Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients.

Cytomegalovirus (CMV) infection constitutes a complication for kidney transplant recipients (KTR) and CMV-specific T cells reduce the risk of viral replication in seropositive patients. CMV promotes the adaptive differentiation and expansion of an NK cell subset, hallmarked by expression of the CD94/NKG2C receptor with additional characteristic features. We previously reported an association of pretransplant NKG2C+ NK cells with a reduced incidence of CMV infection. We have strengthened the analysis in cryopreserved peripheral blood mononuclear cells from an enlarged KTR cohort (n = 145) with homogeneous immunosuppression, excluding cases at low risk of infection (ie, CMV D-R-) or receiving antiviral prophylaxis. Moreover, adaptive NKG2C+ NK cell-associated markers (ie, NKG2A, CD57, Immunoglobulin-like transcript 2 [LIR1 or LILRB1], FcεRI γ chain, and Prolymphocytic Leukemia Zinc Finger transcription factor) as well as T lymphocyte subsets were assessed by multicolor flow cytometry. The relation of NKG2C+ NK cells with T cells specific for CMV antigens was analyzed in pretransplant patients (n = 29) and healthy controls (n = 28). Multivariate Cox regression and Kaplan-Meier analyses supported that NKG2C+ NK cells bearing adaptive markers were specifically associated with a reduced incidence of posttransplant symptomatic CMV infection; no correlation between NKG2C+ NK cells and CMV-specific T cells was observed. These results support that adaptive NKG2C+ NK cells contribute to control CMV infection in KTR.

Adaptive NKG2C+ NK Cell Response and the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients.

CMV infection in kidney transplant recipients (KTRs) has been associated with an increased risk for graft loss and reduced host survival. CMV promotes persistent expansions of NK cells expressing the CD94/NKG2C receptor. The NKG2C (KLRC2) gene is frequently deleted, and copy number influences the adaptive response of NKG2C+ NK cells. The distribution of NKG2C+ NK cells and NKG2C genotypes (NKG2C+/+, NKG2C+/del, NKG2Cdel/del) were studied in cross-sectional (n = 253) and prospective (n = 122) KTR cohorts. Assessment of CMV viremia was restricted to symptomatic cases in the retrospective study, but was regularly monitored in the prospective cohort. Overall, the proportions of NKG2C+ NK cells were significantly higher in KTRs who had suffered posttransplant symptomatic CMV infection in the cross-sectional study. Yet, along the prospective follow-up (3, 6, 12, and 24 mo), posttransplant NKG2C+ NK cell expansions were not observed in every patient with detectable viremia who received preemptive antiviral therapy, suggesting that the adaptive NK cell response may be inversely related with the degree of CMV control. Remarkably, the incidence of posttransplant viremia was reduced among cases with high pretransplant levels of NKG2C+ NK cells. The NKG2C genotype distribution was comparable in KTR and healthy controls, and greater proportions of NKG2C+ cells were detected in NKG2C+/+ than in NKG2C+/del patients. Yet, a trend toward increased NKG2C+/del and reduced NKG2C+/+ frequencies associated with symptomatic infection was appreciated in both cohorts. Altogether, our results indirectly support that adaptive NKG2C+ NK cells are involved in the control of CMV in KTRs.

NKG2C zygosity influences CD94/NKG2C receptor function and the NK-cell compartment redistribution in response to human cytomegalovirus.

