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The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line were found in terms of increased systemic IgM (primary immune responses), increased synthesis of IFN-gamma upon stimulation (Th1) and increased peripheral T cells (mainly “naive” CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 β and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.

Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been demonstrated to exert an effect on human health by modulating the biochemical status in humans. The objective of this study was to assess whether supplementation with hemp protein within a Mediterranean diet context together with exercise could help to ameliorate the metabolic statuses of patients prone to developing metabolic syndrome. For this study, 23 patients followed with Mediterranean diet and engaged in aerobic exercise according to the WHO’s recommendations, while also being supplemented with hemp protein, for 12 weeks. A comparison of anthropometric, biochemical, and mineral data as well as amino acid values was made between the start and the end of the study, with the subjects acting as their own control group. Statistical analyses included a paired t-test, Wilcoxon paired test, Pearson correlation coefficient, and Sparse Partial Least Squares Discriminant Analysis to evaluate significant differences and correlations among parameters. There were statistically significant changes in total cholesterol, HDL-C (+52.3%), LDL-C (−54.0%), and TAG levels (−49.8%), but not in glucose plasma levels. Following the intervention, plasma concentrations of some amino acids, including α-aminoadipic acid, phosphoethanolamine, and 1-metylhistidine, increased, whereas those of asparagine and alanine declined. Different correlations between amino acids and the other parameters evaluated were reported and discussed. A Mediterranean diet combined with regular aerobic exercise, together with protein supplementation, can highly improve the metabolic parameters and anthropometric parameters of subjects with obesity and impaired glucose levels, ameliorating their health status and likely delaying the development of metabolic syndrome.

Background ST‐segment–elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow‐mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow‐mediated hyperemia in patients with ST‐segment–elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN‐FLOW (Treatment of Slow‐Flow After Primary Percutaneous Coronary Intervention With Flow‐Mediated Hyperemia) study, 67 patients with ST‐segment–elevation myocardial infarction and no reflow were randomized to receive either pharmacologic‐mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow‐mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure‐thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P=0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P=0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% (P=0.899). Flow‐mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In‐hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow‐mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST‐segment–elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.

Sr. Editor: El implante percutáneo de válvula aórtica (TAVI, transcatheter aortic valve implantation) es una opción terapéutica habitual en pacientes con estenosis aórtica grave degenerativa. En nuestro medio, tras una TAVI es necesario implantar un marcapasos definitivo en el 14% de los casos1, lo que constituye una causa añadida de morbilidad y aumento del tiempo de estancia hospitalaria, y en los pacientes añosos estos dos aspectos pueden cobrar especial importancia. El marcapasos sin cables Micra (Medtronic, Estados Unidos) es una alternativa reciente a los clásicos marcapasos endocavitarios. La ausencia de electrodo y de bolsa subcutánea para alojar el generador y el implante mediante acceso venoso femoral podrían reducir algunas complicaciones de los marcapasos convencionales (en especial el neumotórax, el hematoma y la infección de la bolsa, y todas las derivadas del propio electrodo). Inicialmente solo estuvo disponible para estimulación en modo VVI, pero en fechas recientes se ha introducido el nuevo dispositivo Micra AV (Medtronic, Estados Unidos) que permite mantener la sincronía auriculoventricular en los pacientes en ritmo sinusal mediante la detección de la contracción mecánica auricular y la estimulación ventricular subsiguiente. Tras más de 120 implantes de Micra, y con una experiencia inicial favorable después de la realización de TAVI2, pudiendo...

To the Editor, Transcatheter aortic valve implantation (TAVI) is a common therapeutic option in patients with degenerative severe aortic stenosis. In our setting, the need for definitive pacemaker implantation after TAVI is around 14%,1 which is an additional cause for morbidity and longer length of stay. In elderly patients both aspects can be especially relevant. Micra leadless pacemaker (Medtronic, United States) is a recent alternative to traditional endocavitary pacemakers. The lack of electrodes or need for subcutaneous bag to carry the generator added to femoral venous access implantation reduce some of the complications associated with conventional pacemakers (especially pneumothorax, hematoma, bag and electrode-related infections). Although initially available for VVI pacing mode only, the new Micra AV (Medtronic, United States) has appeared recently. It maintains atrioventricular synchrony in patients in sinus rhythm by detecting atrial mechanical contraction and the corresponding ventricular pacing. After over 120 Micra implantations including an early favorable experience after TAVI,2 and widening the indication to patients in sinus rhythm too, we thought of the possibility of implanting both devices at the same procedure. In this work we present the very first series of patients who, after TAVI, were implanted with the Micra leadless pacemaker as permanent pacing therapy at...

