Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions.

Importance:HIV-associated cardiovascular disease is increasing in prevalence, but its mechanisms remain poorly understood. Objective:To systematically review data from advanced cardiovascular imaging studies evaluating computed tomographic coronary angiography, positron emission tomography (PET), and cardiac magnetic resonance (MR), in people living with HIV compared with uninfected individuals. Data Sources:Three databases and Google Scholar were searched for studies assessing cardiovascular pathology using computed tomographic coronary angiography, cardiac MR, PET, and HIV from inception to February 11, 2022. Study Selection:Two reviewers selected original studies without any restrictions on design, date, or language, investigating HIV and cardiovascular pathology. Data Extraction and Synthesis:One investigator extracted data checked by a second investigator. Prevalence ratios (PRs) and differences in inflammation among people living with HIV and uninfected individuals were qualitatively synthesized in terms of cardiovascular pathology. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. Main Outcomes and Measures:Primary outcomes were computed tomographic coronary angiography-defined moderate to severe (≥50%) coronary stenosis, cardiac MR-defined myocardial fibrosis identified by late gadolinium enhancement, and PET-defined vascular and myocardial target to background ratio. Prevalence of moderate to severe coronary disease, as well as myocardial fibrosis, and PRs compared with uninfected individuals were reported alongside difference in vascular target to background ratio. Results:Forty-five studies including 5218 people living with HIV (mean age, 48.5 years) and 2414 uninfected individuals (mean age, 49.1 years) were identified. Sixteen studies (n = 5107 participants) evaluated computed tomographic coronary angiography; 16 (n = 1698), cardiac MRs; 10 (n = 681), vascular PET scans; and 3 (n = 146), both computed tomographic coronary angiography and vascular PET scans. No studies originated from low-income countries. Regarding risk of bias, 22% were classified as low; 47% moderate; and 31% high. Prevalence of moderate to severe coronary disease among those with vs without HIV ranged from 0% to 52% and 0% to 27%, respectively, with PRs ranging from 0.33 (95% CI, 0.01-15.90) to 5.19 (95% CI, 1.26-21.42). Prevalence of myocardial fibrosis among those with vs without HIV ranged from 5% to 84% and 0% to 68%, respectively, with PRs ranging from 1.01 (95% CI, 0.85-1.21) to 17.35 (95% CI, 1.10-274.28). Differences in vascular target to background ratio among those with vs without HIV ranged from 0.06 (95% CI, 0.01-0.11) to 0.37 (95% CI, 0.02-0.72). Conclusions and Relevance:In this systematic review of studies of advanced cardiovascular imaging, the estimates of the associations between HIV and cardiovascular pathologies demonstrated large amounts of heterogeneity. The findings provide a summary of the available data but may not be representative of all individuals living with HIV, including those from low-income countries with higher HIV endemicity.

ObjectiveCOVID-19 primarily causes pneumonitis but can also cause myocarditis. Injury may be due to a generalised inflammatory immune process or by direct viral infection. Using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and cardiac magnetic resonance (CMR) imaging we correlated the metabolic activity/injury between the reticuloendothelial system (bone marrow [BM] and spleen) and myocardial/pulmonary tissue.Methods18F-FDG-PET/CT (n=29, fasted n=27) and CMR (n=23) were performed on hospitalised patients with acute COVID-19. 18F-FDG PET/CT standardised uptake values (SUV) were measured in the spleen, spinal BM, myocardial and pulmonary tissue. Cardiac target-to-background ratio (TBR) was calculated by indexing to blood-pool SUV. Myocarditis was assessed using the sensitive 2018 Lake Louise criteria (LLC), and viral load (by cycle threshold).Results13 patients had myocarditis on CMR (57%), 8 (30%) visually on 18F-FDG-PET/CT. There was no statistical difference comparing LLC positive and negative patients for BM (4.21±0.30, 4.98±0.56, P=0.23), spleen (4.40±0.40, 5.15±0.08, P=0.38) and lung (4.08±0.72, 4.16±0.91, P=0.94) SUV. Lung SUV was significantly associated with BM (r=0.61, P<0.001) and spleen (r=0.48, P<0.05) SUV. Cardiac TBR, T1 and T2 mapping showed no significant association with BM and spleen SUV (P>0.05 for all). Cycle threshold did not correlate with either cardiac TBR and T1 or T2 (p>0.05 for all).ConclusionReticuloendothelial system activation strongly correlated with lung activity, suggesting pulmonary injury is part of a systemic inflammatory process. Cardiac inflammation was not associated with either spleen, BM or viral load, suggesting injury is multifactorial.

