Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

False lumen hemodynamics and partial thrombosis in chronic aortic dissection of the descending aorta.

OBJECTIVES: Partial thrombosis of the false lumen (FL) in patients with chronic aortic dissection (AD) of the descending aorta has been associated with poor outcomes. Meanwhile, the fluid dynamic and biomechanical characteristics associated with partial thrombosis remain to be elucidated. This retrospective, single-center study tested the association between FL fluid dynamics and biomechanics and the presence and extent of FL thrombus. METHODS: Patients with chronic non-thrombosed or partially thrombosed FLs in the descending aorta after an aortic dissection underwent computed tomography angiography, cardiovascular magnetic resonance (CMR) angiography, and a 4D flow CMR study. A comprehensive quantitative analysis was performed to test the association between FL thrombus presence and extent (percentage of FL with thrombus) and FL anatomy (diameter, entry tear location and size), fluid dynamics (inflow, rotational flow, wall shear stress, kinetic energy, and flow acceleration and stasis), and biomechanics (pulse wave velocity). RESULTS: Sixty-eight patients were included. In multivariate logistic regression FL kinetic energy (p = 0.038) discriminated the 33 patients with partial FL thrombosis from the 35 patients with no thrombosis. Similarly, in separated multivariate linear correlations kinetic energy (p = 0.006) and FL inflow (p = 0.002) were independently related to the extent of the thrombus. FL vortexes, flow acceleration and stasis, wall shear stress, and pulse wave velocity showed limited associations with thrombus presence and extent. CONCLUSION: In patients with chronic descending aorta dissection, false lumen kinetic energy is related to the presence and extent of false lumen thrombus. CLINICAL RELEVANCE STATEMENT: In patients with chronic aortic dissection of the descending aorta, false lumen hemodynamic parameters are closely linked with the presence and extent of false lumen thrombosis, and these non-invasive measures might be important in patient management. KEY POINTS: • Partial false lumen thrombosis has been associated with aortic growth in patients with chronic descending aortic dissection; therefore, the identification of prothrombotic flow conditions is desirable. • The presence of partial false lumen thrombosis as well as its extent was related with false lumen kinetic energy. • The assessment of false lumen hemodynamics may be important in the management of patients with chronic aortic dissection of the descending aorta.

Three-dimensional aortic geometry mapping via registration of non-gated contrast-enhanced or gated and respiratory-navigated MR angiographies.

BACKGROUND: The measurement of aortic dimensions and their evolution are key in the management of patients with aortic diseases. Manual assessment, the current guideline-recommended method and clinical standard, is subjective, poorly reproducible, and time-consuming, limiting the capacity to track aortic growth in everyday practice. Aortic geometry mapping (AGM) via image registration of serial computed tomography angiograms outperforms manual assessment, providing accurate and reproducible 3D maps of aortic diameter and growth rate. This observational study aimed to evaluate the accuracy and reproducibility of AGM on non-gated contrast-enhanced (CE-) and cardiac- and respiratory-gated (GN-) magnetic resonance angiographies (MRA). METHODS: Patients with thoracic aortic disease followed with serial CE-MRA (n = 30) or GN-MRA (n = 15) acquired at least 1 year apart were retrospectively and consecutively identified. Two independent observers measured aortic diameters and growth rates (GR) manually at several thoracic aorta reference levels and with AGM. Agreement between manual and AGM measurements and their inter-observer reproducibility were compared. Reproducibility for aortic diameter and GR maps assessed with AGM was obtained. RESULTS: Mean follow-up was 3.8 ± 2.3 years for CE- and 2.7 ± 1.6 years for GN-MRA. AGM was feasible in the 93% of CE-MRA pairs and in the 100% of GN-MRA pairs. Manual and AGM diameters showed excellent agreement and inter-observer reproducibility (ICC>0.9) at all anatomical levels. Agreement between manual and AGM GR was more limited, both in the aortic root by GN-MRA (ICC=0.47) and in the thoracic aorta, where higher accuracy was obtained with GN- than with CE-MRA (ICC=0.55 vs 0.43). The inter-observer reproducibility of GR by AGM was superior compared to manual assessment, both with CE- (thoracic: ICC= 0.91 vs 0.51) and GN-MRA (root: ICC=0.84 vs 0.52; thoracic: ICC=0.93 vs 0.60). AGM-based 3D aortic size and growth maps were highly reproducible (median ICC >0.9 for diameters and >0.80 for GR). CONCLUSION: Mapping aortic diameter and growth on MRA via 3D image registration is feasible, accurate and outperforms the current manual clinical standard. This technique could broaden the possibilities of clinical and research evaluation of patients with aortic thoracic diseases.