Malnutrition refers to a person’s status as under- or overnourished, and it is usually associated with an inflammation status, which can subsequently imply a different health status, as the risk of infection is increased, along with a deterioration of the immune system. Children’s immune systems are generally more susceptible to problems than adults. In the situation of malnutrition, because malnourished children’s immune systems are compromised, they are more likely to die. However, little is known about the underlying mechanism of altered immune functioning and how it relates to starvation. Nutritional interventions have been reported as cost-effective strategies to prevent or treat the development of malnourishment, considering the link between food intake and health, especially in children, and also the susceptibility of this population to diseases and how their health status during childhood might affect their long-term physiological growth. The ingestion of specific nutrients (e.g., vitamins or oligoelements) has been reported to contribute to the proper functioning of children’s immune systems. In this review, we aim to describe the basis of malnutrition and how this is linked to the immune system, considering the role of nutrients in the modulation of the immune system and the risk of infection that can occur in these situations in children, as well as to identify nutritional interventions to improve their health.

Background: Quantitative flow ratio (QFR) virtual angioplasty with pre-PCI residual QFR showed better results compared with an angiographic approach to assess post-PCI functional results. However, correlation with pre-PCI residual QFR and post-PCI fractional flow reserve (FFR) is lacking. Methods: A multicenter prospective study including consecutive patients with angiographically 50–90% coronary lesions and positive QFR results. All patients were evaluated with QFR, hyperemic and non-hyperemic pressure ratios (NHPR) before and after the index PCI. Pre-PCI residual QFR (virtual angioplasty) was calculated and compared with post-PCI fractional flow reserve (FFR), QFR and NHPR. Results: A total of 84 patients with 92 treated coronary lesions were included, with a mean age of 65.5 ± 10.9 years and 59% of single vessel lesions being the left anterior descending artery in 69%. The mean vessel diameter was 2.82 ± 0.41 mm. Procedural success was achieved in all cases, with a mean number of implanted stents of 1.17 ± 0.46. The baseline QFR value was 0.69 ± 0.12 and baseline FFR and NHPR were 0.73 ± 0.08 and 0.82 ± 0.11, respectively. Mean post-PCI FFR increased to 0.87 ± 0.05 whereas residual QFR had been estimated as 0.95 ± 0.05, showing poor correlation with post-PCI FFR (0.163; 95% CI:0.078–0.386) and low diagnostic accuracy (30.9%, 95% CI:20–43%). Conclusions: In this analysis, the results of QFR-based virtual angioplasty did not seem to accurately correlate with post-PCI FFR.

Abstract Air pollutants increase the risk and mortality of myocardial infarction (MI). The aim of this study was to assess the inflammatory changes in circulating immune cells and microRNAs in MIs related to short-term exposure to air pollutants. We studied 192 patients with acute coronary syndromes and 57 controls with stable angina. For each patient, air pollution exposure in the 24-h before admission, was collected. All patients underwent systematic circulating inflammatory cell analyses. According to PM2.5 exposure, 31 patients were selected for microRNA analyses. STEMI patients exposed to PM2.5 showed a reduction of CD4+ regulatory T cells. Furthermore, in STEMI patients the exposure to PM2.5 was associated with an increase of miR-146a-5p and miR-423-3p. In STEMI and NSTEMI patients PM2.5 exposure was associated with an increase of miR-let-7f-5p. STEMI related to PM2.5 short-term exposure is associated with changes involving regulatory T cells, miR-146a-5p and miR-423-3p.

Increasing evidence has pointed to the important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed significant CD69 overexpression on Tregs after MI. Our results in mice showed that CD69 expression on Tregs increased survival after left anterior descending (LAD) coronary artery ligation. Cd69–/– mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Tregs, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Tregs into Cd69–/– mice after LAD ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from 2 independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of rehospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex, and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Tregs as a potential prognostic factor and a therapeutic option to prevent HF after MI.

