Fully Three-Dimensional Hemodynamic Characterization of Altered Blood Flow in Bicuspid Aortic Valve Patients With Respect to Aortic Dilatation: A Finite Element Approach

Bicuspid aortic valve; Congenital heart disease; Magnetic resonance imagingVàlvula aòrtica bicúspide; Cardiopatia congènita; Imatges per ressonància magnèticaVálvula aórtica bicúspide; Cardiopatía congénita; Imágenes de resonancia magnéticaBackground and Purpose: Prognostic models based on cardiovascular hemodynamic parameters may bring new information for an early assessment of patients with bicuspid aortic valve (BAV), playing a key role in reducing the long-term risk of cardiovascular events. This work quantifies several three-dimensional hemodynamic parameters in different patients with BAV and ranks their relationships with aortic diameter. Materials and Methods: Using 4D-flow CMR data of 74 patients with BAV (49 right-left and 25 right-non-coronary) and 48 healthy volunteers, aortic 3D maps of seventeen 17 different hemodynamic parameters were quantified along the thoracic aorta. Patients with BAV were divided into two morphotype categories, BAV-Non-AAoD (where we include 18 non-dilated patients and 7 root-dilated patients) and BAV-AAoD (where we include the 49 patients with dilatation of the ascending aorta). Differences between volunteers and patients were evaluated using MANOVA with Pillai's trace statistic, Mann–Whitney U test, ROC curves, and minimum redundancy maximum relevance algorithm. Spearman's correlation was used to correlate the dilation with each hemodynamic parameter. Results: The flow eccentricity, backward velocity, velocity angle, regurgitation fraction, circumferential wall shear stress, axial vorticity, and axial circulation allowed to discriminate between volunteers and patients with BAV, even in the absence of dilation. In patients with BAV, the diameter presented a strong correlation (> |+/−0.7|) with the forward velocity and velocity angle, and a good correlation (> |+/−0.5|) with regurgitation fraction, wall shear stress, wall shear stress axial, and vorticity, also for morphotypes and phenotypes, some of them are correlated with the diameter. The velocity angle proved to be an excellent biomarker in the differentiation between volunteers and patients with BAV, BAV morphotypes, and BAV phenotypes, with an area under the curve bigger than 0.90, and higher predictor important scores. Conclusions: Through the application of a novel 3D quantification method, hemodynamic parameters related to flow direction, such as flow eccentricity, velocity angle, and regurgitation fraction, presented the best relationships with a local diameter and effectively differentiated patients with BAV from healthy volunteers.This work was funded by ANID – Millennium Science Initiative Program – ICN2021_004 and ANID – Millennium Science Initiative Program – NCN17_129, CONICYT-FONDECYT Postdoctorado #3170737, ANID – FONDECYT Postdoctorado #3220266, ANID Ph. D. Scholarship 21170592, ANID FONDECYT de Iniciación en Investigación #11200481, ANID FONDECYT #1181057, ANID Ph. D. Scholarship 21180391, the Spanish Society of Cardiology (SEC/FEC-INV-CLI 20/015) and the Biomedical Research Networking Center on Cardiovascular Diseases (CIBERCV). AG has received funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I)

Oral Presentation No. 121. Aortic stiffness descriptors by cardiac magnetic resonance are correlated with mechanical testing of ex-vivo aortic aneurysms specimens

Background Aortic stiffness independently predicts mayor adverse cardiovascular events and mortality in the general population. Cardiovascular magnetic resonance (CMR) permits the assessment of a number of parameters theoretically linked to aortic stiffness, such as distensibility (AD), pulse wave velocity (PWV) and proximal aorta longitudinal strain. However, no previous study validates these parameters as descriptors of aortic wall stiffness against ex-vivo mechanical testing. Materials and methods Ascending aorta (AAo) specimens were collected from 20 patients undergoing AAo replacement for aneurysms. Patients underwent a CMR protocol in the days leading to the surgery, including 4D flow CMR. Two 15×5 mm specimens (one oriented in the circumferential and the other in the longitudinal aortic direction) were extracted during surgery, and later tested controlling for extension force. Elongation was measured by laser video extensometer and the tangent of the stress-strain curve at diastolic pressure was extracted. AAo PWV and the Eh product (E being Young modulus and h wall thickness) were measured from 4D flow CMR while AD and AAo longitudinal were quantified from cine images. Results and conclusions Marked correlations were found between circumferential elastic modulus and AAo AD (R = −0.502), PWV(R = 0.652) and Eh (R = 0.602). Similarly, strong correlation was identified between AAo longitudinal strain and longitudinal elastic modulus(R = −0.513). In conclusion, PWV and the Eh product are positively related to aortic wall stiffness while aortic distensibility and strain show negative relationships. Thus, these biomarkers are a reliable expression of aortic wall stiffness

