Increased rate of significant findings on brain MRI during the early stage of the COVID-19 pandemic.

OBJECTIVES: To assess the effect of the COVID-19 pandemic on the proportion of abnormal paediatric neuroimaging findings as a surrogate marker for potential underutilisation. METHODS: Consecutive paediatric brain MRIs performed between March 27th and June 19th 2019 (Tbaseline) and March 23rd and June 1st 2020 (Tpandemic) were reviewed and classified according to presence or absence and type of imaging abnormality, and graded regarding severity on a 5-point Likert scale, where grade 4 was defined as abnormal finding requiring non-urgent intervention and grade 5 was defined as acute illness prompting urgent medical intervention. Non-parametric statistical testing was used to assess for significant differences between Tpandemic vs. Tbaseline. RESULTS: Fewer paediatric MRI brains were performed during Tpandemic compared to Tbaseline (12.2 vs 14.7 examinations/day). No significant difference was found between the two time periods regarding sex and age (Tbaseline: 557 females (44.63%), 7.95 ± 5.49 years, Tpandemic: 385 females (44.61%), 7.64 ± 6.11 years; p = 1 and p = .079, respectively). MRI brain examinations during Tpandemic had a higher likelihood of being abnormal, 41.25% vs. 25.32% (p<.0001). Vascular abnormalities were more frequent during Tpandemic (11.01% vs 8.01%, p = .02), congenital malformations were less common (8.34% vs 12.34%, p = .004). Severity of MRI brain examinations was significantly different when comparing group 4 and group 5 individually and combined between Tbaseline and Tpandemic (p = .0018, p < .0001, and p <.0001, respectively). CONCLUSIONS: The rate of abnormality and severity found on paediatric brain MRI was significantly higher during the early phase of the pandemic, likely due to underutilisation.

Greater aortic inflammation and calcification in abdominal aortic aneurysmal disease than atherosclerosis: a prospective matched cohort study.

Objective: Using combined positron emission tomography and CT (PET-CT), we measured aortic inflammation and calcification in patients with abdominal aortic aneurysms (AAA), and compared them with matched controls with atherosclerosis. Methods: We prospectively recruited 63 patients (mean age 76.1±6.8 years) with asymptomatic aneurysm disease (mean size 4.33±0.73 cm) and 19 age-and-sex-matched patients with confirmed atherosclerosis but no aneurysm. Inflammation and calcification were assessed using combined 18F-FDG PET-CT and quantified using tissue-to-background ratios (TBRs) and Agatston scores. Results: In patients with AAA, 18F-FDG uptake was higher within the aneurysm than in other regions of the aorta (mean TBRmax2.23±0.46 vs 2.12±0.46, p=0.02). Compared with atherosclerotic control subjects, both aneurysmal and non-aneurysmal aortae showed higher 18F-FDG accumulation (total aorta mean TBRmax2.16±0.51 vs 1.70±0.22, p=0.001; AAA mean TBRmax2.23±0.45 vs 1.68±0.21, p<0.0001). Aneurysms containing intraluminal thrombus demonstrated lower 18F-FDG uptake within their walls than those without (mean TBRmax2.14±0.43 vs 2.43±0.45, p=0.018), with thrombus itself showing low tracer uptake (mean TBRmax thrombus 1.30±0.48 vs aneurysm wall 2.23±0.46, p<0.0001). Calcification in the aneurysmal segment was higher than both non-aneurysmal segments in patients with aneurysm (Agatston 4918 (2901-8008) vs 1017 (139-2226), p<0.0001) and equivalent regions in control patients (442 (304-920) vs 166 (80-374) Agatston units per cm, p=0.0042). Conclusions: The entire aorta is more inflamed in patients with aneurysm than in those with atherosclerosis, perhaps suggesting a generalised inflammatory aortopathy in patients with aneurysm. Calcification was prominent within the aneurysmal sac, with the remainder of the aorta being relatively spared. The presence of intraluminal thrombus, itself metabolically relatively inert, was associated with lower levels of inflammation in the adjacent aneurysmal wall.

A zero coronary artery calcium score in patients with stable chest pain is associated with a good prognosis, despite risk of non-calcified plaques.