Human cytomegalovirus (HCMV) infection promotes a persistent expansion of a functionally competent NK-cell subset expressing the activating CD94/NKG2C receptor. Factors underlying the wide variability of this effect observed in HCMV-seropositive healthy individuals and exacerbated in immunocompromized patients are uncertain. A deletion of the NKG2C gene has been reported, and an apparent relation of NKG2C genotype with circulating NKG2C(+) NK-cell numbers was observed in HCMV(+) children. We have assessed the influence of NKG2C gene dose on the NK-cell repertoire in a cohort of young healthy adults (N = 130, median age 19 years). Our results revealed a relation of NKG2C copy number with surface receptor levels and with NKG2C(+) NK-cell numbers in HCMV(+) subjects, independently of HLA-E dimorphism. Functional studies showed quantitative differences in signaling (i.e. iCa(2+) influx), degranulation, and IL-15-dependent proliferation, in response to NKG2C engagement, between NK cells from NKG2C(+/+) and hemizygous subjects. These observations provide a mechanistic interpretation on the way the NKG2C genotype influences steady-state NKG2C(+) NK-cell numbers, further supporting an active involvement of the receptor in the HCMV-induced reconfiguration of the NK-cell compartment. The putative implications of NKG2C zygosity over viral control and other clinical variables deserve attention.

Long-term prognostic value for patients with chronic heart failure of estimated glomerular filtration rate calculated with the new CKD-EPI equations containing cystatin C.

BACKGROUND: Correct estimation of renal function is crucial in assessing prognosis of patients with heart failure (HF). Recently, two new equations have been proposed to calculate estimated glomerular filtration rate (eGFR) with cystatin C alone or both creatinine and cystatin C. We assessed the prognostic value of eGFR estimated by these new equations in outpatients with HF. METHODS: The study included 879 patients with median age, 70.4 years; main etiology of HF ischemic heart disease, 52.7%; and median LVEF, 34%. RESULTS: eGFR estimates by the new equations correlated significantly with eGFR estimates from previous equations, with the best correlation observed between the 2 equations containing cystatin C [intraclass correlation coefficient 0.95 (95% confidence interval 0.94-0.95)]. During a median follow-up of 3.94 years, 371 patients died. The Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations containing cystatin C were found to be best for predicting death [area under the ROC curve 0.685 for CKD-EPI-cystatin C and 0.672 for CKD-EPI-creatinine-cystatin C vs 0.632 for simplified Modification of Diet in Renal Disease Study traceable to isotope dilution mass spectrometry and 0.643 for CKD-EPI (all P < 0.001)]. The CKD-EPI-cystatin C equations also showed significantly better calibration and reclassification measurements for both integrated discrimination improvement and net reclassification improvement in predicting death (P < 0.001). Reclassification with these new equations was particularly better in the subgroup with intermediate eGFR [45-74 mL · min(-1) · (1.73 m(2))(-1)]. CONCLUSIONS: The two new CKD-EPI equations containing cystatin C are useful for HF risk stratification and show better prognostic performance than creatinine-only based eGFR equations, mostly in patients with intermediate eGFR. These equations seem appropriate for assessing prognosis of HF patients with moderate renal insufficiency.

Derivation and validation of a set of 10-year cardiovascular risk predictive functions in Spain: the FRESCO Study.

OBJECTIVE: To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. METHOD: Pooled analysis of 11 population-based Spanish cohorts (1992-2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. RESULTS: The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. CONCLUSIONS: The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

On the Role of Personality in Successful Aging: A Scoping Review.

BACKGROUND AND OBJECTIVES: This study aimed to critically examine current knowledge on the role of personality in successful aging, considering Hooker and McAdams' 3-level, 6-foci model of personality. The aim was also to pinpoint knowledge gaps that research should address in the future. RESEARCH DESIGN AND METHODS: We carried out a scoping review of the literature on successful aging and personality, following the 5-step framework proposed by Arksey and O'Malley and further expanded by Levac et al. RESULTS: Research into the role of personality in successful aging has grown significantly over the last 20 years. However, the increasing number of publications on the topic was primarily accounted for by studies focused on Layer 1 and particularly Layer 2 of McAdams' model of personality, with Layer 3 being scarcely addressed. Research that included more than 1 layer of personality was rare. DISCUSSION AND IMPLICATIONS: Our study pinpointed gaps that should be considered in future research in this area. These gaps were related to advancing toward agreed-upon definitions of successful aging and personality, broadening the scope of research on this topic, and integrating personality dimensions on research on successful aging.

