Suchergebnisse

Background-—Data are limited on use patterns of low-dose aspirin and its role for primary prevention of cardiovascular disease (CVD) in different racial and ethnic groups. Methods and Results-—Overall, 65 231 non-Hispanic black and white people aged 40 to 79 years with no history of CVD enrolled from 2002 through 2009 in the SCCS (Southern Community Cohort Study). At cohort entry, the simplified Framingham 10-year CVD risk was calculated, and data related to low-dose aspirin use and clinical and socioeconomic covariates were collected. Raceand ethnicity-specific adjusted odds ratios for characteristics of low-dose aspirin users and hazard ratios for ischemic cardiac death according to aspirin use were calculated using multivariate logistic and Cox regression models. Black participants were less likely to take low-dose aspirin compared with white participants, regardless of CVD risk and covariates (adjusted odds ratio: 0.79; 95% CI, 0.75–0.82). Over a median follow-up of 11.3 years, low-dose aspirin use was associated with a trend toward decreased risk of ischemic cardiac death in white participants (adjusted hazard ratio: 0.86; 95% CI, 0.68–1.10), especially in women (adjusted hazard ratio: 0.72; 95% CI, 0.51–1.02), but not in black participants (adjusted hazard ratio: 1.18; 95% CI, 0.98–1.40). Similar trends were observed when the analysis was restricted to high-risk individuals aged 50 to 69 or 50 to 59 years, ages for which guidelines consider aspirin for CVD primary prevention. Conclusions-—Low-dose aspirin use for primary prevention of CVD is lower among black than white patients. Its use might be associated with a disparate impact on ischemic cardiac death according to race and ethnicity. Although additional studies are required, these findings provide no evidence of a beneficial effect of aspirin among black patients ; The SCCS (Southern Community Cohort Study) is funded by grants R01 CA092447 and U01 CA202979 from the National Cancer Institute, including American Recovery and Reinvestment Act funding (3R01 CA029447-08 S1). Data collection was performed by the Survey and Biospecimen Shared Resource, which is supported in part by the Vanderbilt– Ingram Cancer Center (P30 CA68485). This analysis forms part of a project that has received funding from the American Heart Association under grant no. 14SFRN20490315. Fernandez- Jimenez is a recipient of funding from the European Union Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no. 707642. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III; the Ministerio de Ciencia, Innovaci on y Universidades; and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).

BACKGROUND: Cardiovascular disease (CVD) is a major cause of disability and premature death. Despite European guidelines advocating the use of medical therapies in CVD, many patients still do not achieve the guideline-recommended treatment, which highlights the need for change and innovations in this field. This requirement has been widely recognised by the national ministries of health, several European cardiology societies, and the European Parliament, who support the initiation of strategies to improve and promote cardiovascular health. DISCUSSION: One of the key risk factors to recurrent cardiovascular events is the lack of adherence to medication and this has been added to the agenda of the European Commission. With the intention to improve treatment adherence in CVD, polypills have been investigated and numerous studies demonstrate that they significantly improve medication adherence, which contributes to the improvement of health outcomes. In Europe, the first cardiovascular polypill, developed by a public-private partnership (CNIC-Ferrer), recently became available for general prescription as a therapy for CVD prevention. This polypill significantly improves adherence, preventing fatal and non-fatal cardiovascular events, and appears to be a cost-effective strategy to improve sustainability of the health care systems in CVD. CONCLUSIONS: Given the importance of urgent and simple solutions to restraining the pandemic nature of CVD, the polypill approach should therefore be considered by physicians and public health systems as an available and innovative option to improve cardiovascular health.

Early metoprolol administration protects against myocardial ischemia–reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty. ; This study received funding from the Ministry of Science and Innovation ("RETOS 2019" Grant no. PID2019-107332RB-I00), from the Instituto de Salud Carlos III (ISCIII; PI16/02110) and the European Regional Development Fund (ERDF) "A way of making Europe" (# AC16/00021), and from the Spanish Society of Cardiology through a 2017 Translational Research grant. BI has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC-Consolidator Grant agreement no. 819775). M.L received support from a 2015 Severo Ochoa CNIC intramural grant. X.R. received support from the SEC-CNIC CARDIOJOVEN fellowship program. R.F-J is a recipient of funding from the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (PI19/01704) and has received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 707642. EO is recipient of funds from Programa de Atracción de Talento (2017-T1/BMD-5185) of Comunidad de Madrid.

