Search

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2M-/-CIITA-/-CD47+). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques. The HIP cells survived unrestricted for 16 weeks in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas allogeneic wild-type cells were vigorously rejected. We also differentiated human HIP cells into endocrinologically active pancreatic islet cells and showed that they survived in immunocompetent, allogeneic diabetic humanized mice for 4 weeks and ameliorated diabetes. HIP-edited primary rhesus macaque islets survived for 40 weeks in an allogeneic rhesus macaque recipient without immunosuppression, whereas unedited islets were quickly rejected.

ABSTRACT A substantial number of patients undergoing coronary angiography for angina or ischemia in noninvasive tests have coronary arteries without lesions or with nonsignificant stenosis. Many of these patients have nonobstructive myocardial ischemia (INOCA/ANOCA), which is an entity with prognostic importance that significantly affects patients’ quality of life. The absence of a proper diagnosis leads to inappropriate medical treatment, repeat diagnostic tests, and greater use of social and health resources. An adequate diagnostic strategy is required for individualized treatment that improves symptoms and quality of life. In this document from the SEC-Clinical Cardiology Association, SEC Interventional Cardiology Association, SEC-Ischemic Heart Disease and Acute Cardiac Care Association, and SEC-Cardiovascular Imaging Association of the Spanish Society of Cardiology, we provide simple and practical algorithms, with the aim of facilitating the early diagnosis and most appropriate treatment for patients with ANOCA. Keywords: ANOCA. INOCA. Microvascular dysfunction. Vasospastic angina. RESUMEN Un número importante de aquellos pacientes en quienes se realiza coronariografía por angina o isquemia presentan en pruebas no invasivas arterias coronarias sin lesiones o con estenosis no significativas. Muchos de estos pacientes tienen isquemia miocárdica de causa no obstructiva (INOCA/ANOCA), una condición con importancia pronóstica que afecta de manera considerable la calidad de vida. La ausencia de un diagnóstico que haga...

RESUMEN Un número importante de aquellos pacientes en quienes se realiza coronariografía por angina o isquemia presentan en pruebas no invasivas arterias coronarias sin lesiones o con estenosis no significativas. Muchos de estos pacientes tienen isquemia miocárdica de causa no obstructiva (INOCA/ANOCA), una condición con importancia pronóstica que afecta de manera considerable la calidad de vida. La ausencia de un diagnóstico que haga posible un tratamiento médico efectivo acarrea la repetición de pruebas diagnósticas y un mayor uso de recursos sociosanitarios. Es necesaria una estrategia diagnóstica adecuada para poder realizar un tratamiento personalizado, que mejore los síntomas y la calidad de vida. En este documento de la SEC-Asociación de Cardiología Clínica, SEC-Asociación de Cardiología Intervencionista, SEC-Asociación de Cardiopatía Isquémica y Cuidados Agudos Cardiovasculares, y SEC-Asociación de Imagen Cardiaca, se establecen unos algoritmos sencillos y prácticos con el objetivo de facilitar el diagnóstico precoz y el tratamiento más adecuado de los pacientes con ANOCA. Palabras clave: ANOCA. INOCA. Disfunción microvascular. Angina vasoespástica. ABSTRACT A substantial number of patients undergoing coronary angiography for angina or ischemia in noninvasive tests have coronary arteries without lesions or with nonsignificant stenosis. Many of these patients have nonobstructive myocardial ischemia (INOCA/ANOCA), which is an entity with prognostic importance that significantly affects patients’ quality of...

Este texto presenta el Instituto del Tiempo Suspendido, un pro-yecto artístico y filosófico que propone alternativas a la polí-tica del tiempo en nuestras sociedades. Para ello, utiliza dos estrategias principalmente. Por una parte, aprovecha el arte contemporáneo como una disciplina indisciplinada en la que se pueden armar espacios y tiempos no sometidos a la política neoliberal actual. Por otra parte, se apoya en la reflexión filo-sófica y política para contestar la relación entre poder y tiempo a través de conceptos como crononormatividad, cronodiver-sidad, régimen temporal o tiempo indeterminado. Al final del texto, se ofrece un enlace para realizar un “juicio temporal”.

