Treatment Of Acute Heart Failure Research Articles

Characteristics, Treatment, and Prognosis in Octogenarian and Older Patients With Acute Heart Failure in Japan - Prospective Observational Study on Acute Pharmacotherapy and Prognosis in Management of Acute Heart Failure (POPEYE-AHF Registry).

The number of older people in Japan is increasing more quickly than in other countries; with this aging of society, the number of elderly patients hospitalized for acute heart failure (HF) is also increasing. The treatment and prognosis of acute HF may be changing, but there are insufficient recent data, especially for octogenarian and older patients. This study investigated the characteristics and treatment of acute HF patients in Japan. From 2018 to 2020, 1,146 patients from 7 Tokai area hospitals were followed for at least 1 year. The mean age was 78 years. Compared with patients aged <80 years, those aged ≥80 years were more likely to be female (57.4% vs. 34.2%), have a lower body mass index (22.2 vs. 24.9 kg/m2), and have HF with preserved ejection fraction (43.1% vs. 21.4%), and less likely to have HF with reduced ejection fraction (38.9% vs. 61.7%). During hospitalization, 6.5% died. After discharge, patients faced high risks of rehospitalization for HF and death (27.6 and 14.2 per 100 patient-years, respectively). Notably, prescription rates of HF medications have declined over time for all patients, but especially for those aged ≥80 years. Guideline-directed medical therapy should be provided based on a thorough understanding of an individual's background rather than withheld simply because of clinical inertia due to a patient's advanced age.

Rationale and Design of the DECONGEST (Diuretic Treatment in Acute Heart Failure with Volume Overload Guided by Serial Spot Urine Sodium Assessment) Study

AimsTo evaluate whether early combination diuretic therapy guided by serial post-diuretic urine sodium concentration (UNa+) assessments in acute heart failure (AHF) facilitates safe and effective decongestion. MethodsThe Diuretic Treatment in Acute Heart Failure with Volume Overload Guided by Serial Spot Urine Sodium Assessment (DECONGEST) study is a pragmatic, 2-centre, randomized, parallel-arm, open-label study, aiming to enrol 104 patients with AHF and clinically evident fluid overload, requiring treatment with intravenous loop diuretics. Patients are randomized to receive standard of care or a bundled approach comprising: (1) systematic post-diuretic UNa+ assessments until successful decongestion, defined as no remaining clinical signs of fluid overload with a post-diuretic UNa+ ≤80 mmol/L; (2) thrice-daily intravenous loop diuretic bolus therapy, with dosing according to estimated glomerular filtration rate; (3) upfront use of intravenous acetazolamide (500 mg OD); and (4) full nephron blockade with high-dose oral chlorthalidone (100 mg OD) and intravenous canreonate (200 mg OD) for diuretic resistance, defined as persisting signs of fluid overload with a post-diuretic UNa+ ≤80 mmol/L. The primary endpoint of the DECONGEST study is a hierarchical composite of (1) survival at 30 days; (2) days alive and out of hospital or care facility up to 30 days; and (3) greater relative decrease in natriuretic peptide levels from baseline to day 30. ConclusionThe DECONGEST study aims to determine whether an intensive diuretic regimen focused on early combination therapy, guided by serial post-diuretic UNa+ assessments, safely enhances decongestion, warranting further evaluation in a larger trial powered for clinical events.

Milrinone in pediatric heart failure

Introduction. Heart failure is one of the most dangerous life-threatening conditions in children, requiring complex pathogenetically based treatment aimed at increasing cardiac output.The objective was to analyze publications devoted to assessing the effectiveness and safety of the use of milrinone in critical conditions in children.Materials and methods. The analysis included 60 publications from the PubMed and e-library abstract databases for the period from 2018 to 2023. The search was carried out using the keywords: milrinone, pediatric, neonate, heart failure, acute renal injury, and outcome. After the initial review of the abstracts, 18 articles were excluded from the analysis, if full text was not available or if they did not contain relevant information from a clinical perspective.Results. A significant part of the work is devoted to a comparative analysis of the therapeutic effects of milrinone and levosimendan in the early postoperative period after cardiac surgery in children, the authors of which in most cases believe that these drugs are comparable both in terms of treatment outcomes and side effects. At the same time, the results of a number of studies indicate significant advantages of milrinone, the use of which helps to reduce the level of lactate in the blood, is not accompanied by hypervolemia of the pulmonary circulation, helps to maintain optimal values of average blood pressure and reduce the duration of treatment in the ICU. On the other hand, there is evidence that the use of milrinone in the perioperative period may be associated with an increased need for additional fluid supplementation and an increase in the frequency of deaths after surgery in young children with complex congenital heart defects (CHD). Conclusion. Milrinone is the drug of choice for the treatment of acute heart failure in children with CHD in the early postoperative period and in newborns with persistent pulmonary hypertension.

