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Treatment of heart failure and reduced ejection fraction (HFrEF) using angiotensin receptor-neprilysin inhibitor demonstrates beneficial effects on cardiac remodeling (CR). We assessed the impact of sacubitril/valsartan on the concentrations of HF biomarkers in relation to parameters of CR using imaging techniques in patients with HFrEF. In a prospective single-center open-label study, 68 patients with symptomatic HFrEF were treated with sacubitril/valsartan and followed-up every three months for 12 months. Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin I (hs-cTnI) were measured in blood samples. Additionally, echocardiography and cardiac magnetic resonance imaging (cMRI) were performed to assess heart structural and functional changes. Following treatment initiation, follow-up visits revealed an improved NYHA functional class in these patients, alongside significant decreases in all circulating biomarkers, increases in left ventricular ejection fraction (LVEF), and reductions in volume- and diameter-related LV parameters. Sustained gradual decreases in sST2 concentrations over time correlated with NT-proBNP concentrations (rho=+0.26, P < 0.001). Both biomarkers were inversely correlated with LVEF, and positively correlated with volume- and diameter-related LV parameters from echocardiography and cMRI. However, NT-proBNP concentrations exhibited stronger correlations with these LV parameters and were associated with the number of LV segments showing fibrosis, unlike sST2. Sacubitril/valsartan treatment in HFrEF leads to reduced sST2 and NT-proBNP concentrations with distinct decreasing curves, which are linked to reverse CR through LV-related parameters. In contrast to sST2, NT-proBNP is also associated with fibrosis, suggesting that both biomarkers unveil distinct mechanisms during CR in patients treated with sacubitril/valsartan., Competing Interests: Declaration of Competing Interest Dr. James L. Januzzi is a Trustee of the American College of Cardiology, has received grant support from Abbott, Applied Therapeutics, HeartFlow Inc, Innolife and Roche Diagnostics, consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehringer-Ingelheim, Janssen, Novartis, Merck, and Roche Diagnostics, and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Intercept, Pfizer and Takeda. The other authors have nothing to declare., (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

During domestication, the selection of cultivated plants often reduces microbiota diversity compared with their wild ancestors. Microbiota in compartments such as the phyllosphere or rhizosphere can promote fruit tree health, growth, and development. Cordia dodecandra is a deciduous tree used by Maya people for its fruit and wood, growing, to date, in remnant forest fragments and homegardens (traditional agroforestry systems) in Yucatán. In this work, we evaluated the microbiota's alpha and beta diversity per compartment (phyllosphere and rhizosphere) and per population (forest and homegarden) in the Northeast and Southwest Yucatán regions. Eight composite DNA samples (per compartment/population/region combination) were amplified for 16S-RNA (bacteria) and ITS1-2 (fungi) and sequenced by Illumina MiSeq. Bioinformatic analyses were performed with QIIME and phyloseq. For bacteria and fungi, from 107,947 and 128,786 assembled sequences, 618 and 1092 operating taxonomic units (OTUs) were assigned, respectively. The alpha diversity of bacteria and fungi was highly variable among samples and was similar among compartments and populations. A significant species turnover among populations and regions was observed in the rhizosphere. The core microbiota from the phyllosphere was similar among populations and regions. Forests and homegarden populations are reservoirs of the C. dodecandra phyllosphere core microbiome and significant rhizosphere biodiversity.

