Machine learning for the automatic assessment of aortic rotational flow and wall shear stress from 4D flow cardiac magnetic resonance imaging.

OBJECTIVE: Three-dimensional (3D) time-resolved phase-contrast cardiac magnetic resonance (4D flow CMR) allows for unparalleled quantification of blood velocity. Despite established potential in aortic diseases, the analysis is time-consuming and requires expert knowledge, hindering clinical application. The present research aimed to develop and test a fully automatic machine learning-based pipeline for aortic 4D flow CMR analysis. METHODS: Four hundred and four subjects were prospectively included. Ground-truth to train the algorithms was generated by experts. The cohort was divided into training (323 patients) and testing (81) sets and used to train and test a 3D nnU-Net for segmentation and a Deep Q-Network algorithm for landmark detection. In-plane (IRF) and through-plane (SFRR) rotational flow descriptors and axial and circumferential wall shear stress (WSS) were computed at ten planes covering the ascending aorta and arch. RESULTS: Automatic aortic segmentation resulted in a median Dice score (DS) of 0.949 and average symmetric surface distance of 0.839 (0.632-1.071) mm, comparable with the state of the art. Aortic landmarks were located with a precision comparable with experts in the sinotubular junction and first and third supra-aortic vessels (p = 0.513, 0.592 and 0.905, respectively) but with lower precision in the pulmonary bifurcation (p = 0.028), resulting in precise localisation of analysis planes. Automatic flow assessment showed excellent (ICC > 0.9) agreement with manual quantification of SFRR and good-to-excellent agreement (ICC > 0.75) in the measurement of IRF and axial and circumferential WSS. CONCLUSION: Fully automatic analysis of complex aortic flow dynamics from 4D flow CMR is feasible. Its implementation could foster the clinical use of 4D flow CMR. KEY POINTS: • 4D flow CMR allows for unparalleled aortic blood flow analysis but requires aortic segmentation and anatomical landmark identification, which are time-consuming, limiting 4D flow CMR widespread use. • A fully automatic machine learning pipeline for aortic 4D flow CMR analysis was trained with data of 323 patients and tested in 81 patients, ensuring a balanced distribution of aneurysm aetiologies. • Automatic assessment of complex flow characteristics such as rotational flow and wall shear stress showed good-to-excellent agreement with manual quantification.

False Lumen Flow Assessment by Magnetic Resonance Imaging and Long-Term Outcomes in Uncomplicated Aortic Dissection.

BACKGROUND: Despite the absence of clinical complications after an acute aortic dissection (AD) with persistent patent false lumen (FL), a high risk for clinical events may persist. OBJECTIVES: The aim of this study was to assess the natural evolution of noncomplicated AD and ascertain whether different FL flow patterns by magnetic resonance imaging (MRI) have independent prognostic value for AD-related events beyond established morphologic parameters. METHODS: One hundred thirty-one consecutive patients, 78 with surgically treated type A dissections and 53 with medically treated type B dissections, were followed up prospectively after acute AD with persistent patent FL in the descending aorta. Maximum aortic diameter, true lumen compression, entry tear, and partial FL thrombosis by computed tomography were assessed. Systolic antegrade true lumen and FL flow volumes and diastolic antegrade and retrograde flows were analyzed by MRI during the first year after AD. RESULTS: After a median follow-up period of 8.0 years (IQR: 4.6-10.9 years), 43 patients presented aorta-related events (25 died and 18 required endovascular treatment). FL systolic antegrade flow ≥30% with respect to total systolic antegrade flow and retrograde diastolic flow ≥80% with respect to total diastolic FL flow were predictors of aortic events. In multivariate analysis, aortic diameter >45 mm (HR: 2.91), type B dissection (HR: 2.44), and MRI flow pattern (HR: 16.87) were independent predictors of AD-related events. CONCLUSIONS: High systolic antegrade flow volume in the FL with significant diastolic retrograde flow assessed by MRI and aortic diameter >45 mm identify patients with higher risk for complications in whom more aggressive management would be indicated.

