The megakaryocytic transcription factor ARID3A suppresses leukemia pathogenesis.

Given the plasticity of hematopoietic stem and progenitor cells, multiple routes of differentiation must be blocked in the the pathogenesis of acute myeloid leukemia, the molecular basis of which is incompletely understood. We report that posttranscriptional repression of the transcription factor ARID3A by miR-125b is a key event in the pathogenesis of acute megakaryoblastic leukemia (AMKL). AMKL is frequently associated with trisomy 21 and GATA1 mutations (GATA1s), and children with Down syndrome are at a high risk of developing the disease. The results of our study showed that chromosome 21-encoded miR-125b synergizes with Gata1s to drive leukemogenesis in this context. Leveraging forward and reverse genetics, we uncovered Arid3a as the main miR-125b target behind this synergy. We demonstrated that, during normal hematopoiesis, this transcription factor promotes megakaryocytic differentiation in concert with GATA1 and mediates TGFß-induced apoptosis and cell cycle arrest in complex with SMAD2/3. Although Gata1s mutations perturb erythroid differentiation and induce hyperproliferation of megakaryocytic progenitors, intact ARID3A expression assures their megakaryocytic differentiation and growth restriction. Upon knockdown, these tumor suppressive functions are revoked, causing a blockade of dual megakaryocytic/erythroid differentiation and subsequently of AMKL. Inversely, restoring ARID3A expression relieves the arrest of megakaryocytic differentiation in AMKL patient-derived xenografts. This work illustrates how mutations in lineage-determining transcription factors and perturbation of posttranscriptional gene regulation can interact to block multiple routes of hematopoietic differentiation and cause leukemia. In AMKL, surmounting this differentiation blockade through restoration of the tumor suppressor ARID3A represents a promising strategy for treating this lethal pediatric disease.

Impact of radiographic field-of-view volume on alignment accuracy during virtual implant planning: A noninterventional retrospective pilot study.

OBJECTIVE: To evaluate the impact of reducing the radiographic field of view (FOV) on the trueness and precision of the alignment between cone beam computed tomography (CBCT) and intraoral scanning data for implant planning. MATERIALS AND METHODS: Fifteen participants presenting with one of three clinical scenarios: single tooth loss (ST, n = 5), multiple missing teeth (MT, n = 5) and presence of radiographic artifacts (AR, n = 5) were included. CBCT volumes covering the full arch (FA) were reduced to the quadrant (Q) or the adjacent tooth/teeth (A). Two operators, an expert (exp) in virtual implant planning and an inexperienced clinician, performed multiple superimpositions, with FA-exp serving as a reference. The deviations were calculated at the implant apex and shoulder levels. Thereafter, linear mixed models were adapted to investigate the influence of FOV on discrepancies. RESULTS: Evaluation of trueness compared to FA-exp resulted in the largest mean (AR-A: 0.10 ± 0.33 mm) and single maximum discrepancy (AR-Q: 1.44 mm) in the presence of artifacts. Furthermore, for the ST group, the largest mean error (-0.06 ± 0.2 mm, shoulder) was calculated with the FA-FOV, while for MT, with the intermediate volume (-0.07 ± 0.24 mm, Q). In terms of precision, the mean SD intervals were ≤0.25 mm (A-exp). Precision was influenced by FOV volume (FA < Q < A) but not by operator expertise. CONCLUSIONS: For single posterior missing teeth, an extended FOV does not improve registration accuracy. However, in the presence of artifacts or multiple missing posterior teeth, caution is recommended when reducing FOV.

Coronary atherosclerosis profile in patients with end-stage liver disease prior to liver transplantation due to alcoholic fatty liver: a coronary CTA study.