Background: Calcineurin inhibitors have been implicated in acute and chronic kidney disease after liver transplant (LT). Everolimus (EVR) is a mammalian target of rapamycin inhibitor efficacious in preventing acute cellular rejection while preserving renal function among LT recipients. We evaluated the benefits on renal function of EVR immunosuppression in LT recipients., Methods: We performed a retrospective and observational study in 477 LT recipients in Virgen de las Nieves Hospital from 2002 to 2019 on the use of EVR with tacrolimus minimization or withdrawal in LT recipients with renal dysfunction. The study included 100 patients starting EVR (20.96%); in 66 (66%) the indication was renal dysfunction. The change in renal function was assessed by estimated glomerular filtration rate. Statistical analyses were performed using SPSS 17.0 software (IBM, Munich, Germany)., Results: Fifty 8 patients received mycophenolate mofetil (87.8%), and tacrolimus therapy was stopped in 27 patients (40.9%). Induction therapy with basiliximab was administered in 41 patients (62.12%). There was significant difference between estimated glomerular filtration rate at the time of starting EVR and the first month at last follow-up (49.42 mL/min/1.73 m 2 vs 75.27 mL/min/1.73 m 2 ; P < .001) and at end of follow-up (24 months) (49.42 mL/min/1.73 m 2 vs 64.32 mL/min/1.73 m 2 ; P = .001). The rate of incidence of adverse events was 48.48% (32/66). Seven patients died during follow-up (10.6%), but there were no EVR-related deaths. Eleven patients (16.6%) developed biopsy-proven acute rejection., Conclusion: This study showed that EVR is associated with a beneficial effect on glomerular filtration rate in both the short and long term in LT recipients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Calcineurin inhibitors are associated with the development of de novo tumors and increased recurrence of hepatocellular carcinoma after liver transplant. It has been suggested that mammalian target of rapamycin inhibitors (everolimus [EVR]) may improve prognosis. We analyzed our experience on the use of EVR in malignant neoplasms in liver transplantation., Methods: We performed a retrospective descriptive analysis of 477 transplants performed between 2002 and 2019 at Virgen de las Nieves Hospital. A total of 100 patients received EVR; 23 transplants were because of tumor disease (23%), with de novo tumor in 12 patients and hepatocarcinoma in 11. The statistical study was carried out using the statistical program SPSS 17.0 software., Results: The study included 18 male patients (78.3%) and 5 female patients (21.7%) with an average age of 59.67 years. The most common indications of liver transplant have been alcoholic cirrhosis in 39% and hepatitis C virus cirrhosis in 21.7%. De novo tumors were lung neoplasm in 4 patients (33.3%), lymphoma in 2 patients(16.7%), oropharynx in 2 patients (16.7%), skin tumors in 2 patients (16.7%), and a kidney tumor (8.3%) in 1 patient. As for hepatocellular carcinoma, 8 patients met Milan criteria on the explant (61.5%). Tacrolimus was discontinued in all cases. The average onset time of post-transplant EVR was 2231.42 days in the de novo neoplasms and 307.45 days in those receiving transplants because of hepatocellular carcinoma (P = .05). We observed 5 deaths (21.7%)., Conclusion: Although the beneficial long-term role of EVR in liver transplant recipients with tumor disease is not demonstrated, it is used by most transplant units, both in de novo neoplasms and those receiving transplants because of hepatocellular carcinoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The coexistence of significant mitral regurgitation (MR) and severe aortic stenosis is prevalent, has a prognostic impact and makes treatment in the elderly population a complex issue. The aim of this study is to determine the prevalence of significant MR among a population of octogenarians and its influence on treatment and prognosis., Methods: We used the data from PEGASO (Pronóstico de la Estenosis Grave Aórtica Sintomática del Octogenario), a prospective registry that consecutively included 928 patients aged ≥80 years with severe symptomatic aortic stenosis., Results: The prevalence of significant MR was 8.5% (79 patients) and independently associated with the decision to treat conservatively (odds ratio = 2.28, 95% confidence interval: 1.31-3.95, p = 0.003). The group of patients with significant MR had higher overall mortality at 12 months follow-up (51.9% vs 25%, p < 0.001), which remained on division into subgroups based on the presence of comorbidities (Charlson<5: 49.2% vs 21.9%, p < 0.001; and Charlson ≥5: 62.5% vs 41.7%, p = 0.07). Within the group