Correlación entre la ecografía vascular 3D, resonancia magnética y tomografía por emisión de positrones en la detección y caracterización de la aterioesclerosis en aorta de conejo

La aterosclerosis es una enfermedad que genera un elevado coste tanto en lo económico como en lo social, debido a sus principales consecuencias, el infarto de miocardio y el ictus. Su estudio ha demostrado mejorar la predicción de eventos clínicos sobre los factores de riesgo convencionales, abriendo la posibilidad de incluir la imagen como parte delas estrategias de prevención, especialmente desde las fases más precoces de la enfermedad.La aterosclerosis comienza con la formación de estrías grasas en la pared vascular, que evolucionan acumulando colesterol y células inflamatorias, especialmente monocitos..

R2 prime (R2') magnetic resonance imaging for post-myocardial infarction intramyocardial haemorrhage quantification.

To assess whether R2* is more accurate than T2* for the detection of intramyocardial haemorrhage (IMH) and to evaluate whether T2' (or R2') is less affected by oedema than T2* (R2*), and thus more suitable for the accurate identification of post-myocardial infarction (MI) IMH. Reperfused anterior MI was performed in 20 pigs, which were sacrificed at 120 min, 24 h, 4 days, and 7 days. At each time point, cardiac magnetic resonance (CMR) T2- and T2*-mapping scans were recorded, and myocardial tissue samples were collected to quantify IMH and myocardial water content. After normalization by the number of red blood cells in remote tissue, histological IMH increased 5.2-fold, 10.7-fold, and 4.1-fold at Days 1, 4, and 7, respectively. The presence of IMH was correlated more strongly with R2* (r = 0.69; P = 0.013) than with T2* (r = -0.50; P = 0.085). The correlation with IMH was even stronger for R2' (r = 0.72; P = 0.008). For myocardial oedema, the correlation was stronger for R2* (r = -0.63; P = 0.029) than for R2' (r = -0.50; P = 0.100). Multivariate linear regressions confirmed that R2* values were significantly explained by both IMH and oedema, whereas R2' values were mostly explained by histological IMH (P = 0.024) and were little influenced by myocardial oedema (P = 0.262). Using CMR mapping with histological validation in a pig model of reperfused MI, R2'more accurately detected IMH and was less influenced by oedema than R2* (and T2*). Further studies are needed to elucidate whether R2' is also better suited for the characterization of post-MI IMH in the clinical setting.This study was partially supported by a competitive grant from the Carlos III Institute of Health-Fondo de Investigacion Sanitaria and the European Regional Development Fund (ERDF/FEDER) (PI16/02110), the Spanish Ministry of Science, Innovation and Universities (MICIU), ERDF/FEDER SAF2013-49663-EXP, by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European structural and investment funds. This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare. This research program is part of an institutional agreement between FIIS Fundacion Jimenez Diaz and the CNIC. The CNIC is supported by the Ministry of Science, Innovation and Universities MICIU the Instituto de Salud Carlos III (ISCiii), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (award SEV-2015-0505). X.R. has received support from the DYSEC-CNIC CARDIOJOVEN fellowship program. R.F.-J. is a recipient of funding from the European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie (Agreement No. 707642).S

Metoprolol blunts the time-dependent progression of infarct size.

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. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MICINN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Accurate quantification of atherosclerotic plaque volume by 3D vascular ultrasound using the volumetric linear array method.