Background Acute COVID‐19–related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID‐19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID‐19 were prospectively recruited during hospital admission in this cross‐sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2‐deoxy‐2‐[fluorine‐18]fluoro‐D‐glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance–defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0–55.3] versus 3.5 ng/L [IQR: 2.5–5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4–8.3] versus 3.5 ng/L [IQR: 2.8–7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%–31%) and 11% (IQR: 7%–18%), respectively. Neither were associated with the presence of myocarditis. Conclusions Myocarditis was present in a third patients with acute COVID‐19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994.

Purpose:To assess the association between nonalcoholic fatty liver disease (NAFLD) and quantitative atherosclerotic plaque at CT.Materials and Methods:In this post hoc analysis of the prospective Scottish Computed Tomography of the HEART trial (November 2010 to September 2014), hepatosteatosis and coronary artery calcium score were measured at noncontrast CT. Presence of stenoses, visually assessed high-risk plaque, and quantitative plaque burden were assessed at coronary CT angiography. Multivariable models were constructed to assess the impact of hepatosteatosis and cardiovascular risk factors on coronary artery disease.Results:Images from 1726 participants (mean age, 58 years ± 9 [SD]; 974 men) were included. Participants with hepatosteatosis (155 of 1726, 9%) had a higher body mass index, more hypertension and diabetes mellitus, and higher cardiovascular risk scores (P < .001 for all) compared with those without hepatosteatosis. They had increased coronary artery calcium scores (median, 43 Agatston units [AU] [interquartile range, 0-273] vs 19 AU [0-225], P = .046), more nonobstructive disease (48% vs 37%, P = .02), and higher low-attenuation plaque burden (5.11% [0-7.16] vs 4.07% [0-6.84], P = .04). However, these associations were not independent of cardiovascular risk factors. Over a median of 4.7 years, there was no evidence of a difference in myocardial infarction between those with and without hepatosteatosis (1.9% vs 2.4%, P = .92).Conclusion:Hepatosteatosis at CT was associated with an increased prevalence of coronary artery disease at CT, but this was not independent of the presence of cardiovascular risk factors.Keywords: CT, Cardiac, Nonalcoholic Fatty Liver Disease, Coronary Artery Disease, Hepatosteatosis, Plaque QuantificationClinical trial registration no. NCT01149590 Supplemental material is available for this article. © RSNA, 2022See also commentary by Abohashem and Blankstein in this issue.

ObjectivesTo determine the prevalence of cardiovascular disease (CVD) risk factors and explore associations with high-sensitivity cardiac troponin I (hscTnI) and high-sensitivity C-reactive protein (hsCRP) in people living with HIV (PLHIV) in Kenya.DesignPilot cross-sectional study.SettingData were collected from community HIV clinics across two sites in Nairobi, Kenya, from July 2019 to May 2020.ParticipantsConvenience sample of 200 PLHIV (≥30 years with no prior history of CVD).Outcome measuresPrevalence of cardiovascular risk factors and its association with hsTnI and hsCRP levels.ResultsAcross 200 PLHIV (median age 46 years, IQR 38–53; 61% women), the prevalence of hypercholesterolaemia (total cholesterol >6.1 mmol/L) and hypertension were 19% (n=30/199) and 30% (n=60/200), respectively. Smoking and diabetes prevalence was 3% (n=5/200) and 4% (n=7/200). HscTnI was below the limit of quantification (<2.5 ng/L) in 65% (n=109/169). High (>3 mg/L), intermediate (1–3 mg/L) and low (<1 mg/L) hsCRP levels were found in 38% (n=75/198), 33% (n=65/198) and 29% (n=58/198), respectively. Framingham laboratory-based risk scores classified 83% of PLHIV at low risk with 12% and 5% at intermediate and high risk, respectively. Older age (adjusted OR (aOR) per year increase 1.05, 95% CI 1.01 to 1.08) and systolic blood pressure (140–159 mm Hg (aOR 2.96; 95% CI 1.09 to 7.90) and >160 mm Hg (aOR 4.68, 95% CI 1.55 to 14) compared with <140 mm Hg) were associated with hscTnI levels. No associations were observed between hsCRP and CVD risk factors.ConclusionThe majority of PLHIV—using traditional risk estimation systems—have a low estimated CVD risk likely reflecting a younger aged population predominantly consisting of women. Hypertension and hypercholesterolaemia were common while smoking and diabetes rates remained low. While hscTnI values were associated with increasing age and raised blood pressure, no associations between hsCRP levels and traditional cardiovascular risk factors were observed.

