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INTRODUCTION AND OBJECTIVES According to the wavefront phenomenon described in the late 1970s, myocardial infarction triggered by acute coronary occlusion progresses with increasing duration of ischemia as a transmural wavefront from the subendocardium toward the subepicardium. However, whether wavefront progression of necrosis also occurs laterally has been disputed. We aimed to assess the transmural and lateral spread of myocardial damage after acute myocardial infarction in humans and to evaluate the impact of metoprolol on these. METHODS We assessed myocardial infarction in the transmural and lateral dimensions in a cohort of 220 acute ST-segment elevation myocardial infarction (STEMI) patients from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). The patients underwent cardiac magnetic resonance imaging at 5 to 7 days and 6 months post-STEMI. RESULTS On day 5 to 7 post-STEMI cardiac magnetic resonance, there was a strong linear correlation between the transmural and lateral extent of infarction (delayed gadolinium enhancement) (r=-0.88; P

Resumen Introduccion y objetivos Esta establecido que la necrosis secundaria a una oclusion coronaria se inicia en el subendocario y progresa hacia el subepicardio. Sin embargo, hay controversia sobre la posibilidad de que la onda de progresion del infarto sea lateral, ademas de transmural, y es el objetivo de este trabajo. Metodos Se estudio la extension del infarto en las dimensiones transmural y lateral en 220 pacientes con infarto agudo de miocardio del ensayo METOCARD-CNIC (Efecto del metoprolol en la cardioproteccion durante un infarto agudo de miocardio). Los pacientes se sometieron a 2 resonancias magneticas. Resultados En la resonancia de los dias 5-7 posinfarto, se encontro una fuerte correlacion lineal entre las extensiones transmural y lateral del infarto (realce tardio de gadolinio) (r = -0,88; p Conclusiones Nuestros hallazgos cuestionan el dogma de que la progresion del infarto solo se produce en sentido transmural. Mostramos que el infarto progresa de forma circunferencial (en sentido tanto transmural como lateral). Esto implica que las terapias cardioprotectoras pueden asociarse con miocardio salvado en los bordes laterales del infarto. Este estudio ha sido registrado en ClinicalTrial.gov (Identificador: NCT01311700).

Resumen Introduccion El diagnostico de enfermedad inflamatoria intestinal (EII) se realiza, en un alto porcentaje, durante la edad reproductiva. La EII en remision es el mejor escenario para planificar el embarazo. Objetivos Describir las caracteristicas clinicas del embarazo y del recien nacido, evaluando la actividad de la enfermedad en el momento de la concepcion y en la evolucion del embarazo en un centro terciario en Chile. Metodos Estudio observacional, retrospectivo, incluyo a mujeres con EII que habian tenido un parto durante 2017-2020. Los datos demograficos, clinicos y obstetricos se obtuvieron del Registro de EII. Se realizo analisis estadistico descriptivo y de asociacion (χ2, p ≤ 0,05). Resultados Se incluyeron 60 mujeres en el estudio. Al inicio del embarazo, 21 (35%) presentaban actividad inflamatoria y 39 (65%) estaban en remision. Del grupo con actividad, 16 (66%) permanecieron activas y seis tuvieron un aborto espontaneo. Aquellas en remision, 26 (69%) permanecieron en esta condicion; nueve pacientes (15%) habian suspendido el tratamiento, seis de las cuales presentaron actividad durante el embarazo. El consejo preconcepcional fue realizado en 23/60 pacientes, siendo mayor en el grupo que permanecio en remision durante el embarazo (65% vs. 35%, p = 0,02). Pacientes con brotes durante el embarazo tuvieron mayor probabilidad de embarazo pretermino ( Conclusion La remision durante el embarazo presenta los mejores resultados y el consejo preconcepcional permite un mejor control de la EII durante el embarazo.

espanolIntroduccion El tratamiento de la enfermedad inflamatoria intestinal (EII) puede aumentar el riesgo de infeccion. La inmunizacion es parte del manejo integral de la atencion de estos pacientes. El objetivo de este estudio es describir la prescripcion y adherencia a la vacunacion en pacientes con EII e identificar los posibles factores asociados a esta. Metodos Estudio analitico, descriptivo, transversal en pacientes de un Programa de EII de Chile, entre abril y junio de 2019. A los pacientes se les solicito responder un cuestionario acerca de la adherencia a la vacunacion. La informacion de las vacunas se obtuvo del Registro Nacional de Inmunizaciones. Se realizo analisis estadistico descriptivo y de asociacion (χ2; p Resultados Se incluyeron 243 pacientes con EII (148 colitis ulcerosa [CU], 86 enfermedad de Crohn [EC] y 9 EII no clasificable). Solo 6 pacientes (2%) recibieron el esquema de inmunizacion completo. Las vacunas con los mayores porcentajes fueron contra la influenza (67%), virus hepatitis B (40%), neumococica 13-valente (34%) y neumococica 23-polisacarida (16%), siendo las dos primeras mas frecuentes en EC vs. CU (p ≤ 0,05). La administracion de la vacuna contra la influenza ha aumentado significativamente, alcanzando un 67% el 2019. La encuesta mostro que el 23% no ha sido inmunizado con ninguna vacuna, principalmente por falta de tiempo, falta de prescripcion medica y el alto costo economico. Conclusiones En esta cohorte, aunque las tasas de vacunacion son mas altas que las reportadas previamente, la adherencia al programa de inmunizacion debe mejorar, siendo consideradas desde el diagnostico por el equipo multidisciplinario. EnglishIntroduction Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunizations in IBD and identify possible associated factors. Methods A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary center in Chile, between April – June 2019. Patients were asked to answer a vaccine survey and information also was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p Results A total of 243 patients were included (148 ulcerative colitis (UC), 86 Crohn's disease (CD) and 9 non-classifiable IBD). Only six patients (2%) of IBD patients received a complete immunization schedule. The highest vaccine rates were against influenza (67%), hepatitis B virus (40%), 13-valent pneumococcal (34%) and 23-polysaccharide pneumococcal (16%). The influenza vaccine rate has significantly increased, reaching 67% in 2019. The survey showed that 23% of patients have not been immunized with any vaccine, mainly due to lack of time, lack of medical prescription and high cost. Conclusions In this cohort, although vaccination rates are higher than previously reported, adherence to IBD immunization program would be improved, being considered since diagnosis by the multidisciplinary team.

