Therapy For Acute Heart Failure Research Articles

Diuretic therapy strategies in decompensated acute heart failure: a systematic review and network metanalysis

Abstract Background Congestion in acute heart failure (AHF) is treated with furosemide, mainly in continuous infusion (furosemide continuous, FC) or iv boluses, and combination of different diuretics. Randomized controlled trials (RCTs) only compared the efficacy and safety of some diuretic strategies with discordant results. Purpose To provide a comprehensive synthesis of the effects of diuretic regimens in AHF. Methods The PubMed, EMBASE, SCOPUS and Cochrane databases were searched for phase III RCTs until July 31st, 2023, evaluating diuretics without any other intervention in patients admitted for AHF, with randomization within 48 hours, no run-in period and/or need of clinical stabilization. The arms assigned to iv boluses or undefined schemas of furosemide/loop diuretic (LD) were grouped together as "furosemide bolus" (FB). The endpoints were weight loss over 24 hours (WL), worsening renal function (WRF), total urine output (tUO) and net urine output (nUO) over 24 hours, hypokalemia (hypoK), and hyponatremia (hypoNa). Heterogeneity was estimated by Thompsons’ I2 statistics, and odds ratios (OR) with 95% confidence intervals were calculated by means of a random-effects model with inverse variance weighting. A leave-one-out analysis, an analysis limited to studies with specified mode of furosemide/LD administration, and an analysis of measures of congestion/decongestion were also carried out. Results Twenty-five RCTs were selected, for a total of 7,095 patients with mean age 69.2±11.1 years and mean LVEF 38.1±12.7%. In subjects treated with furosemide/LD, the mean furosemide equivalent dose was 154.7±53.0 mg/24 hours. Heterogeneity was moderate-to-high (37.3%-66.0% across the study endpoints). FC, FB plus tolvaptan, FB plus sodium-glucose cotransporter inhibitor (SGLT2i), and FB plus thiazide were associated with greater WL than FB (Figure 1A). The combination of FB and thiazide or SGLT2i also portended higher odds of WRF than FB alone, as did the combination of FB and acetazolamide (Figure 1B). tUO was greater with FC (OR 2.77 [1.98-3.88]), FB plus tolvaptan (OR 1.69 [1.22-2.35]), and FB plus SGLT2i (OR 1.95 [1.16-3.28]) than with FB, and nUO was greater with FC (OR 1.50 [1.06-2.13]) and FB plus tolvaptan (OR 1.76 [1.06-2.92]) than with FB. Compared with FB, hypoK was more frequent with FB and thiazide (OR 1.68 [1.29-2.19]), while there was a trend for less hypoK events with FB plus tolvaptan (OR 0.86 [0.69-1.08]). No differences in hypoNa rates were found. Sensitivity analyses were consistent with the main one. Thirteen (52%) and 14 (56%) studies had published information about symptoms and signs of congestion, respectively, and 6 (24%) adopted pre-specified scoring systems. Conclusions FC and most combination diuretic regimens have greater efficacy than FB in promoting WL and diuresis, but at the cost of WRF and hyoK, especially when thiazide is used. Congestion has inconsistently been evaluated in RCTs of diuretic therapy in AHF.

ICARUS registry: findings from the first 1595 cases of acute decompensated heart failure in a single center in a latin american country

Abstract Introduction Institutional aCute decompensAted HeaRt FailUre RegiStry (ICARUS) will provide information on clinical characteristics, medical practice, patterns of treatment, and outcomes of patients hospitalized with Acute Decompensated Heart Failure (ADHF) in a hospital in a middle-income country. Objective Describe the methodological aspects, sociodemographic, and clinical characteristics of patients hospitalized with ADHF and their short-term outcomes. Method Prospective cohort of patients with ADHF from the emergency service of a cardiovascular center. Descriptive statistics were used to synthesize sociodemographic characteristics, clinical characteristics during hospitalization, and outcomes. Results 1595 patients with ADHF. The median age was 68 years (Q1=58; Q3=76), and 69.28% were men. The median hospital stay was six days (Q1=4; Q3=11), with an accumulative incidence (AI) for rehospitalization at 30 days of 8.70 % (95% CI 7.18 to 10.40%), in-hospital mortality AI of 4.33% (95% CI 3.38 to 5.44%), and a median change in the quality-of-life score like Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 30 days of -20 points (Q1=-37; Q3=-5). At discharge, all patients had a percentage greater than 70% of the use of quadruple neurohormonal blockade therapy. Conclusions ICARUS is one of the first registries in Latin America since the indication of the use of SGLT2 inhibitors, evaluating the clinical and sociodemographic characteristics, treatment patterns, and outcomes of a preliminary cohort of 1595 patients hospitalized for ADHF. The results indicate that, at discharge, up to 82.79% of patients were receiving quadruple neurohormonal blockade therapy, which is considerably challenging to achieve in Latin America. Considering the results of the Safety, tolerability and efficacy of up-titration of Guideline-Directed Medical therapies for acute heart failure (STRONG-HF study), our study reinforces the benefit of discharge with Guideline-Directed Medical Therapy (GDMT) for heart failure from hospitalization. The use of GDMT for heart failure may have influenced our positive outcomes in terms of in-hospital mortality, improvement in quality of life, and the percentage of short-term rehospitalizations compared to similar cohorts.Proportion of HF drug group

Diuretic Combination Therapy in Acute Heart Failure: An Updated Review.

