Experimental validation and clinical feasibility of 3D reconstruction of coronary artery bifurcation stents using intravascular ultrasound.

The structural morphology of coronary stents and the local hemodynamic environment following stent deployment in coronary arteries are crucial determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to facilitate geometrically accurate three-dimensional (3D) reconstruction of coronary stents. This work presents an innovative algorithm for the 3D reconstruction of coronary artery stents, leveraging intravascular ultrasound (IVUS) and angiography. The accuracy and reproducibility of our method were tested in stented patient-specific silicone models, with micro-computed tomography serving as a reference standard. We also evaluated the clinical feasibility and ability to perform computational fluid dynamics (CFD) studies in a clinically stented coronary bifurcation. Our experimental and clinical studies demonstrated that our proposed algorithm could reproduce the complex 3D stent configuration with a high degree of precision and reproducibility. Moreover, the algorithm was proved clinically feasible in cases with stents deployed in a diseased coronary artery bifurcation, enabling CFD studies to assess the hemodynamic environment. In combination with patient-specific CFD studies, our method can be applied to stenting optimization, training in stenting techniques, and advancements in stent research and development.

Artificial Intelligence, Computational Simulations, and Extended Reality in Cardiovascular Interventions.

Artificial intelligence, computational simulations, and extended reality, among other 21st century computational technologies, are changing the health care system. To collectively highlight the most recent advances and benefits of artificial intelligence, computational simulations, and extended reality in cardiovascular therapies, we coined the abbreviation AISER. The review particularly focuses on the following applications of AISER: 1) preprocedural planning and clinical decision making; 2) virtual clinical trials, and cardiovascular device research, development, and regulatory approval; and 3) education and training of interventional health care professionals and medical technology innovators. We also discuss the obstacles and constraints associated with the application of AISER technologies, as well as the proposed solutions. Interventional health care professionals, computer scientists, biomedical engineers, experts in bioinformatics and visualization, the device industry, ethics committees, and regulatory agencies are expected to streamline the use of AISER technologies in cardiovascular interventions and medicine in general.

Patient-specific computational simulation of coronary artery bypass grafting.

INTRODUCTION: Coronary artery bypass graft surgery (CABG) is an intervention in patients with extensive obstructive coronary artery disease diagnosed with invasive coronary angiography. Here we present and test a novel application of non-invasive computational assessment of coronary hemodynamics before and after bypass grafting. METHODS AND RESULTS: We tested the computational CABG platform in n = 2 post-CABG patients. The computationally calculated fractional flow reserve showed high agreement with the angiography-based fractional flow reserve. Furthermore, we performed multiscale computational fluid dynamics simulations of pre- and post-CABG under simulated resting and hyperemic conditions in n = 2 patient-specific anatomies 3D reconstructed from coronary computed tomography angiography. We computationally created different degrees of stenosis in the left anterior descending artery, and we showed that increasing severity of native artery stenosis resulted in augmented flow through the graft and improvement of resting and hyperemic flow in the distal part of the grafted native artery. CONCLUSIONS: We presented a comprehensive patient-specific computational platform that can simulate the hemodynamic conditions before and after CABG and faithfully reproduce the hemodynamic effects of bypass grafting on the native coronary artery flow. Further clinical studies are warranted to validate this preliminary data.

Role of triggering receptor expressed on myeloid cells-1 in the mechanotransduction signaling pathways that link low shear stress with inflammation.

This study sought to investigate the role of triggering receptor expressed on myeloid cells-1 (TREM-1) in the mechanotransduction signaling pathways that link low shear stress with inflammation. Human coronary artery endothelial cells, human coronary artery smooth muscle cells, and THP-1 monocytes were co-cultured and exposed to varying endothelial shear stress (ESS) conditions: low (5 ± 3 dynes/cm2), medium (10 ± 3 dynes/cm2), and high (15 ± 3 dynes/cm2). We showed that low ESS increased the expression of TREM-1 by the cultured cells leading to increased production of inflammatory mediators and matrix-degrading enzymes, whereas high ESS did not have a significant effect in the expression of TREM-1 and inflammatory mediators. Furthermore, TREM-1 transcriptional inhibition with siRNA in endothelial cells, smooth muscle cells, and monocytes exposed to low ESS, led to a significant reduction in the production of vascular inflammatory mediators and matrix-degrading enzymes. Additionally, we identified the transcription factors that appear to upregulate the TREM-1 gene expression in response to low ESS. To the best of our knowledge, this is the first study to investigate the pathophysiologic association and molecular pathways that link low ESS, TREM-1, and inflammation using a sophisticated in-vitro model of atherosclerosis. Future studies on animals and humans are warranted to investigate the potential of TREM-1 inhibitors as adjunctive anti-atherosclerotic therapies.