Manufacturing autologous chimeric antigen receptor (CAR) T cell therapeutics is complex, and many patients experience treatment delays or cannot be treated at all. Although current allogeneic CAR products have the potential to overcome manufacturing bottlenecks, they are subject to immune rejection and failure to persist in the host, and thus do not provide the same level of efficacy as their autologous counterparts. Here, we aimed to develop universal allogeneic CAR T cells that evade the immune system and produce a durable response. We generated human hypoimmune (HIP) T cells with disrupted B2M, CIITA, and TRAC genes using CRISPR-Cas9 editing. In addition, CD47 and anti-CD19 CAR were expressed using lentiviral transduction. These allogeneic HIP CD19 CAR T cells were compared to allogeneic CD19 CAR T cells that only expressed the anti-CD19 CAR (allo CAR T). In vitro assays for cancer killing and exhaustion revealed no differences between allo CAR T and HIP CAR T cells, confirming that the HIP edits did not negatively affect T cell performance. Clearance of CD19+ tumors by HIP CAR T cells in immunodeficient NSG mice was comparable to that of allo CAR T cells. In fully immunocompetent humanized mice, HIP CAR T cells significantly outperformed allo CAR T cells, showed improved persistence and expansion, and provided lasting cancer clearance. Furthermore, CD47-targeting safety strategies reliably and specifically eliminated HIP CAR T cells. These findings suggest that universal allogeneic HIP CAR T cell-based therapeutics might overcome the limitations associated with poor persistence of allogeneic CAR T cells and exert durable anti-tumor responses.

Introduction and objectives Only about 50% of chronic patients in high-income countries adhere to their treatment. There are methods to measure medication adherence but none of them can be considered optimal. This study will aim to design and validate a questionnaire to measure medication adherence in patients with ischaemic heart disease using a direct method as a gold-standard adherence measure and taking into account the gender perspective. Moreover, the profile of low adherence in these patients will be determined.Methods and analysis First study phase consists on the questionnaire design following the next steps: identification of the dimensions, definition of the target population, questionnaire items and order, response coding, questionnaire instructions, content validity by experts and understandability. In the second phase, a cross-sectional study will be performed to end the questionnaire development and validate it. Four hundred and forty patients (50% female) with acute coronary syndrome receiving treatment within the previous 12 months will be included. Patient will answer the initial questionnaire and adherence to aspirin and statin will be measured using a direct method (drug concentration analysis in blood) and other questionnaires. From the set of preselected questionnaire items, those most closely associated with the gold standard measure will be selected using multivariate statistics.Ethics and dissemination All participants gave their written informed consent before participating in the study. The study protocol follows the recommendations of the Declaration of Helsinki and was approved by the ethics committees of the three participating centres. The results of this study will be displayed at national and international conferences and in peer-reviewed scientific journals.

