Aortic valve cusp size and shape in dilated trileaflet aortic roots.

OBJECTIVES: Objective of the study was to quantify the differences in cusp size and shape in patients with normal and dilated trileaflet aortic roots and in dilated roots with or without aortic regurgitation. METHODS: Retrospective analysis of computed tomography studies in patients with normal and dilated trileaflet aortic roots was performed measuring root and cusp dimensions. Normal root size was defined as sinuses of Valsalva diameter < 40 mm, dilated as ≥ 45 mm. Root measurements normalized to basal ring diameter and cusp measurements normalized to geometric height were analyzed to assess the shape. Additionally, comparison of dilated roots with or without aortic regurgitation was made. RESULTS: We analyzed 146 normal and 104 dilated aortic roots and 73 propensity-matched pairs. Dilated roots were larger in all dimensions and had increased ratio between commissural and basal ring diameter (1.58±0.23 vs. 1.11±0.10, p<0.001). Cusps in dilated roots were larger in all measured dimensions and were elongated with increased normalized cusp insertion length (3.64±0.39 vs. 3.26±0.20, p<0.001) and normalized free margin length (2.53±0.30 vs. 2.16±0.19, p<0.001). In patients with dilated root and no cusp prolapse (n = 83), those with moderate or severe aortic regurgitation had larger commissural diameter but similar cusp dimensions compared to those with no or mild aortic regurgitation. CONCLUSIONS: The cusps in dilated roots elongate transversely and to a lesser degree radially. Functional aortic regurgitation is caused by extensive commissural dilatation and not by inadequate cusp adaptation.

Quantification of anatomical aortic valve area by multi-detector computed tomography: A pilot 3D-morphological modeling of the stenotic aortic valve.

BACKGROUND: Aortic-valve-stenosis (AS) is a frequent degenerative valvular-disease and carries dismal outcome under-medical-treatment. Transvalvular pressure gradient reflects severity of the valve-disease but is highly dependent on flow-conditions and on other valvular/aortic characteristics. Alternatively, aortic-valve-area (AVA) represents a measure of aortic-valve lesion severity conceptually essential and practically widely-recognized but exhibits multiple-limitations. METHODS: We analyzed the 4D multi-detector computed tomography(MDCT) of 20 randomly selected patients with severe AS. For each-patient, we generated the 3D-model of the valve and of its calcifications, and we computed the anatomical AVA accounting for the 3D-morphology of the leaflets in three-different-ways. Finally, we compared our results vs. Doppler-based AVAE measurements and vs. 2D-planimetric AVA-measurements. RESULTS: 3D-reconstruction and identification of the cusps were successful in 90% of the cases. The calcification patterns where highly-variable over patients, ranging from multiple small deposits to wide and c-shaped deposits running from commissure-to-commissure. AVAE was 82 ± 15 mm2. When segmenting 18 image planes, AVATight, AVAProj-Ann, AVAProj-Tip and their average AVAAve were equal to 80 ± 16, 88 ± 20, 93 ± 21 and 87 ± 19 mm2, respectively, while AVAPlan was equal to 143 ± 50 mm2. Linear-regression of the three measurements vs. AVAE yielded regression slopes equal to 1.26, 1.13 and 0.93 for AVAProj-Ann, AVAProj-Tip and AVATight, respectively. The respective Pearson-coefficients were 0.85,0.86 and 0.90. Conversely, when comparing AVAPlan vs. AVAE, linear regression yielded a slope of 1.73 and a Pearson coefficient of 0.53. CONCLUSIONS: We described a new-method to obtain a set of flow-independent quantifications that complement pressure gradient measurements and combine the advantages of previously proposed methods, while bypassing the corresponding-limitations.

Prognostic Value of Aortic Valve Calcification in Nonsevere Aortic Stenosis with Preserved Ejection Fraction.