The prevalence of inflammatory bowel disease (IBD) increased in the last decades. Thus, the number of pregnant women with the condition is also increasing. Given that active disease itself is the main risk factor for complications during pregnancy, it is necessary to achieve a complete remission before planning a pregnancy. Also, pregnant women with IBD must be monitored noninvasively and be treated proactively, including escalated therapies, if needed, to prevent potential flares during pregnancy. Patients can undergo vaginal delivery in most forms of IBD. However, cesarean delivery is still preferable in women with a history of ileal pouch-anal anastomoses (IPAA) or active perianal disease.

Background Checkpoint inhibitors (CPIs) such as Pembrolizumab have recently become the standard treatment for Non-Small Cell Lung Cancers (NSCLC) in patients without Epidermal Growth Factor (EGFR) gene alterations. Previous reports suggest no significant benefit from CPI treatments among EGFR mutant NSCLC patients and recommend the use of Tyrosine Kinase Inhibitors such as Afatinib. Case presentation: Herein, we report a rare case of a 39-year old, light-smoker woman with a metastatic EGFR mutant NSCLC (exon-19 deletion) that exhibited rapid progression and an unusual clinical response to Afatinib without changes in tumor histology. Tumor was negative for PDL1. Biopsy analyses by NGS prior and after Afatinib treatment indicated an increase in focal somatic copy number alterations (fSCNAs) but no T790M or c-MET amplification, and a low Tumor Mutational Burden (TMB). Given her rapid progression and deterioration, and despite its PDL1- status and her low TMB patient started treatment with Pembrolizumab plus chemotherapy. Surprisingly, patient displayed a complete response after just 4 cycles and is soon to complete a year in remission. Conclusions We speculate intratumoral heterogeneity, the combination of radiotherapy plus immunotherapy or the concomitant use of chemotherapy plus immunotherapy could explain the observed response in this patient. Also, based in our data we suggest the SBRT/CPI combination could be an option for Tyrosine Kinase Inhibitor-refractory EGFR mutant NSCLC patients or as a second-line treatment.

Delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging requires novel and time-efficient approaches to characterize the myocardial substrate associated with ventricular arrhythmia in patients with ischemic cardiomyopathy. Using a translational approach in pigs and patients with established myocardial infarction, we tested and validated a novel 3D methodology to assess ventricular scar using custom transmural criteria and a semiautomatic approach to obtain transmural scar maps in ventricular models reconstructed from both 3D-acquired and 3D-upsampled-2D-acquired LGE-CMR images. The results showed that 3D-upsampled models from 2D LGE-CMR images provided a time-efficient alternative to 3D-acquired sequences to assess the myocardial substrate associated with ischemic cardiomyopathy. Scar assessment from 2D-LGE-CMR sequences using 3D-upsampled models was superior to conventional 2D assessment to identify scar sizes associated with the cycle length of spontaneous ventricular tachycardia episodes and long-term ventricular tachycardia recurrences after catheter ablation. This novel methodology may represent an efficient approach in clinical practice after manual or automatic segmentation of myocardial borders in a small number of conventional 2D LGE-CMR slices and automatic scar detection. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación and the ProCNIC Foundation (Madrid, Spain). The CNIC and the Barcelona Supercomputing Center (BSC, Barcelona, Spain) are Severo Ochoa Centers of Excellence (SEV-2015-0505 and SEV-2011-0067, respectively). This study was also supported by grants from the Fondo Europeo de Desarrollo Regional (CB16/11/00458), the Ministerio de Ciencia e Innovación (PID2019-109329RB-I00) and the Heart Rhythm Association of the Spanish Society of Cardiology (ARC). The study was also part of a Master Research Agreement between CNIC and Philips Healthcare. The study was partially supported by the Fundación Interhospitalaria para la Investigación Cardiovascular (FIC, Madrid, Spain) and the Fundación Eugenio Rodríguez Pascual (Madrid, Spain). J.A.-S. is funded by the CompBioMed2 project grant agreement 823712, H2020-EU.1.4.1.3 European Union’s Horizon 2020 research and innovation program, the SILICOFCM project, grant agreement 777204, H2020-EU.3.1.5 and by a Ramón y Cajal fellowship (RYC-2017-22532), MINECO, Spain. L.K.G was funded by the Fundación Carolina-BBVA. Grant TEC2017-82408-R is also acknowledged. Peer Reviewed "Article signat per 25 autors/es: Susana Merino-Caviedes, Lilian K. Gutierrez, José Manuel Alfonso-Almazán, Santiago Sanz-Estébanez, Lucilio Cordero-Grande, Jorge G. Quintanilla, Javier Sánchez-González, Manuel Marina-Breysse, Carlos Galán-Arriola, Daniel Enríquez-Vázquez, Carlos Torres, Gonzalo Pizarro, Borja Ibáñez, Rafael Peinado, Jose Luis Merino, Julián Pérez-Villacastín, José Jalife, Mariña López-Yunta, Mariano Vázquez, Jazmín Aguado-Sierra, Juan José González-Ferrer, Nicasio Pérez-Castellano, Marcos Martín-Fernández, Carlos Alberola-López & David Filgueiras-Rama"

Besides its protective effect against neutrophil-mediated injury at reperfusion, intravenous (IV) metoprolol was recently shown to reduce the progression of ischemic injury in a pig model of ST-segment elevation myocardial infarction (STEMI). Here, we tested the hypothesis that IV metoprolol administration in humans with ongoing STEMI blunts the time‑dependent progression of ischemic injury assessed by serial electrocardiogram (ECG) evaluations before reperfusion. The METOCARD-CNIC trial randomized 270 anterior STEMI patients to IV metoprolol or control before reperfusion by percutaneous coronary intervention (PCI). In 139 patients (69 IV metoprolol, 70 controls), two ECGs were available (ECG-1 before randomization, ECG-2 pre-PCI). Between-group ECG differences were analyzed using univariate and multivariate regression models. No significant between-group differences were observed on ECG-1. On ECG-2, patients who received IV metoprolol had a narrower QRS than those in the control group (84 ms vs. 90 ms, p = 0.029), a lower prevalence of QRS distortion (10% vs. 26%, p = 0.017), and a lower sum of anterior and total ST-segment elevation (10.1 mm vs. 13.6 mm, p = 0.014 and 10.4 mm vs. 14.0 mm, p = 0.015, respectively). Adjusted analysis revealed similar results. Significant associations were observed between ECG-2 variables and cardiac magnetic resonance imaging measurements (extent of myocardial edema, infarct size, microvascular obstruction, and left-ventricular ejection fraction) after STEMI. In summary, IV metoprolol administration before reperfusion ameliorates ECG markers of myocardial ischemia in anterior STEMI patients. These data confirm that IV metoprolol is able to reduce ischemic injury and highlight the ability of ECG analysis to provide relevant real-time information on the effect of cardioprotective therapies before reperfusion. Spanish Ministry of Science and Innovation (MICINN) RETOS2019-107332RB-I00 to B.I. Instituto de Salud Carlos III (ISCIII) PI19/01704 to R.F-J. European Research Council ERC-CoG 819775-MATRIX to B.I. European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 707642 to R.F-J. The METOCARD-CNIC trial was sponsored by the CNIC (Translational Grant 01-2009), the Spanish National Ministry of Health and Social Policy (EC10-042), and the Mutua Madrileña Foundation (AP8695-2011). This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015–0505). Sí