Background: Cardiovascular (CVD) and chronic kidney disease (CKD) in women have unique risk factors related to hormonal status and obstetric history that must be taken into account. Pregnancy complications, such as preeclampsia (PE), can reveal a subclinical predisposition for the development of future disease that may help identify women who could benefit from early CVD and CKD prevention strategies. Materials and methods: Review of PE and its association with future development of CVD and CKD. Results: Multiple studies have established an association between PE and the development of ischemic heart disease, chronic hypertension, peripheral vascular disease, stroke and CKD. It has not been sufficiently clarified if this relation is a causal one or if it is mediated by common risk factors. Nevertheless, the presence of endothelial dysfunction and thrombotic microangiopathy during pregnancies complicated with PE makes us believe that PE may leave a long-term imprint. Early identification of women who have had a pregnancy complicated by PE becomes a window of opportunity to improve women’s health through adequate follow-up and targeted preventive actions. Oxidative stress biomarkers and vascular ultrasound may play a key role in the early detection of this arterial damage. Conclusions: The implementation of preventive multidisciplinary targeted strategies can help slow down CVD and CKD’s natural history in women at risk through lifestyle modifications and adequate blood pressure control. Therefore, we propose a series of recommendations to guide the prediction and prevention of CVD and CKD throughout life of women with a history of PE. Resumen: Antecedentes: La enfermedad cardiovascular (ECV) y renal en la mujer presentan factores de riesgo propios relacionados con el estatus hormonal y los antecedentes obstétricos que deben tenerse en cuenta. Las complicaciones del embarazo, como la preeclampsia (PE), pueden revelar predisposiciones subclínicas a padecer enfermedades futuras que ayuden a identificar a aquellas mujeres que puedan beneficiarse de nuevas oportunidades para la prevención de la ECV y la enfermedad renal crónica. Materiales y métodos: Revisión sobre la PE y su asociación con el desarrollo de ECV y renal futuras. Resultados: Múltiples estudios han establecido una asociación entre PE y el desarrollo de cardiopatía isquémica, hipertensión crónica, enfermedad vascular periférica, accidente cerebrovascular y enfermedad renal. No se ha aclarado suficientemente si esta relación es de causalidad o está mediada por la presencia de factores de riesgo comunes. Sin embargo, la demostración de fenómenos de disfunción endotelial y microangiopatía trombótica en los embarazos que cursan con PE hace suponer que esta puede dejar una impronta a largo plazo. La identificación precoz de las mujeres que han padecido un embarazo complicado con PE es una ventana de oportunidad para mejorar la salud de la mujer, mediante su seguimiento y la adopción de medidas preventivas adecuadas. Los marcadores bioquímicos de daño oxidativo y la ecografía vascular pueden desempeñar un papel clave en la identificación precoz de este daño arterial. Conclusiones: La implantación de estrategias preventivas multidisciplinares y específicas puede ayudar a frenar la historia natural de la ECV y renal en las mujeres de riesgo, a través de la modificación de su estilo de vida y del adecuado control de la tensión arterial. Para ello, proponemos una serie de recomendaciones para guiar el estudio de la predicción y prevención de la ECV tras la PE a lo largo de la vida de la mujer.

Resumen: Antecedentes: La enfermedad cardiovascular (ECV) y renal en la mujer presentan factores de riesgo propios relacionados con el estatus hormonal y los antecedentes obstétricos que deben tenerse en cuenta. Las complicaciones del embarazo, como la preeclampsia (PE), pueden revelar predisposiciones subclínicas a padecer enfermedades futuras que ayuden a identificar a aquellas mujeres que puedan beneficiarse de nuevas oportunidades para la prevención de la ECV y la enfermedad renal crónica. Materiales y métodos: Revisión sobre la PE y su asociación con el desarrollo de ECV y renal futuras. Resultados: Múltiples estudios han establecido una asociación entre PE y el desarrollo de cardiopatía isquémica, hipertensión crónica, enfermedad vascular periférica, accidente cerebrovascular y enfermedad renal. No se ha aclarado suficientemente si esta relación es de causalidad o está mediada por la presencia de factores de riesgo comunes. Sin embargo, la demostración de fenómenos de disfunción endotelial y microangiopatía trombótica en los embarazos que cursan con PE hace suponer que esta puede dejar una impronta a largo plazo. La identificación precoz de las mujeres que han padecido un embarazo complicado con PE es una ventana de oportunidad para mejorar la salud de la mujer, mediante su seguimiento y la adopción de medidas preventivas adecuadas. Los marcadores bioquímicos de daño oxidativo y la ecografía vascular pueden desempeñar un papel clave en la identificación precoz de este daño arterial. Conclusiones: La implantación de estrategias preventivas multidisciplinares y específicas puede ayudar a frenar la historia natural de la ECV y renal en las mujeres de riesgo, a través de la modificación de su estilo de vida y del adecuado control de la tensión arterial. Para ello, proponemos una serie de recomendaciones para guiar el estudio de la predicción y prevención de la ECV tras la PE a lo largo de la vida de la mujer. Abstract: Background: Cardiovascular (CVD) and chronic kidney disease (CKD) in women have unique risk factors related to hormonal status and obstetric history that must be taken into account. Pregnancy complications, such as preeclampsia (PE), can reveal a subclinical predisposition for the development of future disease that may help identify women who could benefit from early CVD and CKD prevention strategies. Materials and methods: Review of PE and its association with future development of CVD and CKD. Results: Multiple studies have established an association between PE and the development of ischemic heart disease, chronic hypertension, peripheral vascular disease, stroke and CKD. It has not been sufficiently clarified if this relation is a causal one or if it is mediated by common risk factors. Nevertheless, the presence of endothelial dysfunction and thrombotic microangiopathy during pregnancies complicated with PE makes us believe that PE may leave a long-term imprint. Early identification of women who have had a pregnancy complicated by PE becomes a window of opportunity to improve women's health through adequate follow-up and targeted preventive actions. Oxidative stress biomarkers and vascular ultrasound may play a key role in the early detection of this arterial damage. Conclusions: The implementation of preventive multidisciplinary targeted strategies can help slow down CVD and CKD's natural history in women at risk through lifestyle modifications and adequate blood pressure control. Therefore, we propose a series of recommendations to guide the prediction and prevention of CVD and CKD throughout life of women with a history of PE.