The immune system is somehow related to all the metabolic pathways, in a bidirectional way, and the nutritional interventions affecting these pathways might have a relevant impact on the inflammatory status of the individuals. Food-derived peptides have been demonstrated to exert several bioactivities by in vitro or animal studies. Their potential to be used as functional food is promising, considering the simplicity of their production and the high value of the products obtained. However, the number of human studies performed until now to demonstrate effects in vivo is still scarce. Several factors must be taken into consideration to carry out a high-quality human study to demonstrate immunomodulatory-promoting properties of a test item. This review aims to summarize the recent human studies published in which the purpose was to demonstrate bioactivity of protein hydrolysates, highlighting the main results and the limitations that can restrict the relevance of the studies. Results collected are promising, although in some studies, physiological changes could not be observed. When responses were observed, they sometimes did not refer to relevant parameters and the immunomodulatory properties could not be clearly established with the current evidence. Well-designed clinical trials are needed in order to evaluate the role of protein hydrolysates in immunonutrition.

The immune-inflammatory, glucose homeostasis, and antioxidant response have a crucial role in the prevention of non-communicable chronic diseases, according to the World Health Organization (WHO) [...]

The defense mechanism against harmful stimuli is inflammation. Indeed, neurodegenerative disorders can arise as a result of a persistent neuroinflammation. Beta-amyloid (Aβ1-42) is an early trigger in the origination of Alzheimer’s disease, leading to synaptic and cognitive impairments. Virgin olive oil (VOO) is correlated with a decreased risk of developing immune-inflammatory disorders, but the potential effects of the phenolic fraction (PF) from VOO in the modulation of neuroinflammatory processes in neutrophils remain unknown. In this study, we investigated the ability of the PF to modulate the activation of Aβ1-42-stimulated primary human neutrophils, focusing on the expression of gene and surface markers and the release of pro-inflammatory and chemoattractant mediators. Down-regulation of pro-inflammatory cytokine gene expression in Aβ1-42-treated neutrophils, among other changes, was reported. Furthermore, pretreatment with PF prevented neutrophil activation. The beneficial effects in the modulation of inflammatory responses show the relevance of VOO to achieve a healthier diet that can help prevent inflammatory diseases.

RESUMEN Introducción y objetivos: La disección coronaria espontánea (DCE) constituye una causa infrecuente, pero cada vez más reconocida, de síndrome coronario agudo. La actitud diagnóstico-terapéutica idónea sigue sin esclarecerse. Métodos: Análisis del seguimiento prospectivo y centralizado de una serie de pacientes consecutivos diagnosticados de DCE desde enero de 2010 hasta diciembre de 2018. Se definió evento cardiovascular adverso mayor como la aparición de muerte de cualquier causa, reinfarto no mortal, revascularización no planificada, arritmia ventricular, insuficiencia cardiaca o ictus. Resultados: Se incluyó a 33 pacientes con DCE (41 lesiones). En el 42% se realizó un estudio con imagen intracoronaria para confirmar el diagnóstico, sin identificar trombo en la luz verdadera en ninguno de ellos. En la mayoría de los casos (82%) se eligió un tratamiento médico conservador. Ningún paciente falleció durante el ingreso, pero el 15% presentó algún evento mayor. En el momento agudo se realizó tomografía computarizada coronaria al 58% de los pacientes y se identificó la DCE en el 79% de los casos. La mayoría de los pacientes con tratamiento conservador recibieron antiagregación simple un tiempo limitado (17 meses [9-35]). Con una mediana de seguimiento de 33 meses [13-49], el 82% no sufrió ningún evento adverso. Al 48% se les realizó control angiográfico a los 6 meses, que mostró resolución en el 86% de los casos. El cribado de anomalías vasculares extracoronarias se realizó en el 97% de los pacientes y se hallaron alteraciones en el 59%, incluyendo 3 pacientes con aneurisma intracraneal. Conclusiones: En esta serie, con una amplia utilización de imagen intracoronaria, no se ha identificado trombo en la luz verdadera en ningún caso de DCE. En los pacientes tratados de forma conservadora, la monoterapia antiagregante es segura y se asocia a buenos resultados clínicos. La tomografía computarizada coronaria durante el ingreso es útil en el seguimiento. El cribado sistemático de anomalías vasculares extracoronarias revela una alta prevalencia de alteraciones.

