A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings.

BACKGROUND: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. DESIGN: Cohort study. (ClinicalTrials.gov: NCT04411147). SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PARTICIPANTS: Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. MEASUREMENTS: All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. RESULTS: 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. LIMITATIONS: Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. CONCLUSION: A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. PRIMARY FUNDING SOURCE: Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

Aortic distensibility in alkaptonuria.

INTRODUCTION: Alkaptonuria (AKU) is a rare inherited disorder of tyrosine metabolism resulting in an accumulation of homogentisic acid oxidation products in the joints and cardiovascular system. Aortic distensibility may be a non-invasive indicator of cardiovascular complications. Descending thoracic aortic distensibility in alkaptonuria has not been studied. METHODS: Patients diagnosed with alkaptonuria underwent Magnetic Resonance Imaging (MRI) and gated non-contrast and contrast-enhanced cardiovascular computed tomography. Using MRI cine images, aortic distensibility of the descending thoracic aorta was determined. RESULTS: Seventy-six patients with alkaptonuria were imaged. When compared to literature normal values, aortic distensibility in AKU was impaired (5.2 vs 6.2 × 10-3, p < .001). Aortic distensibility was inversely related to age (r = -0.6, p = .0001). Hypertensive patients with alkaptonuria had impaired distensibility compared to normotensive patients with alkaptonuria (4.6 vs 5.6 × 10-3, p = .03), and hyperlipidemic patients with alkaptonuria had impaired distensibility compared to non-hyperlipidemic patients with alkaptonuria (4.1 vs 6.0 × 10-3, p = .001). Male hypertensive patients with alkaptonuria had greater distensibility than their female counterparts (5.3 vs 2.9 × 10-3, p = .02). Similarly, male hyperlipidemic patients with alkaptonuria had greater distensibility than their female counterparts (4.8 vs 2.5 × 10-3, p < .01). Of patients with alkaptonuria, those with a coronary artery calcium (CAC) score greater than 100 had more impaired distensibility than those with a CAC score less than 100 (3.5 vs 5.1 × 10-3, p = .01) and those with aortic calcium score greater than 100 had impaired distensibility compared to those with an aortic calcium score less than 100 (3.2 vs 4.9 × 10-3, p = .02). Univariate analysis revealed age, aortic calcification, and hyperlipidemia to be significant factors of distensibility, and multiple regression analysis showed age as the only significant risk factor of distensibility. CONCLUSIONS: Patients with alkaptonuria have impaired aortic distensibility, which is likely an early marker for reduced cardiovascular health. Variables such as age, hypertension, hyperlipidemia, and aortic and coronary calcification were associated with impaired distensibility.

A comparison of cine CMR imaging at 0.55 T and 1.5 T.

BACKGROUND: There is a renewed interest in lower field magnetic resonance imaging (MRI) systems for cardiovascular magnetic resonance (CMR), due to their favorable physical properties, reduced costs, and increased accessibility to patients with implants. We sought to assess the diagnostic capabilities of high-performance low-field (0.55 T) CMR imaging for quantification of right and left ventricular volumes and systolic function in both healthy subjects and patients referred for clinical CMR. METHODS: Sixty-five subjects underwent paired exams at 1.5 T using a clinical CMR scanner and using an identical CMR system modified to operate at 0.55 T. Volumetric coverage of the right ventricle (RV) and left ventricles (LV) was obtained using either a breath-held cine balanced steady-state free-precession acquisition or a motion-corrected free-breathing re-binned cine acquisition. Bland-Altman analysis was used to compare LV and RV end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF), and LV mass. Diagnostic confidence was scored on a Likert-type ordinal scale by blinded readers. RESULTS: There were no significant differences in LV and RV EDV between the two scanners (e.g., LVEDV: p = 0.77, bias = 0.40 mL, correlation coefficient = 0.99; RVEDV: p = 0.17, bias = - 1.6 mL, correlation coefficient = 0.98), and regional wall motion abnormality scoring was similar (kappa 0.99). Blood-myocardium contrast-to-noise ratio (CNR) at 0.55 T was 48 ± 7% of the 1.5 T CNR, and contrast was sufficient for endocardial segmentation in all cases. Diagnostic confidence of images was scored as "good" to "excellent" for the two field strengths in the majority of studies. CONCLUSION: A high-performance 0.55 T system offers good bSSFP CMR image quality, and quantification of biventricular volumes and systolic function that is comparable to 1.5 T in patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT03331380, NCT03581318.

Prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in older adults.

