In vitro analysis of carotid lesions using a preliminary microwave sensor to detect vulnerable plaques: Correlation with histology, Duplex ultrasound examination, and computed tomography scanner: The Imaging and Microwave Phenotyping Assessment of Carotid stenosis Threat (IMPACT) study.

Objective: Progress in best medical treatment have made identification of best candidates for carotid surgery more difficult. New diagnostic modalities could be helpful in this perspective. Microwaves (MWs) can quantify dielectric properties (complex relative permittivity) of biological tissues and MW technology has emerged as a promising field of research for distinguishing abnormal tissues from healthy ones. We here evaluated the ability of a dedicated MW sensor developed in our laboratory to identify vulnerable carotid lesions. Methods: We included 50 carotid lesions in this study. The plaques were analyzed and classified preoperatively by ultrasound (US) examination, computed tomography angiography and tested postoperatively using a MW sensor. Histopathological analysis was used as a gold standard to separate vulnerable plaques (VPs) from nonvulnerable plaques (NVPs). Results: VPs were more frequently types 2 or 3 plaques (on US examination), had a greater proportion of low (<60 Hounsfield unit) and moderate (60-130 Hounsfield unit) attenuation components (computed tomography angiography) and displayed higher dielectric constant values (MW) than NVPs, which had an opposite profile. NVPs were more frequently asymptomatic plaques compared with VPs (P = .035). Multivariate analysis showed that US examination and MW identified VPs with a sensitivity of 77% and a specificity of 76% (cutoff value, -0.045; area under the curve, 0.848; P < .0001). Conclusions: We found that the presence of types 2 to 3 (on US examination) and high dielectric constant plaques in vitro was highly indicative of a VP based on histological analysis. Further studies are needed to determine the potential of MW to identify the most dangerous asymptomatic carotid lesions.

Non-alcoholic fatty liver disease biomarkers estimate cardiovascular risk based on coronary artery calcium score in type 2 diabetes: a cross-sectional study with two independent cohorts.

BACKGROUND: Studies have demonstrated that coronary artery calcification on one hand and non-alcoholic fatty liver disease (NAFLD) on the other hand are strongly associated with cardiovascular events. However, it remains unclear whether NAFLD biomarkers could help estimate cardiovascular risk in individuals with type 2 diabetes (T2D). The primary objective of the present study was to investigate whether the biomarkers of NAFLD included in the FibroMax® panels are associated with the degree of coronary artery calcification in patients with T2D. METHODS: A total of 157 and 460 patients with T2D were included from the DIACART and ACCoDiab cohorts, respectively. The coronary artery calcium score (CACS) was measured in both cohorts using computed tomography. FibroMax® panels (i.e., SteatoTest®, FibroTest®, NashTest®, and ActiTest®) were determined from blood samples as scores and stages in the DIACART cohort and as stages in the ACCoDiab cohort. RESULTS: CACS significantly increased with the FibroTest® stages in both the DIACART and ACCoDiab cohorts (p-value for trend = 0.0009 and 0.0001, respectively). In DIACART, the FibroTest® score was positively correlated with CACS in univariate analysis (r = 0.293, p = 0.0002) and remained associated with CACS independently of the traditional cardiovascular risk factors included in the SCORE2-Diabetes model [ß = 941 ± 425 (estimate ± standard error), p = 0.028]. In the ACCoDiab cohort, the FibroTest® F3-F4 stage was positively correlated with CACS in point-biserial analysis (rpbi = 0.104, p = 0.024) and remained associated with CACS after adjustment for the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (ß = 234 ± 97, p = 0.016). Finally, the prediction of CACS was improved by adding FibroTest® to the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (goodness-of-fit of prediction models multiplied by 4.1 and 6.7 in the DIACART and ACCoDiab cohorts, respectively). In contrast, no significant relationship was found between FibroMax® panels other than FibroTest® and CACS in either cohort. CONCLUSIONS: FibroTest® is independently and positively associated with the degree of coronary artery calcification in patients with T2D, suggesting that FibroTest® could be a relevant biomarker of coronary calcification and cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02431234 and NCT03920683.