of patients in whom conservative treatment was performed, those with significant MR had higher mortality at one year (62.7% vs 35%, p < 0.001). MR was a significant independent predictor of overall mortality at 12-month follow-up (hazard ratio = 1.87, 95% confidence interval: 1.09-3.18, p = 0.022)., Conclusions: Significant MR has a high prevalence and worsens the prognosis of octogenarian patients with severe symptomatic aortic stenosis, especially in patients with conservative treatment, independently of the existence of comorbidities., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol., Objectives: This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity., Methods: The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM., Results: Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10 -5 ), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: -2.3% to -15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients., Conclusions: TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. It is associated to a higher risk of cardiovascular complications, including infective endocarditis (IE)., Methods: Retrospective, observational and single centre study that included all patients with IE diagnosed between 1996 and 2014. An analysis was made of the epidemiological, clinical, microbiological and echocardiographic data, complications during hospital admission, need for surgery, in-hospital mortality, and 1-year follow-up. Cases with endocarditis on prosthetic valves or other locations were excluded, as well as those for which the aortic valve morphology had not been accurately defined. A comparative statistical analysis was performed between BAV and tricuspid (TAV)., Results: Of a total of 328 cases with IE, 118 (35.67%) were on aortic valve, with 18 (16.22%) of them being BAV. The BAV cases were younger than TAV (51±19.06 vs. 60.83±15.73 years, P=.021) and they had less comorbidity (Charlson 0.67±0.77 vs. 1.44±1.64, P=.03).). There was a higher tendency of Staphylococcal origin (38.9 vs. 21.5%, P=.137), and 55.6% showed peri-valvular complications (TAV 16.1%, P=.001), in particular, abscesses (38.9 vs.16.1%, P=.047). BAV was the only predictive factor of peri-valvular complications (OR 7.87, 95% CI; 2.38-26.64, P=.001). Patients with BAV had more surgery during their admission (83.3 vs. 44.1%, P=.004), had less in-hospital mortality, with no statistical significance (5.6 vs. 25.8%, P=.069), and 1-year survival was significantly superior (93.8 vs 69.3%, P=.048)., Conclusions: Patients with IE on BAV are young, with low comorbidity. They frequently present with peri-valvular complications and they often require early surgery. Compared to TAV cases, in-hospital mortality is lower and 1-year survival is significantly higher., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Background: Chronic anticoagulation with vitamin K antagonists (VKAs) is recommended in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF). Direct oral anticoagulants (NOACs) are an alternative to VKAs but there are limited data to support their use in HCM. We sought to describe the pattern of use, thromboembolic events, bleeding and quality of life in patients with HCM and AF treated with NOACs., Methods: Data from patients treated with NOACs (n=99) and VKA (n=433) at 9 inherited cardiac diseases units were retrospectively collected. Annual rates of embolic events, serious bleeding and death were analysed and compared. Quality of life and treatment satisfaction were evaluated with SF-36 and SAFUCA questionnaires in 80 NOAC-treated and 57 VKA-treated patients., Results: After median follow-up of 63 months (IQR: 26-109), thromboembolic events (TIA/stroke and peripheral embolism) occurred in 10% of patients on oral anticoagulation. Major/clinically relevant bleeding occurred in 3.8% and the global mortality rate was 23.3%. Thromboembolic event rate was 0.62 per 100patient-years in the NOAC group vs. 1.59 in the VKA group [subhazard ratio (SHR) 0.32;95%CI:0.04-2.45; p=0.27]. Major/clinically relevant bleeding occurred in 0.62 per 100person-years in the NOAC group vs. 0.60 in the VKA group (SHR 1.28;95%CI 0.18-9.30; p=0.85). Quality of life scores were similar in both groups; however, NOAC-treated patients achieved higher scores in the SAFUCA., Conclusions: HCM patients with AF on NOACs showed similar embolic and bleeding rates to those on VKA. Although quality of life was similar in both groups, the NOAC group reported higher treatment satisfaction., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: The aim of this study was to understand the prevalence of comorbidities and the usefulness of the PROFUND index for the prognostic stratification of