Echocardiographic assessment of COVID19 sequelae in survivors with elevated cardiac biomarkers.

AIMS: We sought to determine, using advanced echocardiography, the prevalence and type of cardiovascular sequelae after COVID19 infection with marked elevation of cardiovascular biomarkers (CVB), and their prognostic implications. METHODS: All patients admitted from March 1st to May 25th, 2020 to a tertiary referral hospital were included. Those with cardiovascular diseases or dead during admission were excluded. Patients with hs-TnI > 45 ng/L, NT-proBNP>300 pg/mL, and D-dimer >8000 ng/mL were matched with COVID controls (three biomarkers within the normal range) based on intensive care requirements and age, and separately analyzed. RESULTS: From 2025 patients, 80 patients with significantly elevated CVB and 29 controls were finally included. No differences in baseline characteristics were observed among groups, but elevated CVB patients were sicker. Follow-up echocardiograms showed no differences among groups regarding LVEF and only slight differences between groups within the normal range. Hs-TnI patients had lower myocardial work and longitudinal strain. The presence of an abnormal echocardiogram was more frequent in the elevated CVB group compared to controls (23.8 vs 10.3%, P = 0.123) but mainly associated with mild abnormalities in deformation parameters. Management did not change in any case and no major cardiovascular events except deep vein thrombosis occurred after a median follow-up of 7 months. CONCLUSION: Minimal abnormalities in cardiac structure and function are observed in COVID19 survivors without previous cardiovascular diseases who presented a significant CVB rise at admission, with no impact on patient management or short-term prognosis. These results do not support a routine screening program after discharge in this population.

Magnetic Resonance Assessment of Left Ventricular Ejection Fraction at Any Time Post-Infarction for Prediction of Subsequent Events in a Large Multicenter STEMI Registry.

BACKGROUND: Magnetic resonance imaging (MRI) is the most accurate imaging technique for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of LVEF assessment at any time after ST-segment elevation myocardial infarction (STEMI) for subsequent major adverse cardiac event (MACE) prediction is uncertain. PURPOSE: To explore the prognostic impact of MRI-derived LVEF at any time post-STEMI to predict subsequent MACE (cardiovascular death or re-admission for acute heart failure). STUDY TYPE: Prospective. POPULATION: One thousand thirteen STEMI patients were included in a multicenter registry. FIELD STRENGTH/SEQUENCE: 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences. ASSESSMENT: Post-infarction MRI-derived LVEF (reduced [r]: <40%; mid-range [mr]: 40%-49%; preserved [p]: ≥50%) was sequentially quantified at 1 week and after >3 months of follow-up. STATISTICAL TESTS: Multi-state Markov model to determine the prognostic value of each LVEF state (r-, mr- or p-) at any time point assessed to predict subsequent MACE. A P-value <0.05 was considered to be statistically significant. RESULTS: During a 6.2-year median follow-up, 105 MACE (10%) were registered. Transitions toward improved LVEF predominated and only r-LVEF (at any time assessed) was significantly related to a higher incidence of subsequent MACE. The observed transitions from r-LVEF, mr-LVEF, and p-LVEF states to MACE were: 15.3%, 6%, and 6.7%, respectively. Regarding the adjusted transition intensity ratios, patients in r-LVEF state were 4.52-fold more likely than those in mr-LVEF state and 5.01-fold more likely than those in p-LVEF state to move to MACE state. Nevertheless, no significant differences were found in transitions from mr-LVEF and p-LVEF states to MACE state (P-value = 0.6). DATA CONCLUSION: LVEF is an important MRI index for simple and dynamic post-STEMI risk stratification. Detection of r-LVEF by MRI at any time during follow-up identifies a subset of patients at high risk of subsequent events. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Registration-based semi-automatic assessment of aortic diameter growth rate from contrast-enhanced computed tomography outperforms manual quantification.