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

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). 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. 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. 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

Decreased rotational flow and circumferential wall shear stress as early markers of descending aorta dilation in Marfan syndrome: a 4D flow CMR study

Marfan syndrome; 4D flow CMR; Helical flowSíndrome de Marfan; Flujo en 4D CMR; Flujo helicoidalSíndrome de Marfan; Flux en 4D CMR; Flux helicoïdalBackground: Diseases of the descending aorta have emerged as a clinical issue in Marfan syndrome following improvements in proximal aorta surgical treatment and the consequent increase in life expectancy. Although a role for hemodynamic alterations in the etiology of descending aorta disease in Marfan patients has been suggested, whether flow characteristics may be useful as early markers remains to be determined. Methods: Seventy-five Marfan patients and 48 healthy subjects were prospectively enrolled. In- and through-plane vortexes were computed by 4D flow cardiovascular magnetic resonance (CMR) in the thoracic aorta through the quantification of in-plane rotational flow and systolic flow reversal ratio, respectively. Regional pulse wave velocity and axial and circumferential wall shear stress maps were also computed. Results: In-plane rotational flow and circumferential wall shear stress were reduced in Marfan patients in the distal ascending aorta and in proximal descending aorta, even in the 20 patients free of aortic dilation. Multivariate analysis showed reduced in-plane rotational flow to be independently related to descending aorta pulse wave velocity. Conversely, systolic flow reversal ratio and axial wall shear stress were altered in unselected Marfan patients but not in the subgroup without dilation. In multivariate regression analysis proximal descending aorta axial (p = 0.014) and circumferential (p = 0.034) wall shear stress were independently related to local diameter. Conclusions: Reduced rotational flow is present in the aorta of Marfan patients even in the absence of dilation, is related to aortic stiffness and drives abnormal circumferential wall shear stress. Axial and circumferential wall shear stress are independently related to proximal descending aorta dilation beyond clinical factors. In-plane rotational flow and circumferential wall shear stress may be considered as an early marker of descending aorta dilation in Marfan patients.This study has been funded by Instituto de Salud Carlos III through the project PI14/0106 (co-founded by European Regional Development Fund), La Marato de TV3 (project number 20151330), by Ministerio de Economia y Competitividad through Retos-Colaboracion 2016 (RTC-2016-5152-1). Guala A. has received funding from the European Union Seventh Framework Programme FP7/People under grant agreement no 267128

Unraveling Bicuspid Aortic Valve Enigmas by Multimodality Imaging: Clinical Implications

Aortic aneurysm; Bicuspid aortic valve; Computed tomographyAneurisma aòrtic; Vàlvula aòrtica bicúspide; Tomografia computadaAneurisma aórtico; Válvula aórtica bicúspide; Tomografía computadaMultimodality imaging is the basis of the diagnosis, follow-up, and surgical management of bicuspid aortic valve (BAV) patients. Transthoracic echocardiography (TTE) is used in our clinical routine practice as a first line imaging for BAV diagnosis, valvular phenotyping and function, measurement of thoracic aorta, exclusion of other aortic malformations, and for the assessment of complications such are infective endocarditis and aortic. Nevertheless, TTE is less useful if we want to assess accurately other aortic segments such as mid-distal ascending aorta, where computed tomography (CT) and magnetic resonance (CMR) could improve the precision of aorta size measurement by multiplanar reconstructions. A major advantage of CT is its superior spatial resolution, which affords a better definition of valve morphology and calcification, accuracy, and reproducibility of ascending aorta size, and allows for coronary artery assessment. Moreover, CMR offers the opportunity of being able to evaluate aortic functional properties and blood flow patterns. In this setting, new developed sequences such as 4D-flow may provide new parameters to predict events during follow up. The integration of all multimodality information facilitates a comprehensive evaluation of morphologic and dynamic features, stratification of the risk, and therapy guidance of this cohort of patients