Aims: Non-ischaemic cardiomyopathies (NICM) can cause heart failure and death. Cardiac magnetic resonance (CMR) detects myocardial scar/fibrosis associated with myocardial infarction (MI) and NICM with late gadolinium enhancement (LGE). The aim of this study was to determine the prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in a community-based sample of older adults. Methods and results: The ICELAND-MI cohort, a substudy of the Age, Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) study, provided a well-characterized population of 900 subjects after excluding subjects with pre-existing heart failure. Late gadolinium enhancement CMR divided subjects into four groups: MI (n = 211), major (n = 54) non-ischaemic fibrosis (well-established, classic patterns, associated with myocarditis, infiltrative cardiomyopathies, or pathological hypertrophy), minor (n = 238) non-ischaemic fibrosis (remaining localized patterns not meeting major criteria), and a no LGE (n = 397) reference group. The primary outcome was time to death or first heart failure hospitalization. During a median follow-up of 5.8 years, 192 composite events occurred (115 deaths and 77 hospitalizations for incident heart failure). After inverse probability weighting, major non-ischaemic fibrosis [hazard ratio (HR) 3.2, P < 0.001] remained independently associated with the primary endpoint, while MI (HR 1.4, P = 0.10) and minor non-ischaemic LGE (HR 1.2, P = 0.39) did not. Major non-ischaemic fibrosis was associated with a poorer outcome than MI (HR = 2.3, P = 0.001) in the adjusted analysis. Conclusion: Major non-ischaemic patterns of myocardial fibrosis portended worse prognosis than no fibrosis/scar in an older community-based cohort. Traditional risk factors largely accounted for the effect of MI and minor non-ischaemic LGE.

Prototype Ultrahigh-Resolution Computed Tomography for Chest Imaging: Initial Human Experience.

OBJECTIVE: The objective of this study was to evaluate a prototype, ultrahigh-resolution computed tomography offering higher reconstruction matrix (1024 × 1024) and spatial resolution (0.15 mm) for chest imaging. METHODS: Higher (1024) matrix reconstruction enabled by ultrahigh-resolution computed tomography scanner (128-detector rows; detector width, 0.25 mm; spatial resolution, 0.15 mm) was compared with conventional (512) reconstruction with image quality grading on a Likert scale (1, excellent; 5, nondiagnostic) for image noise, artifacts, contrast, small detail, lesion conspicuity, image sharpness, and diagnostic confidence. Image noise and signal-to-noise ratio were quantified. RESULTS: Diagnostic image quality was achieved for all scans on 101 patients. The 1024 reconstruction demonstrated increased image noise (20.2 ± 4.0 vs 17.2 ± 3.8, P < 0.001) and a worse noise rating (1.98 ± 0.63 vs 1.75 ± 0.61, P < 0.001) but performed significantly better than conventional 512 matrix with fewer artifacts (1.37 ± 0.43 vs 1.50 ± 0.48, P < 0.001), better contrast (1.50 ± 0.56 vs 1.62 ± 0.57, P < 0.001), small detail detection (1.06 ± 0.19 vs 2.02 ± 0.22, P < 0.001), lesion conspicuity (1.08 ± 0.23 vs 2.02 ± 0.24, P < 0.001), sharpness (1.09 ± 0.24 vs 2.02 ± 0.28, P < 0.001), and overall diagnostic confidence (1.09 ± 0.25 vs 1.18 ± 0.34, P < 0.001). CONCLUSIONS: Ultrahigh-resolution computed tomography enabled a higher reconstruction matrix and improved image quality compared with conventional matrix reconstruction, with a minor increase in noise.

Subtraction CT angiography improves evaluation of significant coronary artery disease in patients with severe calcifications or stents-the C-Sub 320 multicenter trial.