ABSTRACT Introduction and objectives: Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause for acute coronary syndrome. The optimal management and treatment of SCAD is still unknown. Methods: Data analysis of a prospective protocol including centralized care management of a consecutive series of patients with SCAD diagnosed between January 2010 and December 2018. Major adverse cardiovascular events included all-cause mortality, new myocardial infarction, coronary revascularization, ventricular arrhythmia, heart failure or stroke. Results: A total of 33 consecutive patients were included (41 lesions). Intravascular imaging modalities were used to confirm the diagnosis in 42% patients. None of the patient showed images of thrombus formation in the true lumen. Conservative treatment was the initial approach in most of the cases (82%). No deaths were reported during the index admission, but 15% experienced major adverse cardiovascular events. The coronary computed tomography angiography performed in 58% of patients during the admission identified SCADs in 79% of the patients. Most of the patients managed with conservative treatment received only 1 antiplatelet agent for a limited period of time (17 months [9-35]). During a median clinical follow-up of 33 months [13-49], 82% of patients did not have any adverse events. The angiographic surveillance obtained in 48% of patients at the 6-month follow-up confirmed the complete healing of the SCAD image in 86% of the patients. The screening for extracoronary vascular findings (97% of patients) resulted in a high prevalence of abnormalities (59%). Conclusions: The unrestricted use of intravascular imaging modalities showed no thrombus in the true lumen of patients with SCAD. In patients managed with conservative treatment, a limited course of antiplatelet monotherapy is safe and provides good clinical outcomes. Performing a coronary computed tomography angiography in the acute phase of SCAD is useful at the follow-up. The screening for extracoronary vascular findings confirmed a high prevalence of abnormalities.

Background Early generation drug‐eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium‐dependent vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device‐related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable‐polymer everolimus‐eluting Xience (n=44), bioresorbable‐polymer sirolimus‐eluting Orsiro (n=35), polymer‐free biolimus‐eluting Biofreedom (n=24), bioactive endothelial‐progenitor cell‐capturing sirolimus‐eluting Combo DES (n=25), polymer‐based everolimus‐eluting Absorb (n=44), and Mg‐based sirolimus‐eluting Magmaris BRS (n=34) underwent endothelium‐dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow‐up. Crude vasomotor responses of distal segments to low‐dose acetylcholine (10−6 mol/L) were different between groups: bioresorbablepolymer DEShad the worst (−8.4%±12.6%) and durable‐polymer DES had the most physiologic (−0.4%±11.8%; P=0.014). High‐dose acetylcholine (10−4 mol/L) showed similar responses between groups (ranging from −10.8%±11.6% to −18.1%±15.4%; P=0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable‐polymer DES) to 2.5%±4.5% (bioactive DES; P=0.056). In multivariate models, endothelium‐dependent vasomotor response was associated with age, bioresorbable‐polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low‐dose and 68.9% with high‐dose acetylcholine, without differences between groups. Conclusions At follow‐up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.

A prolonged inflammatory response can lead to the development of neurodegenerative diseases such as Alzheimer’s disease. Enzymatic hydrolysis is a sustainable way to increase the value of protein sources by obtaining peptides that can exert bioactivity. Hemp (Cannabis sativa L.) protein hydrolysates have been proven to exert anti-inflammatory activity. In this study, two hemp protein hydrolysate (HPHs), obtained with Alcalase as sole catalyst, or with Alcalase followed by Flavourzyme, were evaluated as inflammatory mediators (TNFα, IL-1β, IL-6, and IL-10), microglial polarization markers (Ccr7, iNos, Arg1, and Ym1), and genes related to inflammasome activation (Nlrp3, Asc, Casp1, and Il18), employing the lipopolysaccharide (LPS)-induced neuroinflammation model in murine BV-2 microglial cells. A significant decrease of the expression of proinflammatory genes (e.g., Tnfα, Ccr7, inos, and Nlrp3, among others) and increase of the expression anti-inflammatory cytokines in microglial cells was observed after treatment with the test HPHs. This result in the cell model suggests a polarization toward an anti-inflammatory M2 phenotype. Our results show that the evaluated HPHs show potential neuroprotective activity in microglial cells via the inflammasome.