Levosimendan: A New Therapeutical Strategy in Patients with Renal Insufficiency.

Levosimendan, a Ca2 + sensitizer with positive inotropic effects, is primarily employed for the short-term treatment of acute decompensated heart failure (ADHF). Levosimendan exerts renal function protection through various mechanisms, including anti-apoptosis, anti-inflammatory, and antioxidant effects in vivo. Additionally, levosimendan may have a protective effect on individuals with heart failure and renal insufficiency, as well as on renal function impairment after cardiac surgery. However, the application of levosimendan in patients with severe renal dysfunction remains controversial. This article delves into the use of levosimendan in severe renal insufficiency, explores its impact on renal function, and provides a comprehensive overview of its impact on renal function after cardiac surgery.

An Unexpected Degradation Pathway of N-Hydroxy-5-Methylfuran-2-Sulfonamide (BMS-986231), a pH Sensitive Prodrug of HNO, in a Prototype Formulation Solution

N-hydroxy-5-methylfuran-2-sulfonamide (BMS-986231, Cimlanod) was being developed as a pH-sensitive prodrug of HNO (nitroxyl) for the treatment of acute decompensated heart failure. During a stressed study of Cimlanod in a prototype formulation solution (pH 4.5) at 40°C, a predominant unknown degradant along with three previously identified degradants were observed. The unknown degradant was isolated from the stressed solution via preparative HPLC but totally decomposed during freeze-drying. LC-HRMS analysis of the isolated unknown degradant, prior to freeze-drying, revealed an empirical formula equivalent to the adduct of Cimlanod with SO2 even though SO2 was not added in the prototype formulation solution. The unknown degradant was synthesized from Cimlanod and DABSO ((1,4-diazabiscyclo[2,2,2]octane bis(sulfur dioxide) adduct) and isolated as a crystalline DABCO (1,4-diazabiscyclo[2,2,2]octane) salt for single crystal X-ray structure elucidation. The degradation of Cimlanod increased when the solution was exposed to air, as compared to N2 atmosphere. A plausible mechanism was postulated for the unexpected degradation pathway of Cimlanod. This study provided in-depth stability knowledge of Cimlanod, which will be beneficial to the subsequent stability indicating method development and validation as well as the registrational applications on the content and qualification of impurities in new drug products.

Association of early doses of diuretics and nitrates in acute heart failure with 30 days outcomes: ancillary analysis of ELISABETH study.

The optimal dose of diuretics and nitrates for acute heart failure treatment remains uncertain. This study aimed to assess the association between intravenous nitrates and loop diuretics doses within the initial 4 h of emergency department presentation and the number of days alive and out of hospital (NDAOH) through 30 days. This was an ancillary study of the ELISABETH stepped-wedge cluster randomized trial that included 502 acute heart failure patients 75 years or older in 15 French emergency departments. The primary endpoint was the NDAOH at 30 days. The total dose of intravenous nitrates and loop diuretics administered in the initial 4 h were each categorized into three classes: 'no nitrate', '> 0-16', and '> 16 mg' for nitrates and '< 60', '60', and '> 60 mg' for diuretics. Secondary endpoints included 30-day mortality, 30-day hospital readmission, and hospital length of stay in patients alive at 30 days. Generalized linear mixed models were used to examine associations with the endpoints. Of 502 patients, the median age was 87 years, with 59% women. The median administered dose within the initial 4 h was 16 mg (5.0; 40.0) for nitrates and 40 mg (40.0; 80.0) for diuretics. The median NDAOH at 30 days was 19 (0.0-24.0). The adjusted ratios of the NDAOH were 0.88 [95% confidence interval (CI): 0.63-1.23] and 0.76 (95% CI: 0.58-1.00) for patients that received 60 and > 60 mg, respectively, compared with patients that received 40 mg or less of diuretics. Compared with patients who did not receive nitrates, the adjusted ratios of the NDAOH were 1.17 (95% CI: 0.82-1.67) and 1.45 (95% CI: 0.90-2.33) for patients who received 1-16 and > 16 mg, respectively. There was no significant association with any of the secondary endpoints. In this ancillary analysis, there was no significant association between different doses of diuretics and nitrates with the NDAOH at 30 days. Point estimates and CIs may suggest that the optimal doses are less than 60 mg of diuretics, and more than 16 mg of nitrates in the first 4 h.