Soluble ST2 serum concentration and renal function in heart failure.

BACKGROUND: Soluble ST2 (sST2) provides important prognostic information in patients with heart failure (HF). How sST2 serum concentration is related to renal function is uncertain. We evaluated the association between sST2 and renal function and compared its prognostic value in HF patients with renal insufficiency. METHODS AND RESULTS: Patients (n = 879; median age 70.4 years; 71.8% men) were divided into 3 subgroups according to estimated glomerular filtration rate (eGFR): ≥60 mL/min/1.73 m(2) (n = 337); 30-59 mL/min/1.73 m(2) (n = 352); and <30 mL/min/1.73 m(2) (n = 190). sST2 (rho = -0.16; P < .001), N-terminal pro-B-type natriuretic peptide (rho = -0.40; P < .001), and high-sensitivity cardiac troponin T (rho = -0.47; P < .001) inversely correlated with eGFR. All-cause mortality was the primary end point. During a median follow-up of 3.46 years, 312 patients (35%) died, 246 of them from the subgroup of 542 patients with eGFR <60 mL/min/1.73 m(2) (45%). Biomarker combination including sST2 showed best discrimination, calibration, and reclassification metrics in renal insufficiency patients (net reclassification improvement 16.6 [95% confidence interval (CI) 8.1-25; P < .001]; integrated discrimination improvement 4.2 [95% CI 2.2-6.2; P < .001]). Improvement in reclassification was higher in these patients than in the total cohort. CONCLUSIONS: The prognostic value of sST2 was not influenced by renal function. On top of other biomarkers, sST2 improved long-term prediction in patients with renal insufficiency even more than in the total cohort.

[Influence of gender and place of residence differences on the evolution and mortality of ischemic cardiopathy in Catalonia: a population-based study.] / Influencia del género y el lugar de residencia sobre la evolución y mortalidad de la cardiopatía isquémica en Cataluña: un estudio de base poblacional.

OBJECTIVE: Some bibliography supports a diagnostic and therapeutic delay in women with high cardiovascular risk. The objective of this paper was to know the incidence of cardiovascular disease (CVD) and mortality in a cohort with Metabolic Syndrome (MetS); analyze possible differences in gender and place of residence, regarding the performance of primary angioplasties in patients with ischemic heart disease (IHD). METHODS: Population cohort study, with SIDIAP database (Sistema de Información para la Investigación en Atención Primaria), in primary care in Catalonia. We selected people of both sexes, between 35-75 years old, exempt from CVD at the beginning (2009), fulfilling MetS criteria (NCEP-ATPIII-National Cholesterol Education Program-Adult Treatment Panel III- criteria diagnoses). We performed descriptive statistics, and ANOVA and Chi-square test to evaluate differences between variables. RESULTS: 167,673 people met MetS criteria (5.2% of the population), 105,969 men (63.2%). 22% of the population belonged to rural areas. Those urban areas with the most socioeconomic differences (urban-1 and urban-5) exhibited the highest incidences of CVD and IHD. We registered 51,129 CVD (30.7%) of which 8,889 were acute myocardial infarctions (AMI) (5,3%) and 24,284 were IHD (14,5%). 1.758 primary angioplasties procedures were performed, 1,467 in men and 291 in women, representing, respectively, 4.4% and 0.9% (p<0.005). CONCLUSIONS: The incidence of IHD and AMI in subjects with MetS is high in Catalonia. There is a difference in the angioplasties performed, according to sex and place of residence. Probably a practical implication would be to detect IHD in time in women with MetS, so that they can benefit from revascularization therapy in the same way as men.