Objective To systematically review and meta-analyse data from advanced cardiovascular imaging studies evaluating computed tomography coronary angiography (CTCA), positron emission tomography (PET), and cardiac magnetic resonance (CMR), in people living with HIV (PLHIV) compared to uninfected individuals. Methods Three databases were searched for studies investigating the association between cardiovascular pathology and HIV using CTCA, CMR and PET in PLHIV from inception to February 11th 2022. Primary outcomes moderate to severe (>50%) coronary stenosis (CTCA), vascular and myocardial target-to-background ratio (PET), late gadolinium enhancement prevalence (CMR). Prevalence and risk ratios (RR) (comparing PLHIV to uninfected individuals) were pooled for using a random effects model. Results Forty-five studies including 5218 PLHIV (mean age 48.5 years) and 2414 uninfected individuals (mean age 49.1 years) met the inclusion criteria. Sixteen studies (n=5107 participants) evaluated CTCA, 10 (n=681) vascular PET, 3 (n=146) both CTCA and vascular PET, and 16 (n=1698) CMR. No studies originated from low-income countries. The prevalence of moderate/severe coronary disease in 17.3% in PLHIV and 13.8% in controls (RR 1.33, 95%CI 0.96–1.82, I2= 62%). The prevalence of myocardial fibrosis was 47.5% in PLHIV and 31.7% in controls (RR 2.34, 95% confidence interval [CI] 1.34–4.08, I2=88%). PET studies indicated that PLHIV have an increase in vascular inflammation however these findings are derived from populations with well controlled HIV in middle age. Conclusion Significant associations were observed between HIV and risk of myocardial fibrosis but not moderate to severe coronary disease. These findings were derived largely from populations in regions of low HIV endemicity.

Background: Understanding trends in the incidence and outcomes of myocardial infarction and stroke, and how these are influenced by changes in cardiovascular risk factors can inform health policy and healthcare provision. Methods: We identified all patients 30 years or older with myocardial infarction or stroke in Scotland. Risk factor levels were determined from national health surveys. Incidence, potential impact fractions and burden attributable to risk factor changes were calculated. Risk of subsequent fatal and non-fatal events (myocardial infarction, stroke, bleeding and heart failure hospitalization) were calculated with multi-state models. Findings: From 1990 to 2014, there were 372,873 (71 +/- 13 years) myocardial infarctions and 290,927 (74 +/- 13 years) ischemic or hemorrhagic strokes. Age-standardized incidence per 100,000 fell from 1,069 (95% confi-dence interval, 1,024-1,116) to 276 (263-290) for myocardial infarction and from 608 (581-636) to 188 (178197) for ischemic stroke. Systolic blood pressure, smoking and cholesterol decreased, but body-mass index increased, and diabetes prevalence doubled. Changes in risk factors accounted for a 74% (57-91%) reduction in myocardial infarction and 68% (55-83%) reduction in ischemic stroke. Following myocardial infarction, the risk of death decreased (30% to 20%), but non-fatal events increased (20% to 24%) whereas the risk of both death (47% to 34%) and non-fatal events (22% to 17%) decreased following stroke. Interpretation: Over the last 25 years, substantial reductions in myocardial infarction and ischemic stroke incidence are attributable to major shifts in risk factor levels. Deaths following the index event decreased for both myocardial infarction and stroke, but rates remained substantially higher for stroke. (C) 2021 The Author(s). Published by Elsevier Ltd.