Loop diuretics are the cornerstone of decongestive therapy in patients presenting with acute heart failure and have been extensively studied in randomized clinical trials. Therefore, in current guidelines, they are the only drug with a class I recommendation to treat signs and symptoms of congestion when present. However, the percentage of patients achieving successful decongestion is suboptimal, and diuretic resistance frequently develops. Patients with a poor response to loop diuretics and those discharged with residual signs of congestion are characterized by a worse prognosis over time. Recently, a renovated interest in different diuretic classes sprouted among heart failure researchers in order to improve decongestion strategies and ameliorate short- and long-term clinical outcomes. Randomized clinical trials investigating associations among diuretic classes and loop diuretics have been performed but yielded variable results. Therefore, despite initial evidence of a possible benefit from some of these compounds, a definite way to approach diuretic resistance via diuretic combination therapy is still missing. The aim of this review is to summarize current clinical evidence on the use of diuretic combination therapy in patients with acute heart failure and to suggest a possible approach to avoid or counteract diuretic resistance.

Adverse events associated with early initiation of Eplerenone in patients hospitalized for acute heart failure

BackgroundThe guidelines recommend the initiation or up-titration of heart failure (HF) treatments following an HF hospitalization; however, concerns about adverse events may limit the use of mineralocorticoid receptor antagonists (MRAs). Patient profiles or disease severity might impact adverse events associated with MRA therapy in acute HF. MethodsThe EARLIER trial included patients with acute HF who were randomized to eplerenone or placebo over 6 months. Adverse events (i.e., worsening renal function [WRF], hyperkalemia, hypotension, and volume depletion/dehydration) were assessed. HF-related outcome included a composite of all-cause mortality, HF re-hospitalization, investigator-reported worsening HF and out-of-hospital diuretic intensification. ResultsIn 297 patients (mean age: 67 ± 13 years; 73% males), adverse events were observed: 44.4% experienced WRF (>20% drop in estimated glomerular filtration rate[eGFR] and/or investigator-reported WRF), 8.4% had hyperkalemia (potassium >5.5 mmol/L and/or investigator-reported hyperkalemia), 27.9% experienced hypotension (systolic blood pressure[SBP] <90 mmHg and/or investigator-reported hypotension), and 16.8% had investigator-reported volume depletion/dehydration. Eplerenone vs. placebo did not elevate the incidence of these events (all-p-values>0.0 5). Multivariable analyses revealed that, irrespective of treatment allocation, older age (>7 5 years), prevalent diabetes, symptomatic congestion, and microalbuminuria were associated with increased risk of WRF. Baseline eGFR<60 ml/min/1.73m2 and SBP < 90 mmHg predicted hyperkalemia and hypotension, respectively, while older patients were more likely to experience volume depletion/dehydration. However, these patient profiles did not alter the benefit of eplerenone on outcomes (HR [9 5%CI] = 0.53 [0.29 to 0.97], P = 0.04; all-p-for-interaction>0.10). ConclusionEplerenone did not increase adverse events compared with placebo in acute HF. Importantly, disease severity and comorbidity burden greatly influence adverse events, but not benefit from eplerenone.

Rapid Uptitration of Guideline-Directed Medical Therapies in Acute Heart Failure With and Without Atrial Fibrillation

BackgroundRapid uptitration of guideline-directed medical therapy (GDMT) before and after discharge in hospitalized heart failure (HF) patients is feasible, is safe, and improves outcomes; whether this is also true in patients with coexistent atrial fibrillation/flutter (AF/AFL) is not known. ObjectivesThis study sought to investigate whether rapid GDMT uptitration before and after discharge for HF is feasible, safe and beneficial in patients with and without AF/AFL. MethodsIn this secondary analysis of the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) trial, GDMT uptitration and patient outcomes were analyzed by AF/AFL status and type (permanent, persistent, paroxysmal). ResultsAmong 1,078 patients enrolled in STRONG-HF, 496 (46%) had a history of AF, including 238 assigned to high-intensity care (HIC) and 258 to usual care (UC), and 581 did not have a history of AF/AFL, including 304 assigned to HIC and 277 to UC. By day 90, the average percent optimal dose of neurohormonal inhibitors achieved in the HIC arm was similar in patients with and without AF/AFL, reaching approximately 80% of the optimal dose (average absolute difference between AF/AFL and non-AF/AFL groups: −0.81%; 95% CI: −3.51 to 1.89). All-cause death or HF readmission by day 180 occurred less frequently in the HIC than the UC arm, both in patients with and without AF (adjusted HR: 0.75 [95% CI: 0.48-1.19] in AF vs adjusted HR: 0.50 [95% CI: 0.31-0.79] in non-AF/AFL patients; P for interaction = 0.2107). Adverse event rates were similar in patients with and without AF/AFL. AF/AFL type did not affect either uptitration or patient outcomes. ConclusionsNearly half of acute HF patients have AF/AFL history. Rapid GDMT uptitration before and early after discharge is feasible, is safe, and may improve outcomes regardless of AF presence or type. (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies [STRONG-HF]; NCT03412201)

