombus during ongoing angina pectoris, coronary angiography was performed during spontaneous ischemic attacks in 37 patients with prolonged rest angina. All patients exhibited significant (greater than 50%) stenoses of at least one major coronary artery. Of the 37 patients, 21 (57%) had intracoronary thrombus in major coronary arteries, whereas 14 (38%) had fixed narrowings without evidence of intracoronary thrombus and two exhibited coronary spasm. ST segment elevation was observed in 16 of 21 patients with thrombus and in all of the patients with coronary spasm, but all the patients with organic stable obstruction showed ST segment depression. Twenty of the 21 patients with thrombus improved after thrombolytic therapy with intracoronary injection of urokinase; obstructed arteries were reopened, or narrowings were attenuated, with relief of ischemic symptoms. In patients with fixed obstructions, the rate-pressure product during active symptoms was significantly higher than during an asymptomatic period, indicating that a transient increase in myocardial oxygen demand may contribute to the ischemic attack in these patients. A high incidence (71%) of recurrent symptoms was observed in patients with intracoronary thrombus even after successful thrombolysis, in contrast to a much lower incidence (36%) in those without intracoronary thrombus. Myocardial infarction within 4 weeks after catheterization was observed more frequently in patients with intracoronary thrombus (24%) than in those without thrombus (7%).(ABSTRACT TRUNCATED AT 250 WORDS)