Profiling Cell Heterogeneity and Fructose Transporter Expression in the Rat Nephron by Integrating Single-Cell and Microdissected Tubule Segment Transcriptomes.

Single-cell RNA sequencing (scRNAseq) is a crucial tool in kidney research. These technologies cluster cells based on transcriptome similarity, irrespective of the anatomical location and order within the nephron. Thus, a transcriptome cluster may obscure the heterogeneity of the cell population within a nephron segment. Elevated dietary fructose leads to salt-sensitive hypertension, in part, through fructose reabsorption in the proximal tubule (PT). However, the organization of the four known fructose transporters in apical PTs (SGLT4, SGLT5, GLUT5, and NaGLT1) remains poorly understood. We hypothesized that cells within each subsegment of the proximal tubule exhibit complex, heterogeneous fructose transporter expression patterns. To test this hypothesis, we analyzed rat kidney transcriptomes and proteomes from publicly available scRNAseq and tubule microdissection databases. We found that microdissected PT-S1 segments consist of 81% ± 12% cells with scRNAseq-derived transcriptional characteristics of S1, whereas PT-S2 express a mixture of 18% ± 9% S1, 58% ± 8% S2, and 19% ± 5% S3 transcripts, and PT-S3 consists of 75% ± 9% S3 transcripts. The expression of all four fructose transporters was detectable in all three PT segments, but key fructose transporters SGLT5 and GLUT5 progressively increased from S1 to S3, and both were significantly upregulated in S3 vs. S1/S2 (Slc5a10: 1.9 log2FC, p < 1 × 10-299; Scl2a5: 1.4 log2FC, p < 4 × 10-105). A similar distribution was found in human kidneys. These data suggest that S3 is the primary site of fructose reabsorption in both humans and rats. Finally, because of the multiple scRNAseq transcriptional phenotypes found in each segment, our findings also imply that anatomical labels applied to scRNAseq clusters may be misleading.

Unraveling the antimicrobial activity of CuS functionalized titanates under visible LED light irradiation.

Titanate nanotubes (TNs) functionalized with CuS nanoparticles using the microwave-assisted hydrothermal method were characterized via XRD, Raman spectroscopy, UV-Vis spectrophotometry, and N2 physisorption. The as-synthesized CuS/TNs had anatase as the main crystalline phase and the band-gap energy was in the visible region, 2.9 eV. The TNs were recrystallized on titania and functionalized with CuS, forming spherical bundles. SEM showed agglomerates of cauliflower-like semispherical particles. The antimicrobial photoactive assets were evaluated against the bacteria Staphylococcus aureus and Escherichia coli. Inhibition was clearly visible in S. aureus after the first 20 min of exposure to a 6-W LED irradiation lamp. The visible-light catalyzed completely and irreversibly the inactivation of S. aureus after 60 min, however, in the case of E. coli, this material only slightly disturbed its growth, which was recovered after 60 min. The successful result obtained with S. aureus can be explained by the fact that it lacks periplasmic superoxide dismutase (SOD) but has staphyloxanthin for external protection against ROS. However, the CuS/TN particles could release Cu2+ ions, which got attached to bacterium structures or entered the cytoplasm; these events together with the generation of ROS under visible LED light helped inactivate quickly staphyloxanthin, thus inflicting permanent damage to the periplasmic membrane.

Knocking Out Sodium Glucose-Linked Transporter 5 Prevents Fructose-Induced Renal Oxidative Stress and Salt-Sensitive Hypertension.

BACKGROUND: A fructose high-salt (FHS) diet increases systolic blood pressure and Ang II (angiotensin II)-stimulated proximal tubule (PT) superoxide (O2-) production. These increases are prevented by scavenging O2- or an Ang II type 1 receptor antagonist. SGLT4 (sodium glucose-linked cotransporters 4) and SGLT5 are implicated in PT fructose reabsorption, but their roles in fructose-induced hypertension are unclear. We hypothesized that PT fructose reabsorption by SGLT5 initiates a genetic program enhancing Ang II-stimulated oxidative stress in males and females, thereby causing fructose-induced salt-sensitive hypertension. METHODS: We measured systolic blood pressure in male and female Sprague-Dawley (wild type [WT]), SGLT4 knockout (-/-), and SGLT5-/- rats. Then, we measured basal and Ang II-stimulated (37 nmol/L) O2- production by PTs and conducted gene coexpression network analysis. RESULTS: In male WT and female WT rats, FHS increased systolic blood pressure by 15±3 (n=7; P<0.0027) and 17±4 mm Hg (n=9; P<0.0037), respectively. Male and female SGLT4-/- had similar increases. Systolic blood pressure was unchanged by FHS in male and female SGLT5-/-. In male WT and female WT fed FHS, Ang II stimulated O2- production by 14±5 (n=6; P<0.0493) and 8±3 relative light units/µg protein/s (n=7; P<0.0218), respectively. The responses of SGTL4-/- were similar. Ang II did not stimulate O2- production in tubules from SGLT5-/-. Five gene coexpression modules were correlated with FHS. These correlations were completely blunted in SGLT5-/- and partially blunted by chronically scavenging O2- with tempol. CONCLUSIONS: SGLT5-mediated PT fructose reabsorption is required for FHS to augment Ang II-stimulated proximal nephron O2- production, and increases in PT oxidative stress likely contribute to FHS-induced hypertension.