Background There is a paucity of outcome data on patients who are morbidly obese (MO) undergoing transcatheter aortic valve replacement. We aimed to determine their periprocedural and midterm outcomes and investigate the impact of obesity phenotype. Methods and Results Consecutive patients who are MO (body mass index, ≥40 kg/m2, or ≥35 kg/m2 with obesity‐related comorbidities; n=910) with severe aortic stenosis who underwent transcatheter aortic valve replacement in 18 tertiary hospitals were compared with a nonobese cohort (body mass index, 18.5–29.9 kg/m2, n=2264). Propensity‐score matching resulted in 770 pairs. Pre–transcatheter aortic valve replacement computed tomography scans were centrally analyzed to assess adipose tissue distribution; epicardial, abdominal visceral and subcutaneous fat. Major vascular complications were more common (6.6% versus 4.3%; P=0.043) and device success was less frequent (84.4% versus 88.1%; P=0.038) in the MO group. Freedom from all‐cause and cardiovascular mortality were similar at 2 years (79.4 versus 80.6%, P=0.731; and 88.7 versus 87.4%, P=0.699; MO and nonobese, respectively). Multivariable analysis identified baseline glomerular filtration rate and nontransfemoral access as independent predictors of 2‐year mortality in the MO group. An adverse MO phenotype with an abdominal visceral adipose tissue:subcutaneous adipose tissue ratio ≥1 (VAT:SAT) was associated with increased 2‐year all‐cause (hazard ratio [HR], 3.06; 95% CI, 1.20–7.77; P=0.019) and cardiovascular (hazard ratio, 4.11; 95% CI, 1.06–15.90; P=0.041) mortality, and readmissions (HR, 1.81; 95% CI, 1.07–3.07; P=0.027). After multivariable analysis, a (VAT:SAT) ratio ≥1 remained a strong predictor of 2‐year mortality (hazard ratio, 2.78; P=0.035). Conclusions Transcatheter aortic valve replacement in patients who are MO has similar short‐ and midterm outcomes to nonobese patients, despite higher major vascular complications and lower device success. An abdominal VAT:SAT ratio ≥1 identifies an obesity phenotype at higher risk of adverse clinical outcomes.

Background: Spontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndromes, particularly in young to middle-aged women. Differentiating acute SCAD from coronary atherothrombosis remains a major clinical challenge. Methods: A case-control study was used to explore the usefulness of circulating miRNAs to discriminate both clinical entities. The profile of miRNAs was evaluated using an unbiased human RT-PCR platform and confirmed using individual primers. miRNAs were evaluated in plasma samples from acute SCAD and atherothrombotic acute myocardial infarction (AT-AMI) from two independent cohorts; discovery cohort (SCAD n = 15, AT-AMI n = 15), and validation cohort (SCAD n = 11, AT-AMI n = 41) with 9 healthy control subjects. Plasma levels of IL-8, TGFB1, TGBR1, Endothelin-1 and MMP2 were analysed by ELISA assays. Findings: From 15 differentially expressed miRNAs detected in cohort 1, we confirmed in cohort 2 the differential expression of 4 miRNAs: miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p, whose expression was higher in SCAD compared to AT-AMI. The combined expression of these 4 miRNAs showed the best predictive value to distinguish between both entities (AUC: 0.879, 95% CI 0.72–1.0) compared to individual miRNAs. Functional profiling of target genes identified an association with blood vessel biology, TGF-beta pathway and cytoskeletal traction force. ELISA assays showed high plasma levels of IL-8, TGFB1, TGFBR1, Endothelin-1 and MMP2 in SCAD patients compared to AT-AMI. Interpretation: We present a novel signature of plasma miRNAs in patients with SCAD. miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p discriminate SCAD from AT-AMI patients and also shed light on the pathological mechanisms underlying this condition. Funding: Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. Instituto de Salud Carlos III (AES 2019): PI19/00565 to F.R, PI19/00545 to P.M. CAM (S2017/BMD-3671-INFLAMUNE-CM) from Comunidad de Madrid to FSM and PM. The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608 the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre.

El implante percutáneo de válvula aórtica (TAVI, transcatheter aortic valve implantation) constituye una estrategia terapéutica generalizada y asentada para el tratamiento de la estenosis aórtica grave sintomática. Disponemos de estudios aleatorizados que demuestran el beneficio pronóstico de esta técnica en pacientes mayores con riesgo quirúrgico alto o muy alto, y es también no inferior o incluso superior cuando se implanta por vía transfemoral en comparación con la cirugía de sustitución valvular aórtica en pacientes de riesgo intermedio y bajo. Por tanto, las recomendaciones actuales respaldan su uso en los pacientes mayores con estenosis aórtica grave independientemente de su riesgo quirúrgico1. Sin embargo, como enfermedad intrínsecamente ligada al envejecimiento y carente de un tratamiento médico eficaz, la prevalencia de la estenosis aórtica grave sigue aumentando en consonancia con la esperanza de vida, siendo una enfermedad con una marcada repercusión tanto en la supervivencia como en la calidad de vida de los pacientes2. En consecuencia, los nonagenarios con estenosis aórtica grave son un grupo en continua expansión, y la mejor manera de tratarlos sigue siendo una cuestión sin resolver. Dado que la mayoría de estos pacientes están escasamente representados en los ensayos clínicos y que existen registros con buenos resultados, pero con un...