Decreased rotational flow and circumferential wall shear stress as early markers of descending aorta dilation in Marfan syndrome : a 4D flow CMR study

Diseases of the descending aorta have emerged as a clinical issue in Marfan syndrome following improvements in proximal aorta surgical treatment and the consequent increase in life expectancy. Although a role for hemodynamic alterations in the etiology of descending aorta disease in Marfan patients has been suggested, whether flow characteristics may be useful as early markers remains to be determined. Seventy-five Marfan patients and 48 healthy subjects were prospectively enrolled. In- and through-plane vortexes were computed by 4D flow cardiovascular magnetic resonance (CMR) in the thoracic aorta through the quantification of in-plane rotational flow and systolic flow reversal ratio, respectively. Regional pulse wave velocity and axial and circumferential wall shear stress maps were also computed. In-plane rotational flow and circumferential wall shear stress were reduced in Marfan patients in the distal ascending aorta and in proximal descending aorta, even in the 20 patients free of aortic dilation. Multivariate analysis showed reduced in-plane rotational flow to be independently related to descending aorta pulse wave velocity. Conversely, systolic flow reversal ratio and axial wall shear stress were altered in unselected Marfan patients but not in the subgroup without dilation. In multivariate regression analysis proximal descending aorta axial (p = 0.014) and circumferential (p = 0.034) wall shear stress were independently related to local diameter. Reduced rotational flow is present in the aorta of Marfan patients even in the absence of dilation, is related to aortic stiffness and drives abnormal circumferential wall shear stress. Axial and circumferential wall shear stress are independently related to proximal descending aorta dilation beyond clinical factors. In-plane rotational flow and circumferential wall shear stress may be considered as an early marker of descending aorta dilation in Marfan patients. The online version of this article (10.1186/s12968-019-0572-1) contains supplementary material, which is available to authorized users

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits

Aortic stenosis; Echocardiography; Heart valve diseaseEstenosis aórtica; Ecocardiografía; Enfermedad de las válvulas del corazónEstenosi aòrtica; Ecocardiografia; Malaltia de les vàlvules cardíaquesObjectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3–30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12–0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13–0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20–0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.AGu has received funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018- 037349-I)

MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells

A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19

Background: current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. Methods: we conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. Results: the analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. Conclusions: postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)

Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial

No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.The authors thank Gerard Carot-Sans, PhD, for providing medical writing support during the revisions of the subsequent drafts of the manuscript; the personnel from the Fights Aids and Infectious Diseases Foundation for their support in administration, human resources and supply chain management; Eric Ubals (Pierce AB) and Òscar Palao (Opentic) for website and database management; Óscar Camps and OpenArms nongovernmental organization for nursing home operations; and Anna Valentí and the Hospital Germans Trias i Pujol Human Resources Department for telephone monitoring. We thank Consorci Sanitari del Maresme, Centre Sociosanitari El Carme, l'Hospital General de Granollers and occupational hazards department of Hospital Germans Trias i Pujol for their contribution with patient enrollment. We are very grateful to Marc Clotet and Natalia Sánchez who coordinated the JoEmCorono crowd-funding campaign. We thank the Hospital Germans Trias Pujol Institutional Review Board and the Spanish Agency of Medicines and Medical Devices for their prompt action for consideration and approvals to the protocol. Financial support. This work was mainly supported by the crowd-funding campaign JoEmCorono (https://www.yomecorono.com/) with contributions from more than 72 000 citizens and corporations. The study also received financial support from Laboratorios Rubió, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®). Foundation Dorneur partly funded lab equipment at Irsi-Caixa.Peer reviewe