OBJECTIVES: To assess the coronary atherosclerosis profile by coronary computed tomography angiography (CTA) in patients with end-stage liver disease (ESLD) due to alcohol-related liver disease (ARLD) evaluated for liver transplantation (LT), in a retrospective matched case-controlled cohort study. METHODS: One hundred forty patients (age 60.6 years ± 9.8, 20.7% females) who underwent coronary CTA were included. Seventy patients with ESLD due to ARLD (ESLD-alc) were propensity score (1:1) matched for age, gender, and the major 5 cardiovascular risk factors with healthy controls. CTA analysis included the following: stenosis severity according to CAD-RADS as (0) = no, (1) minimal < 25%, (2) mild 25-50%, (3) moderate 50-70%, and (4) severe > 70% stenosis, total mixed plaque burden weighted for non-calcified component (G-score) and high-risk plaque criteria (Napkin-Ring, low attenuation plaque, spotty calcification, positive remodeling). RESULTS: Prevalence of coronary artery disease (CAD) was high (84.4%) in the ESLD-alc group but similar to controls. Stenosis severity was similar (CAD-RADS, 1.9 vs. 2.2, p = 0.289). High-grade stenosis (> 70%) was observed in 12.5% of ESLD-alc patients. High-risk plaques were less frequent in the ESLD-alc cohort as compared to controls (4.5% vs. 37.5%, p < 0.001), and total mixed plaque burden was lower (G-score, 4.9 versus 7.4, p = 0.001). Plaque density was lower in controls (56.6HU ± 3.2 vs. 91.3HU ± 4.5, p = 0.007) indicating more lipid-rich in controls, but higher mixed fibro-calcific plaque component in those with alcohol-related ESLD. CONCLUSION: Patients with alcohol-related ESLD exhibit more mixed fibro-calcified plaques but less plaque with high-risk features and less fibro-fatty plaque burden, while total CAD prevalence is high. KEY POINTS: • Patients with ESLD prior to LT have a high total prevalence of CAD and stenosis severity, which is similar to those of healthy controls with an identical cardiovascular risk profile. • Patients with ESLD prior to LT due to alcohol abuse have more calcific but less fibro-fatty plaque and less high-risk plaque. • CTA seems to be a useful imaging technique for risk stratification prior to LT.

Monosodium Urate Crystal Deposition in Coronary Artery Plaque by 128-Slice Dual-Energy Computed Tomography: An Ex Vivo Phantom and In Vivo Study.

OBJECTIVE: Monosodium uric acid (MSU) crystals may accumulate in the coronary plaque. The objective was to assess whether dual-energy computed tomography (DECT) allows for detection of MSU in coronary plaque. METHODS: Patients were examined with 128-slice DECT applying a cardiac electrocardiogram-gated and peripheral extremity protocol. Patients were divided into 3 groups: gout (tophi >1 cm in peripheral joints), hyperuricemia (>6.5 mg/dL serum uric acid), and controls. The groups were matched for cardiovascular risk factors. Monosodium uric acid-positive (+) and calcified plaque were distinguished, and the coronary artery calcium score was calculated. Ex vivo phantom: MSU solutions were diluted in different NaCL solutions (5%/10%/15%/20%/25%). Coronary artery models with 2 different plaque types (MSU+ and calcified) were created. RESULTS: A total of 96 patients were included (37 with gout, 33 with hyperuricemia, and 26 controls). Monosodium uric acid-positive plaques were found more often in patients with gout as compared with controls (91.9% vs 0.38%; P < 0.0001), and the number of plaques was higher (P < 0.0001). Of 102 MSU+ plaques, 26.7% were only MSU+ and 74.2% were mixed MSU+/calcified. Monosodium uric acid-positive plaque had mean 232.3 Hounsfield units (range, 213-264). Coronary artery calcium score was higher in patients with gout as compared with controls (659.1 vs 112.4 Agatston score; P < 0.001). Patients with gout had more MSU+ plaques as compared with patients with hyperuricemia (91.6% vs 2.9%; P < 0.0001), and coronary artery calcium score was higher (659.1 vs 254 Agatston score; P < 0.001), but there was no difference between patients with hyperuricemia and controls. Ex vivo phantom study: MSU crystals were detected by DECT in solutions with a concentration of 15% or greater MSU and could be distinguished from calcified. CONCLUSIONS: Coronary MSU+ plaques can be detected by DECT in patients with gout.

Evaluation of right ventricular function by coronary computed tomography angiography using a novel automated 3D right ventricle volume segmentation approach: a validation study.

OBJECTIVES: To evaluate right ventricle (RV) function by coronary computed tomography angiography (CTA) using a novel automated three-dimensional (3D) RV volume segmentation tool in comparison with clinical reference modalities. METHODS: Twenty-six patients with severe end-stage heart failure [left ventricle (LV) ejection fraction (EF) <35%] referred to CTA were enrolled. A specific individually tailored biphasic contrast agent injection protocol was designed (80%/20% high/low flow) was designed. Measurement of RV function [EF, end-diastolic volume (EDV), end-systolic volume (ESV)] by CTA was compared with tricuspid annular plane systolic excursion (TAPSE) by transthoracic echocardiography (TTE) and right heart invasive catheterisation (IC). RESULTS: Automated 3D RV volume segmentation was successful in 26 (100%) patients. Read-out time was 3 min 33 s (range, 1 min 50s-4 min 33s). RV EF by CTA was stronger correlated with right atrial pressure (RAP) by IC (r = -0.595; p = 0.006) but weaker with TAPSE (r = 0.366, p = 0.94). When comparing TAPSE with RAP by IC (r = -0.317, p = 0.231), a weak-to-moderate non-significant inverse correlation was found. Interobserver correlation was high with r = 0.96 (p < 0.001), r = 0.86 (p < 0.001) and r = 0.72 (p = 0.001) for RV EDV, ESV and EF, respectively. CT attenuation of the right atrium (RA) and right ventricle (RV) was 196.9 ± 75.3 and 217.5 ± 76.1 HU, respectively. CONCLUSIONS: Measurement of RV function by CTA using a novel 3D volumetric segmentation tool is fast and reliable by applying a dedicated biphasic injection protocol. The RV EF from CTA is a closer surrogate of RAP than TAPSE by TTE. KEY POINTS: • Evaluation of RV function by cardiac CTA by using a novel 3D volume segmentation tool is fast and reliable. • A biphasic contrast agent injection protocol ensures homogenous RV contrast attenuation. • Cardiac CT is a valuable alternative modality to CMR for the evaluation of RV function.

