Oxidative stress is a common mediator in pathogenicity of established cardiovascular risk factors. Furthermore, it likely mediates effects of emerging, less well-defined variables that contribute to residual risk not explained by traditional factors. Functional oxidative modifications of cellular proteins, both reversible and irreversible, are a causal step in cellular dysfunction. Identifying markers of oxidative stress has been the focus of many researchers as they have the potential to act as an “integrator” of a multitude of processes that drive cardiovascular pathobiology. One of the major challenges is the accurate quantification of reactive oxygen species with very short half-life. Redox-sensitive proteins with important cellular functions are confined to signalling microdomains in cardiovascular cells and are not readily available for quantification. A popular approach is the measurement of stable by-products modified under conditions of oxidative stress that have entered the circulation. However, these may not accurately reflect redox stress at the cell/tissue level. Many of these modifications are “functionally silent”. Functional significance of the oxidative modifications enhances their validity as a proposed biological marker of cardiovascular disease, and is the strength of the redox cysteine modifications such as glutathionylation. We review selected biomarkers of oxidative stress that show promise in cardiovascular medicine, as well as new methodologies for high-throughput measurement in research and clinical settings. Although associated with disease severity, further studies are required to examine the utility of the most promising oxidative biomarkers to predict prognosis or response to treatment.

High-resolution imaging by OCT delineated calcium modification with fracture as a major mechanism of action of lithoplasty in vivo and demonstrated efficacy in the achievement of significant acute area gain and favorable stent expansion.

In patients with advanced CKD who require revascularization, PCI may safely be performed without contrast using IVUS and physiological guidance with high procedural success and without complications.

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Optical coherence tomography (OCT) has been increasingly utilised to guide percutaneous coronary intervention (PCI). Despite the diagnostic utility of OCT, facilitated by its high resolution, the impact of intracoronary OCT on clinical practice has thus far been limited. Difficulty in transitioning from intravascular ultrasound (IVUS), complex image interpretation, lack of a standardised algorithm for PCI guidance, and paucity of data from prospective clinical trials have contributed to the modest adoption. Herein, we provide a comprehensive up-do-date overview on the utility of OCT in coronary artery disease, including technical details, device set-up, simplified OCT image interpretation, recognition of the imaging artefacts, and an algorithmic approach for using OCT in PCI guidance. We discuss the utility of OCT in acute coronary syndromes, provide a summary of the clinical trial data, list the work in progress, and discuss the future directions. KEYWORDS• ACS/NSTE-ACS • intravascular ultrasound • optical coherence tomography EuroIntervention 2021;17:e105-e123 e 106 Abbreviations ACS acute coronary syndromes BOOM bifurcation and ostial optical coherence tomography mapping DES drug-eluting stents IVUS intravascular ultrasound MI myocardial infarction MINOCA myocardial infarction with non-obstructive coronary arteries MLA minimal lumen area MLD MAX morphology, length, diameter, medial dissection, apposition, expansion MSA minimal stent area NSTEACS non-ST-segment elevation acute coronary syndromes NURD non-uniform rotational distortion OCT optical coherence tomography OFR optical flow ratio PCI percutaneous coronary intervention STEMI ST-segment elevation myocardial infarction TCFA thin-cap fibroatheroma

The advent of intravascular imaging has been a significant advancement in visualization of coronary arteries, particularly with optical coherence tomography (OCT) that allows for high-resolution imaging of intraluminal and transmural coronary structures. Accumulating data support a clinical role for OCT in a multitude of clinical scenarios, including assessing the natural history of atherosclerosis and modulating effects of therapies, mechanisms of acute coronary syndromes, mechanistic insights into the effects of novel interventional devices, and optimization of percutaneous coronary intervention. In this state-of-the-art review, we provide an overview of the published data on the clinical utility of OCT, highlighting the areas that need further investigation and the current barriers for further adoption of OCT in interventional cardiology practice.

BackgroundGlutathionylation of endothelial nitric oxide synthase (eNOS) “uncouples” the enzyme, switching its function from nitric oxide (NO) to O2•− generation. We examined whether this reversible redox modification plays a role in angiotensin II (Ang II)‐induced endothelial dysfunction.Methods and ResultsAng II increased eNOS glutathionylation in cultured human umbilical vein endothelial cells (HUVECs), rabbit aorta, and human arteries in vitro. This was associated with decreased NO bioavailability and eNOS activity as well as increased O2•− generation. Ang II‐induced decrease in eNOS activity was mediated by glutathionylation, as shown by restoration of function by glutaredoxin‐1. Moreover, Ang II‐induced increase in O2•− and decrease in NO were abolished in HUVECs transiently transfected, with mutant eNOS rendered resistant to glutathionylation. Ang II effects were nicotinamide adenine dinucleotide phosphate (NADPH) oxidase dependent because preincubation with gp 91ds‐tat, an inhibitor of NADPH oxidase, abolished the increase in eNOS glutathionylation and loss of eNOS activity. Functional significance of glutathionylation in intact vessels was supported by Ang II‐induced impairment of endothelium‐dependent vasorelaxation that was abolished by the disulfide reducing agent, dithiothreitol. Furthermore, attenuation of Ang II signaling in vivo by administration of an angiotensin converting enzyme (ACE) inhibitor reduced eNOS glutathionylation, increased NO, diminished O2•−, improved endothelium‐dependent vasorelaxation and reduced blood pressure.ConclusionsUncoupling of eNOS by glutathionylation is a key mediator of Ang II‐induced endothelial dysfunction, and its reversal is a mechanism for cardiovascular protection by ACE inhibition. We suggest that Ang II‐induced O2•− generation in endothelial cells, although dependent on NADPH oxidase, is amplified by glutathionylation‐dependent eNOS uncoupling.

The central role of oxidative signalling in cardiovascular pathophysiology positions biometric measures of redox state as excellent markers for research and clinical application. However, despite this tantalizing biological plausibility, no redox biomarker is currently in widespread clinical use. Major recent insights into the mechanistic complexities of redox signalling may yet provide the opportunity to identify markers that most closely reflect the underlying pathobiology. Such redox biomarkers may, in principle, quantify the integrated effects of various known and unknown pathophysiological drivers of cardiovascular disease processes. Recent advances with the greatest potential include assays measuring post-translational oxidative modifications that have significant cellular effects. However, analytical issues, including the relative instability of redox-modified products, remain a major technical obstacle. Appreciation of these challenges may facilitate future development of user-friendly markers with prognostic value in addition to traditional risk factors, and which could be used to guide personalized cardiovascular therapies. We review both established and recently identified biomarkers of redox signalling, and provide a realistic discussion of the many challenges that remain if they are to be incorporated into clinical practice. Despite the current lack of redox biomarkers in clinical application, the integral role of reactive oxygen species in pathogenesis of cardiovascular disease provides a strong incentive for continued efforts.