Background: Preschool-based interventions offer promise to instill healthy behaviors in children, which can be a strategy to reduce the burden of cardiovascular disease later. However, their efficacy in underserved communities is not well established. Objectives: The purpose of this study was to assess the impact of a preschool-based health promotion educational intervention in an underserved community. Methods: This cluster-randomized controlled study involved 15 Head Start preschools in Harlem, New York. Schools and their children were randomized 3:2 to receive either a 4-month (50 h) educational intervention to instill healthy behaviors in relation to diet, physical activity, body/heart awareness, and emotion management; or their standard curriculum (control). The primary outcome was the change from baseline in the overall knowledge, attitudes, and habits (KAH) score of the children at 5 months. As secondary outcomes, we evaluated the changes in KAH subcomponents and emotion comprehension. Linear mixed-effects models were used to test for intervention effects. Results: The authors enrolled 562 preschool children age 3 to 5 years, 51% female, 54% Hispanic/Latino, and 37% African-American. Compared with the control group, the mean relative change from baseline in the overall KAH score was ∼2.2 fold higher in the intervention group (average absolute difference of 2.86 points; 95% confidence interval: 0.58 to 5.14; p = 0.014). The maximal effect was observed in children who received >75% of the curriculum. Physical activity and body/heart awareness components, and knowledge and attitudes domains, were the main drivers of the effect (p values <0.05). Changes in emotion comprehension trended toward favoring intervened children. Conclusions: This multidimensional school-based educational intervention may be an effective strategy for establishing healthy behaviors among preschoolers from a diverse and socioeconomically disadvantaged community. Early primordial prevention strategies may contribute to reducing the global burden of cardiovascular disease. (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health [FAMILIA ; This study is funded by the American Heart Association under grant No. 14SFRN20490315. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Dr. Fernandez-Jimenez is a recipient of funding from the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 707642. Dr. Bansilal is an employee of Bayer Pharmaceuticals

Unhealthy habits in children are increasing at an alarming rate. The school provides a promising setting for effective preventive strategies to improve children's lifestyle behaviors. The SI! Program is a multilevel multicomponent school-based educational intervention aimed at all stages of compulsory education in Spain. Here, we present the design of the SI! Program for Elementary School cluster-randomized controlled trial, targeting children aged 6 to 11 years. This trial aims to study the impact of different timings and intensities of exposure to SI! Program activities on elementary school children and their immediate environment (parents/caregivers, teachers, and school). The trial includes 1770 children from 48 public elementary schools in Madrid (Spain), together with their parents and teachers. Schools and their children were randomly assigned to the intervention group (the SI! curriculum-based educational program over 3 or 6 academic years) or to the control group (standard curriculum). The primary outcomes are the change from baseline at 3-year and 6-year follow-up in children's scores for knowledge, attitudes, and habits (KAH) and health factors (blood pressure, height, weight, waist circumference, and skinfold thickness). Secondary outcomes include 3-year and 6-year changes from baseline in lifestyle questionnaire scores for parents/caregivers and teachers, and in the school environment questionnaire. The overarching goal of the SI! Program is to provide an effective and sustainable health promotion program for the adoption of healthy behaviors in children. The present trial will address the impact and the optimal timing and duration of this educational intervention in the elementary school setting. (Am Heart J 2019;210:9-17.) ; This study is partly funded by the Daniel & Nina Carasso Foundation and the la Caixa Foundation (LCF/PR/CE16/ 10700001). This study forms part of a project that has received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska- Curie grant agreement No. 707642 and from the American Heart Association under grant No. 14SFRN20490315

