Objectives
The study describes the evolution of optical coherence tomography (OCT) adoption and performance during percutaneous coronary intervention (PCI) following implementation of a standardized ...LightLab (LL) workflow.
Background
The purpose of the LL Clinical Initiative was to evaluate the impact of a standardized workflow on physician efficiency, decision making, and image quality.
Methods
The LL Clinical Initiative is a multicenter, prospective, observational clinical program. Data were collected from 48 physicians at 17 U.S. centers from 01/21/19 to 06/08/21. The study included 401 OCT‐guided PCIs during the baseline phase and 1898 during the LL workflow phases. The baseline phase consisted of physicians utilizing OCT at their discretion. After completing the baseline phase, the workflow progressed through multiple phases culminating in the expansion phase, which focused on addressing greater procedural complexity. The LL workflow utilized OCT to assess plaque Morphology, lesion Length, and vessel Diameter before PCI, and optimized results by treating Medial edge dissection, stent mal‐Apposition, and stent under‐eXpansion (MLD MAX). High‐level summary statistics were generated to elucidate trends.
Results
After program implementation, there was a rise in the number of PCIs where the LL workflow was utilized compared to the baseline phase (68% during the expansion phase vs. 41% at baseline; p for trend <0.0001). Adoption of the LL workflow was associated with progressively greater procedural and lesion complexity when OCT was performed pre‐ and post‐PCI (87% vs. 52%, p < 0.0001; 55% vs. 37%, p < 0.0001, respectively). In addition, the quality of OCT imaging obtained improved after LL workflow introduction, with over 95% of pre‐ and post‐PCI pullback quality considered usable during the expansion phase. Finally, there was a reduction in time spent on OCT interpretation, both pre‐PCI (4.6 min vs. 7.5 min, p < 0.0001) and post‐PCI (2.9 min vs. 5.3 min, p < 0.0001).
Conclusions
After completion of the standardized OCT‐guided workflow, there was greater uptake of OCT imaging, incorporation in more complex procedures, procedural efficiency, and image quality.
Condensed
The LightLab Clinical Initiative was a multicenter, prospective, observational study aimed to evaluate the impact of a standardized optical coherence tomography (OCT) workflow on physician efficiency, decision making, and image quality. In this study, the incorporation of a standardized workflow resulted in higher uptake of OCT during percutaneous coronary intervention (PCI), greater procedural efficiency, improved image quality, and decreased time spent on image interpretation. These data suggest that standardizing the OCT imaging workflow during PCI may help address barriers to intravascular imaging and result in higher adoption by physicians.
Background Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) offers tomographic images of the coronary vessels, allowing optimization of stent implantation at ...the time of PCI. However, the long-term beneficial effect of IVUS over PCI guided by coronary angiography (CA) alone remains under question. We sought to investigate the outcomes of IVUS-guided compared with CA-guided PCI. Methods and Results We performed a comprehensive search of PubMed, Medline, and Cochrane Central Register, looking for randomized controlled trials and observational studies that compared PCI outcomes of IVUS with CA. Data were aggregated for the primary outcome measure using the random-effects model as pooled risk ratio (RR). The primary outcomes were the rate of cardiovascular death, need for target lesion revascularization, occurrence of myocardial infarction, and rate of stent thrombosis. A total of 19 studies met the inclusion criteria, comprising 27 610 patients divided into IVUS (n=11 513) and CA (n=16 097). Compared with standard CA-guided PCI, we found that the risks of cardiovascular death (RR, 0.63; 95% CI, 0.54-0.73), myocardial infarction (RR, 0.71; 95% CI, 0.58-0.86), target lesion revascularization (RR, 0.81; 95% CI, 0.70-0.94), and stent thrombosis (RR, 0.57; 95% CI, 0.41-0.79) were all significantly lower using IVUS guidance. Conclusions Compared with standard CA-guided PCI, the use of IVUS imaging guidance to optimize stent implantation is associated with a reduced risk of cardiovascular death and major adverse events, such as myocardial infarction, target lesion revascularization, and stent thrombosis.
Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In ...recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging), as well as in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g., the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in phase II clinical trials. Here, we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term.
Purpose of review
Physiological assessment of coronary artery disease (CAD) is an essential component of the interventional cardiology toolbox. However, despite long-term data demonstrating improved ...outcomes, physiology-guided percutaneous coronary intervention (PCI) remains underutilized in current practice. This review outlines the indications and technical aspects involved in evaluating coronary stenosis physiology, focusing on the latest developments in the field.
Recent findings
Beyond fractional flow reserve (FFR), non-hyperemic pressure ratios (NHPR) that assess coronary physiology at rest without hyperemia now abound. Additional advances in other alternative FFR approaches, including non-invasive coronary CT (FFR
CT
), invasive angiography (FFR
angio
), and optical coherence tomography (FFR
OCT
), are being realized. Artificial intelligence algorithms and robust tools that enable detailed pre-procedure “virtual” intervention are also emerging.