Takotsubo syndrome : A cause of reversible microvascular coronary dysfunction.

Since the first description of takotsubo syndrome 30 years ago, only a little is known on the underlying physiopathology leading to peculiar left ventricular function alteration and myocardial damage related to acute emotional or physical stress. In the present case, we used continuous invasive thermodilution to evaluate coronary microvascular function at the acute phase of takotsubo and after recovery. The acute phase of takotsubo was characterized by a reduced coronary output and altered reserved flow with persistently high resistance during hyperaemia. At 6 weeks, we described a complete recovery of microvascular function, concomitant to LVEF recovery.

Deep Learning-Based Analysis of Aortic Morphology From Three-Dimensional MRI.

BACKGROUND: Quantification of aortic morphology plays an important role in the evaluation and follow-up assessment of patients with aortic diseases, but often requires labor-intensive and operator-dependent measurements. Automatic solutions would help enhance their quality and reproducibility. PURPOSE: To design a deep learning (DL)-based automated approach for aortic landmarks and lumen detection derived from three-dimensional (3D) MRI. STUDY TYPE: Retrospective. POPULATION: Three hundred ninety-one individuals (female: 47%, age = 51.9 ± 18.4) from three sites, including healthy subjects and patients (hypertension, aortic dilation, Turner syndrome), randomly divided into training/validation/test datasets (N = 236/77/78). Twenty-five subjects were randomly selected and analyzed by three operators with different levels of expertise. FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T, 3D spoiled gradient-recalled or steady-state free precession sequences. ASSESSMENT: Reinforcement learning and a two-stage network trained using reference landmarks and segmentation from an existing semi-automatic software were used for aortic landmark detection and segmentation from sinotubular junction to coeliac trunk. Aortic segments were defined using the detected landmarks while the aortic centerline was extracted from the segmentation and morphological indices (length, aortic diameter, and volume) were computed for both the reference and the proposed segmentations. STATISTICAL TESTS: Segmentation: Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetrical surface distance (ASSD); landmark detection: Euclidian distance (ED); model robustness: Spearman correlation, Bland-Altman analysis, Kruskal-Wallis test for comparisons between reference and DL-derived aortic indices; inter-observer study: Williams index (WI). A WI 95% confidence interval (CI) lower bound >1 indicates that the method is within the inter-observer variability. A P-value <0.05 was considered statistically significant. RESULTS: DSC was 0.90 ± 0.05, HD was 12.11 ± 7.79 mm, and ASSD was 1.07 ± 0.63 mm. ED was 5.0 ± 6.1 mm. A good agreement was found between all DL-derived and reference aortic indices (r >0.95, mean bias <7%). Our segmentation and landmark detection performances were within the inter-observer variability except the sinotubular junction landmark (CI = 0.96;1.04). DATA CONCLUSION: A DL-based aortic segmentation and anatomical landmark detection approach was developed and applied to 3D MRI data for achieve aortic morphology evaluation. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Phenotyping coronary plaque by computed tomography in premature coronary artery disease.