Previous studies on the association between dietary habits and cardiovascular risk factors (CVRF) in adolescents have generated conflicting results. The aim of this study was to describe dietary patterns (DP) in a large sample of Spanish adolescents and to assess their cross-sectional relationship with CVRF. In total, 1324 adolescents aged 12.5 ± 0.4 years (51.6% boys) from 24 secondary schools completed a self-reported food frequency questionnaire. DPs were derived by cluster analysis and principal component analysis (PCA). Anthropometric measurements, blood pressure, lipid profile, and glucose levels were assessed. Linear mixed models were applied to estimate the association between DPs and CVRF. Three DP-related clusters were obtained: Processed (29.2%); Traditional (39.1%); and Healthy (31.7%). Analogous patterns were obtained in the PCA. No overall differences in CVRF were observed between clusters except for z-BMI and z-FMI values, total cholesterol, and non-HDL cholesterol, with the Processed cluster showing the lowest mean values. However, differences were small. In conclusion, the overall association between DPs, as assessed by two different methods, and most analyzed CVRF was weak and not clinically relevant in a large sample of adolescents. Prospective analysis may help to disentangle the direction of these associations ; This research was funded by the SHE Foundation, the "la Caixa" Foundation (LCF/PR/CE16//10700001 and LCF/PR/MS19/12220001), and the Fundació la Marató de TV3 (369/C/2016). R.F-J. received funding from the European Union Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie grant No 707642. Support was also provided by the Ministerio de Ciencia, Innovación y Universidades (AGL2016–75329-R) and Generalitat de Catalunya. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

BACKGROUND: Although the role of Th17 and regulatory T cells in the progression of atherosclerosis has been highlighted in recent years, their molecular mediators remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/regulatory T cell immunity, and atherosclerosis development in animal models and in patients with subclinical disease. METHODS: Low-density lipoprotein receptor-deficient chimeric mice expressing or not expressing CD69 on either myeloid or lymphoid cells were subjected to a high fat diet. In vitro functional assays with human T cells were performed to decipher the mechanism of the observed phenotypes. Expression of CD69 and NR4A nuclear receptors was evaluated by reverse transcription-polymerase chain reaction in 305 male participants of the PESA study (Progression of Early Subclinical Atherosclerosis) with extensive (n=128) or focal (n=55) subclinical atherosclerosis and without disease (n=122). RESULTS: After a high fat diet, mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/regulatory T cell ratio in blood. Oxidized low-density lipoprotein was shown to bind specifically and functionally to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% CI, 0.40-0.94; P=0.006) after adjustment for traditional risk factors, the expression of NR4A1, the level of oxidized low-density lipoprotein, and the counts of different leucocyte subsets. CONCLUSIONS: CD69 depletion from the lymphoid compartment promotes a Th17/regulatory T cell imbalance and exacerbates the development of atherosclerosis. CD69 binding to oxidized low-density lipoprotein on T cells induces the expression of anti-inflammatory transcription factors. Data from a cohort of the PESA study with subclinical atherosclerosis indicate that CD69 expression in PBLs inversely correlates with the presence of disease. The expression of CD69 remained an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors. ; Funding was provided by the Spanish Ministry of Economy and Competitiveness: Plan Nacional de Salud SAF2017-82886-R to Dr Sánchez-Madrid, SAF2015-64767-R to Dr Martínez-González; Instituto de Salud Carlos III (AES 2016): PI16/01956 to Dr Martin, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; European Research Council, ERC-2011-AdG294340-GENTRIS to Dr Sánchez-Madrid; Proyecto Integrado de Excelencia PIE13/041 and Fundació La Marató TV3 (20152330 31); and Comunidad Autónoma de Madrid CAM (S2017/BMD-3671) to Drs Martin and Sánchez-Madrid. Dr Tsilingiri is cofunded by the European Union Marie Curie Program. M. Relaño is supported by a Contratos Predoctorales Severo Ochoa para la formación de doctores (BES-2015–072625) from the Spanish Ministry of Economy and Competitiveness. This research has been cofinanced by Fondo Europeo de Desarrollo Regional. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The PESA study is cofunded equally by the Pro CNIC Foundation and Banco Santander, Madrid, Spain.