Subclinical myocardial involvement in a cohort of patients with antisynthetase syndrome.

OBJECTIVES: There is an increasing interest in knowing whether patients with antisynthetase syndrome (ASSD) may have silent myocardial interstitial involvement. Mapping techniques in cardiac magnetic resonance (CMR) can detect subclinical myocardial involvement. The purpose of this study was to identify alterations in multiparametric CMR in ASSD patients without overt cardiac involvement. METHODS: Patients diagnosed with ASSD underwent a CMR along with the standard clinical workup, investigation of specific and associated myositis antibodies, and high-resolution chest CT. The CMR protocol includes routine morphologic, functional, and late gadolinium enhancement sequences in standard cardiac planes, as well as native T1 and T2 mapping sequences and extracellular volume (ECV) calculation. RESULTS: Twenty-five patients were included in this study (56% women; median age 56.3 years). Three patients were considered in the acute phase at the time of inclusion. Eight patients (32%) showed pathological findings in CMR (6 stable disease, 2 acute phase). Elevated T1, T2 and ECV mapping values were found in 20% (5/25), 17% (4/25) and 24% (6/25) of the group, respectively. Two patients in the acute phase had increased values of both T2 and ECV. CONCLUSIONS: Subclinical myocardial involvement in ASSD is not rare (32%) although its clinical significance is uncertain. Myocardial oedema (T2) was the most frequent finding, followed by increased T1 and/or ECV values likely signalling interstitial fibrosis. Of note, patients in the acute phase showed elevated T2 values.

False lumen rotational flow and aortic stiffness are associated with aortic growth rate in patients with chronic aortic dissection of the descending aorta: a 4D flow cardiovascular magnetic resonance study.

BACKGROUND: Patency of the false lumen in chronic aortic dissection (AD) is associated with aortic dilation and long-term aortic events. However, predictors of adverse outcomes in this population are limited. The aim of this study was to evaluate the relationship between aortic growth rate and false lumen flow dynamics and biomechanics in patients with chronic, patent AD. METHODS: Patients with a chronic AD with patent false lumen in the descending aorta and no genetic connective tissue disorder underwent an imaging follow-up including a contrast-enhanced 4D flow cardiovascular magnetic resonance (CMR) protocol and two consecutive computed tomography angiograms (CTA) acquired at least 1 year apart. A comprehensive analysis of anatomical features (including thrombus quantification), and false lumen flow dynamics and biomechanics (pulse wave velocity) was performed. RESULTS: Fifty-four consecutive patients with a chronic, patent false lumen in the descending aorta were included (35 surgically-treated type A AD with residual tear and 19 medically-treated type B AD). Median follow-up was 40 months. The in-plane rotational flow, pulse wave velocity and the percentage of thrombus in the false lumen were positively related to aortic growth rate (p = 0.006, 0.017, and 0.037, respectively), whereas wall shear stress showed a trend for a positive association (p = 0.060). These results were found irrespectively of the type of AD. CONCLUSIONS: In patients with chronic AD and patent false lumen of the descending aorta, rotational flow, pulse wave velocity and wall shear stress are positively related to aortic growth rate, and should be implemented in the follow-up algorithm of these patients. Further prospective studies are needed to confirm if the assessment of these parameters helps to identify patients at higher risk of adverse clinical events.

Gender differences in outcome in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus is an independent risk factor in the development of coronary artery disease (CAD), myocardial infarction (MI), and cardiac death (CD). The major adverse cardiac events (MACEs) between men and women in diabetic patients stratified by CAD (previous MI and/or coronary revascularization, CR) were analyzed. METHODS AND RESULTS: A cohort of 1327 consecutive diabetic patients (age 66.5 ± 9 years) underwent gated SPECT (single-photon emission computed tomography). During a mean follow-up of 4.7 ± 2.2 years post gated SPECT, MACEs (non-fatal MI, CD, and late CR) were evaluated according to gender stratified by CAD. Among diabetic patients without known CAD (N = 731), men had more MACEs (sHR 1.9;95%CI 1.2-3.2) than women. Among diabetic patients with known CAD (N = 596), there was no difference in MACEs in diabetic men and women (sHR 1.15;95%CI 0.73-1.8). Diabetic women with known CAD (n = 143) were the group with the highest risk (sHR 1.7; P = .041) for MACEs (4.5% MACEs/year, [95%CI 3.1%-6.4%]), compared to the remaining diabetic patients (N = 1184) (3% MACEs/year, [95%CI 2.6%-3.5%]). CONCLUSIONS: The prognosis of diabetic patients for MACEs is different in men and women stratified by CAD. The worst prognosis for MACEs occurs in women with known CAD.