OBJETIVO: Existe bibliografía que apoya un retraso diagnóstico y terapéutico en mujeres con alto riesgo cardiovascular. El objetivo de este trabajo fue conocer la incidencia de la enfermedad cardiovascular (ECV) y la mortalidad en una cohorte con Síndrome Metabólico (SM), así como analizar posibles diferencias de género y lugar de residencia, respecto a la realización de angioplastias primarias en pacientes con cardiopatía isquémica (CI). METODOS: Se realizó un estudio de cohorte poblacional apoyándonos en la base de datos SIDIAP (Sistema de Información para la Investigación en Atención Primaria), en Atención Primaria de Cataluña. Seleccionamos personas de ambos sexos, entre 35-75 años, exentos de ECV al inicio (2009), cumpliendo criterios de SM (diagnósticos NCEP-ATPIII [National Cholesterol Education Program-Adult Treatment Panel III]). La variable resultado fue la incidencia a 10 años de ECV y la mortalidad global por toda causa. Registramos variables sociodemográficas (edad, sexo, fenotipo SM, índice socioeconómico MEDEA) y reperfusión coronaria. Se realizó estadística descriptiva, ANOVA y prueba de chi-cuadrado para verificar la diferencia entre variables. RESULTADOS: 167.673 personas cumplieron criterios de SM (5,2% de la población), de las cuales había 105.969 hombres (63,2%). El 22% de población pertenecía a áreas rurales. Aquellas áreas urbanas más dispares socioeconómicamente (urbana-1 y urbana-5), exhibieron las mayores incidencias de ECV y CI. Registramos 51.129 ECV (30,7%) de los cuales 8.889 fueron infartos agudos de miocardio (IAM; 5,3%) y 24.284 fueron CI (14,5%). Se realizaron 1.758 procedimientos de angioplastia primaria, 1.467 en hombres y 291 en mujeres, representando respectivamente un 4,4% y un 0,9% (p<0.005). CONCLUSIONES: La incidencia de IAM y CI en sujetos con SM es alta en Cataluña. Existe diferencia estadísticamente significativa en las angioplastias realizadas, según sexo y lugar de residencia. Probablemente una implicación práctica sería detectar a tiempo la CI en mujeres con SM, para que puedan beneficiarse de la terapia revascularizadora igual que los hombres.

Development and Validation of a Risk Score for Predicting Non-Adherence to Antiretroviral Therapy.

Several patient-related factors that influence adherence to antiretroviral therapy (ART) have been described. However, studies that propose a practical and simple tool to predict nonadherence after ART initiation are still scarce. In this study, we develop and validate a score to predict the risk of nonadherence in people starting ART. The model/score was developed and validated using a cohort of people living with HIV starting ART at the Hospital del Mar, Barcelona, between 2012 and 2015 (derivation cohort) and between 2016 and 2018 (validation cohort),. Adherence was evaluated every 2 months using both pharmacy refills and patient self-reports. Nonadherence was defined as taking <90% of the prescribed dose and/or ART interruption for more than 1 week. Predictive factors for nonadherence were identified by logistic regression. Beta coefficients were used to develop a predictive score. Optimal cutoffs were identified using the bootstrapping methodology, and performance was evaluated with the C statistic. Our study is based on 574 patients: 349 in the derivation cohort and 225 in the validation cohort. A total of 104 patients (29.8%) of the derivation cohort were nonadherent. Nonadherence predictors were patient prejudgment; previous medical appointment failures; cultural and/or idiomatic barriers; heavy alcohol use; substance abuse; unstable housing; and severe mental illness. The cutoff point (receiver operating characteristic curve) for nonadherence was 26.3 (sensitivity 0.87 and specificity 0.86). The C statistic (95% confidence interval) was 0.91 (0.87-0.94). These results were consistent with those predicted by the score in the validation cohort. This easy-to-use, highly sensitive, and specific tool could be easily used to identify patients at highest risk for nonadherence, thus allowing resource optimization and achieving optimal treatment goals.

Combined use of high-sensitivity cardiac troponin T and N-terminal pro-B type natriuretic peptide improves measurements of performance over established mortality risk factors in chronic heart failure.

