Systemic and Mucosal Immunogenicity of Monovalent XBB.1.5-Adapted COVID-19 mRNA Vaccines in Patients with Inflammatory Bowel Disease.

Recently updated COVID-19 mRNA vaccines encode the spike protein of the omicron subvariant XBB.1.5 and are recommended for patients with inflammatory bowel disease (IBD) on immunosuppressive treatment. Nonetheless, their immunogenicity in patients with IBD against rapidly expanding virus variants remains unknown. This prospective multicenter cohort study is the first study to investigate the immunogenicity of XBB.1.5-adapted vaccines in patients with IBD. Systemic and mucosal antibodies targeting the receptor-binding domains (RBDs) of the omicron subvariants XBB.1.5, EG.5.1, and BA.2.86, as well as their neutralization were quantified before and two to four weeks after vaccination with monovalent XBB.1.5-adapted mRNA vaccines. Vaccination increased levels of serum anti-RBD IgG targeting XBB.1.5, EG.5.1, and BA.2.86 (1.9-fold, 1.8-fold, and 2.6-fold, respectively) and enhanced corresponding neutralization responses (2.3-fold, 3.1-fold, and 3.5-fold, respectively). Following vaccination, anti-TNF-treated patients had reduced virus neutralization compared to patients on treatments with other cellular targets. 11.1% and 16.7% of patients lacked EG.5.1 and BA.2.86 neutralization, respectively; all these patients received anti-TNF treatment. At mucosal sites, vaccination induced variant-specific anti-RBD IgG but failed to induce RBD-targeting IgA. Our findings provide a basis for future vaccine recommendations while highlighting the importance of frequent booster vaccine adaptation and the need for mucosal vaccination strategies in patients with IBD.

Role of Physical Activity and Sedentary Behaviors on Vascular and Myocardial Structure and Function in Type 1 Diabetes.

OBJECTIVE: To estimate associations between physical activity and sedentary behaviors and early markers of cardiovascular diseases in adolescents with and without type 1 diabetes. STUDY DESIGN: Cross-sectional data stem from the CARdiovascular Disease risk in pEdiatric type 1 diAbetes (CARDEA) study, a study investigating early cardiovascular disease development in 100 adolescents with type 1 diabetes recruited at Sainte-Justine University Hospital Diabetes Clinic and 97 healthy adolescents without diabetes (14-18 years), in Montreal, Canada. Outcomes included arterial stiffness by pulse-wave velocity, endothelial function (velocity time integral) by flow-mediated dilation test, and cardiac magnetic resonance imaging markers. Moderate-to-vigorous physical activity (MVPA) and sedentary time were estimated by accelerometry and leisure screen time by questionnaire. We estimated multivariable linear regression models stratified by group. RESULTS: In adolescents with type 1 diabetes, 10-minutes daily increase in MVPA was associated with 3.69 g/m (95% CI: -1.16; 8.54) higher left ventricular (LV) mass/height and 1-hour increase in device-measured sedentary time with 0.68 mm (0.20; 1.16) higher wall thickness but only in those with glycated hemoglobin ≤7.5%. In healthy adolescents, a 10-minute increase in MVPA was associated with 1.32 g/m (-0.03; 2.66) higher LV mass/height. Every 1-hour increase in sedentary time was associated with -1.82 cm (-3.25; -0.39) lower velocity time integral, -2.99 g/m (-5.03; -0.95) lower LV mass/height, and -0.47 mm (-0.82; -0.12) lower wall thickness. CONCLUSIONS: Being active and limiting sedentary time appears beneficial for cardiac structure and endothelial function in healthy adolescents; however, adequate glycemic control combined with higher levels of MVPA may be required for adolescents with type 1 diabetes to overcome the impact of diabetes.

Clinical utility of a rapid two-dimensional balanced steady-state free precession sequence with deep learning reconstruction.