Prevalence of childhood obesity in Spain and its relation with socioeconomic status and health behaviors: Population-based cross-sectional study.

OBJECTIVES: This study aims to assess the current state of childhood overweight and obesity in Spain, and its relationship with socioeconomic status and health-related behaviors. METHODS: Population-based cross-sectional observational study, based on the 2017 National Health Survey in minors in Spain. This study included all children surveyed who were aged 1-14 years. Childhood obesity was estimated from the z-score of the body mass index. RESULTS: The study included 4882 children aged 1-14 years (mean 7.5). The prevalence of obesity was 18.6% (95% confidence interval [CI] 18.5-18.7), while 13.5% (95% CI 13.4-13.6) were overweight. These figures represent over a million children in Spain who are obese and nearly 750,000 who are overweight. A north-south geographic gradient was apparent, with higher prevalence of unhealthy body weight in southern Spain. Factors associated with childhood obesity were low socioeconomic status, poor diet and sedentarism, among others. CONCLUSIONS: Childhood overweight in Spain is strongly associated with socioeconomic status and other factors such as diet and sedentarism. Multidisciplinary public health interventions are needed to reduce this serious health problem in children.

Enhancing antioxidant properties of CeO2 nanoparticles with Nd3+ doping: structural, biological, and machine learning insights.

The antioxidant capabilities of nanoparticles are contingent upon various factors, including their shape, size, and chemical composition. Herein, novel Nd-doped CeO2 nanoparticles were synthesized and the neodymium content was varied to investigate the synergistic impact on the antioxidant properties of CeO2 nanoparticles. Incorporating Nd3+ induced changes in lattice parameters and significantly altered the morphology from nanoparticles to nanorods. The biological activity of Nd-doped CeO2 was examined against pathogenic bacterial strains, breast cancer cell lines, and antioxidant models. The antibacterial and anticancer activities of nanoparticles were not observed, which could be associated with the Ce3+/Ce4+ ratio. Notably, the incorporation of neodymium improved the antioxidant capacity of CeO2. Machine learning techniques were employed to forecast the antioxidant activity to enhance understanding and predictive capabilities. Among these models, the random forest model exhibited the highest accuracy at 96.35%, establishing it as a robust computational tool for elucidating the biological behavior of Nd-doped CeO2 nanoparticles. This study presents the first exploration of the influence of Nd3+ on the structural, optical, and biological attributes of CeO2, contributing valuable insights and extending the application of machine learning in predicting the therapeutic efficacy of inorganic nanomaterials.

ß-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: Increasing the patient's heart rate (HR) has emerged as a therapeutic option in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence is conflicting, and the profile of patients who benefit most from this strategy remains unclear. Objective: To assess the association of ß-blocker treatment withdrawal with changes in the percentage of predicted peak oxygen consumption (VO2) across indexed left ventricular diastolic (iLVEDV) and indexed left ventricular systolic volumes (iLVESV), and left ventricular ejection fraction (LVEF) in patients with HFpEF and chronotropic incompetence. Design, Setting, and Participants: This post hoc analysis was conducted using data from the investigator-blinded multicenter, randomized, and crossover clinical trial, PRESERVE-HR, that took place from October 1, 2018, through December 31, 2020, to investigate the short-term effects (2 weeks) of ß-blocker withdrawal on peak oxygen consumption (peak VO2). Patients with stable HFpEF (New York Heart Association functional class II to III) receiving treatment with ß-blocker and chronotropic incompetence were included. Intervention: Participants in the PRESERVE-HR trial were randomized to withdraw vs continue with ß-blocker treatment. After 2 weeks, they were crossed over to receive the opposite intervention. This crossover randomized clinical trial examined the short-term effect of ß-blocker withdrawal on peak VO2. Main Outcomes and Measures: The primary outcome was to evaluate the association between ß-blocker withdrawal and short-term changes in percentage of peak VO2 across iLVEDV, iLVESV, and LVEF in patients with HFpEF and chronotropic incompetence treated with ß-blocker. Results: A total of 52 patients (mean age, 73 [SD, 13] years; 60% female) were randomized. The mean resting HR, peak HR, peak VO2, and percentage of peak VO2 were 65 (SD, 9) beats per minute (bpm), 97 (SD, 15) bpm, 12.4 (SD, 2.9) mL/kg per minute, and 72.4% (SD, 17.7%), respectively. The medians (minimum-maximum) of iLVEDV, iLVESV, and LVEF were 44 mL/m2 (IQR, 19-82), 15 mL/m2 (IQR, 7-32), and 64% (IQR, 52%-78%), respectively. After stopping ß-blocker treatment, the median increase in peak HR was plus 30 bpm (95% CI, 25-35; P < .001). ß-Blocker cessation was differentially associated with change of percentage of peak VO2 across the continuum of iLVESV (P for interaction = .02), indicating a greater benefit in those with lower iLVESV. Conclusions and Relevance: In this study, results showed that in patients with HFpEF and chronotropic incompetence receiving treatment with ß-blocker, lower iLVESV may identify those with a greater short-term improvement in maximal functional capacity after stopping ß-blocker treatment. Further studies are warranted for further investigation. Trial Registration: ClinicalTrials.gov (NCT03871803).

