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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.

Aims The role of non‐invasive telemedicine (TM) combining telemonitoring and teleintervention by videoconference (VC) in patients recently admitted due to heart failure (HF) (‘vulnerable phase’ HF patients) is not well established. The aim of the Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS) trial is to assess the impact on clinical outcomes of implementing a TM service based on mobile health (mHealth), which includes remote daily monitoring of biometric data and symptom reporting (telemonitoring) combined with VC structured, nurse‐based follow‐up (teleintervention). The results will be compared with those of the comprehensive HF usual care (UC) strategy based on face‐to‐face on‐site visits at the vulnerable post‐discharge phase. Methods and results We designed a 24 week nationwide, multicentre, randomized, controlled, open‐label, blinded endpoint adjudication trial to assess the effect on cardiovascular (CV) mortality and non‐fatal HF events of a TM‐based comprehensive management programme, based on mHealth, for patients with chronic HF. Approximately 508 patients with a recent hospital admission due to HF decompensation will be randomized (1:1) to either structured follow‐up based on face‐to‐face appointments (UC group) or the delivery of health care using TM. The primary outcome will be a composite of death from CV causes or non‐fatal HF events (first and recurrent) at the end of a 6 month follow‐up period. Key secondary endpoints will include components of the primary event analysis, recurrent event analysis, and patient‐reported outcomes. Conclusions The HERMeS trial will assess the efficacy of a TM‐based follow‐up strategy for real‐world ‘vulnerable phase’ HF patients combining telemonitoring and teleintervention.

Heart failure (HF) is a progressive condition with periods of apparent stability and repeated worsening HF events. Over time, unless optimization of HF treatment, worsening HF events become more frequent and patients enter into a cycle of recurrent events with high morbidity and mortality. In patients with HF there is an activation of deleterious neurohormonal pathways, such as the renin angiotensin aldosterone system and the sympathetic system, and an inhibition of protective pathways, including natriuretic peptides and guanylate cyclase. Therefore, HF burden can be reduced only through a holistic approach that targets all neurohormonal systems. In this context, vericiguat may play a key role, as it is the only HF drug that activates the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate system. On the other hand, it has been described relevant disparities in the management of HF population. Consequently, it is necessary to homogenize the management of these patients, through an integrated patient-care pathway that should be adapted at the local level. In this context, the development of new technologies (ie, video call, specific platforms, remote control devices, etc.) may be very helpful. In this manuscript, a multidisciplinary group of experts analyzed the current evidence and shared their own experience to provide some recommendations about the therapeutic optimization of patients with recent worsening HF, with a particular focus on vericiguat, and also about how the integrated patient-care pathway should be performed.

Acute coronary syndrome (ACS) is the leading cause of mortality in developed countries. Mitochondrial dysfunction is a hallmark of various cardiometabolic diseases, including ACS. Emerging evidence suggests that evaluating mitochondrial biomarkers in plasma may offer valuable insights into the pathophysiology and management of these conditions. The present study aims to analyse the effect of ACS, sex and their interaction on plasma levels of mitochondrial markers, such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) and citrate syntetase (CS). A total of 18 ACS patients (8 women and 10 men) and 20 controls (8 women and 12 men) were included in this study. Venous blood samples were collected from participants after a 12-h overnight fast. Plasma levels of mitochondrial PGC-1α, MOTS-c and CS were measured. ACS significantly reduced plasma levels of PGC-1α and MOTS-c. Sex did not shown a significant effect on these markers. Additionally, MOTS-c positively correlated with the first troponin and hemoglobin, PGC-1α negatively correlated with glucose and positively with HDL-cholesterol, and CS showed negative correlations with NT-proBNP, C-reactive protein, and hemoglobin. Mitochondria markers, MOTS-c and PGC-1α, are altered in ACS patients, with no observed sex differences. These findings represent an initial step toward integrating personalized medicine into the clinical management of ACS. Nonetheless, further studies are required to fully elucidate the role of these markers in this pathology.

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.