BACKGROUND: Cardiovascular magnetic resonance (CMR) cine imaging is still limited by long acquisition times. This study evaluated the clinical utility of an accelerated two-dimensional (2D) cine sequence with deep learning reconstruction (Sonic DL) to decrease acquisition time without compromising quantitative volumetry or image quality. METHODS: A sub-study using 16 participants was performed using Sonic DL at two different acceleration factors (8× and 12×). Quantitative left-ventricular volumetry, function, and mass measurements were compared between the two acceleration factors against a standard cine method. Following this sub-study, 108 participants were prospectively recruited and imaged using a standard cine method and the Sonic DL method with the acceleration factor that more closely matched the reference method. Two experienced clinical readers rated images based on their diagnostic utility and performed all image contouring. Quantitative contrast difference and endocardial border sharpness were also assessed. Left- and right-ventricular volumetry, left-ventricular mass, and myocardial strain measurements were compared between cine methods using Bland-Altman plots, Pearson's correlation, and paired t-tests. Comparative analysis of image quality was measured using Wilcoxon-signed-rank tests and visualized using bar graphs. RESULTS: Sonic DL at an acceleration factor of 8 more closely matched the reference cine method. There were no significant differences found across left ventricular volumetry, function, or mass measurements. In contrast, an acceleration factor of 12 resulted in a 6% (5.51/90.16) reduction of measured ejection fraction when compared to the standard cine method and a 4% (4.32/88.98) reduction of measured ejection fraction when compared to Sonic DL at an acceleration factor of 8. Thus, Sonic DL at an acceleration factor of 8 was chosen for downstream analysis. In the larger cohort, this accelerated cine sequence was successfully performed in all participants and significantly reduced the acquisition time of cine images compared to the standard 2D method (reduction of 37% (5.98/16) p < 0.0001). Diagnostic image quality ratings and quantitative image quality evaluations were statistically not different between the two methods (p > 0.05). Left- and right-ventricular volumetry and circumferential and radial strain were also similar between methods (p > 0.05) but left-ventricular mass and longitudinal strain were over-estimated using the proposed accelerated cine method (mass over-estimated by 3.36 g/m2, p < 0.0001; longitudinal strain over-estimated by 1.97%, p = 0.001). CONCLUSION: This study found that an accelerated 2D cine method with DL reconstruction at an acceleration factor of 8 can reduce CMR cine acquisition time by 37% (5.98/16) without significantly affecting volumetry or image quality. Given the increase of scan time efficiency, this undersampled acquisition method using deep learning reconstruction should be considered for routine clinical CMR.

Impact of cannabidiol on myocardial recovery in patients with acute myocarditis: Rationale & design of the ARCHER trial.

AIMS: Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). METHODS AND RESULTS: We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. CONCLUSIONS: The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.

Scan With Me: A Train-the-Trainer Program to Upskill MRI Personnel in Low- and Middle-Income Countries.

PURPOSE: Access to MRI in low- and middle-income countries (LMICs) remains among the poorest in the world. The lack of skilled MRI personnel exacerbates access gaps, reinforcing long-standing health disparities. The Scan With Me (SWiM) program aims to sustainably create a network of highly skilled MRI technologists in LMICs who will facilitate the transfer of MRI knowledge and skills to their peers and contribute to the implementation of highly valuable imaging protocols for effective clinical and research use. METHODS: The program introduces a case-based curriculum designed using a novel train-the-trainer approach, integrated with peer-collaborative learning to upskill practicing MRI technologists in LMICs. The 6-week curriculum uses the teach-try-use approach, which combines self-paced didactic lectures covering the basics of MR image acquisition (teach) with hands-on expert-guided scanning experience (try) and the implementation of protocols tailored to provide the best possible images on their infrastructures (use). Each program includes research translation skills training using an established advanced MRI technique relevant to LMICs. A pilot program focused on cardiac MRI (CMR) was conducted to assess the program's curriculum, delivery, and evaluation methods. RESULTS: Forty-three MRI technologists from 16 LMICs participated in the pilot CMR program and, over the course of the training, implemented optimized CMR protocols that reduced acquisition times while improving image quality. The training resources and scanner-specific standardized protocols are published openly for public use in an online repository. In general, at the end of the program, learners reported considerable improvements in CMR knowledge and skills. All respondents to the program evaluation survey agreed to recommend the program to their colleagues, while 87% indicated interest in returning to help train others. CONCLUSIONS: The SWiM program is the first master class in MRI acquisition for practicing imaging technologists in LMICs. The program holds the potential to help reduce disparities in MRI expertise and access. The support of the MRI community, imaging societies, and funding agencies will increase its reach and further its impact in democratizing MRI.