Background: Although the role of Th17 and regulatory T cells in the progression of atherosclerosis has been highlighted in recent years, their molecular mediators remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/regulatory T cell immunity, and atherosclerosis development in animal models and in patients with subclinical disease. Methods: Low-density lipoprotein receptor-deficient chimeric mice expressing or not expressing CD69 on either myeloid or lymphoid cells were subjected to a high fat diet. In vitro functional assays with human T cells were performed to decipher the mechanism of the observed phenotypes. Expression of CD69 and NR4A nuclear receptors was evaluated by reverse transcription-polymerase chain reaction in 305 male participants of the PESA study (Progression of Early Subclinical Atherosclerosis) with extensive (n=128) or focal (n=55) subclinical atherosclerosis and without disease (n=122). Results: After a high fat diet, mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/regulatory T cell ratio in blood. Oxidized low-density lipoprotein was shown to bind specifically and functionally to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% CI, 0.40-0.94; P=0.006) after adjustment for traditional risk factors, the expression of NR4A1, the level of oxidized low-density lipoprotein, and the counts of different leucocyte subsets. Conclusions: CD69 depletion from the lymphoid compartment promotes a Th17/regulatory T cell imbalance and exacerbates the development of atherosclerosis. CD69 binding to oxidized low-density lipoprotein on T cells induces the expression of anti-inflammatory transcription factors. Data from a cohort of the PESA study with subclinical atherosclerosis indicate that CD69 expression in PBLs inversely correlates with the presence of disease. The expression of CD69 remained an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors. ; Funding was provided by the Spanish Ministry of Economy and Competitiveness: Plan Nacional de Salud SAF2017-82886-R to Dr Sánchez-Madrid, SAF2015-64767-R to Dr Martínez-González; Instituto de Salud Carlos III (AES 2016): PI16/01956 to Dr Martin, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; European Research Council, ERC- 2011-AdG294340-GENTRIS to Dr Sánchez-Madrid; Proyecto Integrado de Excelencia PIE13/041 and Fundació La Marató TV3 (20152330 31); and Comunidad Autónoma de Madrid CAM (S2017/BMD-3671) to Drs Martin and Sánchez-Madrid. Dr Tsilingiri is cofunded by the European Union Marie Curie Program. M. Relaño is supported by a Contratos Predoctorales Severo Ochoa para la formación de doctores (BES-2015–072625) from the Spanish Ministry of Economy and Competitiveness. This research has been cofinanced by Fondo Europeo de Desarrollo Regional. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The PESA study is cofunded equally by the Pro CNIC Foundation and Banco Santander, Madrid, Spain

Background: Atherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored. Objectives: This study sought to determine the association between brain metabolism, subclinical atherosclerosis, and CVRFs in middle-aged asymptomatic individuals. Methods: This study included 547 asymptomatic middle-aged participants (50 ± 4 years, 82% men) from the PESA (Progression of Early Subclinical Atherosclerosis) study with evidence of subclinical atherosclerosis. Participants underwent 18F-fluorodeoxyglucose (FDG)-positron emission tomography. Global brain FDG uptake and voxel-wise analyses were used to evaluate the associations of cerebral metabolism with CVRFs and atherosclerotic plaque burden in carotids and femorals assessed by 3-dimensional vascular ultrasound. Results: Global FDG uptake showed an inverse correlation with 30-year Framingham Risk Score (FRS) (β = -0.15, p < 0.001). This association was mainly driven by the presence of hypertension (d = 0.36, p < 0.001). Carotid plaque burden was inversely associated with global brain FDG uptake (β = -0.16, p < 0.001), even after adjusting for 30-year FRS. Voxel-wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30-year FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus. Conclusions: In asymptomatic middle-aged individuals, cardiovascular risk is associated with brain hypometabolism, with hypertension being the modifiable CVRF showing the strongest association. Subclinical carotid plaque burden is also linked to reduced brain metabolism independently of CVRFs. Cerebral areas showing hypometabolism include those known to be affected in dementia. These data reinforce the need to control CVRFs early in life in order to potentially reduce the brain's midlife vulnerability to future cognitive dysfunction. ; The study also receives funding from the Instituto de Salud Carlos III, Madrid, Spain (ISCIII, PI15/02019), the European Regional Development Fund (ERDF–A Way to Build Europe) and the European Social Fund (ESF–Investing in Your Future). Dr. Cortes-Canteli was supported by a Miguel Servet type I research contract (ISCIII, CP16/00174 & MS16/00174) and the Fondo de Investigación Sanitaria (ISCIII, PI17/00590 & PI20/00819). Dr. Toribio-Fernandez was supported by the Iniciativa de Empleo Juvenil of the Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid (PEJD-2018-POST/BMD-9259). Ms. Tristão-Pereira was supported by a "la Caixa" Foundation fellowship (ID 100010434, LCF/BQ/DI19/11730052). Dr. Gispert is supported by the Ministerio de Ciencia e Innovación (MCIN; RYC-2013-13054) and Dr. B. Ibanez by the European Research Council (ERC-2018-CoG 819775-MATRIX). The CNIC is supported by the ISCIII, the MCIN, and the Pro-CNIC Foundation. The BBRC is mainly funded by the "la Caixa" Foundation (ID 100010434) under agreement LCF/PR/GN17/50300004, the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EPAD under grant agreement 115736, and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 115952. This Joint Undertaking receives support from the European Union Horizon 2020 Research and Innovation Programme and the EFPIA. Dr. Molinuevo has served as a consultant for, sat on advisory boards of, or delivered lectures in symposia sponsored by Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, and ProMIS Neurosciences. Dr. Gispert has given lectures in symposia sponsored by General Electric, Philips, and Biogen. Dr. Sanchez-Gonzalez is a Philips employee. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were associated with obesity and eight with dysglycemia in the FHS. Of 32 lipids that were available for replication for obesity and six for dyslipidemia, 28 (88%) replicated for obesity and five (83%) for dysglycemia. Four lipids were associated with longitudinal changes in body mass index and four were associated with changes in fasting blood glucose in the FHS. Conclusions: We identified and replicated several novel lipid biomarkers of key metabolic traits. The lipid moieties identified in this study are involved in biological pathways of metabolic risk and can be explored for prognostic and therapeutic utility. ; The Framingham Heart Study is funded by National Institutes of Health (NIH) contract N01-HC-25195. This study was made possible by a CRADA between BG Medicine, Inc., Boston University, and the NHLBI, and the laboratory work for this research was supported by the Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI). Analytical work was funded by the Division of Intramural Research of NHLBI as well as the Center for Information Technology, NIH, Bethesda, MD. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. The PESA study is supported by a non-competitive unrestricted grant shared between the National Center for Cardiovascular Research Carlos III (CNIC) and the Bank of Santander. The PESA study is a noncommercial study independent of the health and pharmaceutical industry. The CNIC is supported by the Spanish Ministry of Science, Innovation and Universities, the Instituto de Salud Carlos III, and the proCNIC Foundation. The study was partially funded by a grant from AstraZeneca (TANSNIP project). JMO is supported by the US Department of Agriculture, under agreement no. 8050-51000-098-00D. MPO and MJ acknowledge an Institute of Health Carlos III grant (PI 17-00134). This research was in part funded by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (PI14/00328), co-financed by FEDER funds from the European Union ('A way to built Europe'), and the Generalitat of Catalonia, Department of Health(SLT002/16/00250) and Department of Business and Knowledge(2017SGR696) to R.P. MJ is a Serra Húnter Fellow.