Association of mental health-related patient reported outcomes with blood pressure in adults and children with primary proteinuric glomerulopathies.

INTRODUCTION: The prevalence of mental health disorders including anxiety and depression is increasing and is linked to hypertension in healthy individuals. However, the relationship of psychosocial patient-reported outcomes on blood pressure (BP) in primary proteinuric glomerulopathies is not well characterized. This study explored longitudinal relationships between psychosocial patient-reported outcomes and BP status among individuals with proteinuric glomerulopathies. METHODS: An observational cohort study was performed using data from 745 adults and children enrolled in the Nephrotic Syndrome Study Network (NEPTUNE). General Estimating Equations for linear regression and binary logistic analysis for odds ratios were performed to analyze relationships between the exposures, longitudinal Patient-Reported Outcome Measurement Information System (PROMIS) measures and BP and hypertension status as outcomes. RESULTS: In adults, more anxiety was longitudinally associated with higher systolic and hypertensive BP. In children, fatigue was longitudinally associated with increased odds of hypertensive BP regardless of the PROMIS report method. More stress, anxiety, and depression were longitudinally associated with higher systolic BP index, higher diastolic BP index, and increased odds of hypertensive BP index in children with parent-proxy patient-reported outcomes. DISCUSSION/CONCLUSION: Chronically poor psychosocial patient-reported outcomes may be significantly associated with higher BP and hypertension in adults and children with primary proteinuric glomerulopathies. This interaction appears strong in children but should be interpreted with caution, as multiple confounders related to glomerular disease may influence both mental health and BP independently. That said, access to mental health resources may help control BP, and proper disease and BP management may improve overall mental health.

Classification tree obtained by artificial intelligence for the prediction of heart failure after acute coronary syndromes. / Árboles de clasificación obtenidos mediante inteligencia artificial para la predicción de insuficiencia cardiaca tras el síndrome coronario agudo.

BACKGROUND: Coronary heart disease is the leading cause of heart failure (HF), and tools are needed to identify patients with a higher probability of developing HF after an acute coronary syndrome (ACS). Artificial intelligence (AI) has proven to be useful in identifying variables related to the development of cardiovascular complications. METHODS: We included all consecutive patients discharged after ACS in two Spanish centers between 2006 and 2017. Clinical data were collected and patients were followed up for a median of 53months. Decision tree models were created by the model-based recursive partitioning algorithm. RESULTS: The cohort consisted of 7,097 patients with a median follow-up of 53months (interquartile range: 18-77). The readmission rate for HF was 13.6% (964 patients). Eight relevant variables were identified to predict HF hospitalization time: HF at index hospitalization, diabetes, atrial fibrillation, glomerular filtration rate, age, Charlson index, hemoglobin, and left ventricular ejection fraction. The decision tree model provided 15 clinical risk patterns with significantly different HF readmission rates. CONCLUSIONS: The decision tree model, obtained by AI, identified 8 leading variables capable of predicting HF and generated 15 differentiated clinical patterns with respect to the probability of being hospitalized for HF. An electronic application was created and made available for free.

External validation of the FAscore scale to evaluate the risk of atrial fibrillation in patients with arterial hypertension.

BACKGROUND AND AIM: To use a risk scale or predictive model outside the population of origin, it is necessary to evaluate the predictive indicators through external validation. The aim was to validate the FAscore, originally constructed in hypertensive patients in primary care in the Valencian Region, in an external cohort with hypertension in primary care in the Basque Country. METHODS: A retrospective cohort study was designed to perform an external validation of the FAscore app in patients affiliated with 26 health centers in the municipality of Bilbao. The area under the ROC curve and predictive indicators were calculated with their 95% confidence intervals. RESULTS: Thirty-six thousand eight hundred nine patients were included: 53.6% (n=19,719) were women, the mean age was 75.1 years, 41.8% (n=15,381). Over the four-year follow-up period, 1420 patients were diagnosed with AF (cumulative incidence 3.9%). The median risk estimated by FAscore was 4.5%, and the 5th, 25th, 75th, and 95th percentiles were 1.0%, 2.5%, 6.1%, and 14.8%, respectively. The ROC curve for the risk estimated by FAscore and the cases of atrial fibrillation observed was AUC 0.715 (95% CI 0.703-0.727). The 5% risk cutoff provides a sensitivity of 70.8%, specificity of 61.0%, positive predictive value of 6.8%, negative predictive value of 98.1%, and positive and negative likelihood ratios of 1.82 and 0.48, respectively. CONCLUSION: This study reports on the external validation of the atrial fibrillation risk scale in hypertensive patients, which shows an acceptable predictive capacity. The best-performing risk cutoff, providing good predictive indicators, can be set at 5%.

Left ventricular volume and maximal functional capacity in heart failure with preserved ejection fraction: Size matters.

