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Abstract Aims Early diuresis and natriuresis are commonly used to assess the efficacy of decongestive therapy following an acute heart failure episode. There is limited knowledge regarding which parameter better predicts adverse clinical outcomes, especially in the outpatient setting. This study investigated the prognostic value of both metrics in predicting 30-day adverse clinical events in an ambulatory worsening heart failure (WHF) scenario. Methods and results This is a post-hoc analysis of the SALT-HF trial involving 167 patients with ambulatory WHF randomized to receive intravenous furosemide with or without hypertonic saline solution. Early diuretic response was assessed through 3-h urine output and 3-h urinary sodium (uNa+) levels following intravenous (IV) diuretic infusion. We analysed their association with 30-day adverse events (defined as death, heart failure hospitalization, or the need for outpatient IV diuretics) using logistic regression analysis. Both exposures were examined along the continuum and dichotomized in their median. The discriminative ability between the exposures and endpoints was assessed by receiver operating characteristic curves (AUC-ROC). Results The median age of participants was 81 years, predominantly male (69.5%). Patients with lower 3-h urinary sodium and diuresis were older and exhibited reduced kidney function and haemoglobin levels. At 30 days, 50 (29.9%) of the sample experienced the composite endpoint. Multivariate analyses revealed that lower 3-h uNa+ was associated with a higher risk of 30-day adverse events (P = 0.008). Conversely, 3-h diuresis did not significantly predict 30-day adverse outcomes (P = 0.424). There was a trend towards a higher AUC-ROC for the inverse of 3-h natriuresis compared with 3-h diuresis: 0.680 versus 0.601, P = 0.092. Conclusions In patients with ambulatory WHF treated with IV furosemide, 3-h urinary sodium predicted 30-day outcomes whereas 3-h diuresis did not.

Aims Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT‐HF trial participants. Methods and results ‘Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF’ (SALT‐HF) trial was a multicenter, double‐blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1‐h infusion of IV furosemide plus HSS (2.6–3.4% NaCl depending on plasmatic sodium levels) versus a 1‐h infusion of IV furosemide at the same dose (125–250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3‐h diuresis after treatment started. Secondary endpoints included (a) 7‐day changes in congestion data, (b) 7‐day changes in kidney function and electrolytes, (c) 30‐day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all‐cause mortality or HF‐hospitalization). Results A total of 167 participants [median age, 81 years; interquartile range (IQR), 73–87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2–4). Common co‐morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21–25), and plasmatic levels of N‐terminal‐pro‐B‐type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT‐proBNP 4969 pg/mL, IQR: 2508–9328; median CA125 46 U/L, IQR: 20–114). Conclusions SALT‐HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone.

Circulating antigen carbohydrate 125 (CA125) has emerged as a proxy of fluid overload in heart failure. This study aimed to evaluate the effect of dapagliflozin on short-term CA125 levels in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effects on peak oxygen consumption (peakVO 2 ). This study is a post-hoc sub-analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin or placebo to evaluate change in peakVO 2 (NCT04197635). We used linear mixed regression analysis to compare changes in the natural logarithm of CA125 (logCA125) and percent changes from baseline (Δ%CA125). We used the “rwrmed” package to perform mediation analyses. CA125 was available in 87 patients (96.7%). LogCA125 significantly decreased in patients on treatment with dapagliflozin [1-month: Δ − 0.18, (CI 95% = − 0.33 to − 0.22) and 3-month: Δ − 0.23, (CI 95% = − 0.38 to − 0.07); omnibus p-value = 0.012]. Δ%CA125 decreased by 18.4% and 31.4% at 1 and 3-month, respectively (omnibus p-value = 0.026). Changes in logCA125 mediated the effect on peakVO 2 by 20.4% at 1 month (p < 0.001). We did not find significant changes for natural logarithm of NTproBNP (logNT-proBNP) [1-month: Δ − 0.03, (CI 95% = − 0.23 to 0.17; p = 0.794), and 3-month: Δ 0.73, (CI 95% = − 0.13 to 0.28; p-value 0.489), omnibus p-value = 0.567]. In conclusion, in patients with stable HFrEF, dapagliflozin resulted in a significant reduction in CA125. Dapagliflozin was not associated with short-term changes in natriuretic peptides. These changes mediated the effects on peakVO 2.