Prediction of high coronary artery calcium (CAC) scores from aortic arch calcification: An efficient tool for selection of non-optimal candidates for coronary CTA?

PURPOSE: Overutilization of healthcare resources is causing a high socioeconomic burden. Patients with high coronary artery calcium (CAC) scores > 1000AU are not optimal candidates for coronary CTA and better suited for other diagnostic strategies. Therefore, our objective was to evaluate whether a 4-scale aortic arch calcification severity (AoArCa) score from CT and X-Ray predicts high-CAC scores. METHODS: Patients referred to coronary/aortic CT-Angiography were enrolled. The severity of aortic arch calcification (AoArCa) was scored as grade: 0 = absent, 1 = minimal (<25 % of circumference), 2 = mild (25-50 %), 3 = moderate (50-75 %) and 4 = severe (75-100 %) on both thoracic CT and X-ray. RESULTS: In 130 patients, the absence of AoArCa by CT was highly accurate to rule out CAC > 1000AU (sens. 100 %). No or minimal AoArCa had a high NPV of 95.6 % to rule out CAC > 1000 and grade 0,1 + 2 a NPV of 86.96 %. The AUC of AoArCa by CT for predicting high CAC > 1000 was c = 0.84 (p < 0.001; 95 %CI: 0.771--0.91). For moderate-to-severe AoArCa, accuracy was c = 0.792 (p < 0.001). The intermodality agreement between CT and X-Ray based AoArCa Scores was good (r = 0.824, p < 0.001); ICC = 0.902. For X-ray, AUC was c = 0.715 to predict CAC > 1000 (p < 0.001). In regression models, only moderate-or-severe AoArCa, but not the other CVRF predicted CAC > 1000 (p < 0.001), and there was an association of the number of CVRF. CONCLUSIONS: Patients with moderate-to-severe aortic arch calcification have a high probability of CAC > 1000AU, but not those with no, minimal and mild. The absence of AoArCa rules out CAC > 1000AU. AoArCa severity may serve as valuable tool for selecting the diagnostic strategy.

Gender differences in the diagnostic efficacy of coronary CTA: Overutilization of coronary CTA in pre- and perimenopausal females?

OBJECTIVES: Public campaigns such as the "Go-red-for-women"-initiative have raised heart-disease awareness and may trigger overutilization of coronary computed tomography angiography (CTA). Objective was to investigate the diagnostic efficacy of coronary CTA stratified by age and gender. METHODS: 1882 consecutive patients (58.9 ± 11 years;42.5% females) with low-to-intermediate pre-test-probability of coronary artery disease (CAD) referred to coronary CTA according to ESC-2019 guidelines, were included. Diagnostic efficacy was defined by the 1)negative CTA-rate 2)obstructive CAD (>50%stenosis) 3)High-risk-plaque and 4)CAC-score. RESULTS: The negative CTA rate was higher in females compared to males with 360/801 vs 292/1081 (45% vs 27%;p < 0.001). Females had a higher likelihood (OR 2.2:95%CI:1.81-2.67) of a negative CTA than males, despite they were older (p < 0.001). Obstructive disease prevalence was 25.6% and acceptable in both sexes (males vs females: 28.4% vs 21.8%;p = 0.0012). Males had more high-risk-plaque (23.6% vs 11.5%;p < 0.001). When stratifying age groups, negative CTA rate was highest in females <47 years (82.8%), but lower in males with 68.1% (p < 0.001), while obstructive disease prevalence was not different (males:6.5% vs females:4.6%:p = 0.874). Above 50 years, negative CTA rate (39.1% vs 17.6%,p < 0.001;OR 3.02:95%CI:2.381-3.823) was higher, and the obstructive disease rate was lower in females (24.8% vs 34.7%,p = 0.0003). SSPSTm(V.25,IBM) was used for statistical analysis. CONCLUSIONS: Above 50 years of age, diagnostic efficacy of coronary CTA is high in both males and females. In females <47 years, the negative CTA rate was highest with 82.8% and obstructive disease prevalence was low (4.6%), still justifying testing but recommending the use of specific tools (PROMISE minimal risk score) or other clinical tests for pre-selection.