Abstract Manufacturing autologous chimeric antigen receptor (CAR) T cell therapeutics is complex, and many patients experience treatment delays or cannot be treated at all. Although current allogeneic CAR products have the potential to overcome manufacturing bottlenecks, they are subject to immune rejection and failure to persist in the host, and thus do not provide the same level of efficacy as their autologous counterparts. Here, we aimed to develop universal allogeneic CAR T cells that evade the immune system and produce a durable response. We generated human hypoimmune (HIP) T cells with disrupted B2M, CIITA, and TRAC genes using CRISPR-Cas9 editing. In addition, CD47 and anti-CD19 CAR were expressed using lentiviral transduction. These allogeneic HIP CD19 CAR T cells were compared to allogeneic CD19 CAR T cells that only expressed the anti-CD19 CAR (allo CAR T). In vitro assays for cancer killing and exhaustion revealed no differences between allo CAR T and HIP CAR T cells, confirming that the HIP edits did not negatively affect T cell performance. Clearance of CD19+ tumors by HIP CAR T cells in immunodeficient NSG mice was comparable to that of allo CAR T cells. In fully immunocompetent humanized mice, HIP CAR T cells significantly outperformed allo CAR T cells, showed improved persistence and expansion, and provided lasting cancer clearance. Furthermore, CD47-targeting safety strategies reliably and specifically eliminated HIP CAR T cells. These findings suggest that universal allogeneic HIP CAR T cell-based therapeutics might overcome the limitations associated with poor persistence of allogeneic CAR T cells and exert durable anti-tumor responses.

Introduction Life expectancy of patients with psoriasis is reduced by 4–5 years due to cardiovascular disease with an increased risk of myocardial infarction at an earlier age compared with the general population. This increased risk is independent of traditional cardiovascular risk factors and higher in moderate-to-severe forms of psoriasis. Inflammation may play a key role in the development of atherosclerosis in these patients.Methods and analysis A prospective cohort study, Early Detection and Progression of Subclinical Atherosclerosis in Psoriasis (EDSAP), was initiated in January 2020 to investigate the presence and progression of subclinical atherosclerosis in patients with psoriasis. 120 patients aged 30–65 years and eligible for biological treatment have been recruited at Hospital Ramón y Cajal in Madrid, Spain. Patients undergo a baseline visit, and 1-year follow-up visit after starting biological therapy. Each visit includes: assessment of cardiovascular risk factors, screening for subclinical atherosclerosis by two-dimensional/three-dimensional ultrasound of carotid and femoral arteries, cardiac CT of coronary arteries and blood sampling. All baseline visits were completed by December 2022, and the remaining follow-up visits will be concluded by the end of 2023. The EDSAP study aims to identify new molecular and imaging markers associated with the presence of atherosclerosis and its progression in a chronic inflammatory state such as psoriasis. This has the potential to: (1) help improve primary cardiovascular prevention strategies in these patients; (2) understand the effect of biological drugs on the cardiovascular system; and (3) serve as a model for understanding atherosclerosis in other chronic inflammatory diseases.Ethics and dissemination The study protocol has been approved by the Institutional Review Board of the Hospital Ramón y Cajal in Madrid. We will present our findings at national and international congresses, and peer-reviewed journals.Trial Registration number NCT05858099.

