1,721,110 research outputs found
Counterpoint: Natriuresis-Guided Diuresis in Patients Admitted to Hospital With Heart Failure - Barking Up the Wrong Tree? Towards Direct Insights Into the Efficacy of Diuretic Therapy
Full text linkDespite significant advancements in chronic heart failure management over the past 3 decades, the treatment and outcomes of patients hospitalized with acute heart failure (AHF) have remained relatively unchanged. Recent years have seen growing interest in personalizing diuretic therapy based on measures of diuretic or natriuretic response as approximately 40% of AHF patients exhibit an inadequate response to loop diuretics, the only Class IÀrecommended decongestive treatment. 1 The absence of a standard definition for diuretic resistance suggests this number could be even higher. Consequently, early identification of diuretic resistance or insufficient response is essential. Traditional methods such as assessing weight loss, net fluid loss, or diuresis are commonly used to evaluate diuretic therapy response. However, these measures are difficult to obtain precisely in hospitalized patients with AHF and have inherent limitations, leading to inconsistent reliability and reproducibility. For example, the correlation between fluid loss and weight loss during decongestive therapy in AHF is modest at best, with studies showing correlations of around 0.50 and wide 95% limits of agreement. 2 Additionally, there is a large variation in the measured weight depending on the method used to assess weight, with an astonishing mean bias of 1.42 kg between bed scale and standing scale assessment. 3 In 2019, HF experts proposed a novel approach by assessing urinary sodium excretion as a proxy for diuretic efficacy, based on the pharmacologic mechanism of diu-retics promoting sodium excretion. 4 At that time, the data supporting this approach were scarce and largely observational , mainly highlighting associations between reduced natriuretic response and poor outcomes. 5 Since then, this approach has sparked renewed interest in AHF research, yielding valuable insights into contemporary AHF management. First, the notion that water retention is the primary issue for all AHF patients is increasingly being questioned. Evidence points to the variety of AHF phenotypes, with pressure not necessarily equating to volume overload. 6,7 Emerging studies also implicate sodium storage via glyco-saminoglycans as a key mechanism. 8 For example, using 23 Na-magnetic resonance imaging, patients with HF were found to have elevated skin sodium levels comparable to those in hemodialysis patients. 9 Similarly, a study of AHF patients undergoing loop diuretic therapy showed reductions in sodium content in skin and muscle, whereas water content remained unchanged despite significant weight loss of 3.6 kg. 10 These findings underscore the role of desalination over simple fluid loss in AHF. The inability of hypertonic saline to increase natriuresis does not negate urinary sodium's utility as a marker of loop diuretic response. Rather, it emphasizes the sodium avidity of HF and the neutral effects of hypertonic saline in unselected AHF populations. Moreover, data from the ROSE-AHF trial revealed that even with negative fluid balance, insufficient natriuresis (below 2 g/day dietary intake) was linked to higher mortality risk. 11 Second, spot urine does not perfectly correlate with 24-hour natriuresis. Its primary utility lies in its ability to quickly and easily identify patients at risk of poor response to diuretic therapy. These limitations are currently being addressed with predictive tools such as the natriuretic response prediction equation, now under evaluation in From th
Heart failure is associated with accelerated age related metabolic bone disease
Full text linkBackground: The heart failure (HF)-syndrome is associated with neuro-hormonal activation, chronic kidney disease (CKD), inflammation and alterations in the phosphorus-metabolism, all of which are involved in regulation of mineral bone density. However, the role of HF as an independent factor associated with metabolic bone disease (MBD) remains unclear. Methods: HF-patients undergoing dual X-ray absorptiometry (DEXA) were matched in a 1:2 fashion against age and gender matched controls without HF, to determine the proportion of osteoporosis (T-score < −2.5). HF-status was tested against known predictors of MBD. Correlation analysis and Z-score analysis were used to assess the impact of HF on age-related bone demineralisation. Results: A total of 190 HF-patients (age = 80 ± 10 years, female = 61%) were age and gender matched to 380 controls. HF-patients had a higher proportion of osteoporosis (26 vs 17%; p =.007). HF patients had a lower averaged