Cardiovascular Magnetic Resonance Reference Ranges From the Healthy Hearts Consortium.

BACKGROUND: The absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care. OBJECTIVES: This paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date. METHODS: CMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established ventricular and atrial metrics were extracted and stratified by age, sex, and ethnicity. Variations by segmentation method, scanner vendor, and magnet strength were examined. Reference ranges are reported as 95% prediction intervals. RESULTS: The sample included 4,452 (49.0%) men and 4,636 (51.0%) women with average age of 61.1 ± 12.9 years (range: 18-83 years). Among these, 7,424 (81.7%) were from White, 510 (5.6%) South Asian, 478 (5.3%) mixed/other, 341 (3.7%) Black, and 335 (3.7%) Chinese ethnicities. Images were acquired using 1.5-T (n = 8,779; 96.6%) and 3.0-T (n = 309; 3.4%) scanners from Siemens (n = 8,299; 91.3%), Philips (n = 498; 5.5%), and GE (n = 291, 3.2%). CONCLUSIONS: This work represents a resource with healthy CMR-derived volumetric reference ranges ready for clinical implementation.

MRI of cardiac involvement in COVID-19.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to a diverse pattern of myocardial injuries, including myocarditis, which is linked to adverse outcomes in patients. Research indicates that myocardial injury is associated with higher mortality in hospitalized severe COVID-19 patients (75.8% vs 9.7%). Cardiovascular Magnetic Resonance (CMR) has emerged as a crucial tool in diagnosing both ischaemic and non-ischaemic myocardial injuries, providing detailed insights into the impact of COVID-19 on myocardial tissue and function. This review synthesizes existing studies on the histopathological findings and CMR imaging patterns of myocardial injuries in COVID-19 patients. CMR imaging has revealed a complex pattern of cardiac damage in these patients, including myocardial inflammation, oedema, fibrosis, and ischaemic injury, due to coronary microthrombi. This review also highlights the role of LLC criteria in diagnosis of COVID-related myocarditis and the importance of CMR in detecting cardiac complications of COVID-19 in specific groups, such as children, manifesting multisystem inflammatory syndrome in children (MIS-C) and athletes, as well as myocardial injuries post-COVID-19 infection or following COVID-19 vaccination. By summarizing existing studies on CMR in COVID-19 patients and highlighting ongoing research, this review contributes to a deeper understanding of the cardiac impacts of COVID-19. It emphasizes the effectiveness of CMR in assessing a broad spectrum of myocardial injuries, thereby enhancing the management and prognosis of patients with COVID-19 related cardiac complications.

Heterogeneity of coronary vascular function and myocardial oxygenation in women with angina and non-obstructive coronary artery disease.