Background: 8-28% of patients infected with COVID-19 have evidence of cardiac injury, and this is associated with an adverse prognosis. The cardiovascular mechanisms of injury are poorly understood and speculative. We aim to use multimodality cardiac imaging including cardiac magnetic resonance (CMR) imaging, computed tomography coronary angiography (CTCA) and positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro- D-glucose integrated with computed tomography (18F-FDG-PET/CT) to identify the cardiac pathophysiological mechanisms related to COVID-19 infections. Methods: This is a single-centre exploratory observational study aiming to recruit 50 patients with COVID-19 infection who will undergo cardiac biomarker sampling. Of these, 30 patients will undergo combined CTCA & 18F-FDG-PET/CT, followed by CMR. Prevalence of obstructive and non-obstructive atherosclerotic coronary disease will be assessed using CTCA. CMR will be used to identify and characterise myocardial disease including presence of cardiac dysfunction, myocardial fibrosis, myocardial oedema and myocardial infarction. 18F-FDG-PET/CT will identify vascular and cardiac inflammation. Primary endpoint will be the presence of cardiovascular pathology and the association with troponin levels. Discussion: The results of the study will identify the presence and modality of cardiac injury associated COVID-19 infection, and the utility of multi-modality imaging in diagnosing such injury. This will further inform clinical decision making during the pandemic. TRIAL REGISTRATION : This study has been retrospectively registered at the ISRCTN registry (ID ISRCTN12154994) on 14th August 2020. Accessible at www.isrctn.com/ISRCTN12154994

OBJECTIVES This study was designed to investigate whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain. BACKGROUND Important sex differences exist in coronary artery disease. Women presenting with chest pain have different risk factors, symptoms, prevalence of coronary artery disease and prognosis compared to men. METHODS Within a multicenter randomized controlled trial, we explored sex differences in stenosis, adverse plaque characteristics (positive remodeling, low-attenuation plaque, spotty calcification, or napkin ring sign) and quantitative assessment of total, calcified, noncalcified and low-attenuation plaque burden. RESULTS Of the 1,769 participants who underwent coronary computed tomography angiography, 772 (43%) were female. Women were more likely to have normal coronary arteries and less likely to have adverse plaque characteristics (p < 0.001 for all). They had lower total, calcified, noncalcified, and low-attenuation plaque burdens (p < 0.001 for all) and were less likely to have a low-attenuation plaque burden >4% (41% vs. 59%; p < 0.001). Over a median follow-up of 4.7 years, myocardial infarction (MI) occurred in 11 women (1.4%) and 30 men (3%). In those who had MI, women had similar total, noncalcified, and low-attenuation plaque burdens as men, but men had higher calcified plaque burden. Lowattenuation plaque burden predicted MI (hazard ratio: 1.60; 95% confidence interval: 1.10 to 2.34; p = 0.015), independent of calcium score, obstructive disease, cardiovascular risk score, and sex. CONCLUSIONS Women presenting with stable chest pain have less atherosclerotic plaque of all subtypes compared to men and a lower risk of subsequent MI. However, quantitative low-attenuation plaque is as strong a predictor of subsequent MI in women as in men. (C) 2021 by the American College of Cardiology Foundation.