Objectives: To estimate the prevalence of non-calcified coronary artery disease (CAD) in patients with suspected stable angina and a zero coronary artery calcification (CAC) score, and to assess the prognostic significance of a zero CAC in these symptomatic patients. Methods: In this prospective cohort study, consecutive patients with stable chest pain underwent CAC scoring ± CT coronary angiography (CTCA) as part of routine clinical care at a single tertiary centre over 7 years. Major adverse cardiac event (MACE) was defined as cardiac death, non-fatal myocardial infarction and/or non-elective revascularisation. Results: A total of 915 of 1753 (52.2%) patients (mean age 56.8 ± 12.0 years; 46.2% male) had a zero CAC score. Of the 751 (82.1%) patients with a zero CAC in whom CTCA was performed, 674 (89.7%) had normal coronary arteries, 63 (8.4%) had non-calcified CAD with < 50% stenosis and 14 (1.9%) had ≥ 50% stenosis in at least one coronary artery. The negative predictive value of a zero CAC for excluding a ≥ 50% CTCA stenosis was 98.1%. Over a median follow-up period of 2.2 years (range 1.0-7.0 years), the absolute annualised rates of MACE were as follows: zero CAC 1.9 per 1000 person-years and non-zero CAC 7.4 per 1000 person-years (HR 3.8, p = 0.009). However, after adjusting for age, gender and cardiovascular risk factors using a multivariable Cox proportional hazards model, there was no statistically significant difference in the risk of MACE between the two patient cohorts (p = 0.19). After adjusting for age, gender and cardiovascular risk factors, the HR for all-cause mortality among the zero CAC cohort vers non-zero CAC was 2.1 (p = 0.27). Conclusion: A zero CAC score in patients undergoing CT scanning for suspected stable angina has a high negative predictive value for the exclusion of obstructive CAD and is associated with a good medium-term prognosis.

Plaque Structural Stress Estimations Improve Prediction of Future Major Adverse Cardiovascular Events After Intracoronary Imaging.

BACKGROUND: Although plaque rupture is responsible for most myocardial infarctions, few high-risk plaques identified by intracoronary imaging actually result in future major adverse cardiovascular events (MACE). Nonimaging markers of individual plaque behavior are therefore required. Rupture occurs when plaque structural stress (PSS) exceeds material strength. We therefore assessed whether PSS could predict future MACE in high-risk nonculprit lesions identified on virtual-histology intravascular ultrasound. METHODS AND RESULTS: Baseline nonculprit lesion features associated with MACE during long-term follow-up (median: 1115 days) were determined in 170 patients undergoing 3-vessel virtual-histology intravascular ultrasound. MACE was associated with plaque burden ≥70% (hazard ratio: 8.6; 95% confidence interval, 2.5-30.6; P<0.001) and minimal luminal area ≤4 mm(2) (hazard ratio: 6.6; 95% confidence interval, 2.1-20.1; P=0.036), although absolute event rates for high-risk lesions remained <10%. PSS derived from virtual-histology intravascular ultrasound was subsequently estimated in nonculprit lesions responsible for MACE (n=22) versus matched control lesions (n=22). PSS showed marked heterogeneity across and between similar lesions but was significantly increased in MACE lesions at high-risk regions, including plaque burden ≥70% (13.9±11.5 versus 10.2±4.7; P<0.001) and thin-cap fibroatheroma (14.0±8.9 versus 11.6±4.5; P=0.02). Furthermore, PSS improved the ability of virtual-histology intravascular ultrasound to predict MACE in plaques with plaque burden ≥70% (adjusted log-rank, P=0.003) and minimal luminal area ≤4 mm(2) (P=0.002). Plaques responsible for MACE had larger superficial calcium inclusions, which acted to increase PSS (P<0.05). CONCLUSIONS: Baseline PSS is increased in plaques responsible for MACE and improves the ability of intracoronary imaging to predict events. Biomechanical modeling may complement plaque imaging for risk stratification of coronary nonculprit lesions.

Does Vascular Calcification Accelerate Inflammation?: A Substudy of the dal-PLAQUE Trial.