BACKGROUND: Heart failure still maintains a high mortality. Biomarkers reflecting different pathophysiological pathways are under evaluation to better stratify the mortality risk. The objective was to assess high-sensitivity cardiac troponin T (hs-cTnT) in combination with N-terminal pro-B type natriuretic peptide (NT-proBNP) for risk stratification in a real-life cohort of ambulatory heart failure patients. METHODS: We analyzed 876 consecutive patients (median age 70.3 years, median left ventricular ejection fraction 34%) treated at a heart failure unit. A combination of biomarkers reflecting myocyte injury (hs-cTnT) and myocardial stretch (NT-proBNP) was used in addition to an assessment based on established mortality risk factors (age, sex, left ventricular ejection fraction, New York Heart Association functional class, diabetes, estimated glomerular filtration rate, ischemic etiology, sodium, hemoglobin, ß-blocker treatment, and angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment). RESULTS: During a median follow-up of 41.4 months, 311 patients died. In the multivariable Cox proportional hazards model, hs-cTnT and NT-proBNP were independent prognosticators (P = .003 each). The combined elevation of both biomarkers above cut-off values significantly increased the risk of death (HR 7.42 [95% CI, 5.23-10.54], P < .001). When hs-cTnT and NT-proBNP were individually included in a model with established mortality risk factors, measurements of performance significantly improved. Results obtained for hs-cTnT compared with NT-proBNP were superior according to comprehensive discrimination, calibration, and reclassification analysis (net reclassification indices of 7.7% and 1.5%, respectively). CONCLUSIONS: hs-cTnT provides significant prognostic information in a real-life cohort of patients with chronic heart failure. Simultaneous addition of hs-cTnT and NT-proBNP into a model that includes established risk factors improves mortality risk stratification.

Association of atherosclerosis with expression of the LILRB1 receptor by human NK and T-cells supports the infectious burden hypothesis.

OBJECTIVE: The contribution of human cytomegalovirus (HCMV) to vascular disease may depend on features of the immune response not reflected by the detection of specific antibodies. Persistent HCMV infection in healthy blood donors has been associated with changes in the distribution of NK cell receptors (NKR). The putative relationship among HCMV infection, NKR distribution, subclinical atherosclerosis, and coronary heart disease was assessed. METHODS AND RESULTS: NKR expression was compared in acute myocardial infarction (AMI) patients (n=70) and a population-based control sample (n=209). The relationship between NKR expression and carotid intima-media thickness (CIMT) in controls (n=149) was also studied. HCMV infection was associated with higher proportions of NKG2C+ and LILRB1+ NK and T-cells. In contrast, only LILRB1+ NK and CD56+ T-cells were found to be increased in AMI patients, independent of age, sex, conventional vascular risk factors, and HCMV seropositivity. Remarkably, LILRB1 expression in NK and T-cells significantly correlated with CIMT in controls. CONCLUSIONS: The association of overt and subclinical atherosclerotic disease with LILRB1+ NK and T-cells likely reflects a relationship between the immune challenge by infections and cardiovascular disease risk, without attributing a dominant role for HCMV. Our findings may lead to the identification of novel biomarkers of vascular disease.

Sex-related differences in prognosis after myocardial infarction: changes from 1978 to 2007.