Increased Spironolactone Dosing in Acute Heart Failure Alters Potassium Homeostasis but Does not Enhance Decongestion

The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) clinical trial found no improvements in natriuretic peptide levels or clinical congestion when spironolactone 100 mg/day for 96 hours was used in addition to usual treatment for acute heart failure. We performed a post hoc analysis of ATHENA-HF to determine whether spironolactone treatment induced any detectable pharmacodynamic effects and whether patients with potentially greater aldosterone activity experienced additional decongestion. Trial subjects previously treated with spironolactone were excluded. We first examined for changes in renal potassium handling. Using the baseline serum potassium level as a surrogate marker of spironolactone activity, we then divided each treatment arm into tertiles of baseline serum potassium and explored for differences in laboratory and clinical congestion outcomes. Among spironolactone-naïve patients, the change in serum potassium did not differ after 24 hours or 48 hours but was significantly greater with spironolactone treatment compared to placebo at 72 hours (0.23 ± 0.55 vs 0.03 ± 0.60 mEq/L; P = 0.042) and 96 hours (0.32 ± 0.51 vs 0.13 ± 0.72 mEq/L; P = 0.046). Potassium supplementation was similar at treatment start and at 24 hours, but spironolactone-treated patients required substantially less potassium replacement at 48 hours (24% vs 36%; P = 0.048), 72 hours (21% vs 37%; P = 0.013), and 96 hours (11% vs 38%; P < 0.001). When the treatment arms were divided into tertiles of baseline serum potassium, there were no differences in the 96-hour log N-terminal pro-B-type natriuretic peptide levels, net fluid loss, urine output, or dyspnea relief in any of the potassium groups, with no effect modification by treatment exposure. Spironolactone 100 mg/day for 96 hours in patients receiving intravenous loop diuresis for acute heart failure has no clear added decongestive ability but does meaningfully limit potassium wasting.

Sequential Blockade with Loop Diuretics and Acetazolamide: A Novel Strategy in Acute Heart Failure

Abstract Acute decompensated heart failure (HF) is the most common form of acute HF (AHF) and presents with systemic congestion due to left ventricular dysfunction with sodium and water retention. Diuretics are the mainstay of treatment for AHF, with loop diuretics being the first-line therapy. However, in some studies, patients who were given high doses of loop diuretics were discharged from the hospital with residual signs of volume overload. Combining acetazolamide, a carbonic anhydrase inhibitor, with loop diuretics has been shown to be beneficial as it increases the efficacy of loop diuretics and reduces the signs and symptoms of congestion. Further, it can be used for the prevention or treatment of diuretic resistance (DR). Sequential nephron blockade with acetazolamide has emerged as a novel strategy for the treatment of AHF to enhance the efficacy of loop diuretics and prevent DR. This review highlights the combination of acetazolamide with loop diuretics as an alternative and possibly more effective decongestive strategy option in AHF patients. Nevertheless, there is limited evidence to support this combination therapy, and further research is necessary to substantiate its use in AHF patients.

Medication and Outcome in Older Heart Failure Patients: Results from a Prospective Cohort Study.