BACKGROUND: Aortic valve calcification(AVC) is prognostic in patients with aortic stenosis(AS). We assessed the AVC prognostic value in nonsevere AS patients. METHODS AND RESULTS: We conducted a retrospective study of 395 patients with nonsevere AS, LV ejection fraction ≥50%. The Agatston method was used for computed tomography AVC assessment. The log-rank test determined the best AVC cutoffs for survival under medical surveillance: 1185 AU in men and 850 in women, lower than the established-cutoffs for severe AS(2064AU in men and 1274 in women). Patients were divided into three AVC groups based on these cutoffs: low(<1185 AU men and <850 women), sub-severe(1185-2064AU men and 850-1274 women) and severe(>2064AU men and >1274 women). Of 395 patients(mean age 73 ± 12 years, 60.5% men, aortic valve area 1.23 ± 0.30cm2, mean pressure gradient 28 ± 8 mmHg), 218 underwent aortic valve intervention(AVI) and 158 deaths occurred during follow-up, 82 before AVI. Median survival time under medical surveillance was 2.1[0.7-4.9]years. Compared to the low AVC group, both sub-severe and severe AVC groups had higher risk for all-cause death under medical surveillance after comprehensive adjustment including echocardiographic AS severity and coronary artery calcium score(all p ≤ 0.006); while mortality risk was similar between sub-severe and severe AVC groups(all p ≥ 0.2). This mortality risk pattern persisted in the overall survival analysis after adjustment for AVI. AVI was protective of all-cause death in the sub-severe and severe AVC(all p ≤ 0.01), but not in the low AVC groups. CONCLUSIONS: Sub-severe AVC is a robust risk-stratification parameter in patients with nonsevere AS and may inform AVI timing.

Case Report: A myxoma with a far reach.

A 73-year-old woman presented to the emergency department with a syncopal episode and a history of dizzy spells. A transthoracic echocardiogram demonstrated a large left atrial mass extending into the right upper pulmonary veins. Subsequently, cardiac magnetic resonance imaging and coronary computed tomography angiography with three-dimensional reconstruction and printing of the heart and mass were performed, which demonstrated a high index of suspicion for an atypical left atrial myxoma. The mass was excised robotically, and the pathology report confirmed a diagnosis of myxoma.

Segmental analysis of aortic basal ring dimensions in normal and dilated tricuspid aortic roots.

OBJECTIVES: In patients with aortic root aneurysm, the aortic basal ring is frequently dilated. It has been speculated that the muscular part of the basal ring dilates most. The purpose of this study was to analyse the segmental dilatation of the basal ring, comparing normal and dilated roots in patients with tricuspid aortic valves. METHODS: Retrospective analysis of computed tomography studies in patients with normal and dilated aortic roots was performed. Lengths of segments of the basal ring corresponding to each of the 3 sinuses, and to the muscular and fibrous parts were measured. Fractions of these segments relative to the total basal ring perimeter were calculated. RESULTS: We analysed 152 normal and 126 dilated aortic roots and 86 propensity-matched pairs. Basal ring dilatation was present in all segments of dilated aortic roots with subtle differences between the segments corresponding to the 3 sinuses. The muscular part of the basal ring dilated proportionately to its fibrous part, with no difference in fractions of measured muscular part in normal and dilated roots [42.2% (interquartile range 4.3%) vs 42.1% (interquartile range 6.3%)]. CONCLUSIONS: Basal ring dilatation was present in all segments corresponding to the 3 sinuses in dilated aortic roots. Both muscular and fibrous parts dilated equally, supporting the need to stabilize the entire basal ring when performing aortic valve repair surgery.

Motion artifact correction in cardiac CT using cross-phase temporospatial information and synergistic attention gate and spatial transformer sub-networks.

Objectives.To improve quality of coronary CT angiography (CCTA) images using a generalizable motion-correction algorithm.Approach. A neural network with attention gate and spatial transformer (ATOM) was developed to correct coronary motion. Phantom and patient CCTA images (39 males, 32 females, age range 19-92, scan date 02/2020 to 10/2021) retrospectively collected from dual-source CT were used to create training, development, and testing sets corresponding to 140- and 75 ms temporal resolution, with 75 ms images as labels. To test generalizability, ATOM was deployed for locally adaptive motion-correction in both 140- and 75 ms patient images. Objective metrics were used to assess motion-corrupted and corrected phantom and patient images, including structural-similarity-index (SSIM), dice-similarity-coefficient (DSC), peak-signal-noise-ratio (PSNR), and normalized root-mean-square-error (NRMSE). In objective quality assessment, ATOM was compared with several baseline networks, including U-net, U-net plus attention gate, U-net plus spatial transformer, VDSR, and ResNet. Two cardiac radiologists independently interpreted motion-corrupted and -corrected images at 75 and 140 ms in a blinded fashion and ranked diagnostic image quality (worst to best: 1-4, no ties).Main results. ATOM improved quality metrics (p< 0.05) before/after correction: in phantom, SSIM 0.87/0.95, DSC 0.85/0.93, PSNR 19.4/22.5, NRMSE 0.38/0.27; in patient images, SSIM 0.82/0.88, DSC 0.88/0.90, PSNR 30.0/32.0, NRMSE 0.16/0.12. ATOM provided more consistent improvement of objective image quality, compared to the presented baseline networks. The motion-corrected images received better ranks than un-corrected at the same temporal resolution (p< 0.05): 140 ms images 1.65/2.25, and 75 ms images 3.1/3.2. The motion-corrected 75 ms images received the best rank in 65% of testing cases. A fair-to-good inter-reader agreement was observed (Kappa score 0.58).Significance. ATOM reduces motion artifacts, improving visualization of coronary arteries. This algorithm can be used to virtually improve temporal resolution in both single- and dual-source CT.