The purpose of this study is to conduct a literature review on the current role of computed tomography pulmonary angiography (CTPA) in the diagnosis and prognosis of pulmonary embolism (PE). It addresses key topics such as the quantification of the thrombotic burden, its role as a predictor of mortality, new diagnostic techniques that are available, the possibility of analyzing the thrombus composition to differentiate its evolutionary stage, and the applicability of artificial intelligence (AI) in PE through CTPA. The only finding from CTPA that has been validated as a prognostic factor so far is the right ventricle/left ventricle (RV/LV) diameter ratio being >1, which is associated with a 2.5-fold higher risk of all-cause mortality or adverse events, and a 5-fold higher risk of PE-related mortality. The increasing use of techniques such as dual-energy computed tomography allows for the more accurate diagnosis of perfusion defects, which may go undetected in conventional computed tomography, identifying up to 92% of these defects compared to 78% being detected by CTPA. Additionally, it is essential to explore the latest advances in the application of AI to CTPA, which are currently expanding and have demonstrated a 23% improvement in the detection of subsegmental emboli compared to manual interpretation. With deep image analysis, up to a 95% accuracy has been achieved in predicting PE severity based on the thrombus volume and perfusion deficits. These advancements over the past 10 years significantly contribute to early intervention strategies and, therefore, to the improvement of morbidity and mortality outcomes for these patients. [ABSTRACT FROM AUTHOR]

The photovoltaic literature contains a wide range of methods for translating the I–V curves of a solar device to other conditions of irradiance and cell temperature, different from those under which the measurements were performed. Some of these translation methods are included as part of the International Standard IEC 60891. In this paper, these techniques are classified, reviewed, and implemented to perform a deep comparative analysis between them and to discuss their suitability for converting the I–V curves of photovoltaic modules under different scenarios of irradiance and temperature. From the analysis conducted, it can be seen that the interpolation method proposed in IEC 60891 achieves accurate results when it is applied to correct small and medium irradiance and temperature gaps. If no interpolation is possible and for large irradiance corrections, other procedures described in IEC 60891 can be applied. However, certain explicit methods based on the single-diode model or on the double-diode model can overcome the most well-known approaches proposed by the standard.

Abstract Aims To evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation. Methods and results Seventy‐two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high‐sensitivity cardiac troponin T, NT‐proBNP, global longitudinal strain (GLS), left ventricle end‐systolic volume (LVESV), left ventricle end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF

BackgroundLittle is known about whether the overlap syndrome (OS) combining features of chronic obstructive pulmonary disease (COPD) and sleep apnea-hypopnea syndrome increases the risk of stroke associated with COPD itself.MethodsWe prospectively studied 74 COPD patients and 32 subjects without lung disease. Spirometry and cardiorespiratory polygraphy were used to assess the pulmonary function of the study population and ultrasound measurements of intima media thickness (IMT) as well as the volume of plaques in both carotid arteries were also evaluated.ResultsPolygraphic criteria of OS were met in 51% of COPD patients. We found that 79% of patients with OS and 50% of COPD patients without OS had atherosclerotic plaques in the left carotid artery (p = 0.0509). Interestingly, the mean volume of atherosclerotic plaques was significantly higher in the left carotid artery of COPD patients with OS (0.07 ± 0.02 ml) than in those without OS (0.04 ± 0.02 ml, p = 0.0305). However, regardless of the presence of OS, no significant differences were observed in both presence and volume of atherosclerotic plaques in the right carotid artery of COPD patients. Adjusted-multivariate linear regression revealed age, current smoking and the apnea/hypopnea index (OR = 4.54, p = 0.012) as independent predictors of left carotid atherosclerotic plaques in COPD patients.ConclusionsThis study suggests that the presence of OS in COPD patients is associated with larger left carotid atherosclerotic plaques, indicating that OS might be screened in all COPD patients to identify those with higher risk of stroke.

Este texto presenta el Instituto del Tiempo Suspendido, un pro-yecto artístico y filosófico que propone alternativas a la polí-tica del tiempo en nuestras sociedades. Para ello, utiliza dos estrategias principalmente. Por una parte, aprovecha el arte contemporáneo como una disciplina indisciplinada en la que se pueden armar espacios y tiempos no sometidos a la política neoliberal actual. Por otra parte, se apoya en la reflexión filo-sófica y política para contestar la relación entre poder y tiempo a través de conceptos como crononormatividad, cronodiver-sidad, régimen temporal o tiempo indeterminado. Al final del texto, se ofrece un enlace para realizar un “juicio temporal”. This text presents the Institute of Suspended Time, an artistic and philosophical project that proposes alternatives to the po-litics of time in our societies. To do this, it uses two strategies mainly. On the one hand, it takes advantage of contemporary art as an undisciplined discipline in which spaces and times not subject to the politics of neoliberalism can be built. On the other hand, it relies on philosophical and political reflection to question the relationship between power and time, through concepts such as chrononormativity, chronodiversity, temporal regime or indeterminate time. At the end of the text, a link to a “temporal judgment” is offered.