AIMS: Emerging evidence suggests that smaller left ventricular volumes may identify subjects with lower cardiorespiratory fitness. Whether left ventricular size predicts functional capacity in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. This study aimed to explore the association between indexed left ventricular end-diastolic volume (iLVEDV) and maximal functional capacity, assessed by peak oxygen consumption (peakVO2), in stable outpatients with HFpEF. METHODS AND RESULTS: We prospectively analysed data from 133 consecutive stable outpatients who underwent cardiopulmonary exercise testing and echocardiography on the same day. Data were validated in a cohort of HFpEF patients from San Paolo Hospital, Milan, Italy. A multivariable linear regression assessed the association between iLVEDV and peakVO2. The mean age was 73.2 ± 10.5 years, and 75 (56.4%) were women. The median iLVEDV, indexed left ventricular end-systolic volume, and left ventricular ejection fraction were 46 ml/m2 (30-56), 15 ml/m2 (11-19), and 66% (60-74%), respectively. The median peakVO2 and percentage of predicted peakVO2 were 11 ml/kg/min (9-13) and 64.1% (53-74.4), respectively. Adjusted linear regression analysis showed that smaller iLVEDV was associated with lower peakVO2 (p = 0.0001). In the validation cohort, adjusted linear regression analysis showed a consistent pattern: a smaller iLVEDV was associated with a higher likelihood of reduced peakVO2 (p = 0.004). CONCLUSIONS: In stable outpatients with HFpEF, a smaller iLVEDV was associated with a lower maximal functional capacity. These findings suggest a need for further studies to understand the pathophysiological mechanisms underlying these observations and to explore targeted treatment strategies for this patient subgroup.

Identification of novel small molecule-based strategies of COL7A1 upregulation and readthrough activity for the treatment of recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disease caused by loss of function mutations in the gene coding for collagen VII (C7) due to deficient or absent C7 expression. This disrupts structural and functional skin architecture, leading to blistering, chronic wounds, inflammation, important systemic symptoms affecting the mouth, gastrointestinal tract, cornea, and kidney function, and an increased skin cancer risk. RDEB patients have an extremely poor quality of life and often die at an early age. A frequent class of mutations in RDEB is premature termination codons (PTC), which appear in homozygosity or compound heterozygosity with other mutations. RDEB has no cure and current therapies are mostly palliative. Using patient-derived keratinocytes and a library of 8273 small molecules and 20,160 microbial extracts evaluated in a phenotypic screening interrogating C7 levels, we identified three active chemical series. Two of these series had PTC readthrough activity, and one upregulated C7 mRNA, showing synergistic activity when combined with the reference readthrough molecule gentamicin. These compounds represent novel potential small molecule-based systemic strategies that could complement topical-based treatments for RDEB.

Profiling cellular heterogeneity and fructose transporter expression in the rat nephron by integrating single-cell and microdissected tubule segment transcriptomes.

Single-cell RNA sequencing (scRNAseq) is a crucial tool in kidney research. These technologies cluster cells according to transcriptome similarity, irrespective of the anatomical location and ordering within the nephron. Thus, a cluster transcriptome may obscure heterogeneity of the cell population within a nephron segment. Elevated dietary fructose leads to salt-sensitive hypertension, in part by fructose reabsorption in the proximal tubule (PT). However, organization of the four known fructose transporters in apical PTs (SGLT4, SGLT5, GLUT5 and NaGLT1) remains poorly understood. We hypothesized that cells within each subsegment of the proximal tubule exhibit complex, heterogenous fructose transporter expression patterns. To test this hypothesis we analyzed rat and kidney transcriptomes and proteomes from publicly available scRNAseq and tubule microdissection databases. We found that microdissected PT-S1 segments consist of 81±12% cells with scRNAseq-derived transcriptional characteristics of S1, whereas PT-S2 express a mixture of 18±9% S1, 58±8% S2, and 19±5% S3 transcripts, and PT-S3 consists of 75±9% S3 transcripts. The expression of all four fructose transporters was detectable in all three PT segments, but key fructose transporters SGLT5 and GLUT5 progressively increased from S1 to S3, and both were significantly upregulated in S3 vs. S1/S2 (Slc5a10: 1.9 log 2 FC, p<1×10 -299 ; Scl2a5: 1.4 log 2 FC, p<4×10 -105 ). A similar distribution was found in human kidneys. These data suggest that S3 is the primary site of fructose reabsorption in both humans and rats. Finally, because of the multiple scRNAseq transcriptional phenotypes found in each segment our findings also imply that anatomic labels applied to scRNAseq clusters may be misleading.

Improved Hypertension Risk Assessment with Photoplethysmographic Recordings Combining Deep Learning and Calibration.

Hypertension, a primary risk factor for various cardiovascular diseases, is a global health concern. Early identification and effective management of hypertensive individuals are vital for reducing associated health risks. This study explores the potential of deep learning (DL) techniques, specifically GoogLeNet, ResNet-18, and ResNet-50, for discriminating between normotensive (NTS) and hypertensive (HTS) individuals using photoplethysmographic (PPG) recordings. The research assesses the impact of calibration at different time intervals between measurements, considering intervals less than 1 h, 1-6 h, 6-24 h, and over 24 h. Results indicate that calibration is most effective when measurements are closely spaced, with an accuracy exceeding 90% in all the DL strategies tested. For calibration intervals below 1 h, ResNet-18 achieved the highest accuracy (93.32%), sensitivity (84.09%), specificity (97.30%), and F1-score (88.36%). As the time interval between calibration and test measurements increased, classification performance gradually declined. For intervals exceeding 6 h, accuracy dropped below 81% but with all models maintaining accuracy above 71% even for intervals above 24 h. This study provides valuable insights into the feasibility of using DL for hypertension risk assessment, particularly through PPG recordings. It demonstrates that closely spaced calibration measurements can lead to highly accurate classification, emphasizing the potential for real-time applications. These findings may pave the way for advanced, non-invasive, and continuous blood pressure monitoring methods that are both efficient and reliable.