Preprocedural imaging to guide transcoronary ethanol ablation for refractory septal ventricular tachycardia.

BACKGROUND: Radiofrequency ablation (RF) of ventricular tachycardia (VT) due to intramural foci has a high recurrence rate. Several techniques, such as bipolar ablation, irrigated needle ablation catheter, and retrograde coronary venous ethanol ablation have been suggested. Transarterial coronary ethanol ablation (TCEA) can also be effective. We present a case series of TCEA guided with preprocedural imaging to correlated coronary arteries and the intramural substrate. METHODS AND RESULTS: We present three consecutive patients with previous RF of septal VT (100% male; age, 72.6 ± 11.01 years; two patients with hypertrophic cardiomyopathy, one with mechanical aortic valve prosthesis) that underwent TCEA. Cardiac magnetic resonance was performed in two patients and cardiac CT in all patients. Correlation of septal arteries with intramural substrate was analyzed before the procedure so TCEA was attempted according to this analysis. After last TCEA (6.3 ± 2.08 months) the VT burden was reduced in all patients (sum of all implantable cardioverter-defibrillator therapies [antitachycardia pacing and shock] before and after TCEA, 15.8 ± 3.73 vs 0.97 ± 0.63 therapies/month; P = 0.02). No complications occurred during TCEA. CONCLUSIONS: TCEA completely guided with previous magnetic resonance imaging and computed tomography scan to select the coronary artery in relation to the substrate seems to be feasible as an alternative strategy in cases of intramural VT refractory to RF ablation.

Improving the Diagnosis of Infective Endocarditis in Prosthetic Valves and Intracardiac Devices With 18F-Fluordeoxyglucose Positron Emission Tomography/Computed Tomography Angiography: Initial Results at an Infective Endocarditis Referral Center.

BACKGROUND: The diagnosis of infective endocarditis (IE) in prosthetic valves and intracardiac devices is challenging because both the modified Duke criteria (DC) and echocardiography have limitations in this population. The added value of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) and (18)F-FDG PET/CT angiography (PET/CTA) was evaluated in this complex scenario at a referral center with a multidisciplinary IE unit. METHODS AND RESULTS: Ninety-two patients admitted to our hospital with suspected prosthetic valve or cardiac device IE between November 2012 and November 2014 were prospectively included. All patients underwent echocardiography and PET/CT, and 76 had cardiac CTA. PET/CT and echocardiography findings were evaluated and compared, with concordant results in 54% of cases (κ=0.23). Initial diagnoses with DC at admission, PET/CT, and DC+PET/CT were compared with the final diagnostic consensus reached by the IE Unit. DC+PET/CT enabled reclassification of 90% of cases initially classified as possible IE with DC and provided a conclusive diagnosis (definite/rejected) in 95% of cases. Sensitivity, specificity, and positive and negative predictive values were 52%, 94.7%, 92.9%, and 59.7% for DC; 87%, 92.1%, 93.6%, and 84.3% for PET/CT; and 90.7%, 89.5%, 92%, and 87.9% for DC+PET/CT. Use of PET/CTA yielded even better diagnostic performance values than PET/nonenhanced CT (91%, 90.6%, 92.8%, and 88.3% versus 86.4%, 87.5%, 90.2%, and 82.9%) and substantially reduced the rate of doubtful cases from 20% to 8% (P<0.001). DC+PET/CTA reclassified an additional 20% of cases classified as possible IE with DC+PET/nonenhanced CT. In addition, PET/CTA enabled detection of a significantly larger number of anatomic lesions associated with active endocarditis than PET/nonenhanced CT (P=0.006) or echocardiography (P<0.001). CONCLUSIONS: (18)F-FDG PET/CT improves the diagnostic accuracy of the modified DC in patients with suspected IE and prosthetic valves or cardiac devices. PET/CTA yielded the highest diagnostic performance and provided additional diagnostic benefits.

The valve uptake index: improving assessment of prosthetic valve endocarditis and updating [18F]FDG PET/CT(A) imaging criteria.