Transcatheter aortic valve implantation (TAVI) has become a widely used therapeutic strategy to treat symptomatic severe aortic stenosis. Certain randomized clinical trials available have already described the prognostic benefit of this technique in elderly patients with high or very high surgical risk. Also, when implanted via transfemoral access, it has proven non-inferior or even superior compared to surgical aortic valve replacement in low- and intermediate-risk patients. Therefore, the current recommendations support its use in elderly patients with severe aortic stenosis regardless of their surgical risk.1 However, since it is an age-related heart valve disease without an effective medical therapy yet, the prevalence of severe aortic stenosis has been growing parallel to life expectancy. As a matter of fact, this disease has huge repercussions in the patients’ survival rate and quality of life.2 Consequently, nonagenarian patients with severe aortic stenosis are a group in continuous expansion, and, to this date, the best way to treat them is still under discussion. Since most of these patients have traditionally been misrepresented in the clinical trials and there are registries with good results but a possible selection bias, the decision to treat these patients with TAVI is still challenging and is made on an individual...

Published on behalf of the European Society of Cardiology.

BackgroundWe aimed to compare the performance of the recent CASTLE score to J-CTO, CL and PROGRESS CTO scores in a comprehensive database of percutaneous coronary intervention of chronic total occlusion procedures.MethodsScores were calculated using raw data from 1,342 chronic total occlusion procedures included in REBECO Registry that includes learning and expert operators. Calibration, discrimination and reclassification were evaluated and compared.ResultsMean score values were: CASTLE 1.60±1.10, J-CTO 2.15±1.24, PROGRESS 1.68±0.94 and CL 2.52±1.52 points. The overall percutaneous coronary intervention success rate was 77.8%. Calibration was good for CASTLE and CL, but not for J-CTO or PROGRESS scores. Discrimination: the area under the curve (AUC) of CASTLE (0.633) was significantly higher than PROGRESS (0.557) and similar to J-CTO (0.628) and CL (0.652). Reclassification: CASTLE, as assessed by integrated discrimination improvement, was superior to PROGRESS (integrated discrimination improvement +0.036, pConclusionProcedural percutaneous coronary intervention difficulty is not consistently depicted by available chronic total occlusion scores and is influenced by the characteristics of each chronic total occlusion cohort. In our study population, including expert and learning operators, the CASTLE score had slightly better overall performance along with CL score. However, we found only intermediate performance in the c-statistic predicting chronic total occlusion success among all scores.

Background The role of drug‐coated balloons (DCBs) in the treatment of de novo coronary lesions is not well established. Methods and Results Electronic databases and major conference proceedings were searched for randomized controlled trials that compared DCBs with stents or angioplasty for de novo coronary lesions. The primary outcome was target lesion revascularization. Summary estimates were conducted using random‐effects analysis complemented by several subgroup and sensitivity analyses. A total of 14 randomized controlled trials with 2483 patients were included. At a mean follow up of 12 months, DCBs were associated with no difference in the incidence of target lesion revascularization as compared with alternative strategies (risk ratio [RR], 0.79; 95% CI, 0.35–1.76). There was no difference in treatment effect based on the indication (ie, small‐vessel disease, myocardial infarction, bifurcation, or high bleeding risk) (Pinteraction=0.22). DCBs were associated with lower target lesion revascularization compared with bare metal stents and similar target lesion revascularization compared with drug‐eluting stents (Pinteraction=0.03). There was no difference between DCBs and control in terms of major adverse cardiac events, vessel thrombosis, or cardiovascular mortality. However, DCBs were associated with a lower incidence of myocardial infarction (RR, 0.48; 95% CI, 0.25–0.90) and all‐cause mortality (RR, 0.45; 95% CI, 0.22–0.94). Conclusions In patients with de novo coronary lesions, use of DCBs was associated with comparable clinical outcomes irrespective of the indication or comparator device. DCBs had a similar rate of target lesion revascularization compared with drug‐eluting stents. A randomized trial powered for clinical outcomes and evaluating the role of DCBs for all‐comers is warranted.

Spontaneous coronary artery dissection (SCAD) is a relatively infrequent cause of acute coronary syndrome that usually affects young to middle-aged women. Mainly because of its low prevalence, until recently, most of the evidence on this condition was derived from case reports and small series. Over the last 5 years, more robust evidence has become available from larger retrospective and prospective cohorts of patients with SCAD. The increase in knowledge and recognition of this entity has led to the publication of expert consensus on both sides of the Atlantic. However, new data are continuously accumulating from larger cohorts of patients with SCAD, bringing new light to this little-understood condition. The aim of this article is to update the knowledge on SCAD, including new information from recent studies published since the consensus documents from the European Society of Cardiology and the American Heart Association.