mineral bone density expressed in g/cm 2 (p =.030), T-scores (p =.001) and Z-scores (p <.001). After adjusting for the individual osteoporosis risk-factors of the FRAX-score, difference in baseline features, kidney function and phosphorus-metabolism alterations, heart failure remained independently associated with a lower averaged T-score (Adjusted β = –0.189; p =.017). Heart failure was associated with an accelerated age-related decline in mineral bone density (p =.0418). Therapies with ACE-I or ARBs and beta-blockers associated with ameliorated bone demineralisation (p =.023, respectively p =.029), while loop diuretic associated with worsened bone demineralization (p <.001). Conclusion: Heart failure independently associates with MBD and higher prevalence of osteoporosis. Heart failure aggravates the aged related loss in mineral bone density while treatment with neuro-hormonal blockers seemed to ameliorate this finding. </p
Heart failure improvement, remission, and recovery: A European Journal of Heart Failure expert consensus document
Full text linkHeart failure (HF) is a heterogeneous and dynamic syndrome characterized by progressive pathophysiological alterations, variable clinical trajectories, and differential responses to therapeutic interventions. The concept of HF with improved ejection fraction (HFimpEF) underscores this complexity, identifying patients who exhibit an increase in left ventricular ejection fraction (LVEF) following time and/or pharmacological and device-based therapies. However, the distinction between improvement, remission, and recovery remains inconsistently defined and is primarily LVEF-centric, lacking comprehensive assessment of structural, functional, and symptomatic HF status. This expert consensus document delineates HF trajectories, examines factors reflecting HF improvement beyond recovery of LVEF, and explores the prognostic implications of these phenotypic transitions. Emphasis is placed on the necessity of continued guideline-directed medical and device therapy to minimize the risk of relapse. While a subset of patients attains sustained myocardial and clinical recovery, others remain susceptible to relapse, necessitating individualized monitoring and long-term management. Persistent knowledge gaps regarding the safety and feasibility of treatment de-escalation, the role of genetic predisposition, and optimal therapeutic strategies underscore the need for further research to refine risk stratification and evidence-based decision-making in HFimpEF
Urinary sodium analysis: The key to effective diuretic titration? European Journal of Heart Failure expert consensus document
Full text linkIn patients with heart failure, neurohumoral activation leads to increased renal sodium avidity across the entire renal tubules, resulting in a positive sodium and water balance, leading to decompensated heart failure requiring intravenous diuretics. As the dose of diuretic therapy required to achieve euvolaemia is difficult to estimate due to considerable intra- and interindividual differences, the European Society of Cardiology recommends assessment of the diuretic response within hours either via evaluation of the urinary sodium concentration or via urinary volume after initial diuretic administration. All diuretic agents enhance sodium excretion to a different extent depending on their side of action across the renal tubules, and renal adaptation mechanisms due to neurohumoral stimulation. Impaired sodium excretion, even in the presence of fluid loss, is associated with worse clinical outcomes. Therefore, assessing urinary sodium excretion is considered a good and direct marker of the diuretic efficacy. Such natriuresis-guided protocols have been tested prospectively by the Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure and the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure study, both demonstrating increased natriuresis and diuresis. Moreover, the Readily Available Urinary Sodium Analysis in Patients with Acute Decompensated Heart Failure study has demonstrated that a nurse-led natriuresis-guided protocol is feasible through the use of a point-of-care urinary sodium sensor, allowing an immediately readable urinary sodium result, enabling fast changes in diuretic therapy. This review summaries the rationale, current evidence and gaps supporting the role of urinary sodium concentration in patients with acute decompensated heart failure
Adrenomedullin in heart failure: pathophysiology and therapeutic application