AIMS: Premature coronary artery disease (CAD) is an aggressive disease with multiple recurrences mostly related to new coronary lesions. This study aimed to compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: Of 1552 consecutive individuals who underwent CCTA, 106 individuals with history of acute or stable obstructive CAD ≤45 years were matched by age, sex, smoking status, cardiovascular heredity, and dyslipidaemia with 106 controls. CCTA were analysed for Coronary Artery Disease Reporting and Data System score, plaque composition, and high-risk plaque (HRP) features, including spotty calcification, positive remodelling, low attenuation, and napkin-ring sign. The characteristics of 348 premature CAD plaques were compared with those of 167 incidental coronary plaques of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1 vs. 30.2%, P < 0.001), as well as spotty calcification (42.5 vs. 17.9%, P < 0.001), positive remodelling (41.5 vs. 9.4%, P < 0.001), low attenuation (24.5 vs. 3.8%, P < 0.001), and napkin-ring sign (1.9 vs. 0.0%). They exhibited an average of 2.2 (2.7) HRP, while the control group displayed 0.4 (0.8) HRP (P < 0.001). Within a median follow-up of 24 (16, 34) months, individuals with premature CAD and ischaemic recurrence (n = 24) had more HRP [4.3 (3.9)] than those without ischaemic recurrence [1.5 (1.9)], mostly non-calcified with low attenuation and positive remodelling. CONCLUSION: Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of HRP, contributing to disease progression with multiple recurrences. A comprehensive qualitative CCTA assessment of plaque characteristics may further risk stratify our patients, beyond cardiovascular risk factors.

Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis.

Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hôpitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities.

Role of Cardiovascular Imaging in Risk Assessment: Recent Advances, Gaps in Evidence, and Future Directions.

Optimal risk assessment for primary prevention remains highly challenging. Recent registries have highlighted major discrepancies between guidelines and daily practice. Although guidelines have improved over time and provide updated risk scores, they still fail to identify a significant proportion of at-risk individuals, who then miss out on effective prevention measures until their initial ischemic events. Cardiovascular imaging is progressively assuming an increasingly pivotal role, playing a crucial part in enhancing the meticulous categorization of individuals according to their risk profiles, thus enabling the customization of precise therapeutic strategies for patients with increased cardiovascular risks. For the most part, the current approach to patients with atherosclerotic cardiovascular disease (ASCVD) is homogeneous. However, data from registries (e.g., REACH, CORONOR) and randomized clinical trials (e.g., COMPASS, FOURIER, and ODYSSEY outcomes) highlight heterogeneity in the risks of recurrent ischemic events, which are especially higher in patients with poly-vascular disease and/or multivessel coronary disease. This indicates the need for a more individualized strategy and further research to improve definitions of individual residual risk, with a view of intensifying treatments in the subgroups with very high residual risk. In this narrative review, we discuss advances in cardiovascular imaging, its current place in the guidelines, the gaps in evidence, and perspectives for primary and secondary prevention to improve risk assessment and therapeutic strategies using cardiovascular imaging.

Long-Term Outcome and Prognosis of Noninfectious Thoracic Aortitis.

BACKGROUND: Aortitis is a group of disorders characterized by the inflammation of the aorta. The large-vessel vasculitides are the most common causes of aortitis. Aortitis long-term outcomes are not well known. OBJECTIVES: The purpose of this study was to assess the long-term outcome and prognosis of noninfectious surgical thoracic aortitis. METHODS: This was a retrospective multicenter study of 5,666 patients with thoracic aorta surgery including 217 (3.8%) with noninfectious thoracic aortitis (118 clinically isolated aortitis, 57 giant cells arteritis, 21 Takayasu arteritis, and 21 with various systemic autoimmune disorders). Factors associated with vascular complications and a second vascular procedure were assessed by multivariable analysis. RESULTS: Indications for aortic surgery were asymptomatic aneurysm with a critical size (n = 152 [70%]), aortic dissection (n = 28 [13%]), and symptomatic aortic aneurysm (n = 30 [14%]). The 10-year cumulative incidence of vascular complication and second vascular procedure was 82.1% (95% CI: 67.6%-90.6%), and 42.6% (95% CI: 28.4%-56.1%), respectively. Aortic arch aortitis (HR: 2.08; 95% CI: 1.26-3.44; P = 0.005) was independently associated with vascular complications. Descending thoracic aortitis (HR: 2.35; 95% CI: 1.11-4.96; P = 0.031) and aortic dissection (HR: 3.08; 95% CI: 1.61-5.90; P = 0.002) were independently associated with a second vascular procedure, while treatment with statins after aortitis diagnosis (HR: 0.47; 95% CI: 0.24-0.90; P = 0.028) decreased it. After a median follow-up of 3.9 years, 19 (16.1%) clinically isolated aortitis patients developed features of a systemic inflammatory disease and 35 (16%) patients had died. CONCLUSIONS: This multicenter study shows that 82% of noninfectious surgical thoracic aortitis patients will experience a vascular complication within 10 years. We pointed out specific characteristics that identified those at highest risk for subsequent vascular complications and second vascular procedures.