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase.

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.

Computed tomography calcium scoring in aortic stenosis: bicuspid versus tricuspid morphology.

OBJECTIVE: CT aortic valve calcium score (AVCscore) and density (AVCdensity) thresholds have been recommended for aortic stenosis (AS) severity assessment in tricuspid aortic valve (TAV). We aimed to compare AVCscore and AVCdensity in bicuspid aortic valve (BAV) versus TAV. METHODS: Retrospective single-centre study of patients with echocardiographic AS-severity and CT-AVC assessments within 6 months, and left ventricular ejection fraction ≥50%, all referred for clinical AS evaluation.Severe AS was defined as aortic valve area (AVA) ≤1 cm2 or indexed AVA ≤0.6cm2/m2 plus mean gradient ≥40 mm Hg or peak velocity ≥4 m/s. AVC was assessed by Agatston method. RESULTS: Of the 1957 patients, 328 had BAV and 1629 had TAV, age 65±11 vs 80±9 years (p<0.001), men 65% vs 56% (p=0.006), respectively. BAV morphology was associated with higher AVCscore and AVCdensity independent of age, comorbidities and AS severity (p<0.001) in men only (sex and BAV interaction p<0.001). In patients with severe AS, mean AVCscore and AVCdensity were higher in BAV-men than that in TAV-men (both p<0.001), but similar in BAV-women and TAV-women (both p≥0.4). Such patterns remained the same after adjustment for clinical covariates and AS severity. Best thresholds for severe AS diagnosis in BAV-men were 2916 AU by AVCscore and 600 AU/cm2 by AVCdensity which were higher than the guideline-recommended thresholds, while thresholds in BAV-women (1036 AU and 282 AU/cm2) were similar to guideline-recommended ones. CONCLUSION: Valve calcification in AS differs according to valve morphology and sex. BAV-men with severe AS exhibit greater AVCscore and AVCdensity than TAV-men. This presents a diagnostic challenge to the current guidelines, which needs confirmation in larger studies.

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase.

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure activity relationship and the selectivity mechanism.

Ultrasound Enhancing Agents with Transthoracic Echocardiography for Maximal Wall Thickness in Hypertrophic Cardiomyopathy.

Objectives: To determine whether ultrasound enhancing agent (UEA) changes maximal wall thickness (WT) in hypertrophic cardiomyopathy (HCM), and if it improves correlation with magnetic resonance imaging (MRI). Patients and Methods: A total of 107 patients with HCM were prospectively enrolled at a single tertiary referral center between July 10, 2014, and August 31, 2017, and underwent transthoracic echocardiography (TTE) with and without UEA and MRI. Maximal WT measurements were compared, and variability among the 3 modalities was evaluated using a simple linear regression analysis and paired t tests and Bland-Altman plots. Interobserver variability for each technique was assessed. Results: Most (63%) of cardiac imagers found UEA helpful in determining maximal WT by TTE, with 49% reporting change in WT. Of 52 patients where UEA changed WT measurement, 32 (62%) reported an increase and 20 (38%) reported a decrease in WT. The UEA did not alter the median discrepancy in WT between MRI and TTE. However, where UEA increased reported WT, the difference between MRI and TTE improved in 79% of cases (P=.001) from 2.0-0.5mm. In those with scar on MRI, UEA improved agreement of WT between TTE and MRI compared with that of TTE without UEA (79% vs 39%; P=.011). Interclass correlation coefficient for WT for TTE without UEA, with UEA, and MRI was 0.84; (95% CI, 0.61-0.92), 0.88; (95%CI, 0.82-0.92), and 0.97; (95%CI, 0.96-0.98), respectively. Conclusion: Although use of UEA did not eliminate differences in WT discrepancy between modalities, the addition of UEA to TTE aided in WT determination and improved correlation with MRI in those with greater WT and in all patients with myocardial scars.