Synthesis and redox and photophysical properties of benzodifuran-spiropyran ensembles.

Two benzodifuran (BDF)-coupled spiropyran (SP) systems and their BDF reference compounds were obtained in good yields through Huisgen-Meldal-Sharpless "click" chemistry and then subjected to investigation of their electrochemical and photophysical properties. In both SP and merocyanine (MC) forms of the coupled molecules, the BDF-based emission is quenched to around 1 % of the quantum yield of emission from the BDF reference compounds. Based on electrochemical data, this quenching is attributed to oxidative electron-transfer quenching. Irradiation at 366 nm results in ring opening to the MC forms of the BDF-coupled SP compounds and the SP reference compound with a quantum efficiency of about 50 %. The rate constants for the thermal ring closing are approximately 3.4×10(-3)  s(-1). However, in the photostationary states the MC fractions of the coupled molecules are substantially lower than that of the reference SP compound, attributed to the observed acceleration of the ring-closing reaction upon irradiation. As irradiation at 366 nm invariably also excites higher-energy transitions of the BDF units in the coupled compounds, the ring-opening reaction is accelerated relative to the SP reference, which results in lower MC fractions in the photostationary state. Reversible photochromism of these BDF-coupled SP compounds renders them promising in the field of molecular switches.

Undiagnosed chronic respiratory disorders in symptomatic patients with initially suspected and excluded coronary artery disease: insights from a prospective pilot study.

Background: Chronic respiratory diseases represent the third-leading cause of death on a global scale. Due to mutual symptoms with cardiovascular diseases and potential inappropriate attribution of symptoms, pulmonary diseases often remain undiagnosed. Therefore, we aimed to evaluate the prevalence of chronic respiratory disorders among symptomatic patients in whom suspected coronary artery disease (CAD) was ruled out. Methods: After CAD was excluded by invasive coronary angiography (ICA), 50 patients with chest pain or dyspnea were prospectively enrolled in this study. All patients underwent lung function testing, including spirometry and diffusion measurements. At baseline and the 3-month follow-up, standardized assessments of symptoms (CCS chest pain, mMRC score, CAT score) were performed. Results: Chronic respiratory disease was diagnosed in 14% of patients, with a prevalence of 6% for chronic obstructive ventilation disorders. At 3-month follow-up, patients with normal lung function tests revealed a substantial improvement in symptoms (mean mMRC 0.70 to 0.33, p = 0.06; median CAT 8 to 2, p = 0.01), while those with pulmonary findings showed non-significant alterations or unchanged symptoms (mean mMRC 1.14 to 0.71, p = 0.53; median CAT 6 to 6, p = 0.52). Conclusion: A substantial proportion of patients with an initial suspicion of coronary artery disease was diagnosed with underlying chronic respiratory diseases and exhibited persistent symptoms.

Evaluation of the Appropriate Use of Coronary Computed Tomography Angiography: A Retrospective, Single-Center Analysis.

Purpose: We assessed the application of appropriate use criteria of coronary computed tomography angiography (CCTA) in comparison to invasive coronary angiography results and revascularization rates in patients with coronary artery disease (CAD). Methods: 1305 patients referred to invasive coronary angiography (ICA) after CCTA were evaluated retrospectively. The primary indication for CCTA was assessed according to the consensus for intermediate-risk (15−85% pre-test probability) into appropriate (A), inappropriate (I), and uncertain while referring to published guidelines. Patients' risk factors, angina, and heart failure symptoms (Canadian Cardiovascular Society classification (CCSC), New York Heart Association (NYHA); clinical data; and ICA results were gathered. Results: Of 1305 patients referred to CCTA prior to ICA, 496 (38.0%) were appropriate, 766 (56.9%) inappropriate, and 43 (3.3%) uncertain. Of 766 patients with inappropriate CCTA referrals, 370 (48.3%) were classified as "inappropriately low" (<15% pre-test probability) and 396 (51.7%) as "inappropriately high" (>85%) in regard to the recommended CCTA utilization. Sub-analysis of the adherence to the appropriate use criteria did not differ between the source of the referring physicians (intramural tertiary, private practice primary care, or external secondary care hospitals). Obstructive CAD with subsequent revascularization rates (total of 39.2%) did not differ significantly between the appropriate (38.3%), inappropriate (41.0%), or uncertain (23.3%) groups (p = 0.068). Conclusion: The total coronary revascularization rate after CCTA was 39.2% and not different among low, intermediate, and pre-test probability groups. These findings support the role of CCTA as an excellent gatekeeper in patients with suspected obstructive CAD even beyond pre-test probability calculation models.