AIMS: Women with angina and non-obstructive coronary artery disease (ANOCA) have a heightened risk for cardiovascular events, and the pathophysiology for ischaemic symptoms may be related to alterations in microvascular structure and function. We examined the use of breathing-enhanced oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) using vasoactive breathing manoeuvres to assess myocardial oxygenation in women with ANOCA. METHODS AND RESULTS: We recruited women (aged 40-65 years) from two sites in Canada who presented to healthcare with persistent retrosternal chest pain and found to have ANOCA, or without a history of cardiovascular disease. All participants were scanned using a clinical 3T MRI scanner, and OS-CMR images were acquired over a breath hold following paced hyperventilation to measure global and regional measurements of heterogeneity. Fifty-four women with ANOCA (age: 55 ± 6.2 years) and 48 healthy controls (age: 51.2 ± 4.8 years) were recruited. There was no significant difference in volume, function, mass, or global myocardial oxygenation between the two groups [mean %Δ in signal intensity (SI): 4.9 (±7.3) vs. 4.5 (±10.1), P = 0.82]. Women with ANOCA had higher regional variations in myocardial oxygenation in circumferential [median %Δ in SI: 5.1 (2.0-7.6) vs. 2.2 (1.4-3.5), P = 0.0004] and longitudinal directions [median %Δ in SI: 11.4 (5.4-16.7) vs. 6.0 (3.0-7.0), P = 0.001], which remained present in a multivariate model. CONCLUSION: Heterogeneous myocardial oxygenation may explain ischaemic symptoms without any associated epicardial obstructive coronary artery disease. Regional variations in myocardial oxygenation on OS-CMR could serve as an important diagnostic marker for microvascular dysfunction in women with ANOCA.

Meta-Analysis of Normal Reference Values for Right and Left Ventricular Quantification by Cardiovascular Magnetic Resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) reference values are relied upon to accurately diagnose left ventricular (LV) and right ventricular (RV) pathologies. To date, reference values have been derived from modest sample sizes with limited patient diversity and attention to 1 but not both commonly used tracing techniques for papillary muscles and trabeculations. We sought to overcome these limitations by meta-analyzing normal reference values for CMR parameters stemming from multiple countries, vendors, analysts, and patient populations. METHODS: We comprehensively extracted published and unpublished data from studies reporting CMR parameters in healthy adults. A steady-state free-precession short-axis stack at 1.5T or 3T was used to trace either counting the papillary muscles and trabeculations in the LV volume or mass. We used a novel Bayesian hierarchical meta-analysis model to derive the pooled lower and upper reference values for each CMR parameter. Our model accounted for the expected differences between tracing techniques by including informative prior distributions from a large external data set. RESULTS: A total of 254 studies from 25 different countries were systematically reviewed, representing 12 812 healthy adults, of which 52 were meta-analyzed. For LV parameters counting papillary muscles and trabeculations in the LV volume, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 52% to 73% and 54% to 75%, LV end-diastolic volume index of 60 to 109 and 56 to 96 mL/m2, LV end-systolic volume index of 18 to 45 and 16 to 38 mL/m2, and LV mass index of 41 to 76 and 33 to 57 g/m2. For LV parameters counting papillary muscles and trabeculations in the LV mass, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 57% to 74% and 57% to 75%, LV end-diastolic volume index of 60 to 97 and 55 to 88 mL/m2, LV end-systolic volume index of 18 to 37 and 15 to 34 mL/m2, and LV mass index of 50 to 83 and 38 to 65 g/m2. For RV parameters, pooled normative reference ranges in men and women, respectively, were as follows: RV ejection fraction of 47% to 68% and 49% to 71%, RV end-diastolic volume index of 64 to 115 and 57 to 99 mL/m2, RV end-systolic volume index of 23 to 52 and 18 to 42 mL/m2, and RV mass index of 14 to 29 and 13 to 25 g/m2. CONCLUSIONS: Our Bayesian hierarchical meta-analysis provides normative reference values for CMR parameters of LV and RV size, systolic function, and mass, encompassing both tracing techniques across a diverse multinational sample of healthy men and women.

Automated Data Transformation and Feature Extraction for Oxygenation-Sensitive Cardiovascular Magnetic Resonance Images.

Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) is a novel, powerful tool for assessing coronary function in vivo. The data extraction and analysis however are labor-intensive. The objective of this study was to provide an automated approach for the extraction, visualization, and biomarker selection of OS-CMR images. We created a Python-based tool to automate extraction and export of raw patient data, featuring 3336 attributes per participant, into a template compatible with common data analytics frameworks, including the functionality to select predictive features for the given disease state. Each analysis was completed in about 2 min. The features selected by both ANOVA and MIC significantly outperformed (p < 0.001) the null set and complete set of features in two datasets, with mean AUROC scores of 0.89eatures f 0.94lete set of features in two datasets, with mean AUROC scores that our tool is suitable for automated data extraction and analysis of OS-CMR images.

Inter-scanner comparability of Z-scores for native myocardial T1 and T2 mapping.

BACKGROUND: Cardiovascular Magnetic Resonance (CMR) native T1 and T2 mapping serve as robust, contrast-agent-free diagnostic tools, but hardware- and software-specific sources of variability limit the generalizability of data across CMR platforms, consequently limiting the interpretability of patient-specific parametric data. Z-scores are used to describe the relationship of observed values to the mean results as obtained in a sufficiently large normal sample. They have been successfully used to describe the severity of quantifiable abnormalities in medicine, specifically in children and adolescents. The objective of this study was to observe whether z-scores can improve the comparability of T1 and T2 mapping values across CMR scanners, field strengths, and sequences from different vendors in the same participant rather than different participants (as seen in previous studies). METHODS: Fifty-one healthy volunteers (26 men/25 women, mean age = 43 ± 13.51) underwent three CMR exams on three different scanners, using a Modified Look-Locker Inversion Recovery (MOLLI) 5-(3)- 3 sequence to quantify myocardial T1. For T2 mapping, a True Fast Imaging with steady-state free precession (TRUFI) sequence was used on a 3 T Skyra™ (Siemens), and a T2 Fast Spin Echo (FSE) sequence was used on 1.5 T Artist™ (GE) and 3.0 T Premier™ (GE) scanners. The averages of basal and mid-ventricular short axis slices were used to derive means and standard deviations of global mapping values. We used intra-class comparisons (ICC), repeated measures ANOVA, and paired Student's t-tests for statistical analyses. RESULTS: There was a significant improvement in intra-subject comparability of T1 (ICC of 0.11 (95% CI= -0.018, -0.332) vs 0.78 (95% CI= 0.650, 0.866)) and T2 (ICC of 0.35 (95% CI= -0.053, 0.652) vs 0.83 (95% CI= 0.726, 0.898)) when using z-scores across all three scanners. While the absolute global T1 and T2 values showed a statistically significant difference between scanners (p < 0.001), no such differences were identified using z-scores (T1z: p = 0.771; T2z: p = 0.985). Furthermore, when images were not corrected for motion, T1 z-scores showed significant inter-scanner variability (p < 0.001), resolved by motion correction. CONCLUSION: Employing z-scores for reporting myocardial T1 and T2 removes the variation of quantitative mapping results across different MRI systems and field strengths, improving the clinical utility of myocardial tissue characterization in patients with suspected myocardial disease.

The reproducibility of breathing maneuvers as a vasoactive stimulus in the heart: an oxygenation-sensitive resonance imaging study.

