Roadmap Consensus on Carotid Artery Plaque Imaging and Impact on Therapy Strategies and Guidelines: An International, Multispecialty, Expert Review and Position Statement.

Current guidelines for primary and secondary prevention of stroke in patients with carotid atherosclerosis are based on the quantification of the degree of stenosis and symptom status. Recent publications have demonstrated that plaque morphology and composition, independent of the degree of stenosis, are important in the risk stratification of carotid atherosclerotic disease. This finding raises the question as to whether current guidelines are adequate or if they should be updated with new evidence, including imaging for plaque phenotyping, risk stratification, and clinical decision-making in addition to the degree of stenosis. To further this discussion, this roadmap consensus article defines the limits of luminal imaging and highlights the current evidence supporting the role of plaque imaging. Furthermore, we identify gaps in current knowledge and suggest steps to generate high-quality evidence, to add relevant information to guidelines currently based on the quantification of stenosis.

Prediction of high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndromes.

BACKGROUND: About 40% of clopidogrel-treated patients display high platelet reactivity (HPR). Alternative treatments of HPR patients, identified by platelet function tests, failed to improve their clinical outcomes in large randomized clinical trials. A more appealing alternative would be to identify HPR patients a priori, based on the presence/absence of demographic, clinical and genetic factors that affect PR. Due to the complexity and multiplicity of these factors, traditional statistical methods (TSMs) fail to identify a priori HPR patients accurately. The objective was to test whether Artificial Neural Networks (ANNs) or other Machine Learning Systems (MLSs), which use algorithms to extract model-like 'structure' information from a given set of data, accurately predict platelet reactivity (PR) in clopidogrel-treated patients. METHODS: A complete set of fifty-nine demographic, clinical, genetic data was available of 603 patients with acute coronary syndromes enrolled in the prospective GEPRESS study, which showed that HPR after 1month of clopidogrel treatment independently predicted adverse cardiovascular events in patients with Syntax Score >14. Data were analysed by MLSs and TSMs. ANNs identified more variables associated PR at 1month, compared to TSMs. RESULTS: ANNs overall accuracy in predicting PR, although superior to other MLSs was 63% (95% CI 59-66). PR phenotype changed in both directions in 35% of patients across the 3 time points tested (before PCI, at hospital discharge and at 1month). CONCLUSIONS: Despite their ability to analyse very complex non-linear phenomena, ANNs or MLS were unable to predict PR accurately, likely because PR is a highly unstable phenotype.

Impact of bridging with perioperative low-molecular-weight heparin on cardiac and bleeding outcomes of stented patients undergoing non-cardiac surgery.

When patients with coronary stents undergo non-cardiac surgery, bridging therapy with low-molecular-weight heparin (LMWH) is not infrequent in clinical practice. However, the efficacy and safety of this approach is poorly understood. This was a retrospective analysis of patients with coronary stent(s) on any antiplatelet therapy undergoing non-cardiac surgery between March 2003 and February 2012. The primary efficacy endpoint was the 30-day incidence of major adverse cardiac or cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction, acute coronary syndrome leading to hospitalisation, or stroke. The primary safety endpoint was the 30-day composite of Bleeding Academic Research Consortium (BARC) bleedings ≥ 2. Among 515 patients qualifying for the analysis, LMWH bridging was used in 251 (49 %). At 30 days, MACCE occurred more frequently in patients who received LMWH (7.2 % vs 1.1 %, p=0.001), driven by a higher rate of myocardial infarction (4.8 % vs 0 %, p< 0.001). This finding was consistent across several instances of statistical adjustment and after the propensity matching of 179 pairs. Patients bridged with LMWH also experienced a significantly higher risk of BARC bleedings ≥ 2 (21.9 % vs 11.7 %, p=0.002) compared to those who were not, which remained significant across different methods of statistical adjustment and propensity matching. In conclusion, LMWH bridging in patients with coronary stents undergoing surgery is a common and possibly harmful practice, resulting in worse ischaemic outcomes at 30 days, and a significant risk of bleeding.

The Ultimaster® coronary stent system: state of the art.