OBJECTIVES: Diagnostic accuracy of conventional coronary CT angiography (CCTAconv) may be compromised by blooming artifacts from calcifications or stents. Blooming artifacts may be reduced by subtraction coronary CT angiography (CCTAsub) in which non-contrast and contrast CT data sets are subtracted digitally. We tested whether CCTAsub in patients with severe coronary calcification or stents reduces the number of false-positive stenosis evaluations compared with CCTAconv. METHODS: In this study, 180 symptomatic patients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and CT scanned (2013-2016) at three international centers. CCTAconv, and CCTAsub data sets were reconstructed. Target segments were defined as motion-free coronary segments with a suspected stenosis (> 50% of lumen) potentially due to blooming of either calcium or stents. Target segments were evaluated with respect to misregistration artifacts from the CCTAsub reconstruction process, in which case evaluation was omitted. CCTAsub and CCTAconv were compared with ICA. Primary outcome measure was the frequency of false positives by CCTAconv versus CCTAsub to identify > 50% coronary stenosis by ICA on a per-segment level. RESULTS: After exclusion of 76 patients, 104 (14% females) with mean age 67 years and median Agatston score 852 were included. There were 136 target segments with misregistration and 121 target segments without. Accuracy calculations in target segments without misregistration showed a reduction of the false positives from 72% [95% confidence interval (CI): 63-80%] in CCTAconv to 33% (CI:25-42%) in CCTAsub, at the expense of 7% (CI:3-14%) false negatives in CCTAsub. CONCLUSIONS: In severely calcified coronary arteries or stents, CCTAsub reduces the false-positive rate in well-aligned, calcified or stent segments suspected of significant stenosis on CCTAconv. Nevertheless, misregistration artifacts are frequent in CCTAsub. KEY POINTS: • A high calcium-score reduces the diagnostic accuracy in patients scanned with cardiac CT. • These patients would normally need an invasive angiogram for diagnosis. • In this prospective, multicenter study, subtraction CT, when evaluable, reduces false-positive stenosis evaluations. • Subtraction coronary CT angiography may, when evaluable, reduce excessive downstream testing.

Fully quantitative pixel-wise analysis of cardiovascular magnetic resonance perfusion improves discrimination of dark rim artifact from perfusion defects associated with epicardial coronary stenosis.

BACKGROUND: Dark rim artifacts in first-pass cardiovascular magnetic resonance (CMR) perfusion images can mimic perfusion defects and affect diagnostic accuracy for coronary artery disease (CAD). We evaluated whether quantitative myocardial blood flow (MBF) can differentiate dark rim artifacts from true perfusion defects in CMR perfusion. METHODS: Regadenoson perfusion CMR was performed at 1.5 T in 76 patients. Significant CAD was defined by quantitative invasive coronary angiography (QCA) ≥ 50% diameter stenosis. Non-significant CAD (NonCAD) was defined as stenosis by QCA < 50% diameter stenosis or computed tomographic coronary angiography (CTA) < 30% in all major epicardial arteries. Dark rim artifacts had study specific and guideline-based definitions for comparison purposes. MBF was quantified at the pixel-level and sector-level. RESULTS: In a NonCAD subgroup with dark rim artifacts, stress MBF was lower in the subendocardial than midmyocardial and epicardial layers (2.17 ± 0.61 vs. 3.06 ± 0.75 vs. 3.24 ± 0.80 mL/min/g, both p < 0.001) and was also 30% lower than in remote regions (2.17 ± 0.61 vs. 2.83 ± 0.67 mL/min/g, p < 0.001). However, subendocardial stress MBF in dark rim artifacts was 37-56% higher than in true perfusion defects (2.17 ± 0.61 vs. 0.95 ± 0.43 mL/min/g, p < 0.001). Absolute stress MBF differentiated CAD from NonCAD with an accuracy ranging from 86 to 89% (all p < 0.001) using pixel-level analyses. Similar results were seen at a sector level. CONCLUSION: Quantitative stress MBF is lower in dark rim artifacts than remote myocardium but significantly higher than in true perfusion defects. If confirmed in larger series, this approach may aid the interpretation of clinical stress perfusion exams. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00027170 ; first posted 11/28/2001; updated 11/27/2017.

Submillisievert median radiation dose for coronary angiography with a second-generation 320-detector row CT scanner in 107 consecutive patients.