Registro español de marcapasos. XX informe oficial de la Asociación del Ritmo Cardiaco de la Sociedad Española de Cardiología (2022) / Spanish pacemaker registry. 20th official report of the Heart Rhythm Association of the Spanish Society of Cardiology (2022)

Introducción y objetivos: En este informe se comunica la actividad de estimulación cardiaca en 2022: número total de implantes, adherencia a la monitorización a distancia, factores demográficos y clínicos y características del material implantado. Métodos: Las fuentes de información son la plataforma CardioDispositivos, la tarjeta europea del paciente portador de marcapasos y los datos facilitados por los fabricantes. Resultados: Las tasas de marcapasos convencionales y resincronizadores de baja energía fueron de 866 y 34 unidades/millón respectivamente. Se implantaron 815 marcapasos sin cables. Se registraron 16.426 procedimientos de 82 hospitales (9.407 a través de CardioDispositivos), lo que supone un 40% de la actividad. La media de edad fue 78,6 años, con predominio de varones (60,3%). El bloqueo auriculoventricular fue el trastorno más frecuente y el 14,5% de los pacientes estaban en fibrilación auricular. Predomina el modo de estimulación DDD/R (55,6%) y la edad influye en el modo de estimulación, de forma que más de un tercio de los pacientes mayores de 80 años en ritmo sinusal recibieron estimulación monocameral en ventrículo. Se incluyeron en monitorización a distancia el 35% de los marcapasos y el 55% de los resincronizadores de baja energía. Conclusiones: Aumentan en un 5,6% el número de marcapasos convencionales, un 16% los resincronizadores de baja energía y un 25% los marcapasos sin cables. Se estabiliza la adherencia a la monitorización a distancia. Aumenta en un 11% el número de procedimientos incluidos en CardioDispositivos, aunque disminuye el volumen de muestra. El uso extensivo de la plataforma es lo que permitirá en años venideros contar con un registro de calidad.(AU)

Introduction and objectives: This article reports the cardiac pacing activity performed in 2022, including the total number of implants, adherence to remote monitoring, demographic and clinical factors, and the characteristics of the implanted devices. Methods: The information sources were the CardioDispositivos online platform, the European pacemaker patient identification card, and data provided by the manufacturers. Results: The rates of conventional pacemakers and low-energy resynchronizers were 866 and 34 units per million population, respectively. A total of 815 leadless pacemakers were implanted. In all, 16426 procedures performed in 82 hospitals were reported (9407 through CardioDispositivos), representing 40% of the activity. The mean age was 78.6 years, with a predominance of men (60.3%). The most frequent disorder was atrioventricular block, and 14.5% of the patients had atrial fibrillation. There was a predominance of the DDD/R pacing mode (55.6%), and pacing mode was influenced by age, such that more than one-third of patients older than 80 years in sinus rhythm received single-chamber ventricular pacing. The remote monitoring program included 35% of conventional pacemakers and 55% of low-energy resynchronization pacemakers. Conclusions: The number of conventional pacemakers increased by 5.6%, low-energy resynchronizers by 16%, and leadless pacemakers by 25%. Adherence to remote monitoring was stable. The number of procedures included in CardioDispositivos increased by 11%, although the sample volume decreased. In the coming years, the widespread use of the platform will likely lead to a high-quality registry.(AU)

Insuficiencia cardiaca de novo tras un síndrome coronario agudo en pacientes sin insuficiencia cardiaca ni disfunción ventricular izquierda / New-onset heart failure after acute coronary syndrome in patients without heart failure or left ventricular dysfunction

Introducción y objetivos: La cardiopatía isquémica es la primera causa de insuficiencia cardiaca. Nuestro objetivo es analizar el riesgo de insuficiencia cardiaca tras un síndrome coronario agudo en pacientes sin insuficiencia cardiaca previa ni disfunción ventricular izquierda. Métodos: Estudio prospectivo de pacientes consecutivos ingresados por síndrome coronario agudo en 2 hospitales. La incidencia de insuficiencia cardiaca se analizó considerando la muerte como evento competitivo. Resultados: Se incluyó a 5.962 pacientes, y 567 (9,5%) tuvieron al menos 1 reingreso por insuficiencia cardiaca aguda. La mediana de seguimiento fue 63 meses y la mediana de tiempo hasta el reingreso por insuficiencia cardiaca 27,1 meses. La incidencia acumulada de insuficiencia cardiaca fue superior que la de muerte en los primeros 7 años tras el alta. La edad, la diabetes, la cardiopatía isquémica previa, una escala GRACE> 140, la enfermedad arterial periférica, la disfunción renal, la hipertensión arterial y la fibrilación auricular se asociaron con mayor riesgo de reingreso por insuficiencia cardiaca; el tratamiento médico óptimo se asoció con menor riesgo. La incidencia de insuficiencia cardiaca en el primer año fue del 2,73% y no se hallaron variables protectoras. Una sencilla escala de riesgo de insuficiencia cardiaca predijo el riesgo de reingreso por insuficiencia cardiaca. Conclusiones: Uno de cada 10 pacientes dados de alta tras un síndrome coronario agudo sin haber tenido antes insuficiencia cardiaca o disfunción ventricular sufrió insuficiencia cardiaca de novo y el riesgo es superior que el de muerte. Una sencilla escala clínica permite estimar el riesgo individual de reingreso por insuficiencia cardiaca, incluso en pacientes que no han tenido antes insuficiencia cardiaca ni disfunción ventricular izquierda. (AU)