Women with myocardial infarction (MI) have shown a 28-day survival disadvantage compared with men. However, results were less consistent when considering long-term mortality in 28-day survivors. The aim was to estimate the trends for sex-related differences in the three endpoints considered for this study: (1) 28-day mortality or severe ventricular dysfunction (acute pulmonary oedema or cardiogenic shock) during the hospital stay, (2) 28-day mortality and (3) two-year cardiovascular mortality or non-fatal MI in 28-day survivors after a first MI. A cohort of 3,982 consecutive patients with first Q-wave MI admitted to a university tertiary reference hospital between 1978 and 2007 was followed for 2 years. Short-term prognosis improved in women over the studied period; similar rates were observed in both sexes in the 2000s. After adjusting for age, co-morbidities and anterior location of MI, female sex had an odds ratio=1.71 (95% confidence interval [CI] 1.34-2.17) of short-term severe MI or death over the studied period. Overall, sex differences in long-term prognosis remained similar over the studied period (hazard ratio=1.40; 95% CI 1.02-1.91). In conclusion, short-term prognosis improved over the past 30 years for first Q-wave MI patients, becoming similar for both men and women in the most recent decade. Long-term prognosis did not improve in either men or women, indicating that secondary prevention should be reinforced to achieve consistent reductions in the number of cardiovascular events.

Carbohydrate antigen 125 (CA125) as a prognostic marker in the elderly with acute heart failure and preserved ejection fraction. / Antígeno carbohidrato 125 (CA125) como marcador pronóstico en ancianos con insuficiencia cardiaca aguda y fracción de eyección preservada.

BACKGROUND: Carbohydrate antigen 125 (CA125) has emerged as a new biomarker in heart failure. The objective of the study is to determine whether serum CA125 levels predict total mortality and readmissions at one year in patients >70 years old with acute heart failure (AHF) and preserved ejection fraction (PEF). METHODS: Multicenter prospective observational study, which included 359 patients (mean age 81.5 years). The primary endpoint was total all-cause mortality and total readmissions for AHF at 1 year. A negative binomial regression technique was used to evaluate the association between CA125 and both endpoints. RESULTS: At one year of follow-up, 87 deaths (24.2%) were registered. The patients in the lower quartile of CA125 had a lower crude mortality rate (14.4%, 26.7, 26.7, 29.2; p=0.09). After multivariate analysis, the CA125 value was positively associated with a higher risk (p=0.009). Such association was also positive but borderline significant for the risk of readmissions (p=0.089). CONCLUSIONS: In a population older than 70 years hospitalized for AHF with PEF, elevated levels of CA125 are associated with an increased risk of death at one year of follow-up. The association with readmission for AHF was more uncertain. Low levels of CA125 identifies a subgroup at low-risk.

Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension.

AIMS: Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS-HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF-PH treated with sacubitril/valsartan. METHODS AND RESULTS: This single-arm, investigator-initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF-PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre-ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B-line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre-ARNI vs. ARNI ON, mPAP significantly declined by -4.99 mmHg [95% confidence interval (CI) -5.55 to -4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre-ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B-lines, and QoL. Mean loop diuretic management did not differ between periods. CONCLUSIONS: Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF-PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF-PH.

Trends in Q-wave acute myocardial infarction case fatality from 1978 to 2007 and analysis of the effectiveness of different treatments.

BACKGROUND: We sought to analyze the trends in first Q-wave acute myocardial infarction (AMI) case fatality from 1978 to 2007 in a population-based hospital register, to determine the variables related to these changes, and to assess the effectiveness of current AMI management. METHODS: Population-based hospital registry included patients with first Q-wave AMI aged 25 to 74 years admitted between 1978 and 2007. Sociodemographic and clinical characteristics, treatments, and procedures used during hospital stay, and 28-day case fatality were recorded. Logistic regression was used for multivariate analysis of six 5-year periods. RESULTS: The 30-year study included 3,982 patients. Mean 28-day case fatality was 8.96%, with a decreasing trend from 16.6% in the first 5-year period to 4.7% in the sixth (P for trend < .001). Study period was independently associated with case fatality. Case-fatality reduction attributable to pharmacologic treatments was 51% overall; in 24-hour survivors, pharmacologic treatments and broad use of invasive procedures explained 39% and 38%, respectively, of the difference between the observed case fatality in 2003-2007 and 1978-1982. CONCLUSION: A dramatic decrease in 28-day case fatality occurred during this 30-year period and was mainly related to the use of antiplatelet drugs, ß-blockers, thrombolysis, and invasive procedures. These data support the current guidelines for the management of acute coronary syndrome.