BACKGROUND: Endothelial dysfunction and impaired oxygenation of the heart is a hallmark of several diseases, including coronary artery disease, hypertension, diabetes, and sleep apnea. Recent studies indicate that oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging combined with breathing maneuvers may allow for assessing coronary vascular responsiveness as a marker for coronary vascular function in various clinical settings. However, despite the use of OS-CMR in evaluating tissue oxygenation, the reproducibility of these standardized, combined breathing maneuvers as a vasoactive stimulus has yet to be systematically assessed or validated. In this study, we aimed to assess the reproducibility of vasoactive breathing maneuvers to assess vascular function in a population of healthy volunteers. METHODS: Eighteen healthy volunteers were recruited for the study. Inclusion criteria were an age over 18 years and absence of any evidence or knowledge of cardiovascular, neurological, or pulmonary disease. MRI was performed on a clinical 3 T MRI system (MAGNETOM Skyra, Siemens Healthineers, Erlangen, Germany). The OS-CMR acquisition was performed as previously described (1 min hyperventilation followed by a maximal, voluntary breath-hold). Standard statistical tests were performed as appropriate. RESULTS: Data from 18 healthy subjects was analyzed. The healthy volunteers had a mean age of 42 ± 15 years and a mean BMI of 25.4 ± 2.8 kg/m2, with an average heart rate of 72 ± 11 beats per minute, and ten of whom (56%) were female. There were no significant differences between global myocardial oxygenation (%[Formula: see text] SI) after hyperventilation (HV1: - 7.82 [Formula: see text] 5.2; HV2: - 7.89 [Formula: see text] 6.4, p = 0.9) or breath-hold (BH1: 5.34 [Formula: see text] 3.1; BH2: 6.0 [Formula: see text] 3.3, p = 0.5) between the repeated breathing maneuvers. The Bland-Altman analysis showed good agreement (bias: 0.074, SD of bias: 2.93). CONCLUSION: We conclude that in healthy individuals, the myocardial oxygenation response to a standardized breathing maneuver with hyperventilation and a voluntary breath-hold is consistent and highly reproducible. These results corroborate previous evidence for breathing-enhanced OS-CMR as a robust test for coronary vascular function.

Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease.

BACKGROUND: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD). OBJECTIVES: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD. METHODS: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information. RESULTS: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT. CONCLUSIONS: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT.

Prognostic value of negative stress cardiac magnetic resonance imaging in patients with moderate-severe coronary artery stenosis.

Objective: This study aims to evaluate the prognostic value of stress cardiac magnetic resonance (CMR) without inducible ischemia in a real-world cohort of patients with known severe coronary artery stenosis. Background: The prognosis of patients with severe coronary artery stenosis and without inducible ischemia using stress CMR remains uncertain, even though its identification of functionally significant coronary artery disease (CAD) is excellent. Materials and methods: Patients without inducible ischemia and known CAD who underwent stress CMR between February 2015 and December 2016 were included in this retrospective study. These patients were divided into two groups: group 1 with stenosis of 50%-75% and group 2 with stenosis of >75%. The primary endpoint was defined as the occurrence of a major adverse cardiovascular event (MACE) [cardiac death, non-fatal myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]. Results: Real-world data collected from 169 patients with a median age of 69 (60-75) years were included. The median follow-up was 5.5 (IQR 4.1-6.6) years. Events occurred after a mean time of 3.0 ± 2.2 years in group 1 and 3.7 ± 2.0 years in group 2 (p = 0.35). Sixteen (18.8%) patients in group 1 and 23 (27.4%) patients in group 2 suffered from MACE without a significant difference between the two groups (p = 0.33). In group 2, one cardiac death (1.2%), seven non-fatal MI (8.3%), 15 PCI (17.9%), and one CABG (1.2%) occurred. Conclusion: The findings of this pilot study suggest that long-term outcomes in a real-world patient cohort with known severe and moderate coronary artery stenosis but without inducible ischemia were similar. Stress CMR may provide valuable risk stratification in patients with angiographically significant but hemodynamically non-obstructive coronary lesions.

Microvascular Dysfunction as a Possible Link Between Heart Failure and Cognitive Dysfunction.