OBJECTIVES: Manual assessment of aortic diameters on double-oblique reformatted computed tomography angiograms (CTA) is considered the current standard, although the reproducibility for growth rates has not been reported. Deformable registration of CTA has been proposed to provide 3D aortic diameters and growth maps, but validation is lacking. This study aimed to quantify accuracy and inter-observer reproducibility of registration-based and manual assessment of aortic diameters and growth rates. METHODS: Forty patients with ≥ 2 CTA acquired at least 6 months apart were included. Aortic diameters and growth rate were obtained in the aortic root and the entire thoracic aorta using deformable image registration by two independent observers, and compared with the current standard at typical anatomical landmarks. RESULTS: Compared with manual assessment, the registration-based technique presented low bias (0.46 mm), excellent agreement (ICC = 0.99), and similar inter-observer reproducibility (ICC = 0.99 for both) for aortic diameters; and low bias (0.10 mm/year), good agreement (ICC = 0.82), and much higher inter-observer reproducibility for growth rates (root: ICC = 0.96 vs 0.68; thoracic aorta: ICC = 0.96 vs 0.80). Registration-based growth rate reproducibility over a 6-month-long follow-up was similar to that obtained by manual assessment after 2.7 years (LoA = [- 0.01, 0.33] vs [- 0.13, 0.21] mm/year, respectively). Mapping of diameter and growth rate was highly reproducible (ICC > 0.9) in the whole thoracic aorta. CONCLUSIONS: Registration-based assessment of aortic dilation on CTA is accurate and substantially more reproducible than the current standard, even at follow-up as short as 6 months, and provides robust 3D mapping of aortic diameters and growth rates beyond the pre-established anatomic landmarks. KEY POINTS: • Registration-based semi-automatic assessment of progressive aortic dilation on CTA is accurate and substantially more reproducible than the current standard. • The registration-based technique allows robust growth rate assessment at follow-up as short as 6 months, with a similar reproducibility to that obtained by manual assessment at around 3 years. • The use of image registration provides robust 3D mapping of aortic diameters and growth rates beyond the pre-established anatomic landmarks.

Diagnostic value of quantitative parameters for myocardial perfusion assessment in patients with suspected coronary artery disease by single- and dual-energy computed tomography myocardial perfusion imaging.

PURPOSE: To compare performance of visual and quantitative analyses for detecting myocardial ischaemia from single- and dual-energy computed tomography (CT) in patients with suspected coronary artery disease (CAD). METHODS: Eighty-four patients with suspected CAD were scheduled for dual-energy cardiac CT at rest (CTA) and pharmacological stress (CTP). Myocardial CT perfusion was analysed visually and using three parameters: mean attenuation density (MA), transmural perfusion ratio (TPR) and myocardial perfusion reserve index (MPRI), on both single-energy CT and CT-based iodine images. Significant CAD was defined in AHA-segments by concomitant myocardial hypoperfusion identified visually or quantitatively (parameter < threshold) and coronary stenosis detected by CTA. Single-photon emission CT and invasive coronary angiography were used as reference. Perfusion-parameter cut-off values were calculated in a randomly-selected subgroup of 30 patients. RESULTS: The best-performing thresholds for TPR, MPRI and MA were 0.96, 23 and 0.5 for single-energy CT and 0.97, 47 and 0.3 for iodine imaging. For both CT-imaging modalities, TPR yielded the highest area under receiver operating characteristic curve (AUC) (0.99 and 0.97 for single-energy CT and iodine imaging, respectively, in vessel-based analysis) compared to visual analysis, MA and MPRI. Visual interpretation on iodine imaging resulted in higher AUC compared to that on single-energy CT in per-vessel (AUC: 0.93 vs 0.86, respectively) and per-patient (0.94 vs 0.93) analyses. CONCLUSION: Transmural perfusion ratio on both CT-imaging modalities is the best-performing parameter for detecting myocardial ischaemia compared to visual method and other perfusion parameters. Visual analysis on CT-based iodine imaging outperforms that on single-energy CT.