Percutaneous coronary intervention (PCI) has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stent (BMS) and then first- and second-generation drug-eluting stents (DES) have enhanced the results of PCI by improving early results and reducing the risk of restenosis and stent thrombosis (ST). The delay of re-endothelialization and recovery of endothelial function after stenting as well as inhibition of vascular repair after DES implantation, in part related to permanent polymers, are consider important part of ST pathophysiology mechanism. Several progresses have been made to overcome this issue, among them the development of new more biocompatible - first - and completely biodegradable - then - polymer coatings. A third-generation DES using a biodegradable polymer and eluting sirolimus (Ultimaster®, Terumo Corporation, Tokyo, Japan) has been recently introduced to overcome the long-term adverse vascular reactions. Thanks to the polymer coating applied to the outside surface only (abluminal side), the total drug dose applied on the stent platform has been reduced, leaving the luminal side of the stent free from drug and polymer to enhance endothelial coverage. Indeed, 3-4 months after implantation, the Ultimaster® DES has lost most of its coating, acquiring a profile similar to conventional BMS. This article reviews the recent publications investigating the safety and effectiveness of the bioresorbable polymer sirolimus-eluting Ultimaster® stent (BP-SES), for the treatment of coronary artery lesions.

Treatment of coronary bifurcation lesions with bioresorbable vascular scaffolds.

AIM: Aim of the study was to report on the feasibility and early safety and efficacy of Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) for coronary artery bifurcations (CABs) treatment at a single high-volume center. METHODS: All patients treated with Absorb implantation at our institution from March 2013 to March 2014 were enrolled in the prospective, single-center, ongoing, all-comers registry, which has the main purpose of evaluating the safety and efficacy of Absorb implantation in unselected patients treated in daily practice. In-hospital and at follow-up clinical outcomes of 46 patients undergoing treatment with Absorb in 46 CAB lesions were reported in the present study. RESULTS: Treated CAB lesions involved the left main in 13.0% of cases, the left anterior descending artery in 65.0%, the left circumflex in 19.6%, and the right coronary artery in 2.2%. Bifurcations were classified as true (47.8%) and non-true (52.2%) according to the Medina classification. The provisional and the two-BVS techniques were used in 78.3% and 21.7%, respectively. Two-BVS techniques included: mini-crush 13.0%; reverse culotte 2.2%; T-stenting 2.2%; and V-stenting 4.3%. No in-hospital adverse events occurred. At 6 months no adverse events occurred. Only one case of target lesion revascularization was observed at day 227. No stent thrombosis occurred during follow-up. CONCLUSION: Our preliminary experience suggested that CABs treatment with Absorb is feasible and associated with promising immediate and short-term clinical outcomes. However, larger studies with long-term follow-up are needed to adequately address the safety and efficacy of BVS use in CABs.

Self-apposing STENTYS® stent in acute myocardial infarction.

Balloon-expandable stents are currently used with satisfactory results in percutaneous coronary interventions. Unfortunately, in challenging anatomical patterns such as high thrombotic burden lesions, outcomes are often impaired. The STENTYS® stent (STENTYS, Paris, France), with its self-expandable capacity and peculiar Z-shape design, has been recently introduced in the clinical arena as an alternative to balloon-expandable stents for challenging lesion subsets. This article provides an overview of clinical trials, completed and currently on-going, on this self-apposing technology.

Antiplatelet therapy: new pharmacological agents and changing paradigms.

Recurrent atherothrombotic events in patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI) are essentially platelet-driven processes, underscoring the need for effective pharmacological platelet inhibition. Dual antiplatelet therapy with aspirin and clopidogrel has been, for over a decade, the mainstay of antiplatelet management in ACS/PCI. However, atherothrombotic events continue to occur in a relevant proportion of subjects despite the benefit of this combination, which has led to the clinical development of newer and more potent antiplatelet drugs. Two of these, prasugrel and ticagrelor, have been recently approved for clinical use. The scope of this manuscript is to provide an up-to-date overview on new antiplatelet drugs in the setting of ACS and PCI, including the most recent advances on newly approved agents as well as on emerging compounds in clinical development.

Safety and efficacy of protease-activated receptor-1 antagonists in patients with coronary artery disease: a meta-analysis of randomized clinical trials.