The calcified nodule has been established as the least common underlying substrate in the acute coronary syndrome; however calcium can be widely present in other acute-common scenarios. In this setting, the optical coherence tomography (OCT) study has identified 3 different types of calcification according to morphology. Former studies have already documented calcified nodules in patients with peripheral artery disease; however the different patterns that exist beyond coronary arteries remain unknown. An 80-year-old patient was referred for coronary angiography following systolic dysfunction. The coronary angiography performed through right radial approach showed a severely calcified vessel (mid portion of the left anterior descending artery) and mitral and aortic calcification. The OCT pullback performed with 6 mL of contrast at 3 mm/seg through the radial artery removed 4 cm of the radial sheath and showed multiple calcified plaques (mid portion of the artery) defined by the presence of superficial, well-established, low-backscattering and heterogeneous regions (video 1 of the supplementary data). The simultaneous angiography co-registration confirmed the presence of ulnar artery occlusion.

Objectives This study sought to evaluate the effect of early intravenous metoprolol on left ventricular (LV) strain assessed with feature-tracking cardiovascular magnetic resonance (CMR). Background Early intravenous metoprolol before primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) portends better outcomes in the METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial. Methods A total of 197 patients with acute anterior STEMI who were enrolled in the METOCARD-CNIC trial (100 allocated to intravenous metoprolol before primary PCI and 97 control patients) were evaluated. LV global circumferential strain (GCS) and global longitudinal strain (GLS) were measured with feature-tracking CMR at 1 week and 6 months after STEMI and compared between randomization groups. Results Patients who received early intravenous metoprolol had significantly more preserved LV strain compared with the control patients at 1 week after STEMI (GCS −13.9 ± 3.8% vs. −12.6 ± 3.9%, respectively; p = 0.013; GLS −11.9 ± 2.8% vs. −10.9 ± 3.2%, respectively; p = 0.032). In both groups, LV strain significantly improved during follow-up (mean difference between 6-month and 1-week strain for the metoprolol group: GCS −2.9%, 95% confidence interval [CI]: −3.5% to −2.4%; GLS: −2.9%, 95% CI: −3.4% to −2.4%; both p Conclusions In patients with anterior STEMI, early administration of intravenous metoprolol before primary PCI was associated with significantly fewer patients with severely depressed LV GCS and GLS, both at 1 week and 6 months. Feature-tracking CMR represents a complementary tool to evaluate the benefits of cardioprotective therapies. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion [METOCARD-CNIC]: NCT01311700)

Anti-tumour necrosis factor α therapy in inflammatory bowel disease has been shown to be effective in clinical practice. After more than a decade using these therapies the question arises about whether there is an appropriate time to suspend these therapies, and how this should be done. This review aims to evaluate the current evidence on these topics concerning anti-tumour necrosis factor α therapies, and eventually identify conditions and subgroups of patients that could potentially be candidates for withdrawal.

Resumen La efectividad de la terapia con farmacos antifactor de necrosis tumoral α en la enfermedad inflamatoria intestinal ha sido probada en la practica clinica. Tras mas de una decada de uso de este tipo de farmacos, surge la interrogante acerca de si existe un momento apropiado para suspender estas terapias, y de que manera esta debiera realizarse. Esta revision tiene por objetivo evaluar la evidencia actual acerca del retiro de la terapia con antifactor de necrosis tumoral α y, eventualmente, identificar las condiciones o los subgrupos de pacientes potencialmente candidatos a la suspension o el retiro de esta.

Background: Post-COVID-19 patients may incur myocardial involvement secondary to systemic inflammation. Our aim was to detect possible oedema/diffuse fibrosis using cardiac magnetic resonance imaging (CMR) mapping and to study myocardial deformation of the left ventricle (LV) using feature tracking (FT). Methods: Prospective analysis of consecutively recruited post-COVID-19 patients undergoing CMR. T1 and T2 mapping sequences were acquired and FT analysis was performed using 2D steady-state free precession cine sequences. Statistical significance was set to p

Small bowel adenocarcinoma (SBA) is a rare malignancy characterized by poor prognosis. Recent efforts have sought to elucidate the genetic landscape and the molecular drivers behind this disease. Herein, we report the main molecular alterations in two metastatic (stage IV) SBA patients. Interestingly, one of them had gene alterations that affected signaling pathways previously described for SBA. However, a second patient displayed previously unreported alterations in this particular tumor type. Based on these findings we discuss potential treatment options for patients affected by this rare, aggressive disease.

Aims There is a lack of evidence regarding the benefits of β-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF). Methods and results The tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of β-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF >40%, and no history of heart failure (HF). At discharge, patients will be randomized 1:1 to β-blocker therapy (agent and dose according to treating physician) or no β-blocker therapy. The primary endpoint is a composite of all-cause death, non-fatal reinfarction, or HF hospitalization over a median follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Key secondary endpoints include the incidence of the individual components of the primary composite endpoint, the incidence of cardiac death, and incidence of malignant ventricular arrhythmias or resuscitated cardiac arrest. The primary endpoint will be analysed according to the intention-to-treat principle. Conclusion The REBOOT trial will provide robust evidence to guide the prescription of β-blockers to patients discharged after MI without reduced LVEF.