Purpose: Acute heart failure (AHF) is associated with high morbidity and mortality, and the prognosis is particularly poor in older patients. Although the application of guideline-directed medical therapy (GDMT) has shown a positive impact on prognosis, the effects are less clear in older age groups. The aim of this study was to analyze real-world data regarding GDMT and outcomes in older HF patients. Methods: This is a prospective cohort study from a secondary care hospital in central Switzerland. A total of 97 consecutive patients aged ≥60 years were enrolled between January 2019 and 2022. The main outcome parameters were prescribed GDMT at discharge, and in case of rehospitalization, GDMT at readmission, and survival in terms of all-cause mortality and HF-related hospitalizations during a 3-year follow-up period. Results: Follow-up data were available for 93/97 patients. The mean age was 77.8 ± 9.8 years, 46% being female. The mean left ventricular ejection fraction (LVEF) was 35.3 ± 13.9%, with a mean BNP level of 2204.3 ± 239 ng/L. Upon discharge, 86% received beta-blockers and 76.3% received renin-angiotensin system (RAS) inhibitors. At rehospitalization for AHF, beta-blockers use was significantly lower and decreased to 52.8% (p = 0.003), whereas RAS inhibitor use increased slightly to 88.9% (p = 0.07), and SGLT-2 inhibitors showed a significant increase from 5.4% vs. 47.2% (p = 0.04). GDMT prescription was not dependent on LVEF. Overall, 73.1% of patients received two-stage or three-stage GDMT at discharge, whereas this percentage decreased to 61% at rehospitalization (p = 0.01). Kaplan-Meier analysis for the combined outcome rehospitalization and death stratified by LV function showed significant differences between LVEF groups (aHR: 0.6 [95% CI: 0.44 to 0.8]; p = 0.0023). Conclusions: Our results indicate that first, the majority of older AHF patients from a secondary care hospital in Switzerland were not on optimal GDMT at discharge and even fewer at readmission, and second, that prognosis of the population is still poor, with almost half of the patients having been rehospitalized or died during a 3-year follow-up period under real-world conditions, without significant difference between women and men. Our findings underline the need for further improvements in the medical treatment of AHF, in particular in older patients, to improve prognosis and to reduce the burden of disease.

Combining loop with thiazide diuretics in patients discharged home after a heart failure decompensation: Association with 30-day outcomes

ObjectiveTo investigate the association of the addition of thiazide diuretic on top of loop diuretic and standard of care with short-term outcomes of patients discharged after surviving an acute heart failure (AHF) episode. MethodsThis is a secondary analysis of 14,403 patients from three independent cohorts representing the main departments involved in AHF treatment for whom treatment at discharge was recorded and included loop diuretics. Patients were divided according to whether treatment included or not thiazide diuretics. Short-term outcomes consisted of 30-day all-cause mortality, hospitalization (with a separate analysis for hospitalization due to AHF or to other causes) and the combination of death and hospitalization. The association between thiazide diuretics on short-term outcomes was explored by Cox regression and expressed as hazard ratios (HR) with 95 % confidence intervals, which were adjusted for 18 patient-related variables and 9 additional drugs (aside from loop and thiazide diuretics) prescribed at discharge. ResultsThe median age was 81 (interquartile range=73–86) years, 53 % were women, and patients were mainly discharged from the cardiology (42 %), internal medicine or geriatric department (29 %) and emergency department (19 %). There were 1,367 patients (9.5 %) discharged with thiazide and loop diuretics, while the rest (13,036; 90.5 %) were discharged with only loop diuretics on top of the remaining standard of care treatments. The combination of thiazide and loop diuretics showed a neutral effect on all outcomes: death (adjusted HR 1.149, 0.850–1.552), hospitalization (0.898, 0.770–1.048; hospitalization due to AHF 0.799, 0.599–1.065; hospitalization due to other causes 1.136, 0.756–1.708) and combined event (0.934, 0.811–1.076). ConclusionThe combination of thiazide and loop diuretics was not associated with changes in risk of death, hospitalization or a combination of both.

Acute heart failure (AHF)

Acute heart failure (AHF) is a frequent cause for emergency consultations, leads to long hospital stays and is characterized by high mortality and rehospitalization rates, with the first months after hospitalization having the highest risk («vulnerable phase»). The clinical presentation is usually characterized by fluid accumulation. Over the last three decades, few advances have been achieved in the treatment of AHF, as most studies with diuretics or vasodilators failed to show positive effects in terms of mortality and rehospitalization rates. In this context, the treatment of AHF must have an integrative approach, consisting of rapid correction of systemic congestion on the one hand, and specific therapies for the precipitating factors, the underlying cardiac pathology, and non-cardiac comorbidities on the other. Recently, it has been shown that a rapid and intensive up-titration of oral heart failure medical therapy during and immediately after hospitalization can improve the prognosis during the vulnerable phase after AHF. In this article, the principles of optimization and personalization of diuretic therapy and oral heart failure medication during hospitalization and the early outpatient phase after AHF are discussed.