Cardiac Computed Tomography: State of the Art and Future Horizons.

Cardiac computed tomography (CT) has evolved over the past 20 years from an alternative, promising noninvasive imaging modality to a Class I indication for the non-invasive evaluation of patients with low-to-intermediate, pre-test probability of coronary artery disease (CAD), as per the European Society of Cardiology (ESC) guidelines published in 2019 [...].

The Atherosclerosis Profile by Coronary Computed Tomography Angiography (CTA) in Symptomatic Patients with Coronary Artery Calcium Score Zero.

(1) Background: Whether it is safe to exclude coronary artery disease (CAD) in symptomatic patients with coronary artery calcium score (CACS 0), is an open debate. To compare coronary CTA including high-risk plaque (HRP) features in symptomatic patients with CACS 0 (2) Methods: 1709 symptomatic patients (age, mean 57.5 ± 16 years, 39.6% females) referred to coronary CTA for clinical indications were included. CACS, coronary stenosis (CADRADS) severity and HRP features (low-attenuation-plaque, spotty calcification, positive remodeling, NRS) were recorded. (3) Results: Of 1709 patients, 665 with CACS 0 were finally included. 562 (84.5%) had no CAD by CTA while 103 of 665 (15.4%) had CAD. Stenosis was minimal <25% in 79, mild <50% in 20, moderate in 1 and severe >70% in 3 patients. The rate of obstructive CAD was low with 4/665 (0.61%). The majority of patients had non-obstructive CAD (<50% stenosis) (99/103; 96.1%). A high proportion of patients with non-obstructive CAD had at least one HRP (52/103; 50.4%) per patient. (4) Conclusions: The rate of obstructive CAD is very low in symptomatic patients with CACS 0, and non-obstructive CAD domineering. CACS 0 does not rule out non-obstructive CAD and misses patients in which primary preventive measures are indicated. More than half of patients with non-obstructive CAD had high-risk plaque, highlighting the importance of quantitative plaque analysis.

Clinical management and primary prevention of suspected coronary artery disease guided by computed tomography.

AIMS: Despite the well established role of coronary computed tomography angiography (CCTA) as a diagnostic gatekeeper, the yield of subsequent invasive coronary angiographies (ICA) remains low. We evaluated the adherence of CCTA integration in clinical management and primary prevention therapy. METHODS: We retrospectively analyzed patients referred for ICA after CCTA without known coronary artery disease (CAD) or structural cardiac pathologies. Based on computed tomography (CT) findings, patients were classified as appropriately or inappropriately referred to ICA, equaling Coronary Artery Disease - Reporting and Data System (CAD-RADS) categories 0-2 (<50% stenosis) and 3-5 (>50% stenosis), respectively. CT exams were compared regarding invasive findings and revascularizations. Integration of CT results into primary prevention measures was analyzed and compared to measures taken after ICA. RESULTS: Of 1005 patients referred for ICA, 81 (8.1%) had no obstructive CT findings and therefore no ICA indication. ICA inappropriate patients did not differ in symptom characteristics, but had a significantly lower revascularization rate (3.7% vs. 42.1%, P < 0.0001) compared with patients appropriately referred to ICA. In patients with indication for lipid-lowering therapy after the CCTA statin rate was 53.1% and significantly increased after ICA to 76.4% (P < 0.0001). In CCTA, obstructive findings in proximal-only lesions did not increase the revascularization rate (45.6% vs. 42.1%, P = 0.11) but missed nonproximal relevant stenoses (15.0% vs. 2.5%, P < 0.0001) compared with obstructive findings in all segments. CONCLUSION: The overall rate of inappropriateness was low, but there is relevant statin underutilization in eligible patients due to a lack of CT findings integration. Both ICA referrals and primary preventive therapy could be improved by the implementation of CT results based on CAD-RADS recommendations.

Reciprocal communication of pericoronary adipose tissue and coronary atherogenesis.