Utility of CT and MRI in Tricuspid Valve Interventions.

Transcatheter tricuspid valve interventions (TTVIs) comprise a variety of catheter-based interventional techniques for treatment of tricuspid regurgitation (TR) in patients at high surgical risk and those with failed previous surgeries. Several TTVI devices with different mechanisms of action are either currently used or in preclinical evaluation. Echocardiography is the first-line modality for evaluation of tricuspid valve disease that provides information on tricuspid valve morphology, mechanism of TR, and hemodynamics. Cardiac CT and MRI have several advantages for a comprehensive preprocedure evaluation. CT and MRI provide complementary information to that of echocardiography on the mechanism and cause of TR. MRI can quantify the severity of TR using indirect or direct techniques that involve two-dimensional or four-dimensional flow sequences. MRI and CT can also accurately quantify right ventricular volumes and function, which is crucial for timing of intervention. CT provides comprehensive three-dimensional information on the morphology of the valve, annulus, subvalvular apparatus, and adjacent structures. CT is the procedure of choice for evaluation of several device-specific measurements, including tricuspid annulus dimensions, annulus-to-right coronary artery distance, leaflet morphology, coaptation gaps, caval dimensions, and cavoatrial-to-hepatic vein distance. CT allows evaluation of the vascular access as well as optimal procedure fluoroscopic angles and catheter trajectory. Postprocedure CT and MRI are useful in detection of complications such as paravalvular leak, pseudoaneurysm, thrombus, pannus, infective endocarditis, and device migration. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Analysis of Cardiac Computed Tomography Anatomy in Patients With Severe Tricuspid Regurgitation Considered for Transcatheter Intervention.

Background: Severe tricuspid regurgitation (TR) is associated with considerable morbidity/mortality in an elderly population with multiple comorbidities. There is interest in transcatheter interventions to manage severe TR. Understanding complex right heart (RH) geometry and tricuspid valve shape and size has implications for patient/device selection for transcatheter intervention. We characterized RH anatomy by computed tomography in patients with symptomatic severe TR considered for intervention. Methods: The retrospective Mayo Clinic study included 29 patients with an echocardiogram and cardiac computed tomography angiogram considered for intervention of severe TR from March 01, 2016 to December 15, 2020. Patients were divided into 2 groups: intervention (surgical or transcatheter; n = 17) and medical management alone (n = 12). Results: Mean age was 83 ± 8 (83% female), 100% had atrial fibrillation, and 62% had chronic kidney disease ≥3a. Ninety-seven percent were symptomatic, 93% had been prescribed loop diuretics, and 24% had device leads. Mean tricuspid annular plane systolic excursion was 16.8 ± 4.5 mm, effective regurgitant orifice area was 81 ± 33 mm2, and cardiac index was 2.6 ± 0.6 L/min/m2. Forty-one percent had at least moderate right ventricular (RV) dysfunction with a mean RV systolic pressure of 46 ± 16 mmHg. Patients receiving intervention had significantly larger effective regurgitant orifice area (101 ± 33 vs. 63 ± 22 mm2, p = 0.033), shorter tricuspid leaflet tenting length (6.5 ± 3.0 vs. 8.9 ± 2.7 mm, p = 0.042), and smaller annuloplasty diagnostic perimeter during diastole (120.1 ± 16.6 vs. 131.1 ± 7.4 mm, p = 0.041). Intervention patients tended to have better right ventricular function, smaller RV and inferior vena cava size, and more severe symptoms. The maximal tricuspid annulus diameter in systole and diastole was 51 ± 5 and 53 ± 7 mm, respectively. Conclusions: Severe TR patients referred for transcatheter intervention present with severe RH enlargement with a large proportion having tricuspid annulus dimensions outside the range for current devices available in clinical trials. The presented data have implications for device development/selection and procedural feasibility.