Co-culture models of endothelial cells, macrophages, and vascular smooth muscle cells for the study of the natural history of atherosclerosis.

BACKGROUND: This work aims to present a fast, affordable, and reproducible three-cell co-culture system that could represent the different cellular mechanisms of atherosclerosis, extending from atherogenesis to pathological intimal thickening. METHODS AND RESULTS: We built four culture models: (i) Culture model #1 (representing normal arterial intima), where human coronary artery endothelial cells were added on top of Matrigel-coated collagen type I matrix, (ii) Culture model #2 (representing atherogenesis), which demonstrated the subendothelial accumulation and oxidative modification of low-density lipoproteins (LDL), (iii) Culture model #3 (representing intimal xanthomas), which demonstrated the monocyte adhesion to the endothelial cell monolayer, transmigration into the subendothelial space, and transformation to lipid-laden macrophages, (iv) Culture model #4 (representing pathological intimal thickening), which incorporated multiple layers of human coronary artery smooth muscle cells within the matrix. Coupling this model with different shear stress conditions revealed the effect of low shear stress on the oxidative modification of LDL and the upregulation of pro-inflammatory molecules and matrix-degrading enzymes. Using electron microscopy, immunofluorescence confocal microscopy, protein and mRNA quantification assays, we showed that the behaviors exhibited by the endothelial cells, macrophages and vascular smooth muscle cells in these models were very similar to those exhibited by these cell types in nascent and intermediate atherosclerotic plaques in humans. The preparation time of the cultures was 24 hours. CONCLUSION: We present three-cell co-culture models of human atherosclerosis. These models have the potential to allow cost- and time-effective investigations of the mechanobiology of atherosclerosis and new anti-atherosclerotic drug therapies.

First-in-Human Computational Preprocedural Planning of Left Main Interventions Using a New Everolimus-Eluting Stent.

Left main coronary artery stenting requires rigorous planning and optimal execution. This case series presents a new approach to left main stenting guided by preprocedural patient-specific computational simulations. Three patients with significant left main artery disease underwent simulation-guided intervention using a novel stent scaffold purpose-built for large coronary arteries. (Level of Difficulty: Advanced.).

Case Report: Invasive and Non-invasive Hemodynamic Assessment of Coronary Artery Disease: Strengths and Weaknesses.

Coronary angiography has been the gold standard for assessment of coronary artery disease (CAD) and guidance for percutaneous coronary interventions (PCI). Physiology-guided PCI has shown increased safety and efficacy, improved resource utilization, and better clinical outcomes in patients with stable angina and acute coronary syndromes. The three cases presented and discussed in this report illustrate the strengths and weaknesses of the available invasive and non-invasive methods for the physiological assessment of CAD. As technology evolves, invasive non-wire-based (angiography-derived FFR) and non-invasive (FFRCT) modalities for the hemodynamic assessment of CAD appear to provide reliable and user-friendly alternatives to the gold standard invasive wire-based techniques. Interventional cardiologists and cardiovascular healthcare providers should be familiar with the strengths and weaknesses of the available hemodynamic assessment modalities.

Triggering receptor expressed on myeloid cells-1 (TREM-1) inhibition in atherosclerosis.

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.

Case Report: ST-Elevation Myocardial Infarction Secondary to Acute Atherothrombotic Occlusion Treated With No Stent Strategy.