Introduction and objectives: Coronary heart disease is the leading cause of heart failure (HF). The aim of this study was to assess the risk of readmission for HF in patients with acute coronary syndrome without previous HF or left ventricular dysfunction. Methods: Prospective study of consecutive patients admitted for acute coronary syndrome in 2 institutions. Risk factors for HF were analyzed by competing risk regression, taking all-cause mortality as a competing event. Results: We included 5962 patients and 567 (9.5%) experienced at least 1 hospital readmission for acute HF. Median follow-up was 63 months and median time to HF readmission was 27.1 months. The cumulative incidence of HF was higher than mortality in the first 7 years after hospital discharge. A higher risk of HF readmission was associated with age, diabetes, previous coronary heart disease, GRACE score> 140, peripheral arterial disease, renal dysfunction, hypertension and atrial fibrillation; a lower risk was associated with optimal medical treatment. The incidence of HF in the first year of follow-up was 2.73% and no protective variables were found. A simple HF risk score predicted HF readmissions risk. Conclusions: One out of 10 patients discharged after an acute coronary syndrome without previous HF or left ventricular dysfunction had new-onset HF and the risk was higher than the risk of mortality. A simple clinical score can estimate individual risk of HF readmission even in patients without previous HF or left ventricular dysfunction. (AU)

Complicaciones cardiovasculares y pronóstico en pacientes con COVID-19 / Cardiovascular complications and prognosis in COVID-19 patients

La infección por el SARS-CoV-2 de 2019 tiene una baja mortalidad en la mayoría de los casos, pero un 15-20% de los infectados sufre una enfermedad pulmonar con diferentes grados de afección sistémica, denominada enfermedad coronavírica de 2019 (COVID-19), que sí conlleva mayor mortalidad. Desde las primeras descripciones de series de pacientes, se identificó daño miocárdico en muchos pacientes con COVID-19 y su relación con mayor mortalidad. está revisión resume la evidencia sobre la afección cardiovascular y el pronóstico de los pacientes con COVID-19, que guardan mayor relación con las enfermedades cardiovasculares y son las más relevantes para el tratamiento de los pacientes ingresados

Although the risk of death is generally low in patients with SARS-CoV-2 infection, 15-20% of those infected experience lung disease with a varying degree of systemic involvement, which is referred to as coronavirus disease 2019 (COVID-19) and is associated with higher mortality. From the first patient series reported, myocardial damage has been observed in many individuals with COVID-19 and has been linked to an increased risk of death. This review summarizes current knowledge about cardiovascular disease and prognosis in patients with COVID-19, with a particular emphasis on different cardiovascular conditions and on the treatment of hospitalized patients

Registro Español de Marcapasos. XVII Informe Oficial de la Sección de Estimulación Cardiaca de la Sociedad Española de Cardiología (2019) / Spanish Pacemaker Registry. 17th Official Report of the Section on Cardiac Pacing of the Spanish Society of Cardiology (2019)

INTRODUCCIÓN Y OBJETIVOS: Se describe la actividad realizada en España en estimulación cardiaca durante 2019: cuantía y tipo de dispositivos, factores demográficos y clínicos. MÉTODOS: Se analiza la información aportada por la tarjeta europea del paciente portador de marcapasos, los datos incluidos en la plataforma online cardiodispositivos.es y la información remitida por empresas proveedoras sobre el número total de dispositivos. RESULTADOS: Se registran 15.833 procedimientos de 102 centros implantadores, lo que representa el 39% de la actividad total estimada. La tasa de implante de generadores de marcapasos convencionales es de 832 unidades/millón y la de resincronizadores de baja energía, 32 unidades/millón. Se implantaron 431 marcapasos sin cables. Predomina el implante en pacientes de edad avanzada (media, 78,7 años). Los electrodos utilizados son principalmente bipolares y de fijación activa y el 34,1% son compatibles con resonancia magnética. El bloqueo auriculoventricular es la alteración electrocardiográfica más frecuente y predomina la estimulación secuencial bicameral, a pesar de lo cual hasta un 20% de los pacientes en ritmo sinusal reciben un marcapasos monocameral en ventrículo, fundamentalmente mayores de 80 años y mujeres. Se incluyen en monitorización a distancia el 41% de los resincronizadores de baja energía y el 14,8% de los marcapasos convencionales. CONCLUSIONES: En 2019ha aumentado el consumo de generadores de estimulación cardiaca en un 1,6%, sobre todo los resincronizadores de baja energía, que aumentan en un 15,1%. Predomina la estimulación secuencial, influida por la edad y el sexo. Aumenta en un 20,6% la monitorización a distancia de pacientes con resincronización cardiaca con marcapasos y continúa siendo escasa la de los marcapasos convencionales