Background The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta‐blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients. Hypothesis We postulate beta‐blockers may have deleterious effects in HFpEF and ChI. This work aims to evaluate the short‐term effect of beta‐blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI. Methods This is a prospective, crossover, randomized (1:1) and multicenter study. After randomization, the clinical and cardiac rhythm will be continuously registered for 30 days. PeakVO2 is assessed by cardiopulmonary exercise testing (CPET) at 15 and 30 days in both groups. Secondary endpoints include quality of life, cognitive, and safety assessment. Patients with stable HFpEF, functional class New York Heart Association (NYHA) II‐III, chronic treatment with beta‐blockers, and ChI will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 20% loss rate, and delta change of mean peakVO2: +1.2 mL/kg/min (SD ± 2.0)] of 52 patients is necessary to test our hypothesis. Results Patients started enrolling in October 2018. As January 14th, 2020, 28 patients have been enrolled. It is projected to enroll the last patient at the end of July 2020. Conclusions Optimizing therapy that improves functional capacity remains an unmeet priority in HFpEF. Deprescribing beta‐blockers in patients with HFpEF and ChI seems a plausible intervention to improve functional capacity. This trial is an attempt towards precision medicine in this complex syndrome. Trial registration ClinicalTrials.gov: NCT03871803.

Background Iron deficiency (ID) is associated with impaired functional capacity in patients with heart failure (HF), even in those with preserved ejection fraction (HFpEF). This study aimed to evaluate the effect of baseline ferrokinetics on peak oxygen consumption (peakVO2) improvement after a 12‐week physical therapy programme in patients with stable HFpEF. Methods This study is a post‐hoc sub‐analysis of a randomized clinical trial in which 59 stable patients with HFpEF were randomized to receive a 12‐week programme of inspiratory muscle training (IMT), functional electrical stimulation (FES), IMT + FES or usual care (UC) to evaluate change in peakVO2 (NCT02638961). Serum ferritin and transferrin saturation (TSAT) determinations were assessed at baseline. ID was defined as ferritin <100 ng/mL and/or TSAT <20% if ferritin was within 100–299 ng/mL. We used a linear mixed regression model to analyse between‐treatment changes in peakVO2 across ferrokinetics status at 12 and 24 weeks. Results The mean age was 74 ± 9 years, and 36 (61%) had ID. The mean of peakVO2 was 9.9 ± 2.5 mL/kg/min. The median of ferritin and transferrin saturation (TSAT) was 91 (50–181) ng/mL and 23% (16–30), respectively. A total of 52 patients completed the trial (13 patients per arm). Compared with those patients on UC, patients allocated to any of the active arms showed less improvement in peak VO2 when they showed ID (P‐value for interaction <0.001), lower values of ferritin (P‐value for interaction <0.001), or TSAT (P‐value for interaction <0.001). Conclusions Ferrokinetics status plays an essential role in modifying the aerobic capacity response to physical therapies in patients with HFpEF. Further studies are required to confirm these findings.

Background Peritoneal dialysis (PD) has emerged as an effective technique for managing refractory heart failure (HF) in patients unresponsive to diuretics. Previous meta-analyses have demonstrated significant reductions in hospitalization days and improvements in cardiac function among patients with HF treated with PD compared with those receiving standard therapies. However, sodium retention remains a challenge in HF management, as patients often exhibit poor compliance with dietary sodium restrictions. In patients on PD, sodium retention exacerbates fluid overload and cardiovascular complications, highlighting the need for effective sodium elimination strategies. Methods This study will investigate the effects of PD on sodium excretion and its impact on mortality and heart failure exacerbations. We will enroll 31 patients with refractory HF in a continuous ambulatory peritoneal dialysis program. The study design includes randomization, a washout period, and an open-label approach to evaluate the impact of dapagliflozin, a sodium-glucose cotransporter-2(SGLT2) inhibitor, on sodium balance and clinical outcomes. Statistical analysis will be performed to assess changes in sodium excretion and the association between sodium removal levels and clinical outcomes. Expected results We hypothesize that dapagliflozin in patients undergoing PD will enhance net sodium loss by combining its known natriuretic efficacy with the hypothesis of increased sodium elimination in the peritoneal effluent. This effect is expected to be observed independently of the patients’ baseline renal function. Additionally, the study will investigate the safety profile of dapagliflozin in PD patients, monitoring for potential adverse effects and overall tolerability. Conclusions The study aims to provide valuable insights into optimizing HF management in PD patients through innovative therapeutic approaches. The anticipated findings could significantly impact clinical practice by improving sodium and fluid balance, potentially leading to reduced hospitalizations and better overall health outcomes for HF patients on PD. Trial Registration : This study was approved and authorized by both the Spanish Agency of Drugs and Health Products (AEMPS) and the Hospital Clínico Universitario de Valencia Ethical Committee (CEIM). The investigated drug, dapagliflozin, has received approval from the European Medicines Agency (EMA) and has been authorized for commercialization in Spain (CEIM FILE: 148/23, CODE: DAPA-DP, EUDRACT no.: 2023-505571-78-00).