BACKGROUND: Thrombin receptor antagonists blocking protease-activated receptor-1 (PAR-1) on platelets represent a new class of oral antiplatelet agents for patients with atherothrombotic disease manifestations. OBJECTIVES: We investigated the safety and efficacy of PAR-1 antagonists in patients with coronary artery disease (CAD). PATIENTS/METHODS: Randomized, placebo-controlled trials of the PAR-1 antagonists atopaxar or vorapaxar in CAD patients were identified. The primary safety endpoint was the composite of Thrombolysis In Myocardial Infarction (TIMI) clinically significant bleeding. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke. RESULTS: A total of 41 647 patients from eight trials were included. PAR-1 antagonists were associated with higher risks of TIMI clinically significant (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.39-1.57, P < 0.001), major (OR 1.46, 95% CI 1.28-1.67, P < 0.001) and minor (OR 1.67, 95% CI 1.40-2.00, P < 0.001) bleeding than placebo in the fixed-effects model. PAR-1 antagonists reduced the composite of death, MI or stroke as compared with placebo (OR 0.87, 95% CI 0.81-0.92, P < 0.001), driven by a lower risk of MI (OR 0.85, 95% CI 0.78-0.92, P < 0.001). Conversely, PAR-1 antagonists and placebo did not differ in terms of risk of death (OR 0.99, 95% CI 0.90-1.09, P = 0.81) or stroke (OR 0.96, 95% CI 0.84-1.10, P = 0.59). CONCLUSIONS: PAR-1 antagonists decrease ischemic events in patients with CAD as compared with placebo, mainly driven by a reduction in MI, at the cost of an increased risk of clinically significant bleeding.

Contrast transesophageal echocardiography using the Acunav ultrasound catheter through the mouth way as a guide to percutaneous closure of patent foramen ovale.

AIM: Contrast-enhanced transesophageal echo-cardiography (c-TEE) represents the gold standard in the diagnosis of patent foramen ovale (PFO) but it is not always well tolerated by the patient, and it is influenced by his cooperation. Purpose of the present study was to assess feasibility and safety of c-TEE through the oral way using a miniaturized 10-Fr, monoplane probe (Acunav-TEE) and establish its utility in the diagnosis or PFO when compared with c-TEE using the traditional multiplane probe (standard-TEE). METHODS: From January 2008 to September 2008, 54 consecutive patients with presumed paradoxical cerebrovascular events and a suspected PFO were prospectively enrolled in this study. After signing a consensus form, these patients underwent both standard-TEE and Acunav-TEE in the same day by two independent operators. RESULTS: Feasibility of standard-TEE in our study was 96.3% (52/54) while feasibility of Acunav-TEE was 100% (54/54). When compared to standard-TEE, Acunav-TEE required shorter average time to insert the probe (1.0+/-0.2 vs. 4.1+/-1.1 minutes, P<0.001) but longer average time to look for the best projection and start the examination (13.8+/-2.4 vs. 9.1+/-2.7 minutes, P<0.001). Using standard-TEE as gold standard we defined a sensitivity of 100% (20/20) and a specificity of 97% (31/32) for Acunav-TEE. The positive predictive value, the negative predictive value and the global diagnostic accuracy were 95% (20/21), 100% (31/31) and 98% (51/52), respectively. CONCLUSION: Consistent with our experience, Acunav-TEE seems to be a feasible and safe technique when used for the diagnosis of PFO, with excellent sensitivity and specificity as compared with standard-TEE.

Platelet monitoring for PCI: which test is the one to choose?

Despite the clinical benefit associated with the combined use of aspirin and clopidogrel in patients with acute coronary syndrome or those undergoing percutaneous coronary intervention, a considerable interindividual variability in response to these drugs have been consistently reported. There is a growing interest on applying platelet functional tests with the goal of identifying patients at increased risk of recurrent ischaemic events and potentially tailoring antiplatelet treatment regimens. This manuscript will review the state of the art on the most commonly available platelet functional tests, describing their advantages and disadvantages and exploring their applicability in clinical practice.

Long term results of unprotected left main percutaneous coronary intervention with DES versus BMS.