INTRODUCTION AND OBJECTIVES: This report describes Spanish cardiac pacing activity during 2019: quantities and types of devices and demographic and clinical factors. METHODS: The analysis is based on data obtained from the European Pacemaker Patient Identification Card, data submitted to the online platform cardiodispositivos.es, and supplier-reported data on the total number of implanted pacemakers. RESULTS: Information was received on 15 833 procedures from 102 implantation centers, representing 39% of the estimated total activity. The implantation rates of conventional and resynchronization pacemakers were 832 and 32 units per million population, respectively. A total of 431 leadless pacemakers were implanted. Most implantations were performed in elderly patients (mean age, 78.7 years). Most electrodes were bipolar and with active fixation and 34.1% were magnetic resonance imaging-compatible. Atrioventricular block was the most common electrocardiographic abnormality. Dual-chamber sequential pacing predominated; nonetheless, up to 20% of patients in sinus rhythm received a single-chamber ventricular pacemaker, mainly those older than 80 years of age and women. Remote monitoring capability was present in 41% of cardiac resynchronization therapy pacemakers and in 14.8% of conventional pacemakers. CONCLUSIONS: Consumption of pacing generators increased by 1.6%, mainly due to a 15.1% increase in cardiac resynchronization therapy pacemakers. Sequential pacing predominates; its use is influenced by age and sex. Remote monitoring increased by 20.6% in cardiac resynchronization therapy pacemakers and continues to be scarce in conventional pacemakers

Los desafíos del profesorado clínico en la educación médica / The challenges of the clinical teacher in medical education

ANTECEDENTES: La enseñanza clínica en la educación médica tiene una particularidad única: el contexto clínico. Este estudio tiene como objetivo analizar las principales barreras de la enseñanza clínica en una facultad joven de Medicina de España. MÉTODOS: Se trata de un estudio transversal descriptivo en el que se solicitó a todos los profesores clínicos (todos ellos profesores asociados) de una facultad joven de Medicina que respondieran a un cuestionario en línea, anónimo y voluntario sobre aspectos de carga asistencial, promoción de la investigación clínica y reconocimiento de sus carreras profesionales. RESULTADOS: Sesenta y un profesores (42%) respondieron al cuestionario. Los principales hallazgos que se obtuvieron fueron: 1) la falta de tiempo protegido para la enseñanza práctica en la institución sanitaria; 2) el escaso apoyo para la investigación clínica por parte de la institución sanitaria o de la facultad; y 3) el escaso de reconocimiento de la carrera profesional. CONCLUSIONES: La enseñanza clínica en la educación médica es un desafío continuo para el clínico. Son necesarios futuros estudios que analicen estos aspectos de forma más exhaustiva

BACKGROUND: There is a unique particularity of clinical teaching in medical education that is beyond knowledge, skills or teaching methods of each clinician: this is clinical teaching context. This study aimed to analyze the main barriers in clinical teaching in a single medical school in Spain. METHODS: This was a descriptive study in which all the clinical teachers (all of them associate professors) of a single and novel faculty of medicine were asked to answer an online, anonymous and voluntary questionnaire about aspects of support to clinical work, promotion of clinical research and recognition of their professional careers. The questionnaires were organized and analyzed into these three main issues. RESULTS: 61 clinical teachers (42%) answered the questionnaire. The main findings that emerged were: (I) lack of protected time for practical teaching at hospital; (II) lack of support for clinical research from hospital or faculty; and (III) lack of recognition of their professional careers. CONCLUSIONS: The clinical teaching in medical education is a continuing challenge for busy clinicians. Further studies on this topic are needed

Entrenamiento de la musculatura inspiratoria y la electroestimulación muscular funcional en el tratamiento de la insuficiencia cardiaca con función sistólica conservada: estudio TRAINING-HF / Inspiratory muscle training and functional electrical stimulation for treatment of heart failure with preserved ejection fraction: the TRAINING-HF trial

Introducción y objetivos: No se dispone de tratamientos farmacológicos que demuestren reducir la morbimortalidad asociada en pacientes con insuficiencia cardiaca y función sistólica conservada (IC-FEc). El objetivo del presente estudio fue evaluar si en pacientes con IC-FEc, el entrenamiento de la musculatura inspiratoria (EMI), la electroestimulación muscular funcional (EMF) o la combinación de ambas (EMI + EMF) puede mejorar la capacidad funcional, calidad de vida, parámetros de disfunción diastólica o biomarcadores a las 12 y 24 semanas. Métodos: Un total de 61 pacientes estables con IC-FEc (clase funcional de la New York Heart Association II-III) se aleatorizaron (1:1:1:1) a recibir un programa de 12 semanas de EMI, EMF, o EMI + EMF frente a tratamiento médico estándar (control). El objetivo primario fue evaluar el cambio en el consumo máximo de oxígeno. Los objetivos secundarios fueron los cambios en la calidad de vida, parámetros ecocardiográficos y biomarcadores. Se utilizó un modelo lineal mixto para comparar los cambios entre los diferentes grupos. Resultados: La edad media fue 74 +/- 9 años y la proporción de mujeres fue del 58%. El test de consumo máximo de oxígeno fue de 9,9 +/- 2,5ml/min/kg. A las 12 semanas, con respecto al grupo control, el incremento medio de consumo máximo de oxígeno fue de 2,98, 2,93 y 2,47 para EMI, EMF y EMI + EMF, respectivamente (p < 0,001). Este incremento se mantuvo a las 24 semanas (1,95, 2,08 y 1,56, respectivamente; p < 0,001). Resultados similares se observaron en la puntuación del cuestionario de calidad de vida (p < 0,001). Conclusiones: En los pacientes con IC-FEc e importante reducción de la capacidad funcional, tanto el EMI como la EMF se asocian con una marcada mejoría de la capacidad funcional y la calidad de vida