Aims: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and results: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. Conclusion: In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC. Fil: Galán Arriola, Carlos. Centro de Investigacion Biomedica En Red.; España Fil: Villena Gutiérrez, Rocio. Centro de Investigacion Biomedica En Red.; España Fil: Higuero Verdejo, María I.. Centro Nacional de Investigaciones Cardiovasculares; España Fil: Díaz Rengifo, Iván A.. Centro Nacional de Investigaciones Cardiovasculares; España Fil: Pizarro, Gonzalo. Centro de Investigacion Biomedica En Red.; España Fil: López, Gonzalo J.. Centro Nacional de Investigaciones Cardiovasculares; España Fil: de Molina Iracheta, Antonio. Centro Nacional de Investigaciones Cardiovasculares; España Fil: Pérez Martínez, Claudia. Universidad de Leon. Facultad de Veterinaria; Argentina Fil: García, Rodrigo Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: González Calle, David. Centro de Investigacion Biomedica En Red.; España Fil: Lobo, Manuel. Centro de Investigacion Biomedica En Red.; España Fil: Sánchez, Pedro L.. Centro de Investigacion Biomedica En Red.; España Fil: Oliver, Eduardo. Centro de Investigacion Biomedica En Red.; España Fil: Córdoba, Raúl. Hospital Fundacion Jimenez Diaz; España Fil: Fuster, Valentin. Centro Nacional de Investigaciones Cardiovasculares; España Fil: Sánchez González, Javier. No especifíca; Fil: Ibanez, Borja. Centro de Investigacion Biomedica En Red.; España

Introduction Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect occurring in a significant proportion of patients. Irreversible mitochondrial damage is a central mechanism of AIC. Despite many efforts, there is a lack of therapies able to prevent AIC. Remote ischemic preconditioning (RIPC) could be a promising therapy to prevent AIC due to the scheduled application of chemotherapy in cancer patients. Purpose To evaluate the cardioprotective efficacy of RIPC in large animal model of AIC. Methods Large-White pigs (n=20) underwent a validated protocol of AIC consisting on five intracoronary doxorubicin injections (0.45 mg/kg), on weeks 0, 2, 4, 6, 8 of the study. Pigs were randomized before the initiation of the study to remote ischemic pre-conditioning (RIPC, 3 cycles of 5 min lower limb ischemia followed by 5 min reperfusion) or sham procedure immediately before doxorubicin injections. An additional group of 10 pigs without any exposure to doxorubicin was carried out as controls. Pigs underwent a comprehensive serial cardiac magnetic resonance (CMR) exam baseline, and on weeks 6, 8, 12, and 16. After 16-week CMR, pigs were sacrificed and tissue samples collected. A second group of 10 pigs (randomized 1:1 for RIPC) underwent the same protocol but were sacrificed 2 weeks after the third doxorubicin dose for early evaluation of tissue changes. Primary endpoint of the study was CMR-based left ventricular ejection fraction on week 16. Results Until week 6 (time of fourth doxorubicin injection), LVEF remained unchanged in both groups. From there on, a progressive decline in LVEF was observed. LVEF depression trajectory was blunted in RIPC animals. Compared to controls, pigs undergoing RIPC before each doxorubicin dose had a significantly higher LVEF at week 16: median (IQR) 45% (27–50%) vs 33% (19–47%) in RIPC and controls respectively, p=0.04. Improvement in LVEF was mainly due to a more preserved contractile function, as evidence by smaller LVESV, and better regional contractile function. After 3 doxorubicin doses, a time where global (LVEF) and regional contractile function was still unchanged, transmission electron microscopy (TEM) showed fragmented mitochondria with remodeled cristae only in control pigs. At the end of the 16 weeks, TEM evaluation in control pigs (as compared to RIPC pigs) showed overt cardiomyocyte's mitochondrial fragmentation with overt structural derangement. At this time, RIPC pigs had significantly less interstitial fibrosis on histology. Conclusions In a translatable large animal model of AIC, RIPC applied immediately before each doxorubicin cycle resulted in a preservation of cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented the deleterious effects of doxorubicin on mitochondria since early stages of AIC. RIPC is a promising intervention to be tested in clinical trials to prevent cardiotoxicity. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovaciόn and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

The aim of the present study was to investigate the long-term impact of early intravenous metoprolol in ST-segment elevation myocardial infarction (STEMI) patients in terms of left ventricular (LV) strain with feature-tracking cardiovascular magnetic resonance (CMR) and its association with prognosis. A total of 270 patients with first anterior STEMI enrolled in the randomized METOCARD-CNIC clinical trial, assigned to receive up to 15 mg intravenous metoprolol before primary percutaneous coronary intervention versus conventional STEMI therapy, were included. LV global circumferential (GCS) and longitudinal (GLS) strain were assessed with feature-tracking CMR at 1 week after STEMI in 215 patients. The occurrence of major adverse cardiac events (MACE) at 5-year follow-up was the primary end point. Among 270 patients enrolled, 17 of 139 patients assigned to metoprolol arm and 31 of 131 patients assigned to control arm experienced MACE (hazard ratio [HR] 0.500, 95% confidence interval [CI] 0.277 to 0.903; p = 0.022). Impaired LV GCS and GLS strain were significantly associated with increased occurrence of MACE (GCS: HR 1.208, 95% CI 1.076 to 1.356, p =0.001; GLS: HR 1.362, 95% CI 1.180 to 1.573, p < 0.001). On multivariable analysis, LV GLS provided incremental prognostic value over late gadolinium enhancement (LGE) and LV ejection fraction (LVEF) (LGE + LVEF chi-square = 12.865, LGE + LVEF + GLS chi-square = 18.459; p =0.012). Patients with GLS ≥-11.5% (above median value) who received early intravenous metoprolol were 64% less likely to experience MACE than their counterparts with same degree of GLS impairment (HR 0.356, 95% CI 0.129 to 0.979; p = 0.045). In conclusion, early intravenous metoprolol has a long-term beneficial prognostic effect, particularly in patients with severely impaired LV systolic function. LV GLS with feature-tracking CMR early after percutaneous coronary intervention offers incremental prognostic value over conventional CMR parameters in risk stratification of STEMI patients. METOCARD-CNIC trial work was partially supported by the Centro Nacional de Investigaciones Cardiovasculares (CNIC), through CNIC Translational Grant 01-2009. Other sponsors were the Spanish Ministry of Health and Social Policy (EC10-042), the MutuaMadrileña Foundation (AP8695-2011), and a Master Research Agreement (MRA) between Philips healthcare and the CNIC. Dr Ibáñez is recipient of the ISCIII Fondo de Investigación Sanitaria grants and ERDF/FEDER funds (PI16/02110, DTS17/00136, PI13/01979, SAF2015-71613-REDI) related to this topic. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades (MICINN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Dr. Bucciarelli-Ducci is supported by the Bristol National Institute of Health Research (NIHR) Biomedical Research Centre (BRC). Sí

Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (totaln = 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 approximate to 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 Sklodowska-Curie grant agreement No 707642. EO is recipient of funds from Programa de Atraccion de Talento (2017-T1/BMD-5185) of Comunidad de Madrid. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovacion (MICINN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).