Direct quantification of atherosclerotic plaque volume by three-dimensional vascular ultrasound (3DVUS) is more reproducible than 2DUS-based three-dimensional (2D/3D) techniques that generate pseudo-3D volumes from summed 2D plaque areas; however, its accuracy has not been reported. We aimed to determine 3DVUS accuracy for plaque volume measurement with special emphasis on small plaques (a hallmark of early atherosclerosis). The in vitro study consisted of nine phantoms of different volumes (small and medium-large) embedded at variable distances from the surface (superficial vs. >5 cm-depth) and comparison of 3DVUS data generated using a novel volumetric-linear array method with the real phantom volumes. The in vivo study was undertaken in a rabbit model of atherosclerosis in which 3DVUS and 2D/3D volume measurements were correlated against gold-standard histological measurements. In the in vitro setting, there was a strong correlation between 3DVUS measures and real phantom volume both for small (3.0-64.5 mm(3) size) and medium-large (91.1-965.5 mm(3) size) phantoms embedded superficially, with intraclass correlation coefficients (ICC) of 0.99 and 0.98, respectively; conversely, when phantoms were placed at >5 cm, the correlation was only moderate (ICC = 0.67). In the in vivo setting there was strong correlation between 3DVUS-measured plaque volumes and the histological gold-standard (ICC = 0.99 [4.02-92.5 mm(3) size]). Conversely, the correlation between 2D/3D values and the histological gold standard (sum of plaque areas) was weaker (ICC = 0.87 [49-520 mm(2) size]), with large dispersion of the differences between measurements in Bland-Altman plots (mean error, 79.2 mm(2)). 3DVUS using the volumetric-linear array method accurately measures plaque volumes, including those of small plaques. Measurements are more accurate for superficial arterial territories than for deep territories.S

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Estilos de Liderazgo y Desempeño Laboral de los Docentes de la Escuela de Infantería – 2019

El objetivo de este trabajo de investigación es examinar la correlación entre los estilos de liderazgo y el desempeño laboral de los docentes de la Escuela de Infantería – 2019. Siguiendo un criterio metodológico específico, se optó por un enfoque cuantitativo y un diseño no experimental. Esto permitió un nivel de correlación pertinente. Al mismo tiempo, se trabajó con una muestra censal compuesta por 28 docentes. El instrumento estuvo conformado por 24 preguntas en total, se trabajó con la escala de Likert de cinco alternativas y el resultado de confiablidad se halló por medio del estadístico Alfa de Cronbach cuya cifra fue 0.878. Para la contrastación de la hipótesis general y especificas se utilizó el coeficiente Pearson, el resultado que se obtuvo fue 0,924, valor que demostró una correlación positiva muy alta entre las variables. Dado a ello se concluyó que, existe una correlación entre los estilos de liderazgo y el desempeño laboral de los docentes de la Escuela de Infantería – 2019.The objective of this research work is to examine the correlation between leadership styles and the job performance of the teachers of the Infantry School - 2019. Following a specific methodological criterion, a quantitative approach and a non-experimental design were chosen. This allowed a relevant level of correlation. At the same time, we worked with a census sample made up of 28 teachers. The instrument consisted of 24 questions in total, we worked with the Likert scale of five alternatives and the reliability result was found through the Cronbach's Alpha statistic whose figure was 0.878. For the contrasting of the general and specific hypotheses, the Pearson coefficient was used, the result obtained was 0.924, a value that demonstrated a very high positive correlation between the variables. Given this, it was concluded that there is a correlation between leadership styles and the job performance of the teachers of the Infantry School - 2019.ChosicaEscuela de Posgrad

Plasma Metabolic Signature of Atherosclerosis Progression and Colchicine Treatment in Rabbits.