Increase in intracellular and extracellular myocardial mass in patients with acromegaly: a cardiac magnetic resonance imaging study.

BACKGROUND: Acromegaly is associated with an increased left ventricular (LV) mass, as reported in echo-based and, more recently, in a few cardiac magnetic resonance imaging (MRI) studies. One possible explanation for this increased LV mass could be water retention and subsequent myocardial edema. METHODS: In this prospective cross-sectional study, 26 patients with active acromegaly before and after treatment and 31 controls of comparable age and sex were investigated using cardiac MRI. Cardiac morphology, function, and myocardial tissue characteristics were evaluated. Myocardial T2 relaxation time was used as the main outcome measure of myocardial edema. The study was registered with clinicaltrials.gov (NCT02948322). RESULTS: Patients compared to controls had greater LV mass indexes (58.1 [54.7-68.6] vs 46.0 [41.3-49.8] g/m2; P < .001) and end-diastolic volume (EDV) indexes (97.3 [88-101.2] vs 81.6 [78.1-96.2] mL/m2; P = .0069) and had comparable global contractile function. T2 values were not different between patients and controls. Both intracellular (43.83 [41.0-50.0] vs 34.32 [28.9-38.7] g/m2; P < .001) and extracellular (15.06 [13.5-17.1] vs 11.6 [10.8-12.7] g/m2; P < .001) LV mass indexes were higher in patients compared to controls. Log growth hormone correlated with myocardial mass (r = 0.75; P < .001). Sex, systolic blood pressure (BP), and the presence of acromegaly were predictors of the LV mass index. The extracellular LV mass index was associated with sex and the presence of acromegaly, whereas the intracellular LV mass index was associated with sex, systolic BP, and high-density lipoprotein (HDL) cholesterol. Acromegaly treatment reduced EDV and total and intracellular LV mass indexes without significantly affecting extracellular mass. CONCLUSION: Acromegaly results in a disease-specific form of LV hypertrophic remodeling, characterized by an increase in both intra- and extracellular mass. The LV mass index and intracellular mass were decreased by treatment.

Association between Biomarkers of Inflammation and 10-Year Changes in Aortic Stiffness: The Multi-Ethnic Study of Atherosclerosis.

Background. Chronic inflammation is associated with incident cardiovascular events. We study the association between biomarkers of inflammation and subclinical vascular dysfunction measured as proximal aortic stiffness. Methods. MRI imaging was performed in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000) and at the 10-year follow-up. Aortic arch pulse wave velocity (PWV) and ascending and descending aorta distensibility (AAD, DAD) were measured in 1223 asymptomatic individuals at both exams. Linear regression was used to study the association of baseline inflammation-C-reactive protein (CRP), interleukin-6 (IL6), and fibrinogen (Fib)-with baseline and 10-year changes in aortic stiffness (PWV, AAD, DAD). Results. The mean age of the participants was 59 ± 9 years, 47.8% of them were men, 32.6% were hypertensive at baseline, and 7.6% were diabetic. At baseline and follow-up, the mean AAD values were, respectively, 1.73 × 10-3 mmHg-1 and 1.57 × 10-3 mmHg-1, the mean DAD values were 2.19 × 10-3 mmHg-1 and 1.99 × 10-3 mmHg-1, and the mean PWV values were 8.10 m/s and 8.99 m/s. At baseline, the AAD (in 10-3 mmHg-1) and DAD (in 10-3 mmHg-1) were inversely associated with CRP (in mg/L) (AAD coeff: -0.047, p-value: 0.011, DAD coeff: -0.068, p-value: <0.001) and IL6 (in pg/mL) (AAD coeff: -0.098, p-value: 0.003, DAD coeff: -0.14, p-value: <0.001) in a univariable analysis but not after adjustment for demographic variables or cardiovascular risk factors. The baseline DAD was inversely associated with Fib (in mg/dL) (coeff: -0.334, p-value: 0.001). The baseline PWV (in m/s) was positively associated with IL6 (in pg/mL) in a univariable analysis (coeff: 0.054, p-value: 0.014). In a longitudinal analysis, the 10-year changes in DAD were inversely associated with CRP, even after adjustment for demographics and risk factors (DAD coeff: -0.08, p-value 0.044). Conclusions. Higher CRP levels at baseline were independently associated with a 10-year increase in aortic stiffness, measured as decreased aortic distensibility.