Full text linkAdrenomedullin (ADM) is a peptide hormone first discovered in 1993 in pheochromocytoma. It is synthesized by endothelial and vascular smooth muscle cells and diffuses freely between blood and interstitium. Excretion of ADM is stimulated by volume overload to maintain endothelial barrier function. Disruption of the ADM system therefore results in vascular leakage and systemic and pulmonary oedema. In addition, ADM inhibits the renin-angiotensin-aldosterone system. ADM is strongly elevated in patients with sepsis and in patients with acute heart failure. Since hallmarks of both conditions are vascular leakage and tissue oedema, we hypothesize that ADM plays a compensatory role and may exert protective properties against fluid overload and tissue congestion. Recently, a new immunoassay that specifically measures the biologically active ADM (bio-ADM) has been developed, and might become a biomarker for tissue congestion. As a consequence, measurement of bio-ADM might potentially be used to guide diuretic therapy in patients with heart failure. In addition, ADM might be used to guide treatment of (pulmonary) oedema or even become a target for therapy. Adrecizumab is a humanized, monoclonal, non-neutralizing ADM-binding antibody with a half-life of 15 days. Adrecizumab binds at the N-terminal epitope of ADM, leaving the C-terminal side intact to bind to its receptor. Due to its high molecular weight, the antibody adrecizumab cannot cross the endothelial barrier and consequently remains in the circulation. The observation that adrecizumab increases plasma concentrations of ADM indicates that ADM-binding by adrecizumab is able to drain ADM from the interstitium into the circulation. We therefore hypothesize that administration of adrecizumab improves vascular integrity, leading to improvement of tissue congestion and thereby may improve clinical outcomes in patients with acute decompensated heart failure. A phase II study with adrecizumab in patients with sepsis is ongoing and a phase II study on the effects of adrecizumab in patients with acute decompensated heart failure with elevated ADM is currently in preparation
Assessment of Proximal Tubular Function by Tubular Maximum Phosphate Reabsorption Capacity in Heart Failure
No full textBackground and objectives The estimated glomerular filtration rate (eGFR) is a crucial parameter in heart failure. Much less is known about the importance of tubular function. We addressed the effect of tubular maximum phosphate reabsorption capacity (TmP/GFR), a parameter of proximal tubular function, in patients with heart failure. Design, setting, participants, & measurements We established TmP/GFR (Bijvoet formula) in 2085 patients with heart failure and studied its association with deterioration of kidney function (>25% eGFR decrease from baseline) and plasma neutrophil gelatinase–associated lipocalin (NGAL) doubling (baseline to 9 months) using logistic regression analysis and clinical outcomes using Cox proportional hazards regression. Additionally, we evaluated the effect of sodium-glucose transport protein 2 (SGLT2) inhibition by empagliflozin on tubular maximum phosphate reabsorption capacity in 78 patients with acute heart failure using analysis of covariance. Results Low TmP/GFR (<0.80 mmol/L) was observed in 1392 (67%) and 21 (27%) patients. Patients with lower TmP/GFR had more advanced heart failure, lower eGFR, and higher levels of tubular damage markers. The main determinant of lower TmP/GFR was higher fractional excretion of urea ( P <0.001). Lower TmP/GFR was independently associated with higher risk of plasma NGAL doubling (odds ratio, 2.20; 95% confidence interval, 1.05 to 4.66; P =0.04) but not with deterioration of kidney function. Lower TmP/GFR was associated with higher risk of all-cause mortality (hazard ratio, 2.80; 95% confidence interval, 1.37 to 5.73; P =0.005), heart failure hospitalization (hazard ratio, 2.29; 95% confidence interval, 1.08 to 4.88; P =0.03), and their combination (hazard ratio, 1.89; 95% confidence interval, 1.07 to 3.36; P =0.03) after multivariable adjustment. Empagliflozin significantly increased TmP/GFR compared with placebo after 1 day ( P =0.004) but not after adjustment for eGFR change. Conclusions TmP/GFR, a measure of proximal tubular function, is frequently reduced in heart failure, especially in patients with more advanced heart failure. Lower TmP/GFR is furthermore associated with future risk of plasma NGAL doubling and worse clinical outcomes, independent of glomerular function
Tirzepatide, HFpEF, and the Kidney:A Triangular Relationship Requiring Measurement of GFR, Not Guesses
Full text linkFibroblast growth factor 23 is related to profiles indicating volume overload, poor therapy optimization and prognosis in patients with new-onset and worsening heart failure
No full texthttp://dx.doi.org/10.13039/501100000780 European Commissionhttp://dx.doi.org/10.13039/501100002996 Dutch Heart Foundatio
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