Multimodality imaging evaluation of arteriovenous fistulas and grafts: a clinical practice review.

Arteriovenous fistulas (AVFs) and grafts (AVGs) are the preferred forms of vascular access for hemodialysis in patients with severe renal dysfunction. Multimodality imaging plays an important role in the pre-procedural evaluation of these patients. Ultrasound is often used for pre-procedural vascular mapping in preparation for the creation of an AVF or AVG. Pre-procedural mapping includes a comprehensive evaluation of the arterial and venous vasculature including evaluation of vessel diameter, stenosis, course, presence of collateral veins, wall thickness and wall abnormalities. Computed tomography (CT), magnetic resonance imaging (MRI) or catheter angiography are used when sonography is not available or when further characterization of sonographic abnormalities is required. Following the procedure, routine surveillance imaging is not recommended. If there are any clinical concerns or if physical examination is inconclusive, further evaluation with ultrasound is warranted. Ultrasound allows for assessment of vascular access site maturation by evaluating the time-averaged blood flow and helping characterize the outflow vein in the case of an AVF. CT and MRI can play a complementary role to ultrasound. Vascular access site complications include non-maturation, aneurysm, pseudoaneurysm, thrombosis, stenosis, steal phenomena or occlusion typically of the outflow vein, infection, bleeding and rarely angiosarcoma. In this article, we review the role of multimodality imaging in the pre- and post-procedural evaluation of patients with AVF and AVG. Additionally, novel technologies of vascular access site creation using endovascular techniques and upcoming non-invasive imaging techniques for evaluation of AVFs and AVGs are discussed.

Role of Multimodality Imaging and Preoperative Management in Intrapericardial Paragangliomas: Experience From a Case Series.

Intrapericardial paragangliomas are rare, highly vascular tumors that frequently adhere to adjacent structures and blood vessels, making surgical resection challenging. In this case series, we discuss the role of multimodality imaging and preoperative embolization in the management of 3 patients presenting with intrapericardial paragangliomas. (Level of Difficulty: Advanced.).

Pre- and Postprocedure Imaging of Transcatheter Pulmonary Valve Implantation.

Transcatheter pulmonary valve replacement (TPVR) is a minimally invasive procedure for treatment of right ventricular outflow tract (RVOT) dysfunction in surgically repaired congenital heart diseases. TPVR is performed in these patients to avoid the high risk and complexity of repeat surgeries. Several TPVR devices are now available to be placed in the right ventricle (RV) to pulmonary artery (PA) conduit, native RVOT, or surgical bioprosthetic valves. Imaging is used before TPVR to determine patient eligibility and optimal timing, which is critical to avoid irreversible RV dilatation and failure. Imaging is also required for evaluation of contraindications, particularly proximity of the RVOT to the left main coronary artery and its branches. Cross-sectional imaging provides details of the complex anatomy in which the TPVR device will be positioned and measurements of the RVOT, RV-PA conduit, or PA. Echocardiography is the first-line imaging modality for evaluation of the RVOT or conduit to determine the need for intervention, although its utility is limited by the complex RVOT morphology and altered anatomy after surgery. CT and MRI provide complementary information for TPVR, including patient eligibility, assessment of contraindications, and key measurements of the RVOT and PA, which are necessary for procedure planning. TPVR, performed using a cardiac catheterization procedure, includes a sizing step in which a balloon is expanded in the RVOT, which also allows assessment of the risk for extrinsic coronary artery compression. Follow-up imaging with CT and MRI is used for evaluation of postprocedure remodeling and valve function and to monitor complications. ©RSNA, 2022 Online supplemental material is available for this article.

Intra-atrial Pulmonary Venous Conduit Leak in Criss-Cross Heart: Role of Three-Dimensional Modeling.

Three-dimensional (3D) modeling has become an invaluable tool for operative planning in the continually evolving complex field of adult congenital heart surgery. We present a case of an intra-atrial conduit leak after multiple repairs of common atrium and criss-cross morphology. 3D modeling was critical in preoperative evaluation and operative planning for complicated intracardiac anatomy after an uncommon initial approach to preserve a biventricular circulation. In the setting of complex or rare congenital cardiac anomalies, advanced imaging and 3D modeling are helpful with preoperative planning.