In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy.To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile.We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05).Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014).Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.

Background The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1–6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. Aim The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. Methods A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 h post infusion and late reactions for more than 24 h. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p Results Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2–66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. Conclusions In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.

Background Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunizations in IBD and identify possible associated factors. Methods A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary center in Chile, between April – June 2019. Patients were asked to answer a vaccine survey and information also was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p Results A total of 243 patients were included (148 ulcerative colitis (UC), 86 Crohn´s disease (CD) and 9 non-classifiable IBD). Only six patients (2%) of IBD patients received a complete immunization schedule. The highest vaccine rates were against influenza (67%), hepatitis B virus (40%), 13-valent pneumococcal (34%) and 23-polysaccharide pneumococcal (16%). The influenza vaccine rate has significantly increased, reaching 67% in 2019. The survey showed that 23% of patients have not been immunized with any vaccine, mainly due to lack of time, lack of medical prescription and high cost. Conclusion In this cohort, although vaccination rates are higher than previously reported, adherence to IBD immunization program would be improved, being considered since diagnosis by the multidisciplinary team.

Inflammatory bowel disease requires long-term treatment to maintain disease control. Favorable follow-up of patients indicates attention from a multidisciplinary team, in which the nurse's responsibilities have great importance. The aim of this observational, descriptive study was to describe the role of an inflammatory bowel disease nurse in the management of patients in a tertiary center in Chile, including all patients in follow-up between January 2016 and April 2017. Inflammatory bowel disease nurse contacts were recorded and classified. Demographic data, clinical variables, and patient satisfaction were also analyzed. A total of 597 patients (51%) were in follow-up over the 16-month period; 63% had ulcerative colitis, with a median age of 35 years. The inflammatory bowel disease nurse performed 760 contacts in 253 patients (42% of the follow-up patients). The most frequent nurse interventions were reinforcement of medical indications (42%), assessment of laboratory results (17%), and disease follow-up (12%); 49% related to education. Nurse interventions were focused in more severely ill patients; flares during the follow-up, biological therapy, immunomodulators, and steroids were all statistically significant. Of a sample of 107 patients surveyed, 96% perceived the inflammatory bowel disease program as excellent/good. The inflammatory bowel disease nurse plays an important role in the follow-up and management, specifically in education, of more severely ill patients.

Sin financiación 14.805 JCR (2020) Q1, 8/142 Cardiac & Cardiovascular Systems 5.790 SJR (2020) Q1, 5/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

ObjectiveThe effect of early intravenous (IV) beta-blockers (BBs) administration in patients undergoing primary percutaneous coronary intervention (pPCI) on ST-segment deviation is unknown. We undertook a prespecified secondary analysis of the Early Beta-blocker Administration before primary PCI in patients with ST-elevation Myocardial Infarction (EARLY-BAMI) trial to investigate the effect of early IV BB on ST-segment deviation.MethodsThe EARLY-BAMI trial randomised patients with ST-elevation myocardial infarction (STEMI) to IV metoprolol (2×5 mg bolus) or matched placebo before pPCI. The prespecified outcome, evaluated by an independent core laboratory blinded to study treatment, was the residual ST-segment deviation 1 hour after pPCI (ie, the percentage of patients with >3 mm cumulative ST deviation at 1 hour after pPCI).ResultsAn ECG for the evaluation of residual ST-segment deviation 1 hour after pPCI was available in 442 out of 683 randomised patients. The BB group had a lower heart rate after pPCI compared with placebo (71.2±13.2 vs 74.3±13.6, p=0.016); however, no differences were noted in the percentages of patients with >3 mm cumulative ST deviation at 1 hour after pPCI (58.6% vs 54.1%, p=0.38, in BB vs placebo, respectively) neither a significant difference was found for the percentages of patients in each of the four prespecified groups (normalised ST-segment; 1–3 mm; 4–6 mm;>6 mm residual ST-deviation).ConclusionsIn patients with STEMI, who were being transported for primary PCI, early IV BB administration did not significantly affect ST-segment deviation after pPCI compared with placebo. The neutral result of early IV BB administration on an early marker of pharmacological effect is consistent with the absence of subsequent improvement of clinical outcomes.

We aimed to evaluate the effect of early intravenous metoprolol treatment, microvascular obstruction (MVO), intramyocardial hemorrhage (IMH) and adverse left ventricular (LV) remodeling on the evolution of infarct and remote zone circumferential strain after acute anterior ST-segment elevation myocardial infarction (STEMI) with feature-tracking cardiovascular magnetic resonance (CMR). A total of 191 patients with acute anterior STEMI enrolled in the METOCARD-CNIC randomized clinical trial were evaluated. LV infarct zone and remote zone circumferential strain were measured with feature-tracking CMR at 1 week and 6 months after STEMI. In the overall population, the infarct zone circumferential strain significantly improved from 1 week to 6 months after STEMI (- 8.6 ± 9.0% to - 14.5 ± 8.0%; P

Background: Primary non-response and secondary loss of response (LOR) are significant problems of biological therapy for inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) in IBD patients receiving these drugs can improve outcomes. Aim: To measure serum infliximab levels and anti-infliximab antibodies (ATI) in patients with IBD post-induction phase and during maintenance therapy assessing the clinical course of IBD. Patients and Methods: Prospective study of IBD patients receiving infliximab between July 2016-May 2017. Group-A included patients who received induction therapy while Group-B included patients who were in maintenance therapy. TDM was performed in serum samples collected at weeks-14 and 30 in Group-A and before the infliximab maintenance dose in Group-B. Clinical scores, fecal calprotectin and endoscopic score were also evaluated. Results: Of 14 patients in Group-A, 57% achieved endoscopic response. Median serum infliximab concentrations at week-14 and 30 were 2.65 AU/mL (0.23-32.58) and 2.3 AU/mL (0.3-16.8), respectively. Patients with mucosal healing had non-significantly higher median infliximab concentrations at week- 14, as compared to week 30 (median 3.2 vs 2.2 AU/ml, respectively, p 0.6). ATI >10 ug/mL were found in one and seven patients at week-14 and 30, respectively. At 52 weeks of follow-up, four patients (31%) had LOR. Group-B included 36 patients, 33% had LOR. Median serum concentrations of infliximab were 1.4 AU/mL (0.27-7.03). No significant differences in serum infliximab concentration were observed between patients in remission and those with inflammatory activity. Seventeen patients had ATI >10 ug/mL. Conclusions: Clinical algorithms using TDM might help to optimize the pharmacological therapy of IBD.