Balloon catheter endothelial denudation in New Zealand white rabbits fed high cholesterol diet is a validated atherosclerosis model. Well-characterized in terms of atherosclerosis induction and progression, the metabolic changes associated with the atherosclerosis progression remain indeterminate. Non-targeted metabolomics permits to develop such elucidation and allows to evaluate the metabolic consequences of colchicine treatment, an anti-inflammatory drug that could revert these changes. 16 rabbits underwent 18 weeks of atherosclerosis induction by diet and aortic denudation. Thereafter animals were randomly assigned to colchicine treatment or placebo for 18 weeks while on diet. Plasma samples were obtained before randomization and at 36 weeks. Multiplatform (GC/MS, CE/MS, RP-HPLC/MS) metabolomics was applied. Plasma fingerprints were pre-processed, and the resulting matrixes analyzed to unveil differentially expressed features. Different chemical annotation strategies were accomplished for those significant features. We found metabolites associated with either atherosclerosis progression, or colchicine treatment, or both. Atherosclerosis was profoundly associated with an increase in circulating bile acids. Most of the changes associated with sterol metabolism could not be reverted by colchicine treatment. However, the variations in lysine, tryptophan and cysteine metabolism among others, have shown new potential mechanisms of action of the drug, also related to atherosclerosis progression, but not previously described.M.A.I. received funding from Airbus Defense and Space through the CLX-2 program developed with Comando da Aeronáutica (COMAER) and the Brazilian Government. This work has been partially funded by the Ministerio de Ciencia, Innovación y Universidades of Spain (MICINN RTI2018-095166-B-I00), the Spanish Society of Cardiology (“Proyecto investigación traslacional” to BI), the Carlos III Institute of Health (ISCiii FIS-FEDER PI14-01427 to JM), the Ministerio de Economía, Industria y Competitividad (MINECO SAF2017-84494-C2-1R to JR-C), a project granted by the BBVA Foundation to JR-C. This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (MDM-2017-0720). The CNIC is supported by the ISCiii, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity

BACKGROUND: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. OBJECTIVES: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. METHODS: Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. RESULTS: The earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. CONCLUSIONS: T2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy.This study was partially supported by grants from the Ministerio de Ciencia, Innovacion y Universidades through the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (P116/02110), the European Regional Development Fund (SAF2013-49663-EXP), and the Spanish Society of Cardiology (FEC basic science in cardiology grant). This research program is part of an institutional agreement between the CNIC and FIIS-Fundacion Jimenez Diaz. This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare, and is part of a bilateral research program between Hospital de Salamanca Cardiology Department and the CNIC. The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades, and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505). Drs. Galan-Arriola and Villena-Gutierrez are P-FIS fellows (Instituto de Salud Carlos III). Dr. Fernandez-Jimenez has received funding through the European Union Horizon 2020 Research and Innovation program under grant MSCA-IF-GF-707642. Dr. Sanchez -Gonzalez is an employee of Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

Translational large animal model of hibernating myocardium: characterization by serial multimodal imaging

Nonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium. Here we present a large animal model of hibernating myocardium characterized by serial multimodality imaging. Yucatan minipigs underwent a surgical casein ameroid implant around the proximal left anterior descending coronary artery (LAD), resulting in a progressive obstruction of the vessel. Pigs underwent serial multimodality imaging including invasive coronary angiography, cardiac magnetic resonance (CMR), and hybrid 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT). A total of 43 pigs were operated on and were followed for 120 ± 37 days with monthly multimodality imaging. 24 pigs (56%) died during the follow-up. Severe LAD luminal stenosis was documented in all survivors. In the group of 19 long-term survivors, 17 (90%) developed left ventricular systolic dysfunction [median LVEF of 35% (IQR 32.5-40.5%)]. In 17/17, at-risk territory was viable on CMR and 14 showed an increased glucose uptake in the at-risk myocardium on 18FDG-PET/CT. The present pig model resembles most of the human hibernated myocardium characteristics and associated heart failure (systolic dysfunction, viable myocardium, and metabolic switch to glucose). This human-like model might be used to test novel interventions for nonrevascularizable coronary artery disease and ischemia heart failure as a previous stage to clinical trials.his study has been partially funded by the Horizon 2020 European Research Area Network on Cardiovascular Diseases (ERA-CVD) Joint Transnational Call “AC16/00021: FAT-4HEART,” by the Spanish Society of Cardiology through a “Translational Research grant 2019,” and by the Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) through a FIS grant (Ref # PI16/02110). Imaging phenotyping was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European structural and investment funds. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Variations in T2-Mapping-Assessed Area at Risk After Experimental Ischemia/Reperfusion.

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