Sequential Treatment of Acute Heart Failure in the Elderly: Efficacy of Recombinant Human Brain Natriuretic Peptide and Sacubitril-Valsartan

Objective: To explore the clinical efficacy of recombinant human brain natriuretic peptide (rhBNP) and sacubitril-valsartan in the sequential treatment of acute heart failure (AHF) in older individuals. Methods: Clinical data from 64 older patients with AHF were collected for this study. The patients were divided into two groups: a control group (Group A, n = 34) and an observation group (Group B, n = 30) based on different treatment regimens. Group A received rhBNP treatment, while Group B received sequential treatment with rhBNP and Sacubitril-Valsartan. The evaluation of the sequential treatment’s effect on older patients with AHF was conducted using various indicators. Results: The clinical efficacy rate in Group A (93.33%) was significantly higher than that in Group A (73.53%), with a significant difference observed (P &lt; 0.05). Furthermore, after treatment, the clinical efficacy remained significantly higher in Group B than in Group A. Group B exhibited a significantly higher left ventricular ejection fraction (LVEF) and significantly lower systolic blood pressure, diastolic blood pressure, and heart rate compared to Group A (P &lt; 0.05). Although the left ventricular end-diastolic diameter (LVEDD) was lower in Group B after treatment, the difference was not statistically significant (P = 0.127). Moreover, post-treatment levels of NT-proBNP were significantly lower in Group B compared to Group A (P = 0.01). Additionally, Group B had shorter hospitalization times, faster improvement in clinical symptoms, and further 6-minute walking distances after the treatment compared to Group A (P &lt; 0.01). Conclusion: Sequential treatment with rhBNP and Sacubitril-Valsartan demonstrates promising therapeutic effects in older patients with AHF, suggesting its potential for broader adoption and promotion in clinical practice.

HEMODYNAMIC PARAMETERS AND STRUCTURAL CHANGES OF THE MYOCARDIUM IN PATIENTS WITH HEART FAILURE AND ATRIAL FIBRILLATION: THE ROLE OF BRAIN NATRIURETIC PEPTIDE, NT-PRO BNP, GALECTIN-3 AND sST-2

Heart failure remains one of the most common causes of hospitalization, disability, and mortality in the working population in the world, particularly in Ukraine; it has a high prevalence, an unfavorable prognostic course, and also causes significant economic costs. The prevalence of heart failure (HF) in the general population is 1.5 - 2.0%, and among people over 65 years old - 6 - 10% [10]. The main etiological cause of the development of chronic heart failure (CHF) is coronary heart disease (CHD), which is confirmed by the data of multicenter studies. One of the features of CHF is the high heterogeneity of its clinical manifestations and the absence of absolutely pathognomonic symptoms, which often leads to late diagnosis and deterioration of the prognosis of the course of the disease [1-6]. In the last decade, biomarkers for the diagnosis and prognosis of HF have been actively researched in search of the "ideal" one that can characterize the activation of all links of the HF syndrome and provide additional information about natriuretic peptides (NAUP). Given the extremely complex and multifaceted biochemical interactions that underlie the pathophysiology of CHF, scientists are paying more attention to a multimarker strategy for the diagnosis and risk stratification of CHF.Aim. The purpose of the paper is to investigate the role of brain natriuretic peptide (BNP), NT-pro BNP, galectin-3, s-ST2 in the development of heart failure in patients with atrial fibrillation.Material and methods. 468 patients aged 45-65 years (54,3±7,2 years) and 56 healthy people were included in the study. Among the examined were 234 (50,0%) women and 234 (50,0%) men. Group I – control, 56 practically healthy individuals; Group II - patients with CHF without AF (n=234); III group - patients with CHF and AF (n=234).Diagnoses of AF and HF were carried out according to the clinical protocol for providing medical care to patients with atrial fibrillation and heart failure, confirmed by the order of the Ministry of Health of Ukraine №436 of 07.03.2006. and according to the 2021 Recommendations of the European Society of Cardiology (ESC) on the diagnosis and treatment of acute and chronic heart failure. In addition to the general clinical examination, an enzyme immunoassay was also performed to determine the content of brain natriuretic peptide, NT-pro BNP, galectin-3 and sST-2 in the blood.Results. The analysis of structural changes of the myocardium in various phenotypes of CHF revealed a probable increase in the transverse size of the left atrium by 18,5%, the index of the size of the left atrium by 25,4%, the area of the left atrium by 25,3%, the volume of the left atrium by 21,6% and left atrial volume index by 10,1% in patients with CHF and concomitant AF.The study founds a probable increase in the levels of NT-pro BNP (by 50,1%; p&lt;0,05) and brain natriuretic peptide (by 47,3%; p&lt;0,05) in patients with AF and CHF. With an increase in the size of the left atrium against the background of CHF and AF, a probable increase in the concentration of galectin-3 (by 24.3%, p&lt;0.05) and a probable increase in the level of sST-2 (by 41.4%, p&lt;0, 05) were set. It has been proven that an important aspect of the phenotype of CHF with accompanying AF is the enlargement of the left atrium (LA), which probably correlates with the content of brain natriuretic peptide (BNP) (r=0,35; p&lt;0,05), as well as with sST-2 content (r=0,41; p&lt;0,05).