Introduction and objectives: Myocardial interstitial fibrosis, a hallmark of hypertrophic cardiomyopathy (HCM), has been proposed as an arrhythmic substrate. Fibrosis is associated with increased extracellular volume (ECV), which can be quantified by computed tomography (CT). We aimed to analyze the association between CT-determined ECV and malignant ventricular arrhythmias. Methods: A retrospective case-control observational study was conducted in HCM patients with implantable cardioverter-defibrillator, undergoing a CT-protocol with continuous iodine contrast infusion to determine equilibrium ECV. Left ventricular septal and lateral CT-determined ECV was compared between prespecified cases (malignant arrhythmia any time before CT scan) and controls (no prior malignant arrhythmias) and among ECV tertiles. Results: A total of 78 implantable cardioverter-defibrillator HCM patients were included; 24 were women, with a mean age of 52.1 ± 15.6 years. Mean ECV ± standard deviation in the septal left ventricular wall and was 29.8% ± 6.3% in cases (n = 24) vs 31.9% ± 8.5% in controls (n = 54); P = .282. Mean ECV in the lateral wall was 24.5% ± 6.8% in cases vs 28.2% ± 7.4% in controls; P = .043. On comparison of the entire population according to septal ECV tertiles, no significant differences were found in the number of patients receiving appropriate shocks. Conversely, we found a trend (P = .056) for a higher number of patients receiving appropriate shocks in the lateral ECV lowest tertile. Conclusions: Extracellular volume was not increased in implantable cardioverter-defibrillator HCM patients with malignant ventricular arrhythmias vs those without arrhythmias. Our findings do not support the use of ECV (a surrogate of diffuse fibrosis) as a predictor of arrhythmias in high-risk HCM patients. Introducción y objetivos: La fibrosis intersticial en miocardiopatía hipertrófica (MCH) se ha propuesto como substrato de arritmias malignas. La fibrosis se asocia a expansión del volumen extracelular (VEC) que se puede cuantificar por tomografía computarizada (TC). El objetivo es analizar la asociación entre VEC determinado por TC y la presencia de arritmias malignas. Métodos: Estudio observacional de casos y controles en pacientes con MCH y desfibrilador automático implantable sometidos a TC con infusión continua de contraste yodado para cuantificar el VEC en equilibrio. Se comparó el VEC determinado por TC en las paredes septal y lateral de ventrículo izquierdo entre casos (presencia de arritmia maligna previa) y controles (sin arritmias malignas). Resultados: Se incluyó a 78 pacientes con MCH-desfibrilador automático implantable, 24 eran mujeres con una edad media de 52,1 ± 15,6 años. El VEC medio ± desviación estándar en pared septal fue 29,8 ± 6,3% en casos (n = 24) frente a 31,9 ± 8,5% en controles (n = 54); p = 0,282. El VEC medio en pared lateral fue 24,5 ± 6,8% en casos frente a 28,2 ± 7,4% en controles; p = 0,043. No se encontraron diferencias en el número de pacientes con choques apropiados entre los diferentes terciles de VEC. Por el contrario, se encontró una tendencia (p = 0,056) de un mayor número de pacientes dentro del menor tercil de VEC en pared lateral con descargas apropiadas. Conclusiones: El VEC en pacientes con MCH-desfibrilador automático implantable con arritmias malignas no se mostró incrementado comparado con pacientes con MCH-desfibrilador automático implantable sin arritmias. Estos hallazgos no apoyan en uso de VEC (subrogado de fibrosis difusa) como predictor de arritmias malignas en pacientes con MCH de alto riesgo. Sin financiación 5.166 JCR (2017) Q1, 26/128 Cardiac and Cardiovacular Systems UEM

OBJECTIVE To determine the correlation between clinical, fecal, endoscopic and histological activity in patients with ulcerative colitis (UC). METHODS A correlational cross-sectional analysis was performed in patients with UC who underwent colonoscopy between February and December 2016. Clinical, endoscopic, fecal and histological activities were determined using the partial Mayo subscore, Mayo endoscopic subscore and modified Mayo endoscopic subscore, fecal calprotectin and Geboes score and the presence of basal plasmacytosis, respectively. Scores were analyzed using Spearman's rank correlation test. To determine the association between scores and some clinical variables and active UC, univariate and multivariate logistic regressions were used. RESULTS Altogether 105 procedures (93 patients) were included. In 64.8% of the procedures, the mucosa was inflamed; however, 14.7% did not show histological inflammation. Endoscopic remission was observed in the other 35.2% of procedures; however, in biopsies 21.6% exhibited histological inflammation. Mayo endoscopic subscore and modified Mayo endoscopic score were well correlated but were only moderately correlated with clinical and histological scores. Furthermore, there was a moderate correlation between Mayo endoscopic score and Geboes score. Conversely, histological scores were poorly correlated with partial Mayo score. In multivariate analysis, Geboes score and basal plasmacytosis were predictive of active disease (OR 3.505, 95% CI 1.544–7.959 and OR 3.240, 95% CI 1.123–9.349, respectively), whereas biological therapy was found to be protective against UC (OR 0.021, 95% CI 0.000–0.641). CONCLUSION Clinical, endoscopic and histological activities were moderately correlated, while Geboes score and basal plasmacytosis were predictive of endoscopically active UC.

