Endogenous Fibrinolysis : An Important Mediator of Thrombus Formation and Cardiovascular Risk

© 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. PUBLISHED BY ELSEVIER INC.Most acute cardiovascular events are attributable to arterial thrombosis. Plaque rupture or erosion stimulates platelet activation, aggregation, and thrombosis, whilst simultaneously activating enzymatic processes that mediate endogenous fibrinolysis to physiologically maintain vessel patency. Interplay between these pathways determines clinical outcome. If proaggregatory factors predominate, the thrombus may propagate, leading to vessel occlusion. However, if balanced by a healthy fibrinolytic system, thrombosis may not occur or cause lasting occlusion. Despite abundant evidence for the fibrinolytic system regulating thrombosis, it has been overlooked compared with platelet reactivity, partly due to a lack of techniques to measure it. We evaluate evidence for endogenous fibrinolysis in arterial thrombosis and review techniques to assess it, including biomarkers and global assays, such as thromboelastography and the Global Thrombosis Test. Global assays, simultaneously assessing proaggregatory and fibrinolytic pathways, could play a role in risk stratification and in identifying impaired fibrinolysis as a potential target for pharmacological modulation.Peer reviewedFinal Published versio

Physiological predictors of acute coronary syndromes: emerging insights from the plaque to the vulnerable patient

In this review, the authors explore the evolving evidence linking physiological assessment of coronary artery disease with plaque progression and vulnerability. Reducing adverse clinical events remains the ultimate goal for diagnostic tests, and this review highlights evidence supporting the prognostic value of physiological metrics in predicting outcomes. Historical and contemporary studies support synergy among lesion severity, ischemia, plaque vulnerability, and patient prognosis. Ischemia contributes to clinical events through association with plaque burden, but this review addresses the emerging concept that it associates with atherothrombosis via disturbed lesion hemodynamics. Biomechanical pathophysiological forces including endothelial shear stress-the frictional force generated by blood flow on the vessel wall-are increasingly linked with atherogenesis, vulnerable plaque morphology, and platelet and leukocyte activation. The authors conclude by transitioning from the model of the vulnerable plaque to the concept of the "vulnerable patient," looking more broadly at physiological contributors to Virchow's triad underpinning acute coronary syndrome

Time and event-specific deep learning for personalized risk assessment after cardiac perfusion imaging

Standard clinical interpretation of myocardial perfusion imaging (MPI) has proven prognostic value for predicting major adverse cardiovascular events (MACE). However, personalizing predictions to a specific event type and time interval is more challenging. We demonstrate an explainable deep learning model that predicts the time-specific risk separately for all-cause death, acute coronary syndrome (ACS), and revascularization directly from MPI and 15 clinical features. We train and test the model internally using 10-fold hold-out cross-validation (n = 20,418) and externally validate it in three separate sites (n = 13,988) with MACE follow-ups for a median of 3.1 years (interquartile range [IQR]: 1.6, 3.6). We evaluate the model using the cumulative dynamic area under receiver operating curve (cAUC). The best model performance in the external cohort is observed for short-term prediction - in the first six months after the scan, mean cAUC for ACS and all-cause death reaches 0.76 (95% confidence interval [CI]: 0.75, 0.77) and 0.78 (95% CI: 0.78, 0.79), respectively. The model outperforms conventional perfusion abnormality measures at all time points for the prediction of death in both internal and external validations, with improvement increasing gradually over time. Individualized patient explanations are visualized using waterfall plots, which highlight the contribution degree and direction for each feature. This approach allows the derivation of individual event probability as a function of time as well as patient- and event-specific risk explanations that may help draw attention to modifiable risk factors. Such a method could help present post-scan risk assessments to the patient and foster shared decision-making

Quantification and Impact of Untreated Coronary Artery Disease After Percutaneous Coronary Intervention the Residual SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) Score