Bioactive peptides released from the enzymatic hydrolysis of food proteins are currently a trending topic in the scientific community. Their potential as antidiabetic agents, by regulating the glycemic index, and thus to be employed in food formulation, is one of the most important functions of these peptides. In this review, we aimed to summarize the whole process that must be considered when talking about including these molecules as a bioactive ingredient. In this regard, at first, the production, purification and identification of bioactive peptides is summed up. The detailed metabolic pathways described included carbohydrate hydrolases (glucosidase and amylase) and dipeptidyl-peptidase IV inhibition, due to their importance in the food-derived peptides research field. Then, their characterization, concerning bioavailability in vitro and in situ, stability and functionality in food matrices, and ultimately, the in vivo evidence (from invertebrate animals to humans), was described. The future applicability that these molecules have due to their biological potential as functional ingredients makes them an important field of research, which could help the world population avoid suffering from several diseases, such as diabetes.

The tremendous impact that cardiovascular diseases have in modern society is motivating the research of novel imaging techniques that would make possible early diagnosis and, therefore, efficient treatments. Cardiovascular optical coherence tomography (CV-OCT) emerged as a result of such a demand, and it has already been used at the clinical level. Full utilization of CV-OCT requires the development of novel contrast molecular agents characterized by a large scattering efficiency in the infrared (800-1400 nm). Gold nanoparticles (GNPs) seem to be the best candidates, but their scattering properties in the infrared are hardly known. In most of the cases, scattering properties are extracted from numerical simulations. This knowledge gap here is covered by providing an experimental evaluation of the infrared scattering properties of different GNPs (nanoshells, nanostars, and nanorods). These GNPs display remarkable extinction coefficients in the first and second biological windows, including the particular CV-OCT wavelength. We use a unique combination of techniques (thermal loading experiments, infrared optical coherence tomography, infrared dark field microscopy, and optoacoustic spectroscopy) to experimentally determine the scattering efficiency at three different near-infrared wavelengths (808 nm, 980 nm, and 1280 nm), lying in the first and second biological windows. Consequently, this work determines experimentally the influence of particle morphology on the infrared scattering efficiency of GNPs and evidences the existence of remarkable discrepancies between experimental data and numerical simulations.

Abstract We describe the treatment of a patient presenting with very-late stent thrombosis with the use of a drug-coated balloon. In this patient, optical coherence tomography disclosed that ruptured and complicated neoatherosclerosis was the underlying substrate responsible for the episode of very-late stent thrombosis. The potential use of drug-coated balloons in this unique scenario is discussed.

Coronary artery aneurysm (CAA) formation is a rare complication of coronary intervention that may develop after implantation of bare-metal or drug-eluting stents. The etiology of this entity appears to be multifactorial and its prognosis is poorly understood, but it has been associated with an increased risk of stent thrombosis. To date few cases of CAAs related to bioresorbable vascular scaffold (BVS) implantation have been reported, and the development of CAA after BVS implantation for the treatment of in-stent restenosis (ISR) has not been previously described. Here we present two cases of CAA formation after BVS, which represent the first demonstration of CAA formation after the use of BVS for ISR. Resumo: A formação de um aneurisma coronário (CAN) é uma complicação rara após intervenções coronárias. O CAN pode se desenvolver após stent convencional (BMS) e implante de stent farmacológico (DES). A etiologia desta patologia parece ser multifatorial e o prognóstico permanece mal elucidado, mas tem sido associado com um aumento do risco de trombose de stent. Até à data, apenas alguns casos de CAN relacionadas com scaffold bioabsorvível (BVS) foram relatados. O desenvolvimento de CAN após o implante de um BVS para o tratamento da reestenose intra-stent (ISR) não foi anteriormente descrito. Aqui apresentamos dois casos de formação CAN após a BVS, que representam a primeira demonstração de formação CAN após o uso da BVS para ISR. Keywords: Optical coherence tomography, Bioresorbable vascular scaffolds, In-stent restenosis, Coronary artery aneurysm, Palavras-chave: Tomografia de coerência ótica, Suportes vasculares biorreabsorbíveis, Reestenose intra-stent, Aneurisma coronário