BACKGROUND: Atherosclerosis is an inflammatory condition with calcification apparent late in the disease process. The extent and progression of coronary calcification predict cardiovascular events. Relatively little is known about noncoronary vascular calcification. OBJECTIVES: This study investigated noncoronary vascular calcification and its influence on changes in vascular inflammation. METHODS: A total of 130 participants in the dal-PLAQUE (Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging) study underwent fluorodeoxyglucose positron emission tomography/computed tomography at entry and at 6 months. Calcification of the ascending aorta, arch, carotid, and coronary arteries was quantified. Cardiovascular risk factors were related to arterial calcification. The influences of baseline calcification and drug therapy (dalcetrapib vs. placebo) on progression of calcification were determined. Finally, baseline calcification was related to changes in vascular inflammation. RESULTS: Age >65 years old was consistently associated with higher baseline calcium scores. Arch calcification trended to progress more in those with calcification at baseline (p = 0.055). There were no significant differences between progression of vascular calcification with dalcetrapib compared to that with placebo. Average carotid target-to-background ratio indexes declined over 6 months if carotid calcium was absent (single hottest slice [p = 0.037], mean of maximum target-to-background ratio [p = 0.010], and mean most diseased segment [p < 0.001]), but did not significantly change if calcification was present at baseline. CONCLUSIONS: Across multiple arterial regions, higher age is consistently associated with higher calcium scores. The presence of vascular calcification at baseline is associated with progressive calcification; in the carotid arteries, calcification appears to influence vascular inflammation. Dalcetrapib therapy did not affect vascular calcification.

Institutional Switch from Transfemoral to Transradial Vascular Access for Percutaneous Coronary Intervention was Associated with a Reduction in Bleeding Events: A Singlecenter Experience of >10,000 Consecutive Cases.

BACKGROUND: Transradial (TR) access for percutaneous coronary intervention (PCI) reduces bleeding compared with transfemoral (TF) access, and may reduce mortality in specific patient subsets. However, switching from TF to TR access is associated with a learning curve and it is unclear whether benefits observed in randomized trials translate into practice. We sought to characterize the trends in bleeding and mortality rates at our institution, as we changed from being a TF to predominantly TR center over a 5-year period. METHODS AND RESULTS: 10,213 consecutive patients presenting for PCI were included (mean age 65.0 ± 11.6 years, 76.1% male, 48.0% PCI for acute coronary syndrome) over 5 years at a single center with PCI volume >2,000 cases per annum. Patients were stratified by initial arterial access site (TR or TF) and outcome measures included temporal trends in TR procedural failure, 30-day bleeding complications and all-cause 1-year mortality. TR procedural failure fell to a consistently low rate within 1 year (11.8% in 2008 to 2.9% in 2009, P < 0.001). As TR volume increased, the annual 30-day bleeding rate fell (1.64% in 2008 to 0.68% in 2012, P = 0.006). TR access predicted reduced 30-day bleeding (OR 0.17 [95%CI 0.07-0.38], P < 0.001), but was not a predictor of 1-year survival (HR 0.78 [95%CI 0.58-1.05], P = 0.10). CONCLUSION: Successful transition from TF to TR PCI at our institution was rapid and associated with a reduction in 30-day bleeding. These data should encourage other centers considering the adoption of TR access.

PET imaging of atherosclerosis.

Atherosclerosis is a chronic, progressive, multifocal disease of the arterial wall, which is mainly fuelled by local and systemic inflammation, often resulting in acute ischemic events following plaque rupture and vessel occlusion. When assessing the cardiovascular risk of an individual patient, we must consider both global measures of disease activity and local features of plaque vulnerability, in addition to anatomical distribution and degree of established atherosclerosis. These parameters cannot be measured with conventional anatomical imaging techniques alone, which are designed primarily to identify the presence of organic intraluminal obstruction in symptomatic patients. However, molecular imaging with PET, using specifically targeted radiolabeled probes to track active in vivo atherosclerotic mechanisms noninvasively, may potentially provide a method that is better suited for this purpose. Vascular PET imaging can help us to further understand aspects of plaque biology, and current evidence supports a future role as an emerging clinical tool for the quantification of cardiovascular risk in order to guide and monitor responses to antiatherosclerosis treatments and to distinguish high-risk plaques.