PURPOSE: To (a) use a new second-generation wide-volume 320-detector row computed tomographic (CT) scanner to explore optimization of radiation exposure in coronary CT angiography in an unselected and consecutive cohort of patients referred for clinical purposes and (b) compare estimated radiation exposure and image quality with that from a cohort of similar patients who underwent imaging with a previous first-generation CT system. MATERIALS AND METHODS: The study was approved by the institutional review board, and all subjects provided written consent. Coronary CT angiography was performed in 107 consecutive patients with a new second-generation 320-detector row unit. Estimated radiation exposure and image quality were compared with those from 100 consecutive patients who underwent imaging with a previous first-generation scanner. Effective radiation dose was estimated by multiplying the dose-length product by an effective dose conversion factor of 0.014 mSv/mGy ⋅ cm and reported with size-specific dose estimates (SSDEs). Image quality was evaluated by two independent readers. RESULTS: The mean age of the 107 patients was 55.4 years ± 12.0 (standard deviation); 57 patients (53.3%) were men. The median body mass index was 27.3 kg/m(2) (range, 18.1-47.2 kg/m(2)); however, 71 patients (66.4%) were overweight, obese, or morbidly obese. A tube potential of 100 kV was used in 97 patients (90.6%), single-volume acquisition was used in 104 (97.2%), and prospective electrocardiographic gating was used in 106 (99.1%). The mean heart rate was 57.1 beats per minute ± 11.2 (range, 34-96 beats per minute), which enabled single-heartbeat scans in 100 patients (93.4%). The median radiation dose was 0.93 mSv (interquartile range [IQR], 0.58-1.74 mSv) with the second-generation unit and 2.67 mSv (IQR, 1.68-4.00 mSv) with the first-generation unit (P < .0001). The median SSDE was 6.0 mGy (IQR, 4.1-10.0 mGy) with the second-generation unit and 13.2 mGy (IQR, 10.2-18.6 mGy) with the first-generation unit (P < .0001). Overall, the radiation dose was less than 0.5 mSv for 23 of the 107 CT angiography examinations (21.5%), less than 1 mSv for 58 (54.2%), and less than 4 mSv for 103 (96.3%). All studies were of diagnostic quality, with most having excellent image quality. Three of four image quality indexes were significantly better with the second-generation unit compared with the first-generation unit. CONCLUSION: The combination of a gantry rotation time of 275 msec, wide volume coverage, iterative reconstruction, automated exposure control, and larger x-ray power generator of the second-generation CT scanner provides excellent image quality over a wide range of body sizes and heart rates at low radiation doses. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122621/-/DC1.

Regadenoson and adenosine are equivalent vasodilators and are superior than dipyridamole- a study of first pass quantitative perfusion cardiovascular magnetic resonance.

BACKGROUND: Regadenoson, dipyridamole and adenosine are commonly used vasodilators in myocardial perfusion imaging for the detection of obstructive coronary artery disease. There are few comparative studies of the vasodilator properties of regadenoson, adenosine and dipyridamole in humans. The specific aim of this study was to determine the relative potency of these three vasodilators by quantifying stress and rest myocardial perfusion in humans using cardiovascular magnetic resonance (CMR). METHODS: Fifteen healthy normal volunteers, with Framingham score less than 1% underwent vasodilator stress testing with regadenoson (400 µg bolus), dipyridamole (0.56 mg/kg) and adenosine (140 µg /kg/min) on separate days. Rest perfusion imaging was performed initially. Twenty minutes later, stress imaging was performed at peak vasodilation, i.e. 70 seconds after regadenoson, 4 minutes after dipyridamole infusion and between 3-4 minutes of the adenosine infusion. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution. RESULTS: Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 µl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 µl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs. 2.12 ± 0.27, p = NS), but persisted between regadenoson and dipyridamole (2.04 ± 0.34 vs. 1.77 ± 0.33, p = 0.07) and between adenosine and dipyridamole (2.12 ± 0.27 vs. 1.77 ± 0.33, p = 0.01). CONCLUSIONS: Based on fully quantitative perfusion using CMR, regadenoson and adenosine have similar vasodilator efficacy and are superior to dipyridamole.

Sex-Specific Stress Perfusion Cardiac Magnetic Resonance Imaging in Suspected Ischemic Heart Disease: Insights From SPINS Retrospective Registry.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of mortality in women, but current noninvasive cardiac imaging techniques have sex-specific limitations. OBJECTIVES: In this study, the authors sought to investigate the effect of sex on the prognostic utility and downstream invasive revascularization and costs of stress perfusion cardiac magnetic resonance (CMR) for suspected CVD. METHODS: Sex-specific prognostic performance was evaluated in a 2,349-patient multicenter SPINS (Stress CMR Perfusion Imaging in the United States [SPINS] Study) Registry. The primary outcome measure was a composite of cardiovascular death and nonfatal myocardial infarction; secondary outcomes were hospitalization for unstable angina or heart failure, and late unplanned coronary artery bypass grafting. RESULTS: SPINS included 1,104 women (47% of cohort); women had higher prevalence of chest pain (62% vs 50%; P < 0.0001) but lower use of medical therapies. At the 5.4-year median follow-up, women with normal stress CMR had a low annualized rate of primary composite outcome similar to men (0.54%/y vs 0.75%/y, respectively; P = NS). In contrast, women with abnormal CMR were at higher risk for both primary (3.74%/y vs 0.54%/y; P < 0.0001) and secondary (9.8%/y vs 1.6%/y; P < 0.0001) outcomes compared with women with normal CMR. Abnormal stress CMR was an independent predictor for the primary (HR: 2.64 [95% CI: 1.20-5.90]; P = 0.02) and secondary (HR: 2.09 [95% CI: 1.43-3.08]; P < 0.0001) outcome measures. There was no effect modification for sex. Women had lower rates of invasive coronary angiography (3.6% vs 7.3%; P = 0.0001) and downstream costs ($114 vs $171; P = 0.001) at 90 days following CMR. There was no effect of sex on diagnostic image quality. CONCLUSIONS: Stress CMR demonstrated excellent prognostic performance with lower rates of invasive coronary angiography referral in women. Stress CMR should be considered as a first-line noninvasive imaging tool for the evaluation of women. (Stress CMR Perfusion Imaging in the United States [SPINS] Study [SPINS]; NCT03192891).