AIM: Stenosis in the unprotected left main coronary artery (ULMCA) is considered a standard indication for surgical revascularization. Some studies have demonstrated that stenting of the ULMCA is safe and feasible in selected patients. Drug eluting stents (DES) have been shown to be superior to bare metal stents (BMS) in reducing restenosis and major adverse cardiac events (MACE) both in-hospital and at follow-up after treatment of ULMCA disease. Several studies showed that the mid-term prognosis of patients with left main stenting is good, but most of them are limited by small populations and the availability of mid-term results. Thus, we sought to evaluate the very long term impact of DES vs BMS in a large cohort of patients undergoing stent implantation for ULMCA disease in our center. METHODS: Between June 2002 and June 2008 a total of 354 consecutive patients with ULMCA stenosis were treated with percutaneous coronary intervention with BMS (53 patients) or DES (301 patients) implantation. A multivariable adjustment was provided in order to account for baseline differences between groups. RESULTS: The average clinical follow-up was 551+/-512 days. Overall, MACE rate was significantly lower in the DES group (16.6% vs 26.4%, P=0.02). The beneficial effect was driven by a reduction of death (6.0% vs 9.4%, P=0.11), MI (2.7% vs 3.8%, P=0.33) and target vessel revascularization after DES implantation (9.0 % vs 15.1%, P=0.11). After correcting for independent predictors of adverse events, the adjusted hazard ratios (HRs) for the risk of mortality and myocardial infarction after DES implantation relative to BMS implantation were 0.99 (95% CIs 0.30-3.21, P=0.98) and 0.59 (95% CIs 0.01-3.45, P=0.56), respectively. The adjusted HR for two-year MACE was 0.50 (95 CIs 0.25-1.02), P=0.056, mainly driven by a statistical significant reduction of TVR (HR 0.30 [95 CIs 0.11-0.82], P=0.018]. CONCLUSIONS: Patients presenting with ULMCA disease, who are treated with DES have a significant reduction in the rate of target lesion revascularization with no increased risk of death or myocardial infarction.

The usefulness of clinical indexes in the evaluation of cardiovascular risk in non cardiac surgery.

AIM: The preoperative cardiac evaluation of a patient who undergoes noncardiac surgery is a very important problem, particularly for diagnostic tools used. Aim of this study is to test the usefulness of 4 most used clinical indexes for the evaluation of cardiovascular risk in the management of patients who undergo noncardiac surgery. METHODS: The study is based on a retrospective analysis of a group of 45 patients, who underwent extracardiac surgery in biennium 2002-2004. The cardiovascular risk scores of Goldman, Detsky, Lee and Eagle were used; a comparison among the different scores was done. RESULTS: Six out of our 45 patients had perioperative cardiovascular complications, and 4 of them died. The Eagle and Lee scores were more predictive than Goldman and Detsky ones. About the 13 echocardiographic tests recorded, no one of them modified the patient preoperative risk. CONCLUSIONS: In the preoperative assessment of risk, the Eagle score was more useful than the others ones and improved the negative predictive value of the Goldman and Detsky scores. The preventive application of the clinical indexes allows optimizing the preoperative stratification of the risk, limiting the request of useless examinations and offering to the patient a well appropriated preoperative management, reducing the incidence of complications.

The inflammatory abdominal aortic aneurysm and coronary artery disease. Case report and review.

Inflammatory abdominal aortic aneurysm (IAAA) is defined as an unusually thickened aneurysmatic wall, encircled by a wide dense perianeurysmal and/or retroperitoneal fibrosis with adjacent tissues adhesion, and is now considered as an extreme shape of the common phlogistic process involved in atherosclerotic plaque formation. Latest studies demonstrated that inflammation plays an important role in coronary disease and in other atherosclerosis manifestations. We introduce the clinical case of a patient with IAAA who developed an acute myocardial infarction 6 months after the surgical procedure on the aorta. Through a literature review about IAAA we stress the clinical usefulness of the inflammatory markers as independent predictors in management of patients with coronary disease and we present the hypothesis, related to the introduced case, of an advanced coronary disease, aggravated or clinically revealed after the cytokine storm related to important localized inflammatory engagements or great vascular surgery treatments.