Abstract Introduction Mitral valve (MV) prolapse (MVP) is a primary valvular abnormality. We hypothesized that additionally there are concomitant abnormalities of the left ventricle (LV) and MV apparatus in this entity even in the absence of significant mitral regurgitation (MR). Objective To characterize MV and LV anatomic and functional features in MVP with preserved LV ejection fraction, with and without significant MR, using cardiovascular magnetic resonance (CMR). Methods Consecutive MVP patients (n = 80, mean 52 years, 37% males) with preserved LV ejection fraction, and 44 controls (46 years, 52% males) by CMR were included, as well as 13 additional patients with “borderline” MVP. From cine images we quantified LV volumes, MV and LV anatomic measurements (including angle between diastolic and systolic annular planes, annular displacement, and basal inferolateral hypertrophy) and, using feature tracking, longitudinal and circumferential peak systolic strains. Results Significant MR was found in 46 (56%) MVP patients. Compared with controls, MVP patients had LV enlargement, basal inferolateral hypertrophy, higher posterior annular excursion, and reduced shortening of the papillary muscles. LV basal strains were significantly increased, particularly in several basal segments. These differences remained significant in patients without significant MR, and many persisted in “borderline” MVP. Conclusions In patients with MVP and preserved LV ejection fraction there is LV dilatation, basal inferolateral hypertrophy, exaggerated posterior annular displacement and increased basal deformation, even in the absence of significant MR or overt MVP. These findings suggest that MVP is a disease not only of the MV but also of the adjacent myocardium.

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.

Summary: Background: Imaging of subclinical atherosclerosis improves cardiovascular risk prediction on top of traditional risk factors. However, cardiovascular imaging is not universally available. This work aims to identify circulating proteins that could predict subclinical atherosclerosis. Methods: Hypothesis-free proteomics was used to analyze plasma from 444 subjects from PESA cohort study (222 with extensive atherosclerosis on imaging, and 222 matched controls) at two timepoints (three years apart) for discovery, and from 350 subjects from AWHS cohort study (175 subjects with extensive atherosclerosis on imaging and 175 matched controls) for external validation. A selected three-protein panel was further validated by immunoturbidimetry in the AWHS population and in 2999 subjects from ILERVAS cohort study. Findings: PIGR, IGHA2, APOA, HPT and HEP2 were associated with subclinical atherosclerosis independently from traditional risk factors at both timepoints in the discovery and validation cohorts. Multivariate analysis rendered a potential three-protein biomarker panel, including IGHA2, APOA and HPT. Immunoturbidimetry confirmed the independent associations of these three proteins with subclinical atherosclerosis in AWHS and ILERVAS. A machine-learning model with these three proteins was able to predict subclinical atherosclerosis in ILERVAS (AUC [95%CI]:0.73 [0.70–0.74], p

Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart failure and sudden death. Previous family and pathophysiological studies suggest a complex pattern of inheritance. We performed a meta-analysis of 2 genome-wide association studies in 1,412 MVP cases and 2,439 controls. We identified 6 loci, which we replicated in 1,422 cases and 6,779 controls, and provide functional evidence for candidate genes. We highlight LMCD1 (LIM and cysteine-rich domains 1), which encodes a transcription factor and for which morpholino knockdown of the ortholog in zebrafish resulted in atrioventricular valve regurgitation. A similar zebrafish phenotype was obtained with knockdown of the ortholog of TNS1, which encodes tensin 1, a focal adhesion protein involved in cytoskeleton organization. We also showed expression of tensin 1 during valve morphogenesis and describe enlarged posterior mitral leaflets in Tns1(-/-) mice. This study identifies the first risk loci for MVP and suggests new mechanisms involved in mitral valve regurgitation, the most common indication for mitral valve repair.