Resumen Introduccion y objetivos La cuantificacion del area en riesgo (AR) es importante para evaluar los beneficios de las terapias cardioprotectoras; sin embargo, la evaluacion puede estar influida por el territorio miocardico infartado. Nuestro objetivo es validar las secuencias T2-weighted short tau triple-inversion recovery (T2W-STIR) de cardiorresonancia magnetica (CRM) para la cuantificacion del AR en infartos anteriores, laterales e inferiores. Metodos Se utilizo un modelo porcino de isquemia/reperfusion (40 min de oclusion) de la descendente anterior (n = 4), la circunfleja (n = 4) y la coronaria derecha (n = 4). Se realizo CRM de perfusion inmediatamente antes de la oclusion coronaria durante la inyeccion selectiva intracoronaria de gadolinio para delimitar el AR (patron de referencia in vivo) y despues CRM el dia 7 incluyendo secuencias T2W-STIR. Finalmente, se sacrifico a los animales y se realizo histologia mediante tincion de Evans blue (patron de referencia clasico de histologia). Resultados La concordancia entre la CRM de referencia y las secuencias T2W-STIR fue buena para la cuantificacion del AR en los infartos anteriores e inferiores (r = 0,73; p = 0,001; error medio, 0,50% [intervalo, –12,68% a 13,68%], y r = 0,87; p = 0,001; error medio, –1,5% [–8,0% a 5,8%] respectivamente), mientras que fue suboptima para el territorio de la circunfleja (r = 0,21; p = 0,37). Los patrones de referencia para CRM y clasico de histologia presentan una alta correlacion (r = 0,84; p Conclusiones La precision de las secuencias T2W-STIR para cuantificar el AR es alta en infartos anteriores e inferiores; sin embargo, es limitada en infartos laterales. Estos hallazgos tienen implicaciones importantes para el diseno de ensayos clinicos orientados a evaluar terapias cardioprotectoras en el infarto.

Introduction and objectives Area at risk (AAR) quantification is important to evaluate the efficacy of cardioprotective therapies. However, postinfarction AAR assessment could be influenced by the infarcted coronary territory. Our aim was to determine the accuracy of T 2 -weighted short tau triple-inversion recovery (T 2 W-STIR) cardiac magnetic resonance (CMR) imaging for accurate AAR quantification in anterior, lateral, and inferior myocardial infarctions. Methods Acute reperfused myocardial infarction was experimentally induced in 12 pigs, with 40-minute occlusion of the left anterior descending (n = 4), left circumflex (n = 4), and right coronary arteries (n = 4). Perfusion CMR was performed during selective intracoronary gadolinium injection at the coronary occlusion site (in vivo criterion standard) and, additionally, a 7-day CMR, including T 2 W-STIR sequences, was performed. Finally, all animals were sacrificed and underwent postmortem Evans blue staining (classic criterion standard). Results The concordance between the CMR-based criterion standard and T 2 W-STIR to quantify AAR was high for anterior and inferior infarctions ( r = 0.73; P = .001; mean error = 0.50%; limits = −12.68%-13.68% and r = 0.87; P = .001; mean error = −1.5%; limits = −8.0%-5.8%, respectively). Conversely, the correlation for the circumflex territories was poor ( r = 0.21, P = .37), showing a higher mean error and wider limits of agreement. A strong correlation between pathology and the CMR-based criterion standard was observed ( r = 0.84, P Conclusions T 2 W-STIR CMR sequences are accurate to determine the AAR for anterior and inferior infarctions; however, their accuracy for lateral infarctions is poor. These findings may have important implications for the design and interpretation of clinical trials evaluating the effectiveness of cardioprotective therapies.

Anti-tumor necrosis factor-α (TNF) agents have dramatically changed the management of Crohn’s Disease (CD). However, a significant number of these patients do not respond at all or cease to respond to antibodies against TNF. In this clinical situation, the options include intensification of anti-TNF therapy by either increasing the dose or by shortening the administration interval, the use of a second anti-TNF or medications with a different mechanism of action. Among the later, Natalizumab, a humanized IgG4 monoclonal antibody against α4β1 and α4β7 integrins, is safe and effective in inducing and maintaining remission in active CD patient’s refractory to anti-TNF. In spite of this, Natalizumab use has been limited because of an increased risk of progressive multifocal leukoencephalophaty which results from reactivation of the John Cunningham (JC) virus. However, the presence of antibodies against JC virus in serum can be used to reduce the risk for this complication. We report three patients with Crohn’s disease refractory to treatment with infliximab, who responded successfully to the use of Natalizumab.

Background Metoprolol administration before reperfusion has shown relevant cardioprotective effect in the AMI in preclinical setting. However, the translation to clinical arena has controversial results. The time at drug administration in the context of total duration of ischemia have been pointed as fundamental aspects to be studied. Purpose evaluate the cardioprotective effect of metoprolol administration regarding to the total time of ischemia, using a swine model of reperfused AMI. Methods 50 pigs were subjected to 3 temporary protocols of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 30 pigs undergoing 40 minutes of ischemia (T40) were randomized 2:1 to intravenous placebo or metoprolol administrated 20 minutes after LAD occlusion.10 pigs undergoing 20 minutes of ischemia 20 (T20) and 10 pig undergoing 60 minutes of ischemia 60 (T60) were randomized 1:1 to intravenous placebo or metoprolol. Before reperfusion a CT study was performed to stablish the area at risk (AAR). CMR was performed at 7 and 45 days after AMI. Results 48 subjects comprised the 7-day CMR follow-up (1 dead in the metoprolol T40,1 dead in the placebo T40) while 41 subjects comprised the 45-day CMR follow-up (5 deceases in the placebo T40 group, and 2 in the placebo T60 group). AAR was similar among groups (Table 1, Panel B). At 7-day follow-up, IS washigher in the placebo groups as compared to the metoprolol groups, but only reach significant difference in the T40 (29,67% vs. 22,85%, p=0.04, Table 1, Panel A). LVEF measured at 45-day follow-up was higher in the metoprolol groups vs the control groups, but the differences were statistically significance in the T40 (32,76% vs 39,68% p=0.04, Panel C). Table 1 20 mins. Ischemia (T20) 40 mins. Ischemia (T40) 60 mins. Ischemia (T60) P PLACEBO METOPROL P value PLACEBO METOPROL P value PLACEBO METOPROL P value AAR 32 (28.14–37.89) 33.41 (28.12–38.32) 0.82 32.99 (29.25–35.83) 31.42 (26.94–37.83) 0.72 33.28 (29.68–41.14) 33.93 (28.17–40.69) 0.80 0.98 IS 1.96 (0.92–3.61) 0 (0–0.65) 0.063 29.67 (27.23–35.35) 22.85 (14.53–28.10) 0.042 36.21 (33.55–40.91) 33.78 (39.36–35.39) 0.31 Conclusions Metoprolol administrated early before reperfusion reduced IS and improved medium-term LVEF compared to placebo. But only T40 receiving metoprolol shownsignificant protection vs placebo. These findings suggest a relevant effect of metoprolol ischemic/reperfusion injury, but depending on the total ischemic time, establishing a potential temporary cardioprotection opportunity window.