Rationale and design of the ARAMIS trial: Anakinra versus placebo, a double blind randomized controlled trial for the treatment of acute myocarditis.

BACKGROUND: Acute myocarditis is an inflammation of the myocardium that can cause life-threatening events. However, anti-inflammatory strategies did not reduce the risk of clinical outcomes in randomized trials. Recently, experimental studies have suggested that specific blockade of the interleukin-1ß immune innate pathway could be effective in acute myocarditis. AIM: To test the hypothesis that inhibition of the interleukin-1ß immune innate pathway can reduce the risk of clinical events in acute myocarditis. METHODS: The "Anakinra versus placebo double blind Randomized controlled trial for the treatment of Acute MyocarditIS" (ARAMIS) trial (ClinicalTrials.gov identifier: NCT03018834) is a national multicentre randomized parallel-group double blind study among symptomatic patients with elevated cardiac troponin and cardiac magnetic resonance-proven acute myocarditis. Patients (n=120) are randomized within 72hours of hospital admission to receive a daily subcutaneous dose of anakinra 100mg or placebo during the hospitalization, in addition to standard of care, including an angiotensin-converting enzyme inhibitor and a beta-blocker. The primary endpoint is the number of days alive free from any myocarditis complication, including ventricular arrhythmias, heart failure, recurrent chest pain requiring medication and ventricular dysfunction (defined as left ventricular ejection fraction<50%), from randomization to 28 days after hospital discharge. At 28 days after discharge, patients with normal left ventricular ejection fraction are then randomized to angiotensin-converting enzyme inhibitor continuation or discontinuation and all patients are followed for 1 year, with regular left ventricular function evaluation. CONCLUSIONS: ARAMIS is the first trial evaluating inhibition of the interleukin-1ß immune innate pathway in the setting of acute myocarditis. Although of small size, it will be the largest randomized trial in acute myocarditis, a serious and poorly studied cardiac condition.

Associations of aortic stiffness and intra-aortic flow parameters with epicardial adipose tissue in patients with type-2 diabetes.

Background: It has been shown that increased aortic stiffness is related to type-2 diabetes (T2D) which is considered as a risk factor for cardiovascular disease. Among other risk factors is epicardial adipose tissue (EAT) which is increased in T2D and is a relevant biomarker of metabolic severity and adverse outcome. Purpose: To assess aortic flow parameters in T2D patients as compared to healthy individuals and to evaluate their associations with EAT accumulation as an index of cardiometabolic severity in T2D patients. Materials and methods: Thirty-six T2D patients as well as 29 healthy controls matched by age and sex were included in this study. Participants had cardiac and aortic MRI exams at 1.5 T. Imaging sequences included cine SSFP for left ventricle (LV) function and EAT assessment and aortic cine and phase-contrast imaging for strain and flow parameters quantification. Results: In this study, we found LV phenotype to be characterized by concentric remodeling with decreased stroke volume index despite global LV mass within a normal range. EAT was increased in T2D patients compared to controls (p<0.0001). Moreover, EAT, a biomarker of metabolic severity, was negatively correlated to ascending aortic (AA) distensibility (p=0.048) and positively to the normalized backward flow volume (p=0.001). These relationships remained significant after further adjustment for age, sex and central mean blood pressure. In a multivariate model, presence/absence of T2D and AA normalized backward flow (BF) to forward flow (FF) volumes ratio are both significant and independent correlates of EAT. Conclusion: In our study, aortic stiffness as depicted by an increased backward flow volume and decreased distensibility seems to be related to EAT volume in T2D patients. This observation should be confirmed in the future on a larger population while considering additional biomarkers specific to inflammation and using a longitudinal prospective study design.