Aims Valvular heart disease can be identified by calcification on coronary computed tomography angiography (CCTA) and has been associated with adverse clinical outcomes. We assessed aortic and mitral valve calcification in patients presenting with stable chest pain and their association with cardiovascular risk factors, coronary artery disease, and cardiovascular outcomes. Methods and results In 1769 patients (58 +/- 9 years, 56% male) undergoing CCTA for stable chest pain, aortic and mitral valve calcification were quantified using Agatston score. Aortic valve calcification was present in 241 (14%) and mitral calcification in 64 (4%). Independent predictors of aortic valve calcification were age, male sex, hypertension, diabetes mellitus, and cerebrovascular disease, whereas the only predictor of mitral valve calcification was age. Patients with aortic and mitral valve calcification had higher coronary artery calcium scores and more obstructive coronary artery disease. The composite endpoint of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke was higher in those with aortic [hazard ratio (HR) 2.87; 95% confidence interval (CI) 1.60-5.17; P< 0.001] or mitral (HR 3.50; 95% CI 1.47-8.07; P = 0.004) valve calcification, but this was not independent of coronary artery calcification or obstructive coronary artery disease. Conclusion Aortic and mitral valve calcification occurs in one in six patients with stable chest pain undergoing CCTA and is associated with concomitant coronary atherosclerosis. Whilst valvular calcification is associated with a higher risk of cardiovascular events, this was not independent of the burden of coronary artery disease.

Introduction This post-hoc analysis of the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) assessed the frequency and implications of coronary artery disease (CAD) in patients with a zero coronary artery calcium score (CACS). Methods Agatston CACS was assessed on non-contrast and CAD on contrast CT coronary angiography. Adverse plaque characteristics (APC) were visually identified as positive remodelling or low attenuation plaque and quantitative plaque burden was measured. Results Of 642 patients with zero CACS, CAD was present in 105 (16%). Compared to patients with normal coronary arteries, those with zero CACS and CAD were older (55±9 vs 53±10 years, p=0.016) and had higher cardiovascular risk scores (14±9 vs 12±8, p=0.013). On CTCA 92 (14%) had non-obstructive CAD, 13 (2%) obstructive CAD, 14 (2%) APC and 85 (13%) low attenuation plaque burden >4%. Compared to patients with normal coronary arteries, those with zero CACS and CAD were more likely to receive statins (67% vs 17%, p<0.001), antiplatelet therapy (74% vs 28%, p<0.001), angiography (18% vs 2%, p<0.001) and revascularisation (7% vs 0%, p<0.001). Quality-of-life and symptoms were similar in patients with normal coronary arteries and those with zero CACS and CAD (p>0.05). Over 5 years of follow-up, 1 event (1%, myocardial infarction) occurred in patients with zero CACS and CAD compared to 3 events (1%, 2 myocardial infarction and 1 coronary heart disease death) in patients with normal coronary arteries. Conclusion CAD occurs in 16% of patients with zero CACS, with prognostically significant plaque subtypes occurring in some patients, although the overall event-rate is low.

The Coronary Artery Disease Reporting And Data System (CAD-RADS) and Coronary Artery Calcium Data and Reporting System (CAC-DRS) aim to improve communication of results.Images from 1,769 patients from the Scottish Computed Tomography of the HEART (SCOT-HEART) trial were assessed.Patients classifi ed as CAC-DRS 3 were at an increased risk of fatal or non-fatal myocardial infarction.Patients with higher CAD-RADS categories were at an increased risk of fatal or non-fatal myocardial infarction, with patients classifi ed as CAD-RADS 4B at the highest risk .This confi rms that the classifi cation provides additional prognostic discrimination for future coronary heart disease events.

Incidental coronary and cardiac calcification are frequent findings on non-gated thoracic CT. We recommend that the heart is reviewed on all CT scans where it is visualised. Coronary artery calcification is a marker of coronary artery disease and it is associated with an adverse prognosis on dedicated cardiac imaging and on non-gated thoracic CT performed for non-cardiac indications, both with and without contrast. We recommend that coronary artery calcification is reported on all non-gated thoracic CT using a simple patient-based score (none, mild, moderate, severe). Furthermore, we recommend that reports include recommendations for subsequent management, namely the assessment of modifiable cardiovascular risk factors and, if the patient has chest pain, assessment as per standard guidelines. In most cases, this will not necessitate additional investigations. Incidental aortic valve calcification may also be identified on non-gated thoracic CT and should be reported, along with ancillary findings such as aortic root dilation. Calcification may occur in other parts of the heart including mitral valve/annulus, pericardium and myocardium, but in many cases these are an incidental finding without clinical significance.