Aortic flow patterns and wall shear stress maps by 4D-flow cardiovascular magnetic resonance in the assessment of aortic dilatation in bicuspid aortic valve disease.

BACKGROUND: In patients with bicuspid valve (BAV), ascending aorta (AAo) dilatation may be caused by altered flow patterns and wall shear stress (WSS). These differences may explain different aortic dilatation morphotypes. Using 4D-flow cardiovascular magnetic resonance (CMR), we aimed to analyze differences in flow patterns and regional axial and circumferential WSS maps between BAV phenotypes and their correlation with ascending aorta dilatation morphotype. METHODS: One hundred and one BAV patients (aortic diameter ≤ 45 mm, no severe valvular disease) and 20 healthy subjects were studied by 4D-flow CMR. Peak velocity, flow jet angle, flow displacement, in-plane rotational flow (IRF) and systolic flow reversal ratio (SFRR) were assessed at different levels of the AAo. Peak-systolic axial and circumferential regional WSS maps were also estimated. Unadjusted and multivariable adjusted linear regression analyses were used to identify independent correlates of aortic root or ascending dilatation. Age, sex, valve morphotype, body surface area, flow derived variables and WSS components were included in the multivariable models. RESULTS: The AAo was non-dilated in 24 BAV patients and dilated in 77 (root morphotype in 11 and ascending in 66). BAV phenotype was right-left (RL-) in 78 patients and right-non-coronary (RN-) in 23. Both BAV phenotypes presented different outflow jet direction and velocity profiles that matched the location of maximum systolic axial WSS. RL-BAV velocity profiles and maximum axial WSS were homogeneously distributed right-anteriorly, however, RN-BAV showed higher variable profiles with a main proximal-posterior distribution shifting anteriorly at mid-distal AAo. Compared to controls, BAV patients presented similar WSS magnitude at proximal, mid and distal AAo (p = 0.764, 0.516 and 0.053, respectively) but lower axial and higher circumferential WSS components (p < 0.001 for both, at all aortic levels). Among BAV patients, RN-BAV presented higher IRF at all levels (p = 0.024 proximal, 0.046 mid and 0.002 distal AAo) and higher circumferential WSS at mid and distal AAo (p = 0.038 and 0.046, respectively) than RL-BAV. However, axial WSS was higher in RL-BAV compared to RN-BAV at proximal and mid AAo (p = 0.046, 0.019, respectively). Displacement and axial WSS were independently associated with the root-morphotype, and circumferential WSS and SFRR with the ascending-morphotype. CONCLUSIONS: Different BAV-phenotypes present different flow patterns with an anterior distribution in RL-BAV, whereas, RN-BAV patients present a predominant posterior outflow jet at the sinotubular junction that shifts to anterior or right anterior in mid and distal AAo. Thus, RL-BAV patients present a higher axial WSS at the aortic root while RN-BAV present a higher circumferential WSS in mid and distal AAo. These results may explain different AAo dilatation morphotypes in the BAV population.

Computed tomography versus invasive coronary angiography: design and methods of the pragmatic randomised multicentre DISCHARGE trial.

OBJECTIVES: More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266). METHODS: In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines. RESULTS: Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences. CONCLUSIONS: The DISCHARGE trial will assess the comparative effectiveness of CT and ICA. KEY POINTS: • Coronary artery disease (CAD) is a major cause of morbidity and mortality. • Invasive coronary angiography (ICA) is the reference standard for detection of CAD. • Noninvasive computed tomography angiography excludes CAD with high sensitivity. • CT may effectively reduce the approximately 2 million negative ICAs in Europe. • DISCHARGE addresses this hypothesis in patients with low-to-intermediate pretest probability for CAD.