Value of aortic volumes assessed by automated segmentation of 3D MRI data in patients with thoracic aortic dilatation: A case-control study.

PURPOSE: The purpose of this study was to investigate the benefit of aortic volumes compared to diameters or cross-sectional areas on three-dimensional (3D) magnetic resonance imaging (MRI) in discriminating between patients with dilated aorta and matched controls. MATERIALS AND METHODS: Sixty-two patients (47 men and 15 women; median age, 66 years; age range: 33-86 years) with tricuspid aortic valve and ascending thoracic aorta aneurysm (TAV-ATAA) and 43 patients (35 men and 8 women; median age, 51 years; age range: 17-76 years) with bicuspid aortic valve and dilated ascending aorta (BAV) were studied. One group of 54 controls matched for age and sex to patients with TAV-ATAA (39 men and 15 women; median age, 68 years; age range: 33-81 years) and one group of 42 controls matched for age and sex to patients with BAV (34 men and 8 women; median age, 50 years; age range: 17-77 years) were identified. All participants underwent 3D MRI, used for 3D-segmentation for measuring aortic length, maximal diameter, maximal cross-sectional area (CSA) and volume for the ascending aorta. RESULTS: An increase in ascending aorta volume (TAV-ATAA: +107%; BAV: +171% vs. controls; P < 0.001) was found, which was three times greater than the increase in diameter (TAV-ATAA: +29%; BAV: +40% vs. controls; P < 0.001). In differentiating patients with TAV-ATAA from their controls, the indexed ascending aorta volume showed better performances (AUC, 0.935 [95% confidence interval (CI): 0.882-0.989]; accuracy, 88.7% [95% CI: 82.9-94.5]) than indexed ascending aorta length (P < 0.001), indexed ascending aorta maximal diameter (P = 0.003) and indexed ascending aorta maximal CSA (P = 0.03). In differentiating patients with BAV from matched controls, indexed ascending aorta volume showed significantly better performances performance (AUC, 0.908 [95% CI: 0.829-0.987]; accuracy, 88.0% [95% CI: 80.9-95.0]) than indexed ascending aorta length (P = 0.02) and not different from indexed ascending aorta maximal diameter (P = 0.07) or from indexed ascending aorta maximal CSA (P = 0.27) CONCLUSION: Aortic volume measured by 3D-MRI integrates both elongation and luminal dilatation, resulting in greater classification performance than maximal diameter and length in differentiating patients with dilated ascending aorta or aneurysm from controls.