The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century.

Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician's experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio-renal interactions, and HF phenotypes.

Selective SERCA2a activator as a candidate for chronic heart failure therapy

BackgroundThe sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a) depression substantially contributes to diastolic dysfunction in heart failure (HF), suggesting that SERCA2a stimulation may be a mechanism-based HF therapy. Istaroxime is a drug endowed with both a SERCA2a stimulatory activity and a Na+/K+ pump inhibitory activity for acute HF treatment. Its main metabolite PST3093 shows a more favorable therapeutic profile as compared to the parent drug, but it is still unsuitable for chronic usage. Novel PST3093 derivatives have been recently developed for oral (chronic) HF treatment; compound 8 was selected among them and here characterized.MethodsEffects of compound 8 were evaluated in a context of SERCA2a depression, by using streptozotocin-treated rats, a well-known model of diastolic dysfunction. The impact of SERCA2a stimulation by compound 8 was assessed at the cellular level ad in vivo, following i.v. infusion (acute effects) or oral administration (chronic effects).ResultsAs expected from SERCA2a stimulation, compound 8 induced SR Ca2+ compartmentalization in STZ myocytes. In-vivo echocardiographic analysis during i.v. infusion and after repeated oral administration of compound 8, detected a significant improvement of diastolic function. Moreover, compound 8 did not affect electrical activity of healthy guinea-pig myocytes, in line with the absence of off-target effects. Finally, compound 8 was well tolerated in mice with no evidence of acute toxicity.ConclusionsThe pharmacological evaluation of compound 8 indicates that it may be a safe and selective drug for a mechanism-based treatment of chronic HF by restoring SERCA2a activity.Graphical

Spot urine sodium as a marker of urine dilution and decongestive abilities in acute heart failure

The decongestion ability in response to diuretic treatment plays a crucial role in the treatment of acute heart failure. This effectiveness is evaluated through the assessment of sodium concentration and urine volume, which are also treatment goals themselves. However, the bidirectional interconnection between these factors remains not fully understood. The objective of this study is to provide mechanistic insights into the correlation between spot urine sodium concentrations (UNa+) and urine dilution. This aims to better understand of the decongestive abilities in acute heart failure (AHF). The study was single-center, prospective, conducted on a group of 50 AHF patients. Each participant received a standardized furosemide dose of 1 mg per kg of body weight. Hourly diuresis was measured in the first 6 h of the study, and urine composition was assessed at predefined timepoints. The study group presented the exponential (rather than linear) pattern of relationship between UNa+ and 6-h urine volume, whereas relationship between eGFR and 6-h urine volume was linear (r = 0.61, p < 0.001). The relationship between UNa+ and all other analyzed indices of urine dilution, including the change from baseline in urine creatinine concentration, urine osmolarity, and urine osmolarity corrected for urine sodium, also exhibited an exponential relationship. Patients who were chronically exposed to furosemide demonstrated a significantly lower urine dilution (1.78 [1.18–3.54] vs 11.58 [3.9–17.88]; p < 0.001) in comparison to naïve individuals. In conclusion, it should be noted that in AHF higher UNa+ is associated with disproportionally higher urine dilution, and patients naïve to furosemide have significantly greater ability to dilute urine when compare to chronic furosemide users.