Summary
The benefits of coronary physiological assessment to determine lesion functional significance are well established. In addition to stable CAD, coronary physiology can be especially helpful in clinical scenarios such as left main and multivessel CAD, serial lesions, non-infarct-related arteries in acute coronary syndromes, and residual ischemia post-PCI. Today, coronary physiological assessment remains an indispensable tool in the catheterization laboratory, with an exciting technological future that will further refine clinical practice and improve patient care.
Metabolic and molecular imaging continues to advance our understanding of vascular disease pathophysiology. At present,
F-FDG PET imaging is the most widely used clinical tool for metabolic and ...molecular imaging of atherosclerosis. However, novel nuclear tracers and intravascular optical near-infrared fluorescence imaging catheters are emerging to assess new biologic targets in vivo and in coronary arteries. This review highlights current metabolic and molecular imaging clinical and near-clinical applications within atherosclerosis and venous thromboembolism, and explores the potential for metabolic and molecular imaging to affect patient-level risk prediction and disease treatment.
Bioengineering of bladder tissue, particularly for those patients who have advanced bladder disease, requires a source of urothelium that is healthy, capable of significant proliferation in vitro and ...immunologically tolerated upon transplant. As pluripotent stem cells have the potential to fulfill such criteria, they provide a critical cell source from which urothelium might be derived in vitro and used clinically. Herein, we describe the in vitro differentiation of urothelium from the H9 human embryonic stem cell (hESC) line through the definitive endoderm (DE) phase via selective culture techniques. The protocol can be used to derive urothelium from other hESCs or human-induced pluripotent stem cells.
Abstract
Aims
Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin ...(SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.
Methods and results
An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype.
Conclusion
Sortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.
Structured Graphical Abstract
Structured Graphical Abstract
Multi-omic approach to identify the role of sortilin in mediating fibrosis and calcification in calcific aortic valve disease (CAVD). Aortic valve (AV) wire injury in sortilin wild-type (Sort1+/+) and deficient mice (Sort1−/−) showed decreased collagen deposition and calcification in mouse AVs. Valvular interstitial cells (VICs) were collected from human CAVD tissue and cultured in osteogenic conditions. VICs collected at varying time points of culture (Days 7, 14, and 21) were processed for flow cytometry, proteomics, and single-cell RNA-sequencing (scRNA-seq). Multiomics data identified increased sortilin expression following the osteogenic culture of VICs. Protein analysis and scRNA-seq identified increased expression of WNT5a, MAPK, YAP, and IL-6 regulated by the expression of sortilin. ScRNA-seq identified a transitionary VIC subpopulation with an activated myofibroblast phenotype that later transitioned into a combined myofibroblast and osteogenic phenotype. ScRNA-seq data identified an inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) subpopulation that may be a key player in the pathogenesis of CAVD under the regulation of sortilin.
To investigate the biomechanical properties of rat bladder tissue after spinal cord injury (SCI) using uniaxial tensile testing.
Evidence suggests the bladder wall undergoes remodeling following SCI. ...There is limited data describing the biomechanical properties of bladder wall after SCI. This study describes the changes in elastic and viscoelastic mechanical properties of bladder tissue using a rat model after SCI.
Seventeen adult rats received mid-thoracic SCI. Basso, Beattie, and Bresnahan (BBB) locomotor testing was performed on the rats 7–14 days after injury quantifying the degree of SCI. Bladder tissue samples were collected from controls and spinal injured rats at 2- and 9-weeks post-injury. Tissue samples underwent uniaxial stress relaxation to determine instantaneous and relaxation modulus as well as monotonic load-to failure to determine Young’s modulus, yield stress and strain, and ultimate stress.
SCI resulted in abnormal BBB locomotor scores. Nine weeks post-injury, instantaneous modulus decreased by 71.0% (p = 0.03) compared to controls. Yield strain showed no difference at 2 weeks post-injury but increased 78% (p = 0.003) in SCI rats at 9 weeks post-injury. Compared to controls, ultimate stress decreased 46.5% (p = 0.05) at 2 weeks post-injury in SCI rats but demonstrated no difference at 9 weeks post-injury.
The biomechanical properties of rat bladder wall 2 weeks after SCI showed minimal difference compared to controls. By week 9, SCI bladders had a reduction in instantaneous modulus and increased yield strain. The findings indicate biomechanical differences can be identified between control and experimental groups at 2- and 9-week intervals using uniaxial testing.
Atherosclerosis imaging strategies can delineate characteristics of plaques at risk of rupture and thrombosis. Structural plaque imaging identifies high-risk plaque features, including lipid pools, ...thin fibrous caps, and intraplaque hemorrhage. New molecular imaging techniques complement structural imaging approaches by illuminating important features of plaque biology, with a prominent focus on detecting inflammation as a high-risk phenotype. As we unravel the molecular and structural characteristics underlying thrombosis-prone plaques, there is significant promise for eventual early identification and prediction of atherosclerotic plaque complications before they occur. Here we focus on recent imaging insights into high-risk arterial plaques, the etiologic agent of acute myocardial infarction, stroke, and sudden cardiac death.
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