BACKGROUND: Microvascular function in the brain and heart may play an important role in the course of patients with heart failure (HF), but its relationship with ventricular and cognitive function is not well understood. We hypothesized that microvascular function in HF is closely related to both, cardiac and cognitive function. METHODS: In healthy controls and symptomatic patients with HF (New York Heart Association functional class II or III), we used oxygenation-sensitive magnetic resonance imaging during a standardized breathing maneuver to determine the cerebral oxygenation reserve and the myocardial oxygenation reserve (MORE) as markers for microvascular function. A stepwise multivariable linear regression was performed to determine the variables that best predict changes in cerebral oxygenation reserve and MORE. We also measured cognitive function using the Montreal Cognitive Assessment test. RESULTS: Twenty patients with HF (age 64.4±8.3 years; 50% female sex), and 21 healthy controls (age 55.0±5.1 years; 62% female sex) were included in the analysis. In patients with HF, cerebral oxygenation reserve and MORE were lower than in healthy controls (MORE, -0.1±3.3 versus 5.0±4.2, cerebral oxygenation reserve: 0.43±0.47 versus 1.21±0.60, respectively) as were Montreal Cognitive Assessment score results (HF, 23.9±3.7; healthy, 27.8±1.5; P=0.002). The Montreal Cognitive Assessment score in patients was correlated with cardiac output (r=0.55, P=0.011) and MORE (r=0.46, P=0.040). In addition to the presence of HF, significant predictors of cerebral and myocardial oxygenation reserve were cardiac output and end-diastolic volume, respectively. CONCLUSIONS: Our results indicate that heart failure is an independent predictor of coronary and cerebral microvascular dysfunction as defined by a reduced response to a vasodilatory breathing maneuver. This impaired response was associated with reduced cognitive function.

Viral Myocarditis and Dilated Cardiomyopathy as a Consequence-Changing Insights from Advanced Imaging.

Advancements in quantitative cardiac magnetic resonance (CMR) have revolutionized the diagnosis and management of viral myocarditis. With the addition of T1 and T2 mapping parameters in the updated Lake Louise Criteria, CMR can diagnose myocarditis with superior diagnostic accuracy compared with endomyocardial biopsy, especially in stable patients. Additionally, the unique value of CMR tissue characterization continues to improve the diagnosis and risk stratification of myocarditis. This review will discuss new and ongoing developments in cardiovascular imaging and its application to noninvasive diagnosis, prognostication, and management of viral myocarditis and its complications.

STAR SIGN study: Evaluation of COVID-19 vaccine efficacy against the SARS-CoV-2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease.

BACKGROUND: Vaccine-elicited immune responses are impaired in patients with inflammatory bowel disease (IBD) treated with anti-TNF biologics. AIMS: To assess vaccination efficacy against the novel omicron sublineages BQ.1.1 and XBB.1.5 in immunosuppressed patients with IBD. METHODS: This prospective multicentre case-control study included 98 biologic-treated patients with IBD and 48 healthy controls. Anti-spike IgG concentrations and surrogate neutralisation against SARS-CoV-2 wild-type, BA.1, BA.5, BQ.1.1, and XBB.1.5 were measured at two different time points (2-16 weeks and 22-40 weeks) following third dose vaccination. Surrogate neutralisation was based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Primary outcome was surrogate neutralisation against tested SARS-CoV-2 sublineages. Secondary outcomes were proportions of participants with insufficient surrogate neutralisation, impact of breakthrough infection, and correlation of surrogate neutralisation with anti-spike IgG concentration. RESULTS: Surrogate neutralisation against all tested sublineages was reduced in patients with IBD who were treated with anti-TNF biologics compared to patients treated with non-anti-TNF biologics and healthy controls (each p ≤ 0.001) at visit 1. Anti-TNF therapy (odds ratio 0.29 [95% CI 0.19-0.46]) and time since vaccination (0.85 [0.72-1.00]) were associated with low, and mRNA-1273 vaccination (1.86 [1.12-3.08]) with high wild-type surrogate neutralisation in a ß-regression model. Accordingly, higher proportions of patients treated with anti-TNF biologics had insufficient surrogate neutralisation against omicron sublineages at visit 1 compared to patients treated with non-anti-TNF biologics and healthy controls (each p ≤ 0.015). Surrogate neutralisation against all tested sublineages decreased over time but was increased by breakthrough infection. Anti-spike IgG concentrations correlated with surrogate neutralisation. CONCLUSIONS: Patients with IBD who are treated with anti-TNF biologics show impaired neutralisation against novel omicron sublineages BQ.1.1 and XBB.1.5 and may benefit from prioritisation for future variant-adapted vaccines.