Objectives the purpose of this study was to quantify the extent and complexity of residual coronary stenoses following percutaneous coronary intervention (PCI) and to evaluate its impact on adverse ischemic outcomes.Background Incomplete revascularization (IR) after PCI is common, and most studies have suggested that IR is associated with a worse prognosis compared with complete revascularization (CR). However, formal quantification of the extent and complexity of residual atherosclerosis after PCI has not been performed.Methods the baseline Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score (bSS) from 2,686 angiograms from patients with moderate-and high-risk acute coronary syndrome (ACS) undergoing PCI enrolled in the prospective ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial was determined. the SS after PCI was also assessed, generating the residual SS (rSS). Patients with rSS >0 were defined as having IR and were stratified by rSS tertiles, and their outcomes were compared to the CR group.Results the bSS was 12.8 +/- 6.7, and after PCI the rSS was 5.6 +/- 2.2. Following PCI, 1,084 patients (40.4%) had rSS = 0 (CR), 523 (19.5%) had rSS >0 but 2 but 8. Age, insulin-treated diabetes, hypertension, smoking, elevated biomarkers or ST-segment deviation, and lower ejection fraction were more frequent in patients with IR compared with CR. the 30-day and 1-year rates of ischemic events were significantly higher in the IR group compared with the CR group, especially those with high rSS. By multivariable analysis, rSS was a strong independent predictor of all ischemic outcomes at 1 year, including all-cause mortality (hazard ratio: 1.05, 95% confidence interval: 1.02 to 1.09, p = 0.006).Conclusions the rSS is useful to quantify and risk-stratify the degree and complexity of residual stenosis after PCI. Specifically, rSS >8.0 after PCI in patients with moderate-and high-risk ACS is associated with a poor 30-day and 1-year prognosis. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158) (J Am Coll Cardiol 2012;59:2165-74) (C) 2012 by the American College of Cardiology Foundationsanofi-aventisMedicines CompanyAbbott VascularBristol-Myers SquibbAstraZenecaColumbia Univ, Med Ctr, Cardiovasc Res Fdn, New York, NY 10022 USAUniv Montreal, Hop Sacre Coeur Montreal, Montreal, PQ, CanadaUniv Bologna, Inst Cardiol, Bologna, ItalyUniversidade Federal de São Paulo, Hosp Israelita Albert Einstein, Sau Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Sau Paulo, BrazilMt Sinai Med Ctr, New York, NY 10029 USAErasmus Univ, Thoraxctr, NL-3000 DR Rotterdam, NetherlandsUniversidade Federal de São Paulo, Hosp Israelita Albert Einstein, Sau Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Sau Paulo, BrazilWeb of Scienc

Effectiveness of the Chest Pain Choice decision aid in emergency department patients with low-risk chest pain: study protocol for a multicenter randomized trial

BACKGROUND: Chest pain is the second most common reason patients visit emergency departments (EDs) and often results in very low-risk patients being admitted for prolonged observation and advanced cardiac testing. Shared decision-making, including educating patients regarding their 45-day risk for acute coronary syndrome (ACS) and management options, might safely decrease healthcare utilization. METHODS/DESIGN: This is a protocol for a multicenter practical patient-level randomized trial to compare an intervention group receiving a decision aid, Chest Pain Choice (CPC), to a control group receiving usual care. Adults presenting to five geographically and ethnically diverse EDs who are being considered for admission for observation and advanced cardiac testing will be eligible for enrollment. We will measure the effect of CPC on (1) patient knowledge regarding their 45-day risk for ACS and the available management options (primary outcome); (2) patient engagement in the decision-making process; (3) the degree of conflict patients experience related to feeling uninformed (decisional conflict); (4) patient and clinician satisfaction with the decision made; (5) the rate of major adverse cardiac events at 30 days; (6) the proportion of patients admitted for advanced cardiac testing; and (7) healthcare utilization. To assess these outcomes, we will administer patient and clinician surveys immediately after each clinical encounter, obtain video recordings of the patient-clinician discussion, administer a patient healthcare utilization diary, analyze hospital billing records, review the electronic medical record, and conduct telephone follow-up. DISCUSSION: This multicenter trial will robustly assess the effectiveness of a decision aid on patient-centered outcomes, safety, and healthcare utilization in low-risk chest pain patients from a variety of geographically and ethnically diverse EDs. TRIAL REGISTRATION: NCT01969240

Dynamic Aspects of Associations in Coronary Artery Disease: From Intracoronary Imaging to Blood Biomarkers

This thesis focuses mainly on blood biomarkers, that have been studied in relation to coronary atherosclerotic characteristics on intravascular imaging and cardiovascular events. Furthermore, specific genetic polymorphisms have been examined in relation to cardiovascular events, as well as treatment benefit by ACE-inhibitors

The role of intracoronary imaging in translational research

Abstract: Atherosclerotic cardiovascular disease is a key public health concern worldwide and leading cause of morbidity, mortality and health economic costs. Understanding atherosclerotic plaque microstructure in relation to molecular mechanisms that underpin its initiation and progression is needed to provide the best chance of combating this disease. Evolving vessel wall-based, endovascular coronary imaging modalities, including intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS), used in isolation or as hybrid modalities, have been advanced to allow comprehensive visualization of the pathological substrate of coronary atherosclerosis and accurately measure temporal changes in both the vessel wall and plaque characteristics. This has helped further our appreciation of the natural history of coronary artery disease (CAD) and the risk for major adverse cardiovascular events (MACE), evaluate the responsiveness to conventional and experimental therapeutic interventions, and assist in guiding percutaneous coronary intervention (PCI). Here we review the use of different imaging modalities for these purposes and the lessons they have provided thus far.Nicholas J. Montarello, Adam J. Nelson, Johan Verjans, Stephen J. Nicholls, Peter J. Psalti