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1.
Br J Radiol ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656976

RESUMEN

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% versus 9.7%). Cardiovascular Magnetic Resonance (CMR) has emerged as a crucial tool in diagnosing both ischemic and non-ischemic 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 ischemic 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 (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 (Figure of summarized illustration of CMR findings of cardiac involvement in COVID-19).

2.
Artículo en Inglés | MEDLINE | ID: mdl-38613554

RESUMEN

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.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38546135

RESUMEN

AIMS: Women with angina and non-obstructive coronary artery disease (ANOCA) have a heightened risk for cardiovascular events, and the pathophysiology for ischemic 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 maneuvers 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, 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 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 ischemic 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.

4.
Circ Cardiovasc Imaging ; 17(2): e016090, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38377242

RESUMEN

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.


Asunto(s)
Ventrículos Cardíacos , Función Ventricular Izquierda , Adulto , Masculino , Humanos , Femenino , Valores de Referencia , Teorema de Bayes , Ventrículos Cardíacos/diagnóstico por imagen , Volumen Sistólico , Músculos Papilares , Espectroscopía de Resonancia Magnética , Imagen por Resonancia Cinemagnética , Reproducibilidad de los Resultados
5.
Artículo en Inglés | MEDLINE | ID: mdl-38229001

RESUMEN

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.

6.
J Cardiovasc Magn Reson ; 26(1): 100004, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38211657

RESUMEN

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.

7.
J Cardiovasc Magn Reson ; 25(1): 81, 2023 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-38151725

RESUMEN

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.


Asunto(s)
Hiperventilación , Imagen por Resonancia Cinemagnética , Humanos , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Masculino , Hiperventilación/diagnóstico por imagen , Reproducibilidad de los Resultados , Imagen por Resonancia Cinemagnética/métodos , Valor Predictivo de las Pruebas , Corazón
8.
J Am Coll Cardiol ; 82(19): 1828-1838, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37914512

RESUMEN

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.


Asunto(s)
Enfermedad de la Arteria Coronaria , Imagen de Perfusión Miocárdica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peso Corporal , Constricción Patológica , Medios de Contraste , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Gadolinio , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Imagen de Perfusión Miocárdica/métodos , Perfusión , Valor Predictivo de las Pruebas , Estudios Prospectivos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Vasodilatadores
9.
Front Cardiovasc Med ; 10: 1264374, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37868771

RESUMEN

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.

10.
Circ Heart Fail ; 16(11): e010117, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37750336

RESUMEN

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.


Asunto(s)
Disfunción Cognitiva , Insuficiencia Cardíaca , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Corazón , Miocardio , Imagen por Resonancia Magnética , Disfunción Cognitiva/diagnóstico , Volumen Sistólico
11.
Heart Fail Clin ; 19(4): 445-459, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37714586

RESUMEN

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.


Asunto(s)
Cardiomiopatía Dilatada , Miocarditis , Humanos , Cardiomiopatía Dilatada/diagnóstico por imagen , Miocarditis/diagnóstico por imagen , Corazón , Diagnóstico por Imagen , Cateterismo Cardíaco
12.
Aliment Pharmacol Ther ; 58(7): 678-691, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37571863

RESUMEN

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.


Asunto(s)
COVID-19 , Enfermedades Inflamatorias del Intestino , Humanos , Vacunas contra la COVID-19/uso terapéutico , SARS-CoV-2 , Estudios de Casos y Controles , Estudios Prospectivos , COVID-19/prevención & control , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infección Irruptiva , Inmunoglobulina G , Anticuerpos Antivirales
14.
Gastroenterology ; 165(5): 1219-1232, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37507075

RESUMEN

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.


Asunto(s)
Anticuerpos Biespecíficos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animales , Ratones , Linfocitos T Reguladores/metabolismo , Anticuerpos Biespecíficos/genética , Anticuerpos Biespecíficos/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Moléculas de Adhesión Celular , Carcinoma Ductal Pancreático/tratamiento farmacológico , Inmunidad , Microambiente Tumoral , Claudinas
15.
Front Cardiovasc Med ; 10: 1204232, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37416926

RESUMEN

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.

17.
Eur Radiol ; 33(10): 7226-7237, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37145149

RESUMEN

OBJECTIVES: Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. METHODS: Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. RESULTS: The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. CONCLUSION: Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. KEY POINTS: • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction.


Asunto(s)
Fibrilación Atrial , Cardiomiopatías , Disfunción Ventricular Izquierda , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Imagen por Resonancia Cinemagnética/métodos , Imagen por Resonancia Magnética , Atrios Cardíacos/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función del Atrio Izquierdo
19.
J Cardiovasc Imaging ; 31(2): 71-82, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37096671

RESUMEN

BACKGROUND: Cardiac magnetic resonance fingerprinting (cMRF) enables simultaneous mapping of myocardial T1 and T2 with very short acquisition times. Breathing maneuvers have been utilized as a vasoactive stress test to dynamically characterize myocardial tissue in vivo. We tested the feasibility of sequential, rapid cMRF acquisitions during breathing maneuvers to quantify myocardial T1 and T2 changes. METHODS: We measured T1 and T2 values using conventional T1 and T2-mapping techniques (modified look locker inversion [MOLLI] and T2-prepared balanced-steady state free precession), and a 15 heartbeat (15-hb) and rapid 5-hb cMRF sequence in a phantom and in 9 healthy volunteers. The cMRF5-hb sequence was also used to dynamically assess T1 and T2 changes over the course of a vasoactive combined breathing maneuver. RESULTS: In healthy volunteers, the mean myocardial T1 of the different mapping methodologies were: MOLLI 1,224 ± 81 ms, cMRF15-hb 1,359 ± 97 ms, and cMRF5-hb 1,357 ± 76 ms. The mean myocardial T2 measured with the conventional mapping technique was 41.7 ± 6.7 ms, while for cMRF15-hb 29.6 ± 5.8 ms and cMRF5-hb 30.5 ± 5.8 ms. T2 was reduced with vasoconstriction (post-hyperventilation compared to a baseline resting state) (30.15 ± 1.53 ms vs. 27.99 ± 2.07 ms, p = 0.02), while T1 did not change with hyperventilation. During the vasodilatory breath-hold, no significant change of myocardial T1 and T2 was observed. CONCLUSIONS: cMRF5-hb enables simultaneous mapping of myocardial T1 and T2, and may be used to track dynamic changes of myocardial T1 and T2 during vasoactive combined breathing maneuvers.

20.
Radiol Case Rep ; 18(5): 1809-1820, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36915608

RESUMEN

Erdheim-Chester disease (ECD) as a rare non-Langerhans histiocytosis has various clinical manifestations. It is characterized histologically by infiltration of every organ, more commonly bone, retroperitoneum, cardiovascular and CNS systems with foamy, lipid -laden macrophage. Pancreatic involvement as a manifestation of this uncommon disease has very rarely been reported. Here we report a 73-year-old woman with ECD and pancreas involvement in CT, MRI and PET scans. We also aim to increase radiologist knowledge about considering ECD as a differential diagnosis for pancreas mass in the appropriate clinical situation.

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