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Rationale & objectiveHeart failure treatment relies on loop diuretics to induce natriuresis and decongestion, but the therapy is often limited by diuretic resistance. We explored the association of renin-angiotensin-aldosterone system (RAAS) activation with diuretic response.Study designObservational cohort.Setting & populationEuvolemic ambulatory adults with chronic heart failure were administered torsemide in a monitored environment.PredictorsPlasma total renin, active renin, angiotensinogen, and aldosterone levels. Urine total renin and angiotensinogen levels.OutcomesSodium output per doubling of diuretic dose and fractional excretion of sodium per doubling of diuretic dose.Analytical approachRobust linear regression models estimated the associations of each RAAS intermediate with outcomes.ResultsThe analysis included 56 participants, and the median age was 65 years; 50% were women, and 41% were Black. The median home diuretic dose was 80-mg furosemide equivalents. In unadjusted and multivariable-adjusted models, higher levels of RAAS measures were generally associated with lower diuretic efficiency. Higher plasma total renin remained significantly associated with lower sodium output per doubling of diuretic dose (β = -0.41 [-0.76, -0.059] per SD change) with adjustment; higher plasma total and active renin were significantly associated with lower fractional excretion of sodium per doubling of diuretic dose (β = -0.48 [-0.83, -0.14] and β = -0.51 [-0.95, -0.08], respectively) in adjusted models. Stratification by RAAS inhibitor use did not substantially alter these associations.LimitationsSmall sample size; highly selected participants; associations may not be causal.ConclusionsAmong multiple measures of RAAS activation, higher plasma total and active renin levels were consistently associated with lower diuretic response. These findings highlight the potential drivers of diuretic resistance and underscore the need for high-quality trials of decongestive therapy enhanced by RAAS blockade.

Hemoconcentration during the treatment of acute decompensated heart failure is a surrogate for plasma volume reduction and is associated with improved survival, but most definitions only allow for hemoconcentration to be determined retrospectively. An increase in serum creatinine can also be a marker of aggressive decongestion, but in isolation is not specific. Our objective was to determine if combined hemoconcentration and worsening creatinine could better identify patients that were aggressively treated and, as such, may have improved postdischarge outcomes. A total of 4,181 patients hospitalized with acute decompensated heart failure were evaluated. Those who experienced both hemoconcentration and worsening creatinine at any point had a profile consistent with aggressive in-hospital treatment and longer length of stay (p

Background: Torsemide is proposed to have clinically important pharmacokinetic and pharmacodynamic advantages over furosemide. However, clinical outcomes did not differ in the Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM-HF) randomized trial., Methods: We conducted a multicenter mechanistic substudy of patients with heart failure randomized to oral furosemide or torsemide (TRANSFORM-Mechanism). At baseline and 30 days, participants underwent detailed assessments of pharmacokinetic and pharmacodynamic parameters., Results: TRANSFORM-Mechanism enrolled 88 participants. Kidney bioavailability, or the proportion of dose delivered to the tubular site of action, was significantly less with torsemide compared to furosemide [median 17.1%, (IQR 12.3, 23.5%) vs. 24.8% (16.6, 34.1%), p < 0.001]. Furosemide had a longer duration of kidney drug delivery and duration of natriuresis (p≤0.004 for both). Prescribed doses of furosemide and torsemide in TRANSFORM-Mechanism were similar to TRANSFORM-HF, with providers on average using a 2:1 dose equivalence conversion between drugs. However, these doses resulted in a substantially greater natriuresis with torsemide (p<0.001). A dose equivalence of ∼4:1 resulted in similar natriuresis. Higher diuretic doses in the torsemide group resulted in mild perturbations in kidney function and significant increases in renin, aldosterone, and norepinephrine (p<0.05 for all). Plasma volume (p=0.52) and body weight (p=0.89) did not improve with torsemide vs. furosemide., Conclusions: We observed no meaningful pharmacokinetic/pharmacodynamic advantages for torsemide vs. furosemide. The greater natriuresis from higher diuretic doses in the torsemide group was offset by greater neurohormonal activation and kidney dysfunction., (Copyright © 2024 by the American Society of Nephrology.)