AIMS: Diagnosis of prosthetic valve endocarditis (PVE) by positron emission computed tomography angiography (PET/CTA) is based on visual and quantitative morpho-metabolic features. However, the fluorodeoxyglucose (FDG) uptake pattern can be sometimes visually unclear and susceptible to subjectivity. This study aimed to validate a new parameter, the valve uptake index [VUI, maximum standardized uptake value (SUVmax)-mean standardized uptake value (SUVmean)/SUVmax], designed to provide a more objective indication of the distribution of metabolic activity. Secondly, to re-evaluate the utility of traditionally used PVE imaging criteria and determine the potential value of adding the VUI in the diagnostic algorithm of PVE. METHODS AND RESULTS: Retrospective analysis of 122 patients (135 prosthetic valves) admitted for suspicion of endocarditis, with a conclusive diagnosis of definite (N = 57) or rejected (N = 65) PVE, and who had undergone a cardiac PET/CTA scan as part of the diagnostic evaluation. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern, and the presence of endocarditis-related anatomic lesions. The VUI, SUVmax, and SUVratio values were 0.54 ± 0.1 vs. 0.36 ± 0.08, 7.68 ± 3.07 vs. 3.72 ± 1.11, and 4.28 ± 1.93 vs. 2.16 ± 0.95 in the 'definite' PVE group vs. the 'rejected' group, respectively (mean ± SD; P < 0.001). A cut-off value of VUI > 0.45 showed a sensitivity, specificity, and diagnostic accuracy for PVE of 85%, 88%, and 86.7% and increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria. CONCLUSIONS: The VUI demonstrated good diagnostic accuracy for PVE, even increasing the diagnostic power of the traditionally used morphometabolic parameters, which also confirmed their own diagnostic performance. More research is needed to assess whether the integration of the VUI into the PVE diagnostic algorithm may clarify doubtful cases and thus improve the diagnostic yield of PET/CTA.

Emergent Percutaneous Closure of a Free-Wall Perforation During Impella Implantation.

Free wall perforation during percutaneous manipulation of devices and wires into the ventricular cavities is an uncommon but life-threatening complication that should be managed with emergent surgery whenever possible. However, the number of patients with prohibitive surgical risk that undergo complex percutaneous cardiac procedures is increasing. Some cases of ventricle perforation during Impella® (Abiomed; Danvers, MA) implantation have been previously reported but in all previous reported cases the patient underwent emergent surgery. We present a case of iatrogenic perforation during Impella® implantation that was emergently treated using an Amplatzer® Duct Occluder II device (Abbott Vascular; Santa Clara, CA).

Differences in the Area of Proximal and Distal Entry Tears at CT Angiography Predict Long-term Clinical Outcomes in Aortic Dissection.

PURPOSE: To identify entry tear variables that are related to adverse clinical events by using CT angiography (CTA) performed during the subacute phase of aortic dissection. MATERIALS AND METHODS: In this prospective study conducted from January 2000 to December 2013, participants with an aortic dissection with a patent false lumen and no comorbidities underwent CTA during the subacute phase. Participants were followed up for a survival analysis to assess the time to an adverse aortic event (AAE). The maximum aortic diameter (MAD), proximal and distal tear areas and difference between these areas, and partial false-lumen thrombosis were assessed by using Cox regression for adverse events. RESULTS: Seventy-two participants (mean age, 55 years ± 12 [standard deviation]; 55 men) were evaluated: 47 were surgically treated (type A aortic dissection) and 25 were medically treated (type B aortic dissection). Twenty-two participants had an AAE manifest during follow-up (9.22 years ± 5.78): There were 18 elective surgeries for aneurysmal degeneration, two emergent surgeries for acute aortic syndrome, and two aortic condition-related deaths. A categorical model composed of genetic aortic disease (GAD) (hazard ratio [HR], 3.4 [95% CI: 1.2, 9.9]; P = .02), MAD greater than 45 mm (HR, 6.1 [95% CI: 2.4, 15.8]; P < .001), and tear dominance (HR, 5.2 [95% CI: 2.1, 13]; P < .001), defined as an absolute tear area difference of greater than 1.2 cm2, was used to stratify participants into three risk groups: low, without any risk factors (57% [41 of 72] and 7% [three of 41] had events); intermediate, with one risk factor (31% [22 of 72] and 50% [11 of 22] had events); and high, with two or more risk factors (13% [nine of 72] and 89% [eight of nine] had events; log rank P < .001). CONCLUSION: Tear dominance demonstrated at CTA performed in the subacute phase of aortic dissection was related to long-term adverse events. Participants without GAD, dominant tears, or MAD greater than 45 mm had conditions that were safely managed with optimal medical treatment and imaging follow-up.Keywords: CT Angiography, Vascular, Aorta, Dissection Supplemental material is available for this article. © RSNA, 2021See also commentary by Fleischmann and Burris in this issue.

Aortic Branch Aneurysms and Vascular Risk in Patients With Marfan Syndrome.