Community Risk Factors in the COVID-19 Incidence and Mortality in Catalonia (Spain). A Population-Based Study.

The heterogenous distribution of both COVID-19 incidence and mortality in Catalonia (Spain) during the firsts moths of the pandemic suggests that differences in baseline risk factors across regions might play a relevant role in modulating the outcome of the pandemic. This paper investigates the associations between both COVID-19 incidence and mortality and air pollutant concentration levels, and screens the potential effect of the type of agri-food industry and the overall land use and cover (LULC) at area level. We used a main model with demographic, socioeconomic and comorbidity covariates highlighted in previous research as important predictors. This allowed us to take a glimpse of the independent effect of the explanatory variables when controlled for the main model covariates. Our findings are aligned with previous research showing that the baseline features of the regions in terms of general health status, pollutant concentration levels (here NO2 and PM10), type of agri-food industry, and type of land use and land cover have modulated the impact of COVID-19 at a regional scale. This study is among the first to explore the associations between COVID-19 and the type of agri-food industry and LULC data using a population-based approach. The results of this paper might serve as the basis to develop new research hypotheses using a more comprehensive approach, highlighting the inequalities of regions in terms of risk factors and their response to COVID-19, as well as fostering public policies towards more resilient and safer environments.

[Markers of myocardial injury in the prediction of short-term COVID-19 prognosis]. / Marcadores de daño miocárdico en la predicción del pronóstico a corto plazo de los pacientes con COVID-19.

INTRODUCTION AND OBJECTIVES: COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19. METHODS: We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT > 14 ng/L, the upper 99th percentile. Levels of NT-proBNP > 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV). RESULTS: Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87). CONCLUSIONS: Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.

Markers of myocardial injury in the prediction of short-term COVID-19 prognosis.

INTRODUCTION AND OBJECTIVES: COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19. METHODS: We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT> 14ng/L, the upper 99th percentile. Levels of NT-proBNP> 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV). RESULTS: Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87). CONCLUSIONS: Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.

[Chronic obstructive pulmonary disease on inpatients with heart failure. GESAIC study results]. / Enfermedad pulmonar obstructiva crónica en pacientes ingresados por insuficiencia cardiaca. Resultados del Grupo para el Estudio y Significado de la Anemia en la Insuficiencia Cardiaca (GESAIC).

BACKGROUND AND OBJECTIVE: The clinical relevance of Heart failure (HF) and chronic obstructive pulmonary disease (COPD) in the same patient is not well established. We decided to study the prevalence of COPD in patients admitted due to HF, to define their clinical profile and the relationship with adrenergic beta-blockers (BB) treatment. PATIENTS AND METHOD: Prospective cohort of inpatients with HF admitted in 15 Internal Medicine Services from October 2005 to March 2006. Diagnosis of COPD was established according to clinical criteria or spirometry. Data about neurohormonal treatment (before, during the admission, and at discharge) were collected. Statistical analyses were performed using Ji square test and T Student test. A logistic regression model was designed with data. P<0.05 being considered statistically significant. RESULTS: About 391 patients were included . CPOD was present in 25.1% of patients. In two thirds of patients, the COPD diagnosis was established by clinical criteria. Regarding GOLD, 23.5% of patients had moderate or severe COPD severity. Bivariate analysis showed that male (<0.05), poor Charlson's Index and overweight (p=0.04 both) had all relationship with COPD. The regression model indicated that only left ventricular ejection fraction (LVEF) and BB treatment before admission had statistical significance (p=0.03 and p<0.001 respectively). At discharge, 27,6% of patients received BB. CONCLUSIONS: COPD in HF patients is common and most frequent patients are aged men high comorbidity and overweight. BB treatment is conditioned by LVEF, without relationship with COPD severity.