Background: Intravascular imaging plays a vital role in the pathophysiology-based diagnosis and treatment of patients with ST-elevation myocardial infarction (STEMI). We present a case of STEMI due to plaque erosion, which was managed with a no stent approach. Case Summary: A 43-year-old female with a history of tobacco abuse presented with an anterior STEMI. Coronary angiography revealed acute thrombotic occlusion of the left anterior descending artery with spontaneous recanalization. Intravascular imaging with optical coherence tomography (OCT) demonstrated plaque erosion as the underlying etiology for the acute thrombotic occlusion. A no stent strategy with aspiration thrombectomy and dual antiplatelet therapy was used to manage the patient given that there was no evidence of plaque rupture. Repeat coronary imaging was done at 2 months to assess the status of the lesion. Conclusion: A 43-year-old female with STEMI due to plaque erosion was successfully managed only by thrombus aspiration and not by angioplasty and stent placement. Individualized treatment approaches in patients with acute coronary syndromes, can not only achieve optimal management goals but also avoid unnecessary complications associated with interventions. This case illustrates how intracoronary imaging and pathophysiology-guided treatment can dramatically change management. In this young patient, STEMI was managed purely by thrombus aspiration. Intravascular imaging obviated the need for stent placement possibly preventing stent-related complications including restenosis and thrombosis.

Management of venous thromboembolism in pregnancy.

Venous thromboembolism (VTE) in pregnancy, consisting of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major factor of maternal mortality. Several patient-specific risk factors along with the physiologic changes of pregnancy promote a state of hypercoagulability in pregnant women. Detailed assessment of all pregnant women can establish a risk profile that would guide clinical decisions, and balance potential therapeutic benefits with side effects. Differentiating between physiologic changes of pregnancy and symptoms of VTE can be challenging and warrants meticulous clinical evaluation. Timely and accurate diagnosis of VTE with proper imaging is essential for its management, and systemic anticoagulation remains the cornerstone of VTE prevention and therapy. Furthermore, advanced invasive treatment options such as inferior vena cava filters and thrombectomy can be considered for complex cases. Importantly, the risk of systemic anticoagulation should be balanced against the risk of VTE-associated morbidity and mortality for mother and fetus, and an informed decision should be made. In this review, we present an up-to-date overview of VTE management in pregnancy and the postpartum period.

A 37-Year-Old Woman with Hypertrophic Cardiomyopathy with a Dual-Chamber Implantable Cardioverter-Defibrillator Requiring Percutaneous Transvenous Lead Extraction and Multidisciplinary Management.

BACKGROUND Percutaneous transvenous lead extraction (TLE) of cardiac implantable electronic devices can be performed with a high success rate. However, TLE has its limitations and challenges. Recognizing the challenges at an early stage during the procedure is vital for appropriate patient management. We present a challenging case of implantable cardioverter-defibrillator (ICD) lead extraction in which we aborted TLE in favor of elective surgical extraction (SE). This potentially prevented a major catastrophic complication of vascular tear, which would have required an emergent thoracotomy. CASE REPORT A 37-year-old woman with history of hypertrophic cardiomyopathy had a primary prevention dual-chamber ICD implant in 2001 and underwent right ventricular ICD lead revision in 2009 due to lead fracture. In 2019, she was again found to have right ventricular ICD lead malfunction. TLE was attempted, but no meaningful progression could be made despite using multiple extraction tools. Therefore, TLE was aborted in favor of SE. During elective SE, significant adhesions were noted, and the innominate vein was completely avulsed during removal of the leads, requiring venous reconstruction by the vascular surgery team. After SE and vascular reconstruction, an epicardial ICD system was placed, and the patient had an uneventful postoperative recovery. CONCLUSIONS This case report highlights the limitations of TLE and the importance of recognizing them in a timely manner. In all challenging cases, conversion to elective SE should be considered to avoid potential injuries warranting emergent surgical repair.

Patient-specific computational simulation of coronary artery bifurcation stenting.

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.

Three dimensional reconstruction of coronary artery stents from optical coherence tomography: experimental validation and clinical feasibility.

The structural morphology of coronary stents (e.g. stent expansion, lumen scaffolding, strut apposition, tissue protrusion, side branch jailing, strut fracture), and the local hemodynamic environment after stent deployment are key determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to enable the geometrically accurate three-dimensional (3D) reconstruction of coronary stents. The aim of this work was to present a novel algorithm for 3D stent reconstruction of coronary artery stents based on optical coherence tomography (OCT) and angiography, and test experimentally its accuracy, reproducibility, clinical feasibility, and ability to perform computational fluid dynamics (CFD) studies. Our method has the following steps: 3D lumen reconstruction based on OCT and angiography, stent strut segmentation in OCT images, packaging, rotation and straightening of the segmented struts, planar unrolling of the segmented struts, planar stent wireframe reconstruction, rolling back of the planar stent wireframe to the 3D reconstructed lumen, and final stent volume reconstruction. We tested the accuracy and reproducibility of our method in stented patient-specific silicone models using micro-computed tomography (µCT) and stereoscopy as references. The clinical feasibility and CFD studies were performed in clinically stented coronary bifurcations. The experimental and clinical studies showed that our algorithm (1) can reproduce the complex spatial stent configuration with high precision and reproducibility, (2) is feasible in 3D reconstructing stents deployed in bifurcations, and (3) enables CFD studies to assess the local hemodynamic environment within the stent. Notably, the high accuracy of our algorithm was consistent across different stent designs and diameters. Our method coupled with patient-specific CFD studies can lay the ground for optimization of stenting procedures, patient-specific computational stenting simulations, and research and development of new stent scaffolds and stenting techniques.