OBJECTIVE: Pericoronary adipose tissue (PCAT) has been linked to underlying coronary artery disease (CAD) and proposed to modulate adjacent atherosclerotic plaque formation over pro-inflammatory pathways. In vitro and ex vivo studies support the bilateral communication of adipose tissue and vessel wall. We quantified PCAT and its dynamics in a low coronary risk cohort with a semi-automated software in serial coronary computed tomography angiography (CTA). METHODS: We retrospectively included patients from a tertiary care hospital who underwent serial coronary CTA with a low cardiovascular risk profile. All examinations were evaluated in a standardized approach: epicardial adipose tissue (EAT) volume and attenuation was quantified in total, in the atrioventricular (RCA, LCX) or interventricular (LAD) sulcus and within a 5 mm radius for each coronary artery (PCAT). Coronary plaques were quantified using a semi-automated software and compared for progression, stability or regression. RESULTS: Of 120 patients (27% females), 59.2% showed atherosclerotic plaques. After 36 months mean follow-up, 22 (18.3%) showed plaque regression, 39 (32.5%) were stable and 49 (40.8%) were progressive. Total EAT volume decreased by -15.6 ±â€¯37.2 mm³ in the regressive group, increased by 2.7 ±â€¯30.6 mm³ in the stable group and by 24.3 ±â€¯37.1 mm³ in the progressive group (p = 0.003). Per-vessel analysis showed a significant decrease of PCAT attenuation in patients with CAD regression (-3.8 ±â€¯7.6HU) compared to the stable (1.2 ±â€¯9.1HU) and progressive group (3.5 ±â€¯8.2HU, p < 0.0001). Mean sulcus EAT attenuation did not show a significant change (p = 0.135). CONCLUSION: Epicardial adipose tissue volume is mutually changing with the progression or regression of coronary artery disease. Perivascular but not epicardial attenuation levels correlate to adjacent plaque and support a direct bilateral influence.

Structural Cardiac Remodeling in Atrial Fibrillation.

OBJECTIVES: This study sought to evaluate preablation computed tomography angiography (CTA) for atrial and epicardial features to predict atrial fibrillation (AF) recurrence after ablation. BACKGROUND: Structural atrial remodeling is a process associated with occurrence or persistence of AF. Different anatomical imaging features have been proposed to influence atrial remodeling both negatively and positively as substrate for AF. METHODS: Patients with nonvalvular AF underwent cardiac CTA before pulmonary vein isolation at 2 high-volume centers. Left atrial (LA) and right atrial volumes, LA wall thickness (LAWT), and epicardial adipose tissue volume and attenuation were evaluated. Additional subanalyses of electroanatomical maps were made. Follow-up was performed for at least 12 months, including subanalysis of repeated cardiac CTA studies. Interrater variability was assessed. RESULTS: Of 732 patients, 270 (36.9%) had AF recurrence after a mean of 7 months. CT analysis revealed larger indexed LA volume (47.3 mL/m2 vs 43.6 mL/m2; P = 0.0001) and higher mean anterior (1.91 mm vs 1.65 mm; P < 0.0001) and posterior (1.61 mm vs 1.39 mm; P = 0.001) LAWT in patients with AF recurrence. Epicardial adipose tissue volume in patients with AF recurrence was higher (144.5 mm³ vs 128.5 mm³; P < 0.0001) and further progressed significantly in a subset of 85 patients after 2 years (+11.8 mm2 vs -3.5 mm2; P = 0.041). Attenuation levels were lower, indicating a higher lipid component associated with AF recurrence (-69.1 HU vs -67.5 HU; P = 0.001). A total of 103 atrial voltage maps were highly predictive of AF recurrence and showed good discriminatory power for patients with low voltage >50% and LAWT (1.55 ± 0.5 mm vs 1.81 ± 0.6 mm; P = 0.032). Net reclassification improvement (NRI) showed a significant incremental benefit (NRI = 0.279; P < 0.0001) when adding LAWT to established risk models. CONCLUSIONS: Atrial wall thickness, epicardial fat volume, and attenuation are associated with AF recurrence in patients undergoing ablation therapy.

The Effect of Vitamin D on Coronary Atherosclerosis: A Propensity Score Matched Case-Control Coronary CTA Study.