CLDN18.2 BiTE Engages Effector and Regulatory T Cells for Antitumor Immune Response in Preclinical Models of Pancreatic Cancer.

BACKGROUND & AIMS: BiTE (bispecific T-cell engager) immune therapy has demonstrated clinical activity in multiple tumor indications, but its influence in the tumor microenvironment remains unclear. CLDN18.2 is overexpressed in solid tumors including gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC), both of which are characterized by the presence of immunosuppressive cells, including regulatory T cells (Tregs) and few effector T cells (Teffs). METHODS: We evaluated the activity of AMG 910, a CLDN18.2-targeted half-life extended (HLE) BiTE molecule, in GC and PDAC preclinical models and cocultured Tregs and Teffs in the presence of CLDN18.2-HLE-BiTE. RESULTS: AMG 910 induced potent, specific cytotoxicity in GC and PDAC cell lines. In GSU and SNU-620 GC xenograft models, AMG 910 engaged human CD3+ T cells with tumor cells, resulting in significant antitumor activity. AMG 910 monotherapy, in combination with a programmed death-1 (PD-1) inhibitor, suppressed tumor growth and enhanced survival in an orthotopic Panc4.14 PDAC model. Moreover, Treg infusion enhanced the antitumor efficacy of AMG 910 in the Panc4.14 model. In syngeneic KPC models of PDAC, treatment with a mouse surrogate CLDN18.2-HLE-BiTE (muCLDN18.2-HLE-BiTE) or the combination with an anti-PD-1 antibody significantly inhibited tumor growth. Tregs isolated from mice bearing KPC tumors that were treated with muCLDN18.2-HLE-BiTE showed decreased T cell suppressive activity and enhanced Teff cytotoxic activity, associated with increased production of type I cytokines and expression of Teff gene signatures. CONCLUSIONS: Our data suggest that BiTE molecule treatment converts Treg function from immunosuppressive to immune enhancing, leading to antitumor activity in immunologically "cold" tumors.

Predictors of persistent symptoms after mRNA SARS-CoV-2 vaccine-related myocarditis (myovacc registry).

Aims: Epidemiological surveillance has raised safety concerns for mRNA SARS-CoV-2-vaccination-related myocarditis. We aimed to analyze epidemiological, clinical and imaging findings associated with clinical outcomes in these patients in an international multi-center registry (NCT05268458). Methods and results: Patients with clinical and CMR diagnosis of acute myocarditis within 30 days after mRNA SARS-CoV-2-vaccination were included from five centers in Canada and Germany between 05/21 and 01/22. Clinical follow-up on persistent symptoms was collected. We enrolled 59 patients (80% males, mean age 29 years) with CMR-derived mild myocarditis (hs-Troponin-T 552 [249-1,193] ng/L, CRP 28 [13-51] mg/L; LVEF 57 ± 7%, LGE 3 [2-5] segments). Most common symptoms at baseline were chest pain (92%) and dyspnea (37%). Follow-up data from 50 patients showed overall symptomatic burden improvement. However, 12/50 patients (24%, 75% females, mean age 37 years) reported persisting symptoms (median interval 228 days) of chest pain (n = 8/12, 67%), dyspnea (n = 7/12, 58%), with increasing occurrence of fatigue (n = 5/12, 42%) and palpitations (n = 2/12, 17%). These patients had initial lower CRP, lower cardiac involvement in CMR, and fewer ECG changes. Significant predictors of persisting symptoms were female sex and dyspnea at initial presentation. Initial severity of myocarditis was not associated with persisting complaints. Conclusion: A relevant proportion of patients with mRNA SARS-CoV-2-vaccination-related myocarditis report persisting complaints. While young males are usually affected, patients with persisting symptoms were predominantly females and older. The severity of the initial cardiac involvement not predicting these symptoms may suggest an extracardiac origin.