Objectives: To assess the prognostic implications of standardized reporting systems for coronary computed tomography angiography (CCTA) and coronary artery calcium scores (CACS) in patients with stable chest pain. Background: The Coronary Artery Disease Reporting And Data System (CAD-RADS) and Coronary Artery Calcium - Data and Reporting System (CAC-DRS) aim to improve communication of CACS and CCTA results, but its influence on prognostication is unknown. Methods: Images from 1769 patients who underwent CCTA as part of the Scottish Computed Tomography of the HEART (SCOT-HEART) multi-center randomized controlled trial were assessed. CACS were classified as CAC-DRS 0 to 3 based on Agatston scores. CCTA were classified as CAD-RADS 0 to 5 based on the most clinically relevant finding per patient. The primary outcome was the five-year events of fatal and non-fatal myocardial infarction. Results: Patients had a mean age of 58 +/- 10 years and 56% were male. CAC-DRS 0, 1, 2 and 3 occurred in 642 (36%), 510 (29%), 239 (14%) and 379 (21%) patients respectively. CAD-RADS 0, 1, 2, 3, 4A, 4B and 5 occurred in 622 (35%), 327 (18%), 211 (12%), 165 (9%), 221 (12%), 42 (2%) and 181 (10%) patients respectively. Patients classified as CAC-DRS 3 were at an increased risk of fatal or non-fatal myocardial infarction compared to CAC-DRS 0 patients (hazard ratio (HR) 9.41; 95% confidence interval (CI) 3.24, 27.31; p < 0.001). Patients with higher CAD-RADS categories were at an increased risk of fatal or non-fatal myocardial infarction, with patients classified as CAD-RADS 4B at the highest risk compared to CAD-RADS 0 patients (HR 19.14; 95% CI 4.28, 85.53; p < 0.001). Conclusion: Patients with higher CAC-DRS and CAD-PADS scores were at increased risk of subsequent fatal and non-fatal myocardial infarction. This confirms that the classification provides additional prognostic discrimination for future coronary heart disease events.

We assessed whether non-calcific low-density plaque on coronary CT angiography (CCTA) might improve risk stratification independent of classic risk markers. In the multicenter SCOT-HEART randomized controlled trial, we investigated associations between the risk of fatal or non-fatal myocardial

Objectives Ultra-small superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect cellular inflammation within tissues and may help non-invasively identify cardiac transplant rejection. Here, we aimed to determine the normal reference values for USPIO-enhanced MRI in patients with a prior cardiac transplant and examine whether USPIO-enhanced MRI could detect myocardial inflammation in patients with transplant rejection. Methods Ten volunteers and 11 patients with cardiac transplant underwent T2, T2* and late gadolinium enhancement 1.5T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Results Ten patients with clinically stable cardiac transplantation were retained for analysis. Myocardial T2 values were higher in patients with cardiac transplant versus healthy volunteers (53.8±5.2 vs 48.6±1.9 ms, respectively; p=0.003). There were no differences in the magnitude of USPIO-induced change in R2* in patients with transplantation (change in R2*, 26.6±7.3 vs 22.0±10.4 s-1 in healthy volunteers; p=0.28). After 3 months, patients with transplantation (n=5) had unaltered T2 values (52.7±2.8 vs 52.12±3.4 ms; p=0.80) and changes in R2* following USPIO (29.42±8.14 vs 25.8±7.8 s-1; p=0.43). Conclusion Stable patients with cardiac transplantation have increased myocardial T2 values, consistent with resting myocardial oedema or fibrosis. In contrast, USPIO-enhanced MRI is normal and stable over time suggesting the absence of chronic macrophage-driven cellular inflammation. It remains to be determined whether USPIO-enhanced MRI may be able to identify acute cardiac transplant rejection. Trial registration number NCT02319278349 (https://clinicaltrials.gov/ct2/show/NCT02319278) Registered 03.12.2014 EUDraCT 2013-002336-24.