BACKGROUND: Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown. OBJECTIVES: The goal of this study was to assess the prevalence of aortic branch aneurysms in MFS and their relationship with aortic prognosis. METHODS: MFS patients with a pathogenic FBN1 genetic variant and at least one magnetic resonance or computed tomography angiography study assessing aortic branches were included. Aortic events and those related to aneurysm complications were recorded during follow-up. RESULTS: A total of 104 aneurysms were detected in 50 (26.7%) of the 187 patients with MFS (mean age 37.9 ± 14.4 years; 54% male) included in this study, with the iliac artery being the most common location (45 aneurysms). Thirty-one patients (62%) had >1 peripheral aneurysm, and surgery was performed in 5 (4.8%). Patients with aneurysms were older (41.9 ± 12.7 years vs. 36.7 ± 14.8 years; p = 0.040) and had more dilated aortic root (42.2 ± 6.4 mm vs. 38.8 ± 8.0 mm; p = 0.044) and dyslipidemia (31.0% vs. 9.7%; p = 0.001). In a subgroup of 95 patients with no previous aortic surgery or dissection followed up for 3.3 ± 2.6 years, the presence of arterial aneurysms was associated with a greater need for aortic surgery (hazard ratio: 3.4; 95% confidence interval: 1.1 to 10.3; p = 0.028) in a multivariable Cox analysis adjusted for age and aortic diameter. CONCLUSIONS: Aortic branch aneurysms are present in one-quarter of patients with MFS and are related to age and aortic dilation, and they independently predict the need for aortic surgery. The systematic use of whole-body vascular assessment is recommended to identify other sites of vascular involvement at risk for complications and to define the subgroup of patients with more aggressive aortic disease.

Morpho-metabolic post-surgical patterns of non-infected prosthetic heart valves by [18F]FDG PET/CTA: "normality" is a possible diagnosis.

AIMS: To define characteristic PET/CTA patterns of FDG uptake and anatomic changes following prosthetic heart valves (PVs) implantation over time, to help not to misdiagnose post-operative inflammation and avoid false-positive cases. METHODS AND RESULTS: Prospective evaluation of 37 post-operative patients without suspected infection that underwent serial cardiac PET/CTA examinations at 1, 6, and 12 months after surgery, in which metabolic features (FDG uptake distribution pattern and intensity) and anatomic changes were evaluated. Standardized uptake values (SUVs) were obtained and a new measure, the valve uptake index (VUI), (SUVmax-SUVmean)/SUVmax, was tested to homogenize SUV results.In total, 111 PET/CTA scans were performed in 37 patients (19 aortic and 18 mitral valves). FDG uptake was visually detectable in 79.3% of patients and showed a diffuse, homogeneous distribution pattern in 93%. Quantitative analysis yielded a mean maximum standardized uptake value (SUVmax) of 4.46 ± 1.50 and VUI of 0.35 ± 0.10. There were no significant differences in FDG distribution or uptake values between 1, 6, or 12 months. No abnormal anatomic changes or endocarditis lesions were detected in any patient during follow-up. CONCLUSIONS: FDG uptake, often seen in recently implanted PVs, shows a characteristic pattern of post-operative inflammation and, in the absence of associated anatomic lesions, could be considered a normal finding. These features remain stable for at least 1 year after surgery, so questioning the recommended 3-month safety period. A new measure, the VUI, can be useful for evaluating the FDG distribution pattern.

Left main coronary artery compression by a large pulmonary artery aneurysm in the absence of pulmonary hypertension: a case report.

BACKGROUND: Pulmonary artery aneurysms (PAAs) are rare and they are infrequently diagnosed due to the non-specificity of their symptoms. However, their related complications, mainly described in patients with pulmonary hypertension (PH), are associated with significant morbidity and mortality. CASE SUMMARY: We report the case of a 64-year-old woman previously operated on for pulmonary valve stenosis, who presented with rapid worsening of dyspnoea and sudden onset of chest pain. Physical examination did not show heart failure symptoms, and an echocardiogram showed significant but not severe pulmonary regurgitation with preserved right and left ventricular function. Estimated pulmonary artery (PA) pressure was normal. As myocardial ischaemia was suspected the patient underwent a coronary computed tomography angiography that showed compression of the left main coronary artery by a large PAA. Early diagnosis led to surgery that solved her symptoms. DISCUSSION: Comprehensive medical evaluation of symptomatic patients with PA dilatation, even in the absence of PH, is key to rule out the possibility of serious complications as soon as possible.

Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis.

BACKGROUND: Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. METHODS AND RESULTS: Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126-2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19-6.78]; P<0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 [95% confidence interval, 1.39-9.73]; P=0.010). CONCLUSIONS: Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.