Feasibility of a New Regional Myocardial Strain Parameter for the Detection of Wall Motion Abnormalities in Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose: To evaluate a cardiac MRI feature tracking (FT)-derived parameter that combines right ventricular (RV) longitudinal and radial motions in detecting arrhythmogenic right ventricular cardiomyopathy (ARVC). Materials and Methods: Patients with ARVC (n = 47; median age, 46 [IQR, 30-52] years; 31 men) were compared with controls (n = 39; median age, 46 [IQR, 33-53] years; 23 men) and separated into two groups based on fulfillment of major structural 2020 International criteria. Cine data from 1.5-T cardiac MRI examinations were analyzed using FT, resulting in conventional strain parameters and a novel composite index named the longitudinal-to-radial strain loop (LRSL). Receiver operating characteristic (ROC) analysis was used to assess diagnostic performance of RV parameters. Results: Volumetric parameters differed significantly between patients in the major structural criteria group and controls but not between patients in the no major structural criteria group and controls. Patients in the major structural criteria group had significantly lower magnitudes of all FT parameters than controls, including RV basal longitudinal strain, radial motion fraction, circumferential strain, and LRSL (-15.6% ± 6.4 vs -26.7% ± 13.9; -9.6% ± 4.89 vs -13.8% ± 4.7; -6.9% ± 4.6 vs -10.1% ± 3.8; and 217.0 ± 128.9 versus 618.6 ± 356.3, respectively). Only LRSL differed between patients in the no major structural criteria group and controls (359.5 ± 195.8 vs 618.6 ± 356.3; P < .0001). Parameters with the highest area under the ROC curve values for discriminating patients in the no major structural criteria group from controls were LRSL, RV ejection fraction, and RV basal longitudinal strain (0.75, 0.70, and 0.61, respectively). Conclusion: A new parameter combining RV longitudinal and radial motions showed good diagnostic performance in ARVC, even in patients without major structural abnormalities.Keywords: Arrhythmogenic Right Ventricular Dysplasia, Strain, Wall Motion Abnormalities, Right Ventricle, MRI, Inherited Cardiomyopathy Supplemental material is available for this article. © RSNA, 2023.

Firibastat Versus Ramipril After Acute Mechanical Reperfusion of Anterior Myocardial Infarction: A Phase 2 Study.

BACKGROUND: Preclinical data suggest that central renin-angiotensin system blockade by the brain aminopeptidase-A inhibitor firibastat can improve left ventricular ejection fraction (LVEF) after myocardial infarction (MI). OBJECTIVES: This study aimed to compare the effect of firibastat versus ramipril on post-MI LVEF. METHODS: In this phase 2, randomized, double-blind trial, patients selected within 24 h of first acute anterior MI treated by primary percutaneous coronary intervention were randomly assigned (1:1:1) to firibastat 100 mg, firibastat 500 mg or ramipril 5 mg, each twice daily for 12 weeks. The primary endpoint was change in LVEF on cardiac magnetic resonance imaging (cMRI) from baseline to day 84 in the modified intent-to-treat (mITT) population (at least one dose received and one follow-up cMRI available) for each treatment group. RESULTS: From June 4, 2019 to April 12, 2021, 294 patients were randomized and 229 were evaluable for the mITT analysis. After 12 weeks, mean ± standard deviation (SD) percent change in LVEF was 5.6 ± 1.2 with firibastat 100 mg, 5.3 ± 1.1 with firibastat 500 mg and 5.7 ± 1.1 with ramipril. The absolute ± SE adjusted difference in LVEF change from baseline between firibastat 500 mg and ramipril was - 0.36 ± 1.32% (p = 0.79). Occurrence of treatment-related adverse events was similar in the three groups. CONCLUSIONS: Firibastat was not superior to ramipril for prevention of left ventricular dysfunction after first acute anterior MI, and their safety profiles were similar. REGISTRATION: ClinicalTrials.gov identifier NCT03715998.

Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis.

Immune-checkpoint-inhibitor (ICI)-associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and are highly fatal. We report the results of a strategy that included identification of individuals with severe ICI myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with the CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib. Forty cases with definite ICI myocarditis were included with pathologic confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. The abatacept dose was adjusted using CD86 receptor occupancy on circulating monocytes. The myotoxicity-related fatality rate was 3.4% (1/30) in these 30 patients versus 60% in the first quartile (P < 0.0001). These clinical results are hypothesis-generating and need further evaluation. SIGNIFICANCE: Early management of respiratory muscle failure using mechanical ventilation and high-dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe ICI myocarditis. See related commentary by Dougan, p. 1040. This article is highlighted in the In This Issue feature, p. 1027.