patients with comorbidities in a hospital cardiology unit., Patients and Methods: We consecutively analysed all patients hospitalized in 2012 in the department of cardiology. We recorded the comorbidities, length of stay, hospital mortality, Charlson indices and PROFUND indices. In the patients with comorbidities, we also recorded the readmissions and mortality during a 1-year follow-up., Results: The study included 1,033 patients (mean age, 67±13.1 years; 35% women), 381 (36.9%) of whom had comorbidities, with a mean Charlson index of 6.4±1.7 and a mean PROFUND index of 2.5±2.5. Compared with the other patients, the patients with comorbidities were older (72 vs. 64 years, p<.001), had a higher mortality rate (2.9% vs. 1.1%, p=.046) and longer hospital stays (8±5.5 vs. 6±5.7 days, p<.001) and were more often admitted for heart failure (42.3% vs. 15.8%, p<.001). The PROFUND index was independently associated with overall mortality (hazard ratio [HR], 1.13; 95% CI: 1.01-1.27; p=.034) and with the presence of major adverse events during the 12-month follow-up (HR, 1.09; 95% CI: 1.01-1.18; p=.026)., Conclusions: A high percentage of patients hospitalized in the department of cardiology had comorbidities. These patients had a higher prevalence of cardiovascular risk factors, longer stays and greater hospital mortality. The PROFUND index independently predicted mortality and adverse events during the follow-up., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Objective: To evaluate the safety and efficacy of various immunosuppressant regimens using mycophenolate mofetil (MMF)., Patients and Methods: This prospective, observational, multicenter study of 226 patients undergoing liver transplantation was carried out in 2005-2006, with 24-month follow-up. Studied variables were as follows: indicators of kidney, liver, and blood function; intercurrent infections; cardiovascular risk; acute and chronic episodes of rejection; recurrent hepatitis C virus infection; de novo tumors; and survival. Patients were classified into 4 groups according to treatment: no MMF (group 1, n = 91); MMF from induction (group 2, n = 83); late administration of MMF (group 3, n = 30); and MMF at induction, with early withdrawal (group 4, n = 22)., Results: Biodemographic characteristics were similar in all 4 groups. The MMF groups were at higher risk and had worse Model for End-Stage Liver Disease and Child-Pugh scores and worse pretransplantation blood and kidney function values. Significant differences were observed in creatinine concentration between groups 2 and 3: 0.45 mg/dL at 1 month (P < .01), 0.27 mg/dL at 3 months (P < .01), and 0.3 mg/dL at 6 months (P < .05). In contrast, differences of 0.34 mg/dL (P < .01) were observed between groups 1 and 3 at 1 month and 0.17 mg/dL (P < .05) between groups 1 and 2 at 3 months. No differences were noted in white blood cell counts, episodes of acute rejection (19%) and chronic rejection (5%), graft survival (80%), and rate of recurrent hepatitis C virus infection (75%) between the 4 groups. The infection rate at 3 months in groups 2 and 4 was 34.5%, and in groups 1 and 3 was 34.5% (P < .05)., Conclusions: Use of MMF at induction and introduction of MMF in the first 3 months posttransplantation helps to preserve and restore creatinine levels in patients with worsened kidney function, and aids in keeping them stable, without increasing the risk of rejection while optimizing the anticalcineurin dosage.

Objective: This study was undertaken to determine the prevalence, epidemiology, and mother-child repercussions of increased alanine-aminotransferase levels from week 16 of pregnancy., Study Design: A longitudinal observational study of 381 pregnant women. The cause of increased alanine-aminotransferase levels during pregnancy and repercussions on the neonate were studied in 283 cases. Statistical analysis was performed with Mann-Whitney test, chi2 test, or the Fisher exact test., Results: The mean age of the mothers was 29.9 +/- 4.8 years. Twenty-five percent presented increased gamma-glutamyl-transpeptidase, alkaline phophatase, and dehydrogenase lactate from week 32. Increased alanine-aminotransferase was observed in 7.4% (95% CI, 5.00%-10.57%) of cases. Clinical disorders were light, transitory, and with no apparent cause, except for 1 hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, 3 preeclampsias, and 1 gravidic cholestasis. No statistically significant differences were observed in the group of mother-child with alanine-aminotransferase normal or increased., Conclusion: Most increases in alanine-aminotransferase from week 16 of pregnancy are transitory, non-specific, and have no repercussions on mother or child.