Evaluación del flujo retrógrado diastólico en la aorta descendente para cuantificar la insuficiencia aórtica / Descending Aorta Diastolic Retrograde Flow Assessment for Aortic Regurgitation Quantification

Introducción: El flujo diastólico retrógrado en la aorta descendente se ha relacionado con la gravedad de la insuficiencia aórtica; sin embargo, la mayoría de los parámetros vinculados con la velocidad del flujo no se encuentran validados con una técnica de imágenes de referencia. Objetivo: Evaluar la utilidad del flujo retrógrado diastólico en la aorta torácica descendente y la aorta abdominal en la cuan-tificación de la insuficiencia aórtica utilizando como referencia la resonancia magnética. Material y métodos: Se incluyeron 40 pacientes consecutivos en un estudio prospectivo de ecocardiografía y resonancia magnética. Por Doppler pulsado se analizaron los siguientes parámetros: a) la integral velocidad-tiempo del flujo retrógrado diastólico y b) la velocidad máxima telediastólica del flujo regurgitante, ambos en la aorta torácica, y c) el flujo holodiastólico inverso en la aorta abdominal. El protocolo de resonancia magnética incluyó secuencias de contraste de fase para calcular la fracción regurgitante. Valores > 30% se consideraron diagnósticos de insuficiencia aórtica grave. Resultados: Once pacientes (30%) tenían una fracción regurgitante > 30%. La integral velocidad-tiempo del flujo retrógrado diastólico demostró la mayor precisión en el diagnóstico de insuficiencia aórtica grave: ABC = 0,87; p < 0,001. Un punto de corte para la integral velocidad-tiempo del flujo retrógrado diastólico > 15 cm demostró una sensibilidad del 91% y una especificidad del 86% para detectar insuficiencia aórtica grave. El flujo pandiastólico inverso en la aorta abdominal mostró una excelente especificidad (100%) para el diagnóstico de insuficiencia aórtica grave, aunque con baja sensibilidad (50%). Conclusiones: La evaluación del flujo retrógrado diastólico en la aorta torácica descendente permite un diagnóstico adecuado de la insuficiencia aórtica grave. El flujo holodiastólico inverso, aunque es poco sensible, muestra una alta especificidad.

Multimodality Assessment of Ascending Aortic Diameters: Comparison of Different Measurement Methods.

BACKGROUND: Transthoracic echocardiography (TTE), multidetector computed tomography (MDCT), and magnetic resonance imaging (MRI) have been widely used to monitor aortic diameters, with no consensus as to the best measurement approach. Thus, the aim of this study was to establish the best measurement methods by two-dimensional (2D) TTE, MDCT, and MRI to achieve comparable aortic diameters. METHODS: One hundred forty patients with severe aortic valvular disease or aortic dilatation were prospectively evaluated using 2D TTE and MDCT (n = 70) or MRI (n = 70). The aorta was measured at three different levels: sinuses of Valsalva, sinotubular junction, and ascending aorta. Three different measurements were made by 2D TTE-inner edge to inner edge, leading edge to leading edge (L-L), and outer edge to outer edge-and then compared with the inner edge-to-inner edge and outer edge-to-outer edge measurements of cusp-to-cusp and cusp-to-commissure diameters by MDCT or MRI. Inter- and intraobserver variability was analyzed. RESULTS: Aortic diameters by 2D TTE, MDCT, and MRI showed excellent inter- and intraobserver variability using all conventions. Significant underestimation was observed of all aortic diameters assessed by 2D TTE using the inner edge-to-inner edge convention compared with those obtained by MDCT or MRI (P < .0001). However, excellent accuracy was observed by 2D TTE when the L-L convention was used and compared with the internal diameter by MDCT and MRI (mean differences, 0.6 ± 2.6 mm [P = .158] for MDCT and 0.4 ± 3.5 mm [P = .852] for MRI). Cusp-to-cusp diameters were slightly larger than cusp-to-commissure diameters. The diameter by 2D TTE using the L-L convention correlated best with the noncoronary cusp-to-right coronary cusp diameter determined by both MDCT and MRI. CONCLUSIONS: Aortic root and ascending aortic diameters measured by 2D TTE using the L-L convention showed accurate and reproducible values compared with internal diameters assessed by MDCT or MRI. This approach permits a multimodality follow-up of patients with aortic diseases and avoids disparities in measurements obtained by different conventions.