High incidence of elderly depression motivates use of screening depression scales in aging; the most used scales by specialized and nonspecialized healthcare staff is Geriatric Depression Scale. Short version of this scale (15 items) was propose in 1982 whit a high effort in his construction and with no modification since there. The aim of this study was to determine the confiability of these 15 item-short version and ultrashort versions (5, 3, and 2 items). This study used information of the Encuesta Salud Bienestar y Envejecimiento SABE in Bogotá/Colombia (1957 registers). Statistical analysis showed a high variability in homogeneity items’ Cronbach analysis (between 0,59 until 0,23). Factorial analysis showed 3 factors in the scale. This seems to be part of a need to contextualize the scale because the use of it since 1982 without changes and a dynamic depression concept through the years.

Background/Objectives: C-shaped canals represent a challenge in endodontic procedures. The present study aimed to investigate the prevalence and characteristics of C-shaped canals in mandibular second molars in Guayaquil, Ecuador. Methods: CBCT records from two radiology centers were examined (2020–2022). A total of 400 CBCT scans (800 mandibular second molars) were analyzed using Fan’s classification. Data on the presence or absence of C-shaped canals, gender, and bilateral occurrence were collected. Statistical analysis included the test for differences in proportions and the chi-squared test to assess the significance of correlations between variables. Results: C-shaped canals were found in 28% of mandibular second molars, affecting 33.75% of the patient sample. The prevalence was significantly higher in females (42.9%) compared to males (20.4%). Bilateral occurrences were observed in 63% of affected patients. Morphologic variability was pronounced, with Fan C1 and C4 dominating in the coronal and apical thirds, respectively, while a shift toward Fan C2 and C3 was observed in the middle third. Only 19.2% of the teeth maintained a consistent morphology. Conclusions: C-shaped canals were found in 28% of mandibular second molars and occurred predominantly in females. Notably, most cases were bilateral, highlighting the importance of effectively adapting endodontic techniques to treat this unique anatomical variation. Further research into genetic and environmental influences could deepen our understanding and help develop refined diagnostic and therapeutic strategies.

El presente artículo trata de dar una nueva visión de la evolución geológica Terciaria del occidente de la Costa Atlántica, separando los diferentes ambientes de sedimentación y tratando de reconstruir la paleogeografía de la región.

BackgroundCurrent evidence supports the role of circulating carbohydrate antigen 125 (CA125) in risk assessment, disease monitoring and therapeutic guidance in heart failure (HF). However, there is limited data on its diagnostic applicability. This study aimed to assess the diagnostic performance of CA125 in identifying HF with preserved ejection fraction (HFpEF) in an outpatient population.MethodsThis was a prospective, multicentre study involving 246 consecutive patients with clinically suspected HF. Patients with a left ventricular ejection fraction <50% (n=8) and those with a history of malignancy (n=22) were excluded. The final study cohort comprised 210 patients. The diagnosis of HFpEF was confirmed by a trained cardiologist blinded to the biomarker levels.ResultsThe mean age of the study cohort was 69.7±15 years, and 69% were women. Median levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and CA125 were 125 pg/mL (IQR: 51–332) and 11 U/mL (IQR: 8–17), respectively. HFpEF was diagnosed in 65 (31%) patients. For HFpEF diagnosis, NT-proBNP and CA125 levels demonstrated comparable areas under the receiver operating characteristic curves 0.765 (95% CI: 0.686 to 0.843) vs 0.715 (95% CI: 0.636 to 0.793), respectively (p=0.323). Optimal cut points were identified as 12.2 U/mL for CA125 (sensitivity: 0.69; specificity: 0.68) and 243 pg/mL for NT-proBNP (sensitivity: 0.65; specificity: 0.83). Elevated CA125 levels (>23 U/mL, 12.4% of the sample) exhibited high specificity (0.97), a positive predictive value of 80.8% and correctly classified 77.1% of cases as HFpEF. Conversely, CA125 levels<9 U/mL were associated with a high negative predictive value (85.7%).ConclusionIn an ambulatory setting, CA125 exhibits acceptable diagnostic performance for identifying HFpEF and may complement NT-proBNP in clinical practice.