Background
Defining the optimal conduction of percutaneous‐coronary‐intervention (PCI) to treat bifurcation lesions has been the subject of many clinical studies showing that the applied stenting ...technique may influence clinical outcome. Accordingly, bifurcation stenting classifications and technical sequences should be standardized to allow proper reporting and comparison.
Methods
The European Bifurcation Club (EBC) is a multidisciplinary group dedicated to optimize the treatment of bifurcations and previously created a classification of bifurcation stenting techniques that is based on the first stent implantation site. Since some techniques have been abandoned, others have been refined and dedicated devices became available, EBC promoted an international task force aimed at updating the classification of bifurcation stenting techniques as well as at highlighting the best practices for most popular techniques. Original descriptive images obtained by drawings, bench tests and micro‐computed‐tomographic reconstructions have been created in order to serve as tutorials in both procedure reporting and clinical practice.
Results
An updated Main‐Across‐Distal‐Side (MADS)‐2, classification of bifurcation stenting techniques has been realized and is reported in the present article allowing standardized procedure reporting in both clinical practice and scientific studies. The EBC‐promoted task force deeply discussed, agreed on and described (using original drawings and bench tests) the optimal steps for the following major bifurcation stenting techniques: (a) 1‐stent techniques (“provisional” and “inverted provisional”) and (b) 2‐stent techniques (“T/TAP,” “culotte,” and “DK‐crush”).
Conclusions
The present EBC‐promoted paper is intended to facilitate technique selection, reporting and performance for PCI on bifurcated lesions during daily clinical practice.
Abstract
Patient-specific and lesion-specific computational simulation of bifurcation stenting is an attractive approach to achieve individualized pre-procedural planning that could improve outcomes. ...The objectives of this work were to describe and validate a novel platform for fully computational patient-specific coronary bifurcation stenting. Our computational stent simulation platform was trained using n = 4 patient-specific bench bifurcation models (n = 17 simulations), and n = 5 clinical bifurcation cases (training group, n = 23 simulations). The platform was blindly tested in n = 5 clinical bifurcation cases (testing group, n = 29 simulations). A variety of stent platforms and stent techniques with 1- or 2-stents was used. Post-stenting imaging with micro-computed tomography (μCT) for bench group and optical coherence tomography (OCT) for clinical groups were used as reference for the training and testing of computational coronary bifurcation stenting. There was a very high agreement for mean lumen diameter (MLD) between stent simulations and post-stenting μCT in bench cases yielding an overall bias of 0.03 (− 0.28 to 0.34) mm. Similarly, there was a high agreement for MLD between stent simulation and OCT in clinical training group bias 0.08 (− 0.24 to 0.41) mm, and clinical testing group bias 0.08 (− 0.29 to 0.46) mm. Quantitatively and qualitatively stent size and shape in computational stenting was in high agreement with clinical cases, yielding an overall bias of < 0.15 mm. Patient-specific computational stenting of coronary bifurcations is a feasible and accurate approach. Future clinical studies are warranted to investigate the ability of computational stenting simulations to guide decision-making in the cardiac catheterization laboratory and improve clinical outcomes.
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a transmembrane protein expressed on endothelial cells, white blood cells, smooth muscle cells and platelets. TREM-1 plays an important ...role in innate immunity. TREM-1 activation pathways are implicated both in sepsis and in non-infectious inflammatory conditions, including atherosclerosis. TREM-1 enhances the subendothelial lipid accumulation and expression of pro-inflammatory cytokines and matrix-degrading enzymes, thereby promoting inflammation and plaque destabilization. TREM-1 inhibitors attenuate the inflammatory process in the atherosclerotic plaque, leading to plaque stabilization. This review focuses on the role of TREM-1 in the pathophysiology of atherosclerosis and the effects of TREM-1 inhibition in the natural history of the disease.
The Bifurcation Academic Research Consortium (Bif-ARC) project originated from the need to overcome the paucity of standardization and comparability between studies involving bifurcation coronary ...lesions. This document is the result of a collaborative effort between academic research organizations and the most renowned interventional cardiology societies focused on bifurcation lesions in Europe, the United States, and Asia. This consensus provides standardized definitions for bifurcation lesions; the criteria to judge the side branch relevance; the procedural, mechanistic, and clinical endpoints for every type of bifurcation study; and the follow-up methods. Considering the complexity of bifurcation lesions and their evaluation, detailed instructions and technical aspects for site and core laboratory analysis of bifurcation lesions are also reported. The recommendations included within this consensus will facilitate pooled analyses and the effective comparison of data in the future, improving the clinical relevance of trials in bifurcation lesions, and the quality of care in this subset of patients.
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•There is a paucity of standardization and comparability across studies involving coronary bifurcation lesions.•This document provides standardized definitions and criteria for use in studies of such lesions, from diagnosis through follow-up.•Implementation of these recommendations in clinical trials will improve their relevance and improve the quality of care for patients with bifurcation coronary artery disease.
Abstract Several epidemiological studies have reported that an elevated heart rate is associated with coronary atherosclerosis independently of other risk factors. In this review we explore the ...pathophysiologic mechanisms involved in the pro-atherosclerotic effect of elevated heart rate, apart from its association with sympathetic tone. An elevated heart rate enhances the magnitude and frequency of the tensile stress imposed on the arterial wall and prolongs the exposure of coronary endothelium to the systolic low and oscillatory shear stress. Moreover, increased heart rate intensifies the pulsatile motion of the heart and, therefore, the frequency of the periodically changing geometry of the coronary arteries, thereby affecting the local hemodynamic environment. All these processes induce structural and functional changes of the endothelial cells, which are accumulated over the time in atherosclerosis-prone regions promoting atherosclerosis. Heart rate should be considered in every patient with coronary heart disease, especially since it is an easily measurable and reproducible parameter. Slowing the heart rate could potentially decrease the progression of atherosclerosis by reducing the local pro-atherosclerotic vascular environment. This effect may be involved in any beneficial role of heart rate lowering agents in preventing coronary heart disease.