AKAP1 in Renal Patients with AHF to Reduce Ferroptosis of Cardiomyocyte.

This study mainly investigated the mechanism and effects of AKAP1 in renal patients with acute heart failure (AHF). Patients with renal patients with AHF and normal volunteers were collected. The left anterior descending arteries (LAD) of mice were ligated to induce myocardial infarction. AKAP1 messenger RNA (mRNA) expression was found to be down-regulated in renal patients with AHF. The serum levels of AKAP1 mRNA expression were negatively correlated with collagen I/III in patients. AKAP1 mRNA and protein expression in the heart tissue of mice with AHF were also found to be down-regulated in a time-dependent manner. Short hairpin (Sh)-AKAP1 promotes AHF in a mouse model. AKAP1 up-regulation reduces reactive oxygen species (ROS)-induced oxidative stress in an In Vitro model. AKAP1 up-regulation also reduces ROS-induced lipid peroxidation ferroptosis in an In Vitro model. AKAP1 induces NDUFS1 expression to increase GPX4 activity levels. AKAP1 protein interlinked with the NDUFS1 protein. Up-regulation of the AKAP1 gene reduced NDUFS1 ubiquitination, while down-regulation of the AKAP1 gene increased NDUFS1 ubiquitination in a model. In vivo imaging showed that the sh-AKAP1 virus reduced NDUFS1 expression in the heart of a mouse model. AKAP1 reduced ROS-induced lipid peroxidation ferroptosis through the inhibition of ubiquitination of NDUFS by mitochondrial damage in model of renal patients with AHF, suggest a novel target for AHF treatment.

Unlocking the Potential of Acetazolamide: A Literature Review of an Adjunctive Approach in Heart Failure Management.

Background: Heart failure (HF) patients often experience persistent fluid overload despite standard diuretic therapy. The adjunctive use of acetazolamide, a carbonic anhydrase inhibitor, in combination with loop diuretics has shown promise in improving decongestion and diuretic efficacy. This literature review aims to analyze six studies evaluating the effectiveness of acetazolamide as an additive treatment for acute decompensated heart failure (ADHF) and its impact on various outcomes. Methods: We searched the PubMed database using the terms "acetazolamide heart failure". We refined our search with specific filters (as shown our PRISMA flow diagram) and exclusion criteria, narrowing down our results to five studies. We included an extra study via expert recommendation, ultimately including six studies for comprehensive analysis. Results: The review highlights the positive effects of acetazolamide on decongestion, natriuresis, and diuresis in HF patients. However, it also showcases the limitations of these trials. Discussion: While the reviewed studies demonstrate the potential benefits of acetazolamide in enhancing decongestion and diuretic efficiency, there are limitations to consider, including small sample sizes, lack of blinding, and limited external validity. Further research is needed to confirm these findings, compare acetazolamide with other diuretic combinations, and explore its effects in a broader population of heart failure patients, including those in the United States. The use of acetazolamide in HF management warrants continued investigation to optimize its role in improving decongestion and patient outcomes.

Network Meta-analysis of different Chinese medicine injections combined with conventional western medicine in treatment of acute heart failure