Computational and experimental mechanical performance of a new everolimus-eluting stent purpose-built for left main interventions.

Left main (LM) coronary artery bifurcation stenting is a challenging topic due to the distinct anatomy and wall structure of LM. In this work, we investigated computationally and experimentally the mechanical performance of a novel everolimus-eluting stent (SYNERGY MEGATRON) purpose-built for interventions to large proximal coronary segments, including LM. MEGATRON stent has been purposefully designed to sustain its structural integrity at higher expansion diameters and to provide optimal lumen coverage. Four patient-specific LM geometries were 3D reconstructed and stented computationally with finite element analysis in a well-validated computational stent simulation platform under different homogeneous and heterogeneous plaque conditions. Four different everolimus-eluting stent designs (9-peak prototype MEGATRON, 10-peak prototype MEGATRON, 12-peak MEGATRON, and SYNERGY) were deployed computationally in all bifurcation geometries at three different diameters (i.e., 3.5, 4.5, and 5.0 mm). The stent designs were also expanded experimentally from 3.5 to 5.0 mm (blind analysis). Stent morphometric and biomechanical indices were calculated in the computational and experimental studies. In the computational studies the 12-peak MEGATRON exhibited significantly greater expansion, better scaffolding, smaller vessel prolapse, and greater radial strength (expressed as normalized hoop force) than the 9-peak MEGATRON, 10-peak MEGATRON, or SYNERGY (p < 0.05). Larger stent expansion diameters had significantly better radial strength and worse scaffolding than smaller stent diameters (p < 0.001). Computational stenting showed comparable scaffolding and radial strength with experimental stenting. 12-peak MEGATRON exhibited better mechanical performance than the 9-peak MEGATRON, 10-peak MEGATRON, or SYNERGY. Patient-specific computational LM stenting simulations can accurately reproduce experimental stent testing, providing an attractive framework for cost- and time-effective stent research and development.

3D reconstruction of coronary artery bifurcations from coronary angiography and optical coherence tomography: feasibility, validation, and reproducibility.

The three-dimensional (3D) representation of the bifurcation anatomy and disease burden is essential for better understanding of the anatomical complexity of bifurcation disease and planning of stenting strategies. We propose a novel methodology for 3D reconstruction of coronary artery bifurcations based on the integration of angiography, which provides the backbone of the bifurcation, with optical coherence tomography (OCT), which provides the vessel shape. Our methodology introduces several technical novelties to tackle the OCT frame misalignment, correct positioning of the OCT frames at the carina, lumen surface reconstruction, and merging of bifurcation lumens. The accuracy and reproducibility of the methodology were tested in n = 5 patient-specific silicone bifurcations compared to contrast-enhanced micro-computed tomography (µCT), which was used as reference. The feasibility and time-efficiency of the method were explored in n = 7 diseased patient bifurcations of varying anatomical complexity. The OCT-based reconstructed bifurcation models were found to have remarkably high agreement compared to the µCT reference models, yielding r2 values between 0.91 and 0.98 for the normalized lumen areas, and mean differences of 0.005 for lumen shape and 0.004 degrees for bifurcation angles. Likewise, the reproducibility of our methodology was remarkably high. Our methodology successfully reconstructed all the patient bifurcations yielding favorable processing times (average lumen reconstruction time < 60 min). Overall, our method is an easily applicable, time-efficient, and user-friendly tool that allows accurate and reproducible 3D reconstruction of coronary bifurcations. Our technique can be used in the clinical setting to provide information about the bifurcation anatomy and plaque burden, thereby enabling planning, education, and decision making on bifurcation stenting.