Renal sympathetic denervation, a potentially revolutionary interventional treatment for hypertension, faces an existential problem due to the inability to confirm successful ablation of the targeted ...renal sympathetic nerves. Based on the observation that renal sympathetic nerve activity exerts rhythmic, baroreflex-driven, and vasoconstrictive control of the renal vasculature, we developed a novel technique for identifying rhythmic sympathetic vascular control using a time-varying, 2-component Windkessel model of the renal circulation. This technology was tested in 2 different animal models of renal denervation; 10 rabbits underwent chronic, surgical renal denervation, and 9 pigs underwent acute, functional renal denervation via intrathecal administration of ropivacaine. Both methods of renal denervation reduced negative admittance gain, negative phase shift renal vascular control at known sympathetic vasomotor frequencies, consistent with a reduction in vasoconstrictive, baroreflex-driven renal sympathetic vasomotion. Classic measures like mean renal blood flow and mean renal vascular resistance were not significantly affected in either model of renal denervation. Renal sympathetic vasomotion monitoring could provide intraprocedural feedback for interventionists performing renal denervation and serve more broadly as a platform technology for the evaluation and treatment of diseases affecting the sympathetic nervous system.
•Drug velocity from a catheter was optimized to noninvasively reach a high-risk plaque.•Drug volume fraction along the artery wall increased with increasing injection velocity.•An injection velocity ...threshold was found that yields safe shear stress.•Drug velocities of 15–20 m/s from a catheter pore are optimal for local delivery.
Early identification and treatment of high-risk plaques before they rupture, and precipitate adverse events constitute a major challenge in cardiology today. Computational simulations are a time- and cost-effective way to study the performance, and to optimize a system. The main objective of this work is to optimize the flow of a novel atraumatic local drug delivery catheter for the treatment of coronary atherosclerosis. The mixing and spreading effectiveness of a drug fluid was analyzed utilizing computational fluid dynamics (CFD) in a coronary artery model. The optimum infusion flow of the nanoparticle-carrying drug fluid was found by maximizing the drug volume fraction and minimizing drug velocity at the artery wall, while maintaining acceptable wall shear stress (WSS). Drug velocities between 15 m/s and 20 m/s are optimum for local drug delivery. The resulting parameters from this study will be used to fabricate customized prototypes for future in-vivo experiments.
Purpose of Review
Clinical trials with PCSK9 inhibitors have shown a robust decrease in plasma LDL levels and a significant reduction in the incidence of cardiovascular atherosclerotic events. ...However, the role of PCSK9 in atherosclerosis is not well investigated and it remains unclear whether PCSK9 inhibition has direct, LDL-independent, anti-atherosclerotic effects. This review outlines the molecular pathways and targets of PCSK9 in atherosclerosis and summarizes the experimental and clinical data supporting the anti-atherosclerotic (pleiotropic) actions of PCSK9 inhibitors.
Recent Findings
PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g., endothelial cell, smooth muscle cell, and macrophage) and is detected inside human atherosclerotic plaque. Preclinical studies have shown that inhibition of PCSK9 can attenuate atherogenesis and plaque inflammation.
Summary
Besides increasing plasma LDL, PCSK9 appears to promote the initiation and progression of atherosclerosis. Inhibition of PCSK9 may confer atheroprotection that extends beyond its lipid-lowering effects.
HMG-CoA reductase inhibitors ('statins') represent the most effective and widely prescribed drugs currently available for the reduction of low-density lipoprotein cholesterol, a critical therapeutic ...target for primary and secondary prevention of cardiovascular atherosclerotic disease. In the face of the established lipid lowering and the emerging pleiotropic properties of statins, the patient population suitable for long-term statin treatment is expected to further expand. An overall positive safety and tolerability profile of statins has been established, although adverse events have been reported. Skeletal muscle-related events are the most common adverse events of statin treatment. Statin-induced myopathy can (rarely) manifest with severe and potentially fatal cases of rhabdomyolysis, thus rendering the identification of the underlying predisposing factors critical. The purpose of this review is to summarize the factors that increase the risk of statin-related myopathy. Data from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects were reviewed. Briefly, the epidemiology, clinical spectrum and molecular mechanisms of statin-associated myopathy are discussed. We further analyse in detail the risk factors that precipitate or increase the likelihood of statin-related myopathy. Individual demographic features, genetic factors and co-morbidities that may account for the significant interindividual variability in the myopathic risk are presented. Physicochemical properties of statins have been implicated in the differential risk of currently marketed statins. Pharmacokinetic interactions with concomitant medications that interfere with statin metabolism and alter their systemic bioavailability are reviewed. Of particular clinical interest in cases of resistant dyslipidaemia is the interaction of statins with other classes of lipid-lowering agents; current data on the relative safety of available combinations are summarized. Finally, we provide an update of current guidelines for the prevention and management of statin myopathy. The identification of patients with an increased proclivity to statin-induced myopathy could allow more cost-effective approaches of monitoring and screening, facilitate targeted prevention of potential complications, and further improve the already overwhelmingly positive benefit-risk ratio of statins.
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