Extracellular volume fraction mapping in the myocardium, part 2: initial clinical experience.

BACKGROUND: Diffuse myocardial fibrosis, and to a lesser extent global myocardial edema, are important processes in heart disease which are difficult to assess or quantify with cardiovascular magnetic resonance (CMR) using conventional late gadolinium enhancement (LGE) or T1-mapping. Measurement of the myocardial extracellular volume fraction (ECV) circumvents factors that confound T1-weighted images or T1-maps. We hypothesized that quantitative assessment of myocardial ECV would be clinically useful for detecting both focal and diffuse myocardial abnormalities in a variety of common and uncommon heart diseases. METHODS: A total of 156 subjects were imaged including 62 with normal findings, 33 patients with chronic myocardial infarction (MI), 33 with hypertrophic cardiomyopathy (HCM), 15 with non-ischemic dilated cardiomyopathy (DCM), 7 with acute myocarditis, 4 with cardiac amyloidosis, and 2 with systemic capillary leak syndrome (SCLS). Motion corrected ECV maps were generated automatically from T1-maps acquired pre- and post-contrast calibrated by blood hematocrit. Abnormally-elevated ECV was defined as >2SD from the mean ECV in individuals with normal findings. In HCM the size of regions of LGE was quantified as the region >2 SD from remote. RESULTS: Mean ECV of 62 normal individuals was 25.4 ± 2.5% (m ± SD), normal range 20.4%-30.4%. Mean ECV within the core of chronic myocardial infarctions (without MVO) (N=33) measured 68.5 ± 8.6% (p<0.001 vs normal). In HCM, the extent of abnormally elevated ECV correlated to the extent of LGE (r=0.72, p<0.001) but had a systematically greater extent by ECV (mean difference 19 ± 7% of slice). Abnormally elevated ECV was identified in 4 of 16 patients with non-ischemic DCM (38.1 ± 1.9% (p<0.001 vs normal) and LGE in the same slice appeared "normal" in 2 of these 4 patients. Mean ECV values in other disease entities ranged 32-60% for cardiac amyloidosis (N=4), 40-41% for systemic capillary leak syndrome (N=2), and 39-56% within abnormal regions affected by myocarditis (N=7). CONCLUSIONS: ECV mapping appears promising to complement LGE imaging in cases of more homogenously diffuse disease. The ability to display ECV maps in units that are physiologically intuitive and may be interpreted on an absolute scale offers the potential for detection of diffuse disease and measurement of the extent and severity of abnormal regions.

MultiContrast Delayed Enhancement (MCODE) improves detection of subendocardial myocardial infarction by late gadolinium enhancement cardiovascular magnetic resonance: a clinical validation study.