Este escrito presenta una posible respuesta a la pregunta: ¿es la política económica un factor crítico para la economía mexicana, comparando sus efectos con la actividad económica de EUA? Y si lo es ¿cuál es la relevancia del impacto de sus componentes sobre el producto mexicano ? Así, el trabajo trata de responder basándose en análisis estadístico y economé - trico, utilizando como variables representativas: la Base Monetaria, la Tasa de Interés Real, el Déficit Primario, el Tipo de Cambio Real, el Índice General de la Actividad Económica (como proxy del producto mexicano) y el Índice de la Actividad Nacional de la fed -Chicago (como proxy del producto de EUA). El objetivo principal de la investigación es determinar cuál de dichas variables es aquella que tienen las consecuencias más altas sobre la actividad económica mexicana, enmarcando las interrelaciones entre ellas, y arribando a la conclusión de la política monetaria local como aquella a la que la economía responde a un mayor grado aun sobre el producto foráneo, y a la cual se subordina la política fiscal.

Very late stent thrombosis is a rare but devastating complication after percutaneous coronary revascularization. Pathological studies have demonstrated that neoatherosclerosis plays a major role in certain patients with very late stent thrombosis. Optical coherence tomography is able to unravel the underlying pathophysiology and may be used to select the best treatment option. This case report describes the use of a bioresorbable vascular scaffold (BVS) in a patient suffering from very late stent thrombosis due to a complicated plaque in the setting of intrastent neoatherosclerosis. To our knowledge, this therapeutic strategy has not been previously reported in patients suffering from very late stent thrombosis. In this scenario, BVS implantation might represent an attractive strategy in selected patients. Resumo: A trombose de stent muito tardia é uma complicação rara mas preocupante após a revascularização coronária percutânea. Estudos patológicos têm demonstrado que a neoaterosclerose desempenha um papel importante em doentes selecionados com trombose de stent muito tardia. A tomografia de coerência ótica contribui para a compreensão da fisiopatologia subjacente, permitindo selecionar a melhor opção de tratamento. No presente caso descrevemos a utilização de um stent vascular bioabsorvível num doente que apresentava trombose de stent muito tardia devido a placa complexa no contexto de neoaterosclerose intrastent. De acordo com a nossa experiência, esta estratégia terapêutica não tem sido apresentada em doentes com trombose de stent muito avançada. Neste cenário, a implantação de suportes vasculares bioabsorbíveis pode representar uma estratégia atrativa em doentes selecionados. Keywords: Optical coherence tomography, Bioresorbable vascular scaffolds, Stent thrombosis, Neoatherosclerosis, Palavras-chave: Tomografia de coerência ótica, Suportes vasculares biorreabsorbíveis, Trombose de stent, Neoateroasclerose

A 49-year-old man was admitted to the emergency department suffering from a large anterior myocardial infarction that was treated by rescue PCI. The patient also had a moderate but complex lesion in the proximal segment of the right coronary artery. Optical coherence tomography showed striking images of a ruptured and ulcerated plaque with significant thrombus content. Although the lumen was not compromised, these unique findings prompted us to treat this non-culprit lesion. We selected a bioresorbable vascular scaffold with the aim of sealing and passivating this complicated and high-risk plaque. Resumo: Homem de 49 anos, admitido no serviço de urgência, que padecia de enfarte do miocárdio anterior extenso e que tinha sido tratado com intervenção coronária percutânea (ICP) de recurso. O doente também apresentou lesão moderada mas complexa no segmento mais próximo da coronária direita. A tomografia de coerência óptica revelou imagens impressionantes de uma placa com rotura e ulcerada com trombos significativos. Embora o lúmen não tenha sido comprometido, estas constatações únicas levaram-nos a tratar rapidamente esta lesão não culpada. Selecionámos um suporte vascular bioabsorbível com o objetivo de selar e de solucionar o caso desta placa complicada e de alto risco. Keywords: Optical coherence tomography, Non-culprit lesion, Bioresorbable vascular scaffolds, Palavras-chave: Tomografia de coerência ótica, Lesão não culpada, Suportes vasculares bioabsorbíveis

Varón de 60 años con antecedentes de hipertensión arterial, dislipemia y cardiopatía isquémica, esta última con debut 8 años antes por angina inestable; en ese momento se realizó coronariografía que mostró enfermedad de la coronaria derecha (CD): un vaso ectásico, con importante remodelado positivo y lesiones graves en su segmento distal, y en el proximal de la rama posterolateral. Se trató mediante implante de dos stents no farmacoactivos. Desde entonces el paciente permaneció asintomático, con buen control de los factores de riesgo cardiovascular.