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI. Methods and results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320). Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI ; This study was sup-ported by grants from Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RD12/0042/0036, CB16/11/00458), Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission [ERA-CVD Joint Call (JTC2016/APCIN-ISCIII-2016), grant#AC16/00021]. The study was also partially supported by the Fundación Interhospitalaria para la Investigación Cardiovascular (FIC, Madrid, Spain), the Spanish Society of Cardiology (Dr. Pedro Zarco award) and the Heart Rhythm section of the Spanish Society of Cardiology (DFR). J.J. is supported by R01 Grant HL122352 from the National Heart Lung and Blood Institute, USA National Institutes of Health. J.A.S. is funded by the CompBioMed project, H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant#675451. D.G.L. has received financial support through the 'la Caixa' Fellowship Grant for Doctoral Studies, 'la Caixa' Banking Foundation, Barcelona, Spain.

This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold. CMR is the reference tool for cardiac imaging but is time-consuming. A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine+LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences. Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE. ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in <1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort. ; Funding included Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) Grants DTS17/00136 to Dr. Ibáñez and PI19/01704 to Dr. Fernandez-Jimenez; Spanish Society of Cardiology Translational Research Grant 2016 to Dr. Ibáñez; European Research Council ERC-CoG 819775-MATRIX to Dr. Ibáñez; Comunidad de Madrid S2017/BMD-3867-RENIM-CM to Drs. Desco and Ibáñez; and Ministerio de Ciencia e Innovación (MICINN) RETOS2019-107332RB-I00 to Dr. Ibáñez. Dr. Fernandez-Jimenez received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie Hrant Agreement No. 707642. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation. Drs. Fernandez-Jimenez, Nothnagel, Fuster, Ibáñez, and Javier Sánchez-González are inventors of a joint patent (Philips/CNIC) for the new cine imaging method here described and validated/protected under the IP #2014P00960EP. Drs. Nothnagel, Kouwenhoven, Clemence, and Javier Sánchez-González are Philips employees. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. ; Sí