BACKGROUND: Myocardial infarction (MI) documented by late gadolinium enhancement (LGE) has clinical and prognostic importance, but its detection is sometimes compromised by poor contrast between blood and MI. MultiContrast Delayed Enhancement (MCODE) is a technique that helps discriminate subendocardial MI from blood pool by simultaneously providing a T2-weighted image with a PSIR (phase sensitive inversion recovery) LGE image. In this clinical validation study, our goal was to prospectively compare standard LGE imaging to MCODE in the detection of MI. METHODS: Imaging was performed on a 1.5 T scanner on patients referred for CMR including a LGE study. Prospective comparisons between MCODE and standard PSIR LGE imaging were done by targeted, repeat imaging of slice locations. Clinical data were used to determine MI status. Images at each of multiple time points were read on separate days and categorized as to whether or not MI was present and whether an infarction was transmural or subendocardial. The extent of infarction was scored on a sector-by-sector basis. RESULTS: Seventy-three patients were imaged with the specified protocol. The majority were referred for vasodilator perfusion exams and viability assessment (37 ischemia assessment, 12 acute MI, 10 chronic MI, 12 other diagnoses). Forty-six patients had a final diagnosis of MI (30 subendocardial and 16 transmural). MCODE had similar specificity compared to LGE at all time points but demonstrated better sensitivity compared to LGE performed early and immediately before and after the MCODE (p = 0.008 and 0.02 respectively). Conventional LGE only missed cases of subendocardial MI. Both LGE and MCODE identified all transmural MI. Based on clinical determination of MI, MCODE had three false positive MI's; LGE had two false positive MI's including two of the three MCODE false positives. On a per sector basis, MCODE identified more infarcted sectors compared to LGE performed immediately prior to MCODE (p < 0.001). CONCLUSION: While both PSIR LGE and MCODE were good in identifying MI, MCODE demonstrated more subendocardial MI's than LGE and identified a larger number of infarcted sectors. The simultaneous acquisition of T1 and T2-weighted images improved differentiation of blood pool from enhanced subendocardial MI.

DeepHeartCT: A fully automatic artificial intelligence hybrid framework based on convolutional neural network and multi-atlas segmentation for multi-structure cardiac computed tomography angiography image segmentation.

Cardiac computed tomography angiography (CTA) is an emerging imaging modality for assessing coronary artery as well as various cardiovascular structures. Recently, deep learning (DL) methods have been successfully applied to many applications of medical image analysis including cardiac CTA structure segmentation. However, DL requires a large amounts of data and high-quality labels for training which can be burdensome to obtain due to its labor-intensive nature. In this study, we aim to develop a fully automatic artificial intelligence (AI) system, named DeepHeartCT, for accurate and rapid cardiac CTA segmentation based on DL. The proposed system was trained using a large clinical dataset with computer-generated labels to segment various cardiovascular structures including left and right ventricles (LV, RV), left and right atria (LA, RA), and LV myocardium (LVM). This new system was trained directly using high-quality computer labels generated from our previously developed multi-atlas based AI system. In addition, a reverse ranking strategy was proposed to assess the segmentation quality in the absence of manual reference labels. This strategy allowed the new framework to assemble optimal computer-generated labels from a large dataset for effective training of a deep convolutional neural network (CNN). A large clinical cardiac CTA studies (n = 1,064) were used to train and validate our framework. The trained model was then tested on another independent dataset with manual labels (n = 60). The Dice score, Hausdorff distance and mean surface distance were used to quantify the segmentation accuracy. The proposed DeepHeartCT framework yields a high median Dice score of 0.90 [interquartile range (IQR), 0.90-0.91], a low median Hausdorff distance of 7 mm (IQR, 4-15 mm) and a low mean surface distance of 0.80 mm (IQR, 0.57-1.29 mm) across all segmented structures. An additional experiment was conducted to evaluate the proposed DL-based AI framework trained with a small vs. large dataset. The results show our framework also performed well when trained on a small optimal training dataset (n = 110) with a significantly reduced training time. These results demonstrated that the proposed DeepHeartCT framework provides accurate and rapid cardiac CTA segmentation that can be readily generalized for handling large-scale medical imaging applications.

The Future of Cardiac Magnetic Resonance Clinical Trials.

Over the past 2 decades, cardiac magnetic resonance (CMR) has become an essential component of cardiovascular clinical care and contributed to imaging-guided diagnosis and management of coronary artery disease, cardiomyopathy, congenital heart disease, cardio-oncology, valvular, and vascular disease, amongst others. The widespread availability, safety, and capability of CMR to provide corresponding anatomical, physiological, and functional data in 1 imaging session can improve the design and conduct of clinical trials through both a reduction of sample size and provision of important mechanistic data that may augment clinical trial findings. Moreover, prospective imaging-guided strategies using CMR can enhance safety, efficacy, and cost-effectiveness of cardiovascular pathways in clinical practice around the world. As the future of large-scale clinical trial design evolves to integrate personalized medicine, cost-effectiveness, and mechanistic insights of novel therapies, the integration of CMR will continue to play a critical role. In this document, the attributes, limitations, and challenges of CMR's integration into the future design and conduct of clinical trials will also be covered, and recommendations for trialists will be explored. Several prominent examples of clinical trials that test the efficacy of CMR-imaging guided pathways will also be discussed.