BACKGROUND: Vitamin D supplementation may be associated with lower cardiovascular (CV) events, but the data are controversial. It remains speculative whether vitamin D supplementation has a direct effect on coronary atherosclerosis. We therefore set out to assess the influence of vitamin D supplementation on the coronary atherosclerosis profile quantified by coronary computed tomography angiography (CTA) in a retrospective case-control cohort study. METHODS: 176 patients (age: 62.4 ± 10.4) referred to coronary CTA for clinical indications were included. A total of 88 patients receiving vitamin D supplementation (mean duration 65.3 ± 81 months) were 1:1 propensity score matched with 88 controls for age, gender, smoking, arterial hypertension, positive family history, dyslipidemia, and diabetes. Coronary stenosis severity (CAD-RADSTM), mixed plaque burden (weighted for non-calcified), high-risk-plaque (HRP) features, and plaque density (HU) were quantified by CTA. Serum 25-hydroxyvitamin D (OH)-levels were measured in 138 patients and categorized into four groups (0: <20 ng/mL; 1: 20-40 ng/mL; 2: 40-60 ng/mL; and 3: >60 ng/mL) and compared with CTA. RESULTS: The prevalence of atherosclerosis by CTA was similar in both groups (75.6% versus 74.3%, p = 0.999), >50% coronary stenosis was slightly higher in controls (p = 0.046), but stenosis severity score (CAD-RADS) was not different (p = 0.106). Mixed plaque burden (weighted for non-calcified) was lower in patients receiving vitamin D supplementation (p = 0.002) and high-risk-plaque prevalence was markedly lower (3.8% versus 32%, p < 0.001). CT plaque density (HU) was higher (p < 0.001) in the vitamin D group. Patients with serum vitamin D (OH) levels >60 ng/mL had higher plaque density (p = 0.04), indicating more calcified and less vulnerable plaque. CONCLUSIONS: In this retrospective case-control cohort study, vitamin D supplementation was associated with less high-risk plaque, less non-calcified plaque burden, and a higher calcified plaque independent of CV risk factors.

The effect of omega-3 fatty acids on coronary atherosclerosis quantified by coronary computed tomography angiography.

BACKGROUND & AIMS: Data on the effects omega-3 fatty acids on coronary artery disease (CAD) are contradictory. While a recent metanalysis could not show improved cardiovascular outcomes, anti-atherogenic mechanisms are well known. OBJECTIVE: Aim was to assess the influence of Omega-3 polyunsaturated long-chain fatty acids (PUFA) supplementation on coronary atherosclerosis quantified by coronary computed tomography angiography (CTA). METHODS: 106 patients (59.4y± 10.7; 50% females) with low-to-intermediate risk referred to CTA were included. 53 patients under omega 3-PUFA (docosahexaenoic acid, DHA and eicosapentaenoic acid, EPA) supplementation were retrospectively matched with 53 controls (CR) for age, gender and coronary risk profile (smoking, arterial hypertension, family history, dyslipidemia, c-LDL, Cholesterol, TG, diabetes) (1:1, propensity score) and lifestyle habits (exercise, alcohol consumption and nutrition). CTA analysis included 1) stenosis severity score >70%severe, 50-70% moderate, 25-50%mild, <25% minimal), 2) total plaque burden (segment involvement score (SIS) and mixed non-calcified plaque burden (G-score) and 3) high-risk-plaque features (Napkin-Ring-Sign, low attenuation plaque (LAP), spotty calcification<3 mm, RI>1.1). CT-Density (Hounsfield Units, HU) of plaque was quantified by CTA. RESULTS: Prevalence of coronary atherosclerosis (any plaque: 83% vs. 90.6%, p = 0.252), >50% stenosis and stenosis severity score (p = 0.134) were not different between groups. Total and non-calcified plaque burden scores were lower in the omega-3 group (2.7 vs. 3.5, p = 0.08 and 4.5 vs. 7.4, p = 0.027 for SIS and G-score, resp.). Coronary artery calcium score (CACS) was similar (84.7 vs. 87.1AU). High-risk-plaque prevalence was lower in the Omega-3 group (3.8% vs. 32%, p < 0.001); the number of high-risk-plaques (p < 0.001) and Napkin-Ring-Sign prevalence was lower (3.8% vs. 20.9%) (p < 0.001), resp. CT-density (HU) of plaque was higher in the Omega-3 group (131.6 ± 2 vs. 62.1 ± 27, p = 0.02) indicating more fibrous-dense plaque component rather than lipid-rich atheroma. Mean duration of Omega-3 intake was 38.6 ± 52 months (range, 2-240). CONCLUSIONS: Omega-3-PUFA supplementation is associated with less coronary atherosclerotic "high-risk" plaque (lipid-rich) and lower total non-calcified plaque burden independent on cardiovascular risk factors. Our study supports direct anti-atherogenic effects of Omega-3-PUFA.

Gender Differences in the Atherosclerosis Profile by Coronary CTA in Coronary Artery Calcium Score Zero Patients.