Introduction and objectives: Despite the prevalence of heart failure with preserved ejection fraction (HFpEF), there is currently no evidence-based effective therapy for this disease. This study sought to evaluate whether inspiratory muscle training (IMT), functional electrical stimulation (FES), or a combination of both (IMT + FES) improves 12- and 24-week exercise capacity as well as left ventricular diastolic function, biomarker profile, and quality of life in HFpEF. Methods: A total of 61 stable symptomatic patients (New York Heart Association functional class II-III) with HFpEF were randomized (1:1:1:1) to receive a 12-week program of IMT, FES, or IMT + FES vs usual care. The primary endpoint of the study was to evaluate change in peak exercise oxygen uptake at 12 and 24 weeks. Secondary endpoints were changes in quality of life, echocardiogram parameters, and prognostic biomarkers. We used a mixed-effects model for repeated-measures to compare endpoints changes. Results: Mean age and peak exercise oxygen uptake were 74 +/- 9 years and 9.9 +/- 2.5mL/min/kg, respectively. The proportion of women was 58%. At 12 weeks, the mean increase in peak exercise oxygen uptake (mL/kg/min) compared with usual care was 2.98, 2.93, and 2.47 for IMT, FES, and IMT + FES, respectively (P < .001) and this beneficial effect persisted after 24 weeks (1.95, 2.08, and 1.56; P < .001). Significant increases in quality of life scores were found at 12 weeks (P < .001). No other changes were found. Conclusions: In HFpEF patients with low aerobic capacity, IMT and FES were associated with a significant improvement in exercise capacity and quality of life

Razón internacional normalizada y mortalidad de los pacientes con insuficiencia cardiaca y fibrilación auricular tratados con antagonistas de la vitamina K / International normalized ratio and mortality risk in acute heart failure and nonvalvular atrial fibrillation patients receiving vitamin K antagonists

Introducción y objetivos: Los pacientes con insuficiencia cardiaca en tratamiento con antagonistas de la vitamina K (AVK) por fibrilación auricular no valvular (FANV) a menudo presentan valores alterados de la razón internacional normalizada (INR). El objetivo es evaluar la asociación entre la INR al ingreso por insuficiencia cardiaca y el riesgo de mortalidad en el seguimiento. Métodos: Estudio observacional retrospectivo en el que se evaluó la INR al ingreso de 1.137 pacientes consecutivos con insuficiencia cardiaca aguda en tratamiento con AVK por FANV. Esta se categorizó en: INR en rango óptimo (INR = 2-3, n = 210), infraterapéutica (INR < 2, n = 660) o supraterapéutica (INR > 3, n = 267). La asociación independiente entre INR y mortalidad se evaluó mediante cálculo restringido de las diferencias en tiempos de supervivencia media, dado que la INR no cumple la condición de proporcionalidad de riesgos de mortalidad. Resultados: Tras una mediana de 2,15 [0,71-4,29] años, fallecieron 495 pacientes (43,5%). En el análisis multivariable, tanto la INR infraterapéutica como la supraterapéutica se asociaron con un mayor riesgo de mortalidad, con unas diferencias en tiempos de supervivencia media a 5 años de -0,50 años (IC95%,-0,77 a -0,23; p < 0,001) y -0,40 años (IC95%, -0,70 a -0,11; p = 0,007) con respecto a los pacientes con INR 2-3. Conclusiones: La INR fuera de rango óptimo al ingreso de los pacientes con insuficiencia cardiaca aguda en tratamiento con AVK por FANV se asocia de manera independiente con un mayor riesgo de mortalidad en el seguimiento a largo plazo

Introduction and objectives: Heart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up. Methods: In this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, restricted mean survival time differences were used to evaluate the association among INR categories and the risk of all-cause mortality. Results: During a median [interquartile range] follow-up of 2.15 years [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients with subtherapeutic and supratherapeutic INR showed higher risks of all-cause mortality, as evidenced by their restricted mean survival time differences at 5 years' follow-up: -0.50; 95%CI, -0.77 to -0.23 years; P < .001; and -0.40; 95%CI, -0.70 to -0.11 years; P = .007, respectively, compared with INR 2-3. Conclusions: In acute heart failure patients on treatment with VKA for NVAF, INR values out of normal range at admission were independently associated with a higher long-term mortality risk