The role of intracoronary imaging in translational research

Abstract: Atherosclerotic cardiovascular disease is a key public health concern worldwide and leading cause of morbidity, mortality and health economic costs. Understanding atherosclerotic plaque microstructure in relation to molecular mechanisms that underpin its initiation and progression is needed to provide the best chance of combating this disease. Evolving vessel wall-based, endovascular coronary imaging modalities, including intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS), used in isolation or as hybrid modalities, have been advanced to allow comprehensive visualization of the pathological substrate of coronary atherosclerosis and accurately measure temporal changes in both the vessel wall and plaque characteristics. This has helped further our appreciation of the natural history of coronary artery disease (CAD) and the risk for major adverse cardiovascular events (MACE), evaluate the responsiveness to conventional and experimental therapeutic interventions, and assist in guiding percutaneous coronary intervention (PCI). Here we review the use of different imaging modalities for these purposes and the lessons they have provided thus far.Nicholas J. Montarello, Adam J. Nelson, Johan Verjans, Stephen J. Nicholls, Peter J. Psalti

Inflammation in coronary atherosclerosis and its therapeutic implications

OnlinePubl.Atherosclerotic coronary artery disease has a complex pathogenesis which extends beyond cholesterol intimal infiltration. It involves chronic inflammation of the coronary artery wall driven by systemic and local activation of both the adaptive and innate immune systems, which can ultimately result in the rupture or erosion of atherosclerotic plaque, leading to thrombosis and myocardial infarction (MI). Despite current best practice care, including the widespread use of cholesterol-lowering statins, atherothrombotic cardiovascular events recur at alarming rates post-MI. To a large extent, this reflects residual inflammation that is not adequately controlled by contemporary treatment. Consequently, there has been increasing interest in the pharmacological targeting of inflammation to improve outcomes in atherosclerotic cardiovascular disease. This has comprised both novel pathway-specific agents, most notably the anti-interleukin-1 beta monoclonal antibody, canakinumab, and the repurposing of established, broad-acting drugs, such as colchicine, that are already approved for the management of other inflammatory conditions. Here we discuss the importance of inflammation in mediating atherosclerosis and its complications and provide a timely update on "new" and "old" anti-inflammatory therapies currently being investigated to target it.Nicholas J. Montarello, Mau T. Nguyen, Dennis T.L. Wong, Stephen J. Nicholls, Peter J. Psalti

Prevalence and real-world management of NSTEMI with multivessel disease

Background: Non-ST elevation myocardial infarction (NSTEMI) has higher post-discharge mortality than ST-elevation myocardial infarction (STEMI). Prognosis worsens in those with multivessel coronary disease (MVD). However, information about the prevalence and extent of MVD in NSTEMI is limited, in turn limiting insights into optimal treatment strategies. This study aimed to define the prevalence and extent of MVD, preferred treatment strategies and the predictors of MVD in a real-world NSTEMI population. Methods: The Coronary Angiogram Database of South Australia (CADOSA) was used to identify consecutive patients presenting to major teaching hospitals with NSTEMI between 2012 and 2016. Obtaining clinical and angiographic details, patients were stratified by the number of significantly diseased vessels (0,1,2,3-VD), defined by a stenosis of ≥70%, or ≥50% in the left main coronary artery. Data was analysed retrospectively. Results: The prevalence of MVD (2- or 3-VD) was 42% amongst 3,722 NSTEMI presentations. Multivariate logistic regression modelling showed age, male gender, diabetes, dyslipidaemia and prior myocardial infarction predicted MVD over 1-VD or 0-VD. Percutaneous coronary intervention (PCI) was performed in 42% of patients with MVD. This comprised 61% of 2-VD patients and only 22% of 3-VD patients, with 24% and 66% of each group referred for coronary bypass grafting, respectively. Among MVD patients treated with PCI, 76% had their culprit lesion treated alone in the index admission. Conclusions: In this NSTEMI cohort, over 40% had MVD. Notably, a minority of patients with MVD undergoing PCI received multivessel revascularisation. This real-world practice emphasises that further evaluation is required to determine whether complete revascularisation is beneficial in NSTEMI, as reported for STEMI.Angus A. W. Baumann, Rosanna Tavella, Tracy M. Air, Aashka Mishra, Nicholas J. Montarello, Margaret Arstall, Chris Zeitz, Matthew I. Worthley, John F. Beltrame, Peter J. Psalti