Background: The coronary artery calcium score (CACS) is a powerful tool for cardiovascular risk stratification. Coronary computed tomography angiography (CTA) allows for a more distinct analysis of atherosclerosis. The aim of the study was to assess gender differences in the atherosclerosis profile of CTA in patients with a CACS of zero. Methods: A total of 1451 low- to intermediate-risk patients (53 ± 11 years; 51% females) with CACS <1.0 Agatston units (AU) who underwent CTA and CACS were included. Males and females were 1:1 propensity score-matched. CTA was evaluated for stenosis severity (Coronary Artery Disease - Reporting and Data System (CAD-RADS) 0-5: minimal <25%, mild 25-49%, moderate 50-69%, severe ≥70%), mixed-plaque burden (G-score), and high-risk plaque (HRP) criteria (low-attenuation plaque, spotty calcification, napkin-ring sign, and positive remodeling). All-cause mortality, cardiovascular mortality, and major cardiovascular events (MACEs) were collected. Results: Among the patients, 88.8% had a CACS of 0 and 11.2% had an ultralow CACS of 0.1-0.9 AU. More males than females (32.1% vs. 20.3%; p < 0.001) with a CACS of 0 had atherosclerosis, while, among those with an ultralow CACS, there was no difference (88% vs. 87.1%). Nonobstructive CAD (25.9% vs. 16.2%; p < 0.001), total plaque burden (2.2 vs. 1.4; p < 0.001), and HRP were found more often in males (p < 0.001). After a follow-up of mean 6.6 ± 4.2 years, all-cause mortality was higher in females (3.5% vs. 1.8%, p = 0.023). Cardiovascular mortality and MACEs were low (0.2% vs. 0%; p = 0.947 and 0.3% vs. 0.6%; p = 0.790) for males vs. females, respectively. Females were more often symptomatic for chest pain (70% vs. 61.6%; p = 0.004). (4) Conclusions: In patients with a CACS of 0, males had a higher prevalence of atherosclerosis, a higher noncalcified plaque burden, and more HRP criteria. Nonetheless, females had a worse long-term outcome and were more frequently symptomatic.

Bicuspid Aortic Valve Is Associated with Less Coronary Calcium and Coronary Artery Disease Burden.

(1) Background. Bicuspid aortic valve (BAV) is associated with genetic defects (NOTCH 1, GATA 5) and aortopathy. Differences in the flow patterns and a genetic predisposition could also affect coronary arteries. The objective was to assess the coronary artery calcium score (CACS) and coronary artery disease (CAD) burden by coronary computed tomography angiography (CTA) in patients with BAV stenosis, as compared to stenotic tricuspid aortic valves (TAV). (2) Methods. A retrospective case-control study. A total of 47 patients with BAV stenosis (68.9 years ± 12.9, 38.3% females) who underwent CTA were matched with 47 TAV stenosis patients for age, gender, smoking, arterial hypertension, dyslipidemia, diabetes, body-mass-index and chronic kidney disease. (3) Results. The coronary artery calcium score (CACS) was lower in BAV (237.4 vs. 1013.3AU; p < 0.001) than in TAV, and stenosis severity was less (CAD-RADTM: p < 0.001). More patients with BAV had CACS zero (27.7% vs. 0%; p < 0.001). The majority (68.1%) of patients with BAV had no or non-obstructive CAD but only 25.5% of TAV (p < 0.001). Obstructive CAD (>50% stenosis) by CTA was more frequently observed in patients with TAV (68.1%; p < 0.001). (4) Conclusions and Relevance. Patients with BAV stenosis have markedly less coronary calcium and less severe coronary stenosis. CTA succeeds to rule out obstructive CAD in the majority of BAV, with adherent implications for TAVR planning.

Coronary Artery Dimensions in Endurance Athletes by Computed Tomography Angiography: A Quantitative Analysis.

(1) Background: The athlete's heart may develop permanent vessel enlargement. The purpose of our study was to define normal values for coronary artery dimensions of endurance athletes by coronary computed tomography angiography (CTA). (2) Methods: Ninety-eight individuals (56.2 ± 11 years) were included into this retrospective matched case-controlled-study. Endurance athletes had regular training volumes of ≥1 h per unit, ≥3-7 times per week (either cycling, running or mountain-endurance). Athletes were matched for age and gender with sedentary controls using propensity score. Quantitative CTA analysis included coronary vessel dimensions (two diameters and area) of the LM, LAD, CX and RCA for all AHA-16-segments. (3) Results: Proximal LAD area and diameter (p = 0.019); proximal/mid CX (diameter and area; p = 0.026 and p = 0.018/p = 0.008 and p = 0.009); mid RCA diameter and area; and proximal RCA diameter were significantly larger in endurance athletes (p < 0.05). The left main area (p = 0.708) and diameter (p = 0.809) as well as the mid LAD and distal segments were not different. We present the histograms and data for normal values ±1 and ± 2 SD. (4) Conclusions: Endurance athletes have larger proximal LAD, proximal/mid CX and RCA vessel dimensions, while LM and distal segments are similar. Hence, dilated coronary arteries in endurance athletes ("Athlete's arteries") have to be distinguished from diffuse ectatic segments developing during Kawasaki disease or multisystemic inflammation syndrome after COVID-19.