Evaluation of Coronary Plaques and Stents with Conventional and Photon-counting CT: Benefits of High-Resolution Photon-counting CT.

PURPOSE: To compare the performance of energy-integrating detector (EID) CT, photon-counting detector CT (PCCT), and high-resolution PCCT (HR-PCCT) for the visualization of coronary plaques and reduction of stent artifacts in a phantom model. MATERIALS AND METHODS: An investigational scanner with EID and PCCT subsystems was used to image a coronary artery phantom containing cylindrical probes simulating different plaque compositions. The phantom was imaged with and without coronary stents using both subsystems. Images were reconstructed with a clinical cardiac kernel and an additional HR-PCCT kernel. Regions of interest were drawn around probes and evaluated for in-plane diameter and a qualitative comparison by expert readers. A linear mixed-effects model was used to compare the diameter results, and a Shrout-Fleiss intraclass correlation coefficient was used to assess consistency in the reader study. RESULTS: Comparing in-plane diameter to the physical dimension for nonstented and stented phantoms, measurements of the HR-PCCT images were more accurate (nonstented: 4.4% ± 1.1 [standard deviation], stented: -9.4% ± 4.6) than EID (nonstented: 15.5% ± 4.0, stented: -19.5% ± 5.8) and PCCT (nonstented: 19.4% ± 2.5, stented: -18.3% ± 4.4). Our analysis of variance found diameter measurements to be different across image groups for both nonstented and stented cases (P < .001). HR-PCCT showed less change on average in percent stenosis due to the addition of a stent (-5.5%) than either EID (+90.5%) or PCCT (+313%). For both nonstented and stented phantoms, observers rated the HR-PCCT images as having higher plaque conspicuity and as being the image type that was least impacted by stent artifacts, with a high level of agreement (interclass correlation coefficient = 0.85). CONCLUSION: Despite increased noise, HR-PCCT images were able to better visualize coronary plaques and reduce stent artifacts compared with EID or PCCT reconstructions.Keywords: CT-Spectral Imaging (Dual Energy), Phantom Studies, Cardiac, Physics, Technology Assessment© RSNA, 2021.

The relationship between systemic inflammation and increased left ventricular mass is partly mediated by noncalcified coronary artery disease burden in psoriasis.

OBJECTIVE: Increased left ventricular (LV) mass is an important precursor to heart failure. Inflammation plays an important role in increasing LV mass. However, the contribution of subclinical coronary artery disease (CAD) to the inflammation-LV mass relationship is unknown. In subjects with psoriasis, a chronic inflammatory skin disease, we evaluated if systemic inflammation assessed by plasma glycoprotein A (GlycA) associated with LV mass measured on coronary CT angiography (CCTA). Additionally, we analyzed whether this relationship was mediated by early CAD assessed as noncalcified coronary burden (NCB). METHODS: We performed an observational longitudinal study of 213 subjects with psoriasis free of known cardiovascular disease, 189 of whom were followed over one year. All participants had GlycA measurements by nuclear magnetic resonance spectroscopy and LV mass and NCB quantified by CCTA. RESULTS: The cohort had a mean age of 50.3 (±12.9) years and 59% were male. There was moderate psoriasis severity and low cardiovascular risk. LV mass increased by GlycA tertiles [1st tertile:24.6 g/m2.7(3.8), 2nd tertile:25.5 g/m2.7(3.8), 3rd tertile:27.7 g/m2.7(5.5), p<0.001]. Both GlycA (ß=0.24, p = 0.001) and NCB (ß=0.50, p<0.001) associated with LV mass in models adjusted for age, sex, hypertension, hypertension therapy, lipid therapy, biologic therapy for psoriasis, waist:hip ratio, psoriasis disease duration and severity. In multivariable-adjusted mediation analyses, NCB accounted for 32% of the GlycA-LV mass relationship. Finally, over one year, change in NCB independently associated with change in LV mass (ß=0.25, p = 0.002). CONCLUSIONS: Both systemic inflammation and coronary artery NCB were associated with LV mass beyond cardiovascular risk factors in psoriasis. Furthermore, a substantial proportion of the inflammatory-LV mass relationship was mediated by NCB. These findings underscore the possible contribution of early coronary artery disease to the relationship between systemic inflammation and LV mass.

Stress CMR in patients with obesity: insights from the Stress CMR Perfusion Imaging in the United States (SPINS) registry.