This study aims to evaluate the efficacy and safety of Chinese medicine injection in the treatment of acute heart failure. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, Wanfang, and SinoMed were searched for the randomized controlled trial(RCT) of Chinese medicine injection combined with conventional western medicines in the treatment of acute heart failure with the time interval from the inception to July 10, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 15.1 was used to perform network Meta-analysis. A total of 117 RCTs were included, involving 10 529 patients and 7 Chinese medicine injections: Shenfu Injection, Shenmai Injection, Danhong Injection, Puera-rin Injection, Xinmailong Injection, Shengmai Injection, and Yiqi Fumai Injection. Network Meta-analysis yielded the following results.(1) In terms of improving the total response rate, the surface under the cumulative ranking curve(SUCRA) ranking was Shengmai Injection + conventional western medicine &gt; Danhong Injection + conventional western medicine &gt; Shenmai Injection + conventio-nal western medicine &gt; Shenfu Injection + conventional western medicine &gt; Xinmailong Injection + conventional western medicine &gt; Yiqi Fumai Injection + conventional western medicine &gt; Puerarin Injection + conventional western medicine &gt; conventional western medicine.(2)In terms of reducing brain natriuretic peptide(BNP), the SUCRA ranking was Danhong Injection + conventional western medicine &gt; Xinmailong Injection + conventional western medicine &gt; Yiqi Fumai Injection + conventional western medicine &gt; Shenfu Injection + conventional western medicine &gt; Shenmai Injection + conventional western medicine &gt; Puerarin Injection + conventional wes-tern medicine &gt; Shengmai Injection + conventional western medicine &gt; conventional western medicine.(3)In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the SUCRA ranking was Shenmai Injection + conventional western medicine &gt; Yiqi Fumai Injection + conventional western medicine &gt; Xinmailong Injection + conventional western medicine &gt; Shengmai Injection + conventional western medicine &gt; Shenfu Injection + conventional western medicine &gt; Puerarin Injection + conventional western medicine &gt; Danhong Injection + conventional western medicine &gt; conventional western medicine.(4) In terms of improving the left ventricular ejection fraction(LVEF), the SUCRA ranking was Shenmai Injection + conventional western medicine &gt; Xinmailong Injection + conventional western medicine &gt; Shenfu Injection + conventional western medicine &gt; Yiqi Fumai Injection + conventional western medicine &gt; Puerarin Injection + conventional western medicine &gt; Danhong Injection + conventional western medicine &gt; Shengmai Injection + conventional western medicine &gt; conventional western medicine.(5) In terms of decreasing the left ventricular end-diastolic diameter(LVEDD), the SUCRA ranking was Shenmai Injection + conventional western medicine &gt; Shenfu Injection + conventional western medicine=Xinmailong Injection + conventional western medicine &gt; Shengmai Injection + conventional western medicine &gt; Yiqi Fumai Injection + conventional western medicine &gt; conventional western medicine &gt; Puerarin Injection + conventional western medicine.(6) In terms of increasing the 6-min walk trail(6MWT), the SUCRA ranking was Xinmailong Injection + conventional western medicine &gt; Shenfu Injection + conventional western medicine &gt; Shenmai Injection + conventional western medicine &gt; Yiqi Fumai Injection + conventional western medicine &gt; conventional western medicine.(7) In terms of reducing the Minnesota heart failure quality of life scale(MLHFQ) scores, the SUCRA ranking was Xinmailong Injection + conventional western medicine &gt; Shenmai Injection + conventional western medicine &gt; Shenfu Injection + conventional western medicine &gt; conventional western medicine.(8)In terms of safety, the group of Chinese medicine injection combined with conventional western medicine had lower incidence of adverse reactions than the control group. The current evidence shows that combining Chinese medicine injection with conventional western medicine treatment can improve the therapeutic effect on acute heart failure, with high safety. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC.

Document Reviewers: Rudolf A. de Boer (CPG Review Co-ordinator) (Netherlands), P. Christian Schulze (CPG Review Co-ordinator) (Germany), Elena Arbelo (Spain), Jozef Bartunek (Belgium), Johann Bauersachs (Germany), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Elisabetta Cerbai (Italy), Erwan Donal (France), Frank Edelmann (Germany), Gloria Färber (Germany), Bettina Heidecker (Germany), Borja Ibanez (Spain), Stefan James (Sweden), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Josep Masip (Spain), John William McEvoy (Ireland), Robert Mentz (United States of America), Borislava Mihaylova (United Kingdom), Jacob Eifer Møller (Denmark), Wilfried Mullens (Belgium), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Leyla Elif Sade (United States of America/Türkiye), Hannah Schaubroeck (Belgium), Elena Tessitore (Switzerland), Mariya Tokmakova (Bulgaria), Peter van der Meer (Netherlands), Isabelle C. Van Gelder (Netherlands), Mattias Van Heetvelde (Belgium), Christiaan Vrints (Belgium), Matthias Wilhelm (Switzerland), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands) All experts involved in the development of this Focused Update have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the Focused Update. The report is also available on the ESC website www.escardio.org/guidelines See the European Heart Journal online for supplementary documents that include evidence tables.