ObjectiveThe main objective of the present study was to compare the use of four-dimensional (4D) flow MRI with the habitual sequence (two-dimensional phase-contrast (2DPC) MRI) for the assessment of aortic regurgitation (AR) in the clinical routine.MethodsThis was a retrospective, observational cohort study of patients with varying grades of AR. For the purposes of the present study, we selected all the cases with a regurgitant fraction (RF)>5% as determined by 2DPC MRI (n=34). In all cases, both sequences (2DPC and 4D flow MRI) were acquired in a single session to ensure comparability. We compared the results of the two techniques by evaluating forward flow, regurgitant flow and regurgitation fraction. Then, the patients were divided into subgroups to determine if these factors had any influence on the measurements: aortic diameter (≤ vs >38 mm), valve anatomy (tricuspid vs bicuspid/quadricuspid), stenosis (gradient ≥15 vs ResultsNo statistically significant differences were observed between the two techniques with Pearson’s correlation coefficients (r) of forward flow (r=0.826/p valueConclusionsThe findings of this study confirm the value of 4D flow MRI for grading AR in clinical practice with an excellent correlation with the standard technique (2DPC MRI).

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. Sí

Background The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established. Objectives This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing the effect of early IV beta-blockers before PPCI in a general ST-segment elevation myocardial infarction (STEMI) population. Methods STEMI patients presenting

BACKGROUND Pre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI). OBJECTIVES This study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-to-reperfusion interval. METHODS We performed a post hoc analysis of the METOCARD-CNIC (effect of METOprolol of CARDioproteCtioN during an acute myocardial InfarCtion) trial, which randomized anterior STEMI patients to IV metoprolol or control before mechanical reperfusion. Treated patients were divided into short-and long-interval groups, split by the median time from 15 mg metoprolol bolus to reperfusion. We also performed a controlled validation study in 51 pigs subjected to 45 min ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (-25 min) or short (-5 min) pre-perfusion interval, IV metoprolol post-reperfusion (+60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed in the acute and chronic phases in both clinical and experimental settings. RESULTS For 218 patients (105 receiving IV metoprolol), the median time from 15 mg metoprolol bolus to reperfusion was 53 min. Compared with patients in the short-interval group, those with longer metoprolol exposure had smaller infarcts (22.9 g vs. 28.1 g; p = 0.06) and higher left ventricular ejection fraction (LVEF) (48.3\% vs. 43.9\%; p = 0.019) on day 5 CMR. These differences occurred despite total ischemic time being significantly longer in the long-interval group (214 min vs. 160 min; p < 0.001). There was no between-group difference in the time from symptom onset to metoprolol bolus. In the animal study, the long-interval group (IV metoprolol 25 min before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR). CONCLUSIONS In anterior STEMI patients undergoing primary angioplasty, the sooner IV metoprolol is administered in the course of infarction, the smaller the infarct and the higher the LVEF. These hypothesis-generating clinical data are supported by a dedicated experimental large animal study. (C) 2016 by the American College of Cardiology Foundation. The authors thank Noemi Escalera and Maite Rodriguez, who were outstanding in the management of the clinical trial and imaging analyses. The authors are also indebted to the generous dedication of time and effort to the METOCARD-CNIC trial by all coinvestigators from SUMMA112, 061 Galicia, and SAMUR. The coordinating center at SCU-SUMMA112 was crucial for the proper conduct of the trial. Tamara Cordoba, Oscar Sanz, Ruben Mota, Santiago Rodriguez, Eugenio Fernández, and the rest of the team at the CNIC Animal Facility and farm provided outstanding animal care and support. Simon Bartlett (CNIC) provided English editing. Sí

The recent work by Turagam et al. [(1)][1] found a significant reduction in systolic blood pressure after epicardial left atrial appendage (LAA) exclusion when compared with the endocardial method. Although the procedural risks associated with epicardial LAA exclusion have decreased significantly

Objectives The aim of this study was to assess the type and prevalence of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease (IBD) who are treated at our center. Design Observational, cross-sectional questionnaire-based study that included patients from the IBD program of our center. Setting Tertiary clinical center in Santiago, Chile. Main outcome measures Types of CAM being used by patients with IBD. Results A total of 200 patients were included, 68% ulcerative colitis, 29% Crohn’s disease, and 3% non-classifiable IBD. Overall, 25% of the patients reported current use of CAM, 30% reported using in it the past, and 45% indicated that they had never used it before. The use of CAM was recommended in 20% of the patients by other healthcare professionals and in 10% of the patients by the gastroenterologist. Forty-nine percent of the patients informed the gastroenterologist that they were using CAM. Overall, 86% of the patients did not modify the conventional medical treatment (CMT). None of the patients who were using curcumin, homeopathic medicine, acupuncture or biomagnetism modified the CMT. Conclusions The type of CAM being used plays an important role when the patient makes the decision to inform the gastroenterologist. Other healthcare professionals play an important role in providing the advice to start CAM. Gastroenterologists must be aware of the high prevalence of CAM use in IBD patients, actively ask about CAM use and guide the patients who want to use CAM in a responsible and safe manner.

ST-segment elevation acute myocardial infarction (STEMI) is a major health problem. The implementation of reperfusion strategies has resulted in a very significant reduction of shortterm mortality. However, STEMI survivors with large infarctions are at high risk of chronic heart failure and associated comorbidities. The possibility of reducing infarct size might help alleviating the epidemics of heart failure. In many cases, despite optimal opening of the occluded epicardial coronary artery, tissue perfusion is inadequate due to microvascular obstruction (MVO). Given the central role of MVO in final infarct size, it is the target of different interventions. In the past decades, many strategies (pharmacological and mechanical) have been tested with the aim of reducing MVO and in turn lessen infarct size. Many interventions have failed in the translation from positive experimental studies into clinical trials, while some others have passed the initial checkpoint of pilot trials and are being tested in properly sized endpoints-oriented clinical trials. In this chapter we will describe the state of the art of the different strategies that are actively being tested in this field.

The clinical presentation of ulcerative colitis at the moment of diagnosis is variable, and its clinical course is difficult to predict. It can range from a quiescent to a refractory chronic course that may require hospitalization and surgical procedures. It can also have complications such as colorectal cancer. In this review we discuss the role of demographic, clinical, endoscopic, histological and associated factors, which can help to predict the clinical course of the disease at the moment of diagnosis, and to individualize therapy according to this clinical risk. Accurate identification of patients with a newly diagnosed ulcerative colitis who are at high risk of an unfavorable outcome is still a challenge. However, an effective evaluation allows an early diagnosis, a timely and effective treatment.