AIMS: Non-invasive assessment and risk stratification of coronary artery disease in patients with large body habitus is challenging. We aim to examine whether body mass index (BMI) modifies the prognostic value and diagnostic utility of stress cardiac magnetic resonance imaging (CMR) in a multicentre registry. METHODS AND RESULTS: The SPINS Registry enrolled consecutive intermediate-risk patients who presented with a clinical indication for stress CMR in the USA between 2008 and 2013. Baseline demographic data including BMI, CMR indices, and ratings of study quality were collected. Primary outcome was defined by a composite of cardiovascular death and non-fatal myocardial infarction. Of the 2345 patients with available BMI included in the SPINS cohort, 1177 (50%) met criteria for obesity (BMI ≥ 30) with 531 (23%) at or above Class 2 obesity (BMI ≥ 35). In all BMI categories, >95% of studies were of diagnostic quality for cine, perfusion, and late gadolinium enhancement (LGE) sequences. At a median follow-up of 5.4 years, those without ischaemia and LGE experienced a low annual rate of hard events (<1%), across all BMI strata. In patients with obesity, both ischaemia [hazard ratio (HR): 2.14; 95% confidence interval (CI): 1.30-3.50; P = 0.003] and LGE (HR: 3.09; 95% CI: 1.83-5.22; P < 0.001) maintained strong adjusted association with the primary outcome in a multivariable Cox regression model. Downstream referral rates to coronary angiography, revascularization, and cost of care spent on ischaemia testing did not significantly differ within the BMI categories. CONCLUSION: In this large multicentre registry, elevated BMI did not negatively impact the diagnostic quality and the effectiveness of risk stratification of patients referred for stress CMR.

Improving multi-atlas cardiac structure segmentation of computed tomography angiography: A performance evaluation based on a heterogeneous dataset.

Multi-atlas based segmentation is an effective technique that transforms a representative set of atlas images and labels into a target image for structural segmentation. However, a significant limitation of this approach relates to the fact that the atlas and the target images need to be similar in volume orientation, coverage, or acquisition protocols in order to prevent image misregistration and avoid segmentation fault. In this study, we aim to evaluate the impact of using a heterogeneous Computed Tomography Angiography (CTA) dataset on the performance of a multi-atlas cardiac structure segmentation framework. We propose a generalized technique based upon using the Simple Linear Iterative Clustering (SLIC) supervoxel method to detect a bounding box region enclosing the heart before subsequent cardiac structure segmentation. This technique facilitates our framework to process CTA datasets acquired from distinct imaging protocols and to improve its segmentation accuracy and speed. In a four-way cross comparison based on 60 CTA studies from our institution and 60 CTA datasets from the Multi-Modality Whole Heart Segmentation MICCAI challenge, we show that the proposed framework performs well in segmenting seven different cardiac structures based upon interchangeable atlas and target datasets acquired from different imaging settings. For the overall results, our automated segmentation framework attains a median Dice, mean distance, and Hausdorff distance of 0.88, 1.5 mm, and 9.69 mm over the entire datasets. The average processing time was 1.55 min for both datasets. Furthermore, this study shows that it is feasible to exploit heterogenous datasets from different imaging protocols and institutions for accurate multi-atlas cardiac structure segmentation.

Simultaneous Multi-Structure Segmentation of the Heart and Peripheral Tissues in Contrast Enhanced Cardiac Computed Tomography Angiography.

Contrast enhanced cardiac computed tomography angiography (CTA) is a prominent imaging modality for diagnosing cardiovascular diseases non-invasively. It assists the evaluation of the coronary artery patency and provides a comprehensive assessment of structural features of the heart and great vessels. However, physicians are often required to evaluate different cardiac structures and measure their size manually. Such task is very time-consuming and tedious due to the large number of image slices in 3D data. We present a fully automatic method based on a combined multi-atlas and corrective segmentation approach to label the heart and its associated cardiovascular structures. This method also automatically separates other surrounding intrathoracic structures from CTA images. Quantitative assessment of the proposed method is performed on 36 studies with a reference standard obtained from expert manual segmentation of various cardiac structures. Qualitative evaluation is also performed by expert readers to score 120 studies of the automatic segmentation. The quantitative results showed an overall Dice of 0.93, Hausdorff distance of 7.94 mm, and mean surface distance of 1.03 mm between automatically and manually segmented cardiac structures. The visual assessment also attained an excellent score for the automatic segmentation. The average processing time was 2.79 minutes. Our results indicate the proposed automatic framework significantly improves accuracy and computational speed in conventional multi-atlas based approach, and it provides comprehensive and reliable multi-structural segmentation of CTA images that is valuable for clinical application.