Tandem lesions associate with angiographic progression of coronary artery stenoses

Available online 3 May 2024Background: Although the clinical factors associated with progression of coronary artery disease have been well studied, the angiographic predictors are less defined. Objectives: Our objective was to study the clinical and angiographic factors that associate with progression of coronary artery stenoses. Methods: We conducted a retrospective analysis of consecutive patients undergoing multiple, clinically indicated invasive coronary angiograms with an interval greater than 6 months, between January 2013 and December 2016. Lesion segments were analysed using Quantitative Coronary Angiography (QCA) if a stenosis ≥ 20 % was identified on either angiogram. Stenosis progression was defined as an increase ≥ 10 % in stenosis severity, with progressor groups analysed on both patient and lesion levels. Mixed-effects regression analyses were performed to evaluate factors associated with progression of individual stenoses. Results: 199 patients were included with 881 lesions analysed. 108 (54.3 %) patients and 186 (21.1 %) stenoses were classified as progressors. The median age was 65 years (IQR 56–73) and the median interval between angiograms was 2.1 years (IQR 1.2–3.0). On a patient level, age, number of lesions and presence of multivessel disease at baseline were each associated with progressor status. On a lesion level, presence of a stenosis downstream (OR 3.07, 95 % CI 2.04–4.63, p < 0.001) and circumflex artery stenosis location (OR 1.81, 95 % CI 1.21–2.7, p = 0.004) were associated with progressor status. Other lesion characteristics did not significantly impact progressor status or change in stenosis severity. Conclusion: Coronary lesions which have a downstream stenosis may be at increased risk of stenosis progression. Further research into the mechanistic basis of this finding is required, along with its implications for plaque vulnerability and clinical outcomes.Kyle B. Franke, Nicholas J. Montarello, Adam J. Nelson, Jessica A. Marathe, Dennis T.L. Wong, Rosanna Tavella, Margaret Arstall, Christopher Zeitz, Matthew I. Worthley, John F. Beltrame, Peter J. Psalti

Assessing the impact of colchicine on coronary plaque phenotype after myocardial infarction with optical coherence tomography: rationale and design of the COCOMO-ACS study

Published: 25 August 2021 OnlinePublIntroduction Recurrent event rates after myocardial infarction (MI) remain unacceptably high, in part because of the continued growth and destabilization of residual coronary atherosclerotic plaques, which may occur despite lipid-lowering therapy. Inflammation is an important contributor to this ongoing risk. Recent studies have shown that the broad-acting anti-inflammatory agent, colchicine, may reduce adverse cardiovascular events in patients post-MI, although the mechanistic basis for this remains unclear. Advances in endovascular arterial wall imaging have allowed detailed characterization of the burden and compositional phenotype of coronary plaque, along with its natural history and responsiveness to treatment. One such example has been the use of optical coherence tomography (OCT) to demonstrate the plaque-stabilizing effects of statins on both fibrous cap thickness and the size of lipid pools within plaque. Methods The Phase 2, multi-centre, double-blind colchicine for coronary plaque modification in acute coronary syndrome (COCOMO-ACS) study will evaluate the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI. Recruitment for the trial has been completed with 64 participants with non-ST elevation MI randomized 1:1 to colchicine or placebo in addition to guideline recommended therapies, including high-intensity statins. The primary endpoint is the effect of colchicine on the minimal fibrous cap thickness of non-culprit plaque over an 18-month period. Summary The COCOMO-ACS study will determine whether addition of colchicine 0.5 mg daily to standard post-MI treatment has incremental benefits on high-risk features of coronary artery plaques. If confirmed, this will provide new mechanistic insights into how colchicine may confer clinical benefits in patients with atherosclerotic cardiovascular disease.Nicholas J. Montarello, Kuljit Singh, Ajay Sinhal, Dennis T. L. Wong, Richard Alcock, Sharmalar Rajendran ... et al