Aims: Incomplete decongestion due to lack of titration of diuretics to effective doses is a common reason for readmission in patients with acute decompensated heart failure (ADHF). The natriuretic response prediction equation (NRPE) is a novel tool that proved to be rapid and accurate to predict natriuretic response and does not need urine collection. However, the NRPE has not been externally validated. The goal of this study was to externally validate the discrimination capacity of the NRPE in patients with ADHF and fluid overload., Methods and Results: Patients admitted with ADHF who required intravenous loop diuretics were included. A spot urine sample was obtained ~2 h following diuretic administration, and a timed 6-h urine collection by study staff was carried out. Urine sodium and urine creatinine from the spot urine sample were used to predict the 6-h natriuretic response using the NRPE. The primary goal was to validate the NRPE to discriminate poor loop diuretic natriuretic response (sodium output <50 mmol in the 6 h following diuretic administration). The NRPE was compared with urine sodium and measured urine output which are the methods currently recommended by international guidelines to assess diuretic response. Eighty-seven diuretic administrations from 49 patients were analysed. Mean age of patients was 57 ± 17 years and 67% were male. Mean estimated glomerular filtration rate was 65 ± 28 mL/min/1.73 m 2 , and ejection fraction was 35 ± 15%. Median dose of intravenous furosemide equivalents administered the day of the study was 80 mg (IQR 40 - 160). Poor natriuretic response occurred in 39% of the visits. The AUC of the NRPE to predict poor natriuretic response during the 6-h urine collection was 0.91 (95% CI 0.85-0.98). Compared with the NRPE, spot urine sodium concentration (AUC 0.75) and urine output during the corresponding nursing shift (AUC 0.74) showed lower discrimination capacity., Conclusions: In this cohort of patients with ADHF, the NRPE outperformed spot urine sodium concentration and all other metrics related to diuretic response to predict poor natriuretic response. Our findings support the use of this equation at other settings to allow rapid and accurate prediction of natriuretic response., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Chronic heart failure continues to be one of the main causes of impairment in the functioning and quality of life of people who suffer from it, as well as one of the main causes of mortality in our country and around the world. Mexico has a high prevalence of risk factors for developing heart failure, such as high blood pressure, diabetes, and obesity, which makes it essential to have an evidence-based document that provides recommendations to health professionals involved in the diagnosis and treatment of these patients. This document establishes the clinical practice guide (CPG) prepared at the initiative of the Mexican Society of Cardiology (SMC) in collaboration with the Iberic American Agency for the Development and Evaluation of Health Technologies, with the purpose of establishing recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. This document complies with international quality standards, such as those described by the US Institute of Medicine (IOM), the National Institute of Clinical Excellence (NICE), the Intercollegiate Network for Scottish Guideline Development (SIGN) and the Guidelines International Network (G-I-N). The Guideline Development Group was integrated in a multi-collaborative and interdisciplinary manner with the support of methodologists with experience in systematic literature reviews and the development of CPG. A modified Delphi panel methodology was developed and conducted to achieve an adequate level of consensus in each of the recommendations contained in this CPG. We hope that this document contributes to better clinical decision making and becomes a reference point for clinicians who manage patients with chronic heart failure in all their clinical stages and in this way, we improve the quality of clinical care, improve their quality of life and reducing its complications., (Copyright: © 2024 Permanyer.)

Congestion is the primary pathophysiological lesion in most heart failure (HF) hospitalizations. Renal congestion increases renal tubular pressure, reducing glomerular filtration rate (GFR) and diuresis. Because each nephron is a fluid-filled column, renal negative pressure therapy (rNPT) applied to the urinary collecting system should reduce tubular pressure, potentially improving kidney function. We evaluated the renal response to rNPT in congestive HF. Ten anesthetized ∼80-kg pigs underwent instrumentation with bilateral renal pelvic JuxtaFlow catheters. GFR was determined by iothalamate clearance (mGFR) and renal plasma flow (RPF) by para-aminohippurate clearance. Each animal served as its own control with randomization of left versus right kidney to -30 mmHg rNPT or no rNPT. mGFR and RPF were measured simultaneously from the rNPT and no rNPT kidney. Congestive HF was induced via cardiac tamponade maintaining central venous pressure at 20-22.5 mmHg throughout the experiment. Before HF induction, rNPT increased natriuresis, diuresis, and mGFR compared with the control kidney ( P < 0.001 for all). Natriuresis, diuresis, and mGFR decreased following HF ( P < 0.001 for all) but were higher in rNPT kidney versus control ( P < 0.001 for all). RPF decreased during HF ( P < 0.001) without significant differences between rNPT treatments. During HF, the rNPT kidney had similar diuresis and natriuresis ( P > 0.5 for both) and higher fractional excretion of sodium ( P = 0.001) compared with the non-rNPT kidney in the no HF period. In conclusion, rNPT resulted in significantly increased diuresis, natriuresis, and mGFR, with or without experimental HF. rNPT improved key renal parameters of the congested cardiorenal phenotype.

Aims: Atrial fibrillation (AF) has been associated with tricuspid annulus (TA) dilation in patients with severe functional tricuspid regurgitation (TR); however, the impact of AF is less clear in patients without severe TR. Our aim was to characterize TA remodelling in patients with AF in the absence of severe TR using 3D transoesophageal echocardiography (TOE)., Methods and Results: Ninety patients underwent clinically indicated transthoracic and TOE: non-structural (NS)-AF (n = 30); AF with left heart disease (LHD) (n = 30), and controls in sinus rhythm (n = 30). Three-dimensional TOE datasets were analysed to measure TA dimensions using novel dedicated tricuspid valve software. The NS-AF group showed biatrial dilatation and normal right ventricular (RV) size with decreased longitudinal function compared to controls, whereas the LHD-AF group showed biatrial dilatation, RV enlargement, decreased biventricular function, and higher systolic pulmonary artery pressure compared with the other groups. Indexed TA area, minimum diameter, maximum diameter, and total perimeter were significantly larger in the NS-AF group than in controls (measurements in end-diastole: 6.4 ± 1.1 vs. 5.0 ± 0.6 cm2/m2, 1.8 ± 0.3 vs. 1.6 ± 0.2 cm/m2, 2.1 ± 0.3 vs. 1.9 ± 0.2 cm/m2, and 6.6 ± 0.9 vs. 5.9 ± 0.7 cm/m2, respectively, all P < 0.05). There was no significant difference in any indexed TA parameter between AF groups. TA circularity index (ratio between minimum and maximal diameters) and TA fractional area change between end-diastole and end-systole were no different among the three groups., Conclusion: AF is associated with right atrial and tricuspid annular remodelling independent of the presence of LHD in patients with intrinsically normal tricuspid leaflets without severe TR., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)