[Study of the efficacy and safety of losartan versus atenolol for aortic dilation in patients with Marfan syndrome]. / Valoración de la eficacia y la seguridad del losartán frente al atenolol en la prevención de la dilatación de la aorta en el síndrome de Marfan.

INTRODUCTION AND OBJECTIVES: Marfan syndrome is an inherited disease of the connective tissue. Recent trials have indicated the use of losartan (a transforming growth factor beta inhibitor) in these patients prevents aortic root enlargement. The aim of our clinical trial is to assess the efficacy and safety of losartan versus atenolol in the prevention of progressive dilation of the aorta in patients with Marfan syndrome. METHODS: This is a phase III clinical trial conducted in two institutions. A total of 150 subjects diagnosed with Marfan syndrome, aged between 5 and 60 years, of both sexes, and who meet the Ghent diagnostic criteria will be included in the study, with 75 patients per treatment group. It will be a randomized, double blind trial with parallel assignment to atenolol versus losartan (50 mg per day in patients below 50 kg and 100 mg per day in patients over 50 kg). Both growth and distensibility of the aorta will be assessed with echocardiography and magnetic resonance. Follow-up will be 3 years. CONCLUSIONS: Efficacy of losartan versus atenolol in the prevention of progressive dilation of the aorta, improved aortic distensibility, and prevention of adverse events (aortic dissection or rupture, cardiovascular surgery, or death) will be assessed in this study. It will also show the possible treatment benefits at different age ranges and with relation to the initial level of aortic root dilation.

Usefulness of real-time three-dimensional transoesophageal echocardiography in the assessment of chronic aortic dissection.

AIMS: To assess the usefulness of three-dimensional transoesophageal echocardiography (3D-TOE) vs. two-dimensional (2D)-TOE in the evaluation of morphological and dynamic findings of aortic dissection, and compare the results with those obtained by multi-slice computed tomography (CT). METHODS AND RESULTS: Twenty-six patients (21 men and 5 women, median age: 67 years, range: 28-74 years) diagnosed of chronic aortic dissection with patent false lumen were studied. A comprehensive 2D-TOE and a real-time 3D-TOE study targeted at assessing dissection variables were performed and compared with CT within 3 months. Both 3D-TOE and 2D-TOE visualized the intimal flap extension and presence of flow in aortic dissection lumina in the same aortic segments. Three-dimensional TOE correctly identified true lumen in all cases, being superior to 2D-TOE in three cases with a spiroidal course of the dissection in descending aorta. Maximum entry tear diameter measured by 3D-TOE showed a better correlation with CT than 2D-TOE (0.96 and 0.87, P< 0.001, respectively). Compared with CT, 2D-TOE underestimated maximum entry tear diameter (-1.75 ± 3.28 mm, P< 0.01) but 3D-TOE did not (-0.20 ± 1.92 mm, P: n.s.). However, entry tear area measured by 3D-TOE and CT showed the best correlation (r: 0.97) and agreement (0.05 ± 0.20 cm(2), P: n.s.). CONCLUSION: Three-dimensional TOE provides additional information to 2D-TOE in aortic dissection assessment, particularly in entry tear size quantification. Agreement between entry tear area defined by 3D-TOE and CT was excellent. Three-dimensional TOE permits better morphological and dynamic understanding of aortic dissection when the flap is spiroidal.