Inferior vena CAVA and lung ultraSound-guided therapy in acute heart failure: A randomized pilot study (CAVAL US-AHF study)

The optimal assessment of systemic and lung decongestion during acute heart failure is not clearly defined. We evaluated whether inferior vena cava (IVC) and pulmonary ultrasound (CAVAL US) guided therapy is superior to standard care in reducing subclinical congestion at discharge in patients with AHF. CAVAL US-AHF was an investigator-initiated, single-center, single-blind, randomized controlled trial. A daily quantitative ultrasound protocol using the 8-zone method was used and treatment was adjusted according to an algorithm. The primary endpoint was the presence of more than 5 B-lines and/or an increase in IVC diameter and collapsibility at discharge. And secondary endpoint exploratory outcome was the composite of readmission for HF, unplanned visit for worsening HF or death at 90 days RESULTS: Sixty patients were randomized to CAVAL US (n = 30) or control (n = 30). The primary endpoint was achieved in 4 patients (13.3%) in the CAVAL US group and 20 patients (66.6%) in the control group (P < .001). A significant reduction in HF readmission, unplanned visit for worsening HF or death at 90 days was seen in the CAVAL US group (13.3% vs 36.7%; log rank P = .038). Other endpoints such as NT-proBNP reduction at discharge showed a nonstatistically significant reduction in the CAVAL US group (48% IQR 27-67 vs 37% -3-59; P = .09). Safety outcomes were similar in both groups. IVC and lung ultrasound-guided therapy in AHF patients significantly reduced subclinical congestion at discharge. CAVAL US-AHF provides preliminary evidence for the potential use of a simple technique to guide decongestive therapy during hospitalization for AHF, which may reduce the composite outcome at 90 days.

Extended Follow-Up of Spot Urinary Sodium Guided Titration of Intravenous Diuretic therapy in Acute Heart Failure: A Pilot Randomised Controlled Trial

Extended Follow-Up of Spot Urinary Sodium Guided Titration of Intravenous Diuretic therapy in Acute Heart Failure: A Pilot Randomised Controlled Trial

Science of left ventricular unloading.

The concept of left ventricular unloading has its foundation in heart physiology. In fact, the left ventricular mechanics and energetics represent the cornerstone of this approach. The novel sophisticated therapies for acute heart failure, particularly mechanical circulatory supports, strongly impact on the mechanical functioning and energy consuption of the heart, ultimately affecting left ventricle loading. Notably, extracorporeal circulatory life support which is implemented for life-threatening conditions, may even overload the left heart, requiring additional unloading strategies. As a consequence, the understanding of ventricular overload, and the associated potential unloading strategies, founds its utility in several aspects of day-by-day clinical practice. Emerging clinical and pre-clinical research on left ventricular unloading and its benefits in heart failure and recovery has been conducted, providing meaningful insights for therapeutical interventions. Here, we review the current knowledge on left ventricular unloading, from physiology and molecular biology to its application in heart failure and recovery.

Corticosteroid burst therapy in patients with acute heart failure: Design of the CORTAHF pilot study.

Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID-19. Our hypothesis is that in patients with AHF and elevated C-reactive protein (CRP) levels without symptoms or signs of infection, a 7-day course of steroid therapy will lead to reduced inflammation and short-term improvement in quality of life and a reduced risk of worsening HF (WHF) events. The study, which is currently ongoing, will include 100 patients with AHF ages 18-85, regardless of ejection fraction, screened within 12h of presentation. Patients will be included who have NT-proBNP>1500pg/mL and CRP>20mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7days with 40mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow-up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ-5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed. The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti-inflammatory therapies in AHF.

#1816 CA 125 as a surrogate marker for plasma volume in patients with cardiorenal syndrome

Abstract Background and Aims Assessing volume status in heart failure (HF) and end-stage chronic kidney disease (CKD) is challenging. Plasma volume expansion is an early step in the pathophysiology of decompensated HF and an independent risk factor for death and HF hospitalization, and should be addressed early. Evaluating plasma volume, especially its variation with diuretic therapy, can be a useful clinical tool for guiding decongestive therapy. There's a growing need for accurate and simple tools to guide clinician decisions on patient volume management. Cancer antigen 125 (CA125), a glycoprotein produced in mesothelial cells in the pericardium, pleura, or peritoneum, is primarily associated with ovarian and gynecological malignancies. Recent studies link CA125 to inflammation and congestion. In acute HF, elevated CA125 is associated with fluid overload indicators like increased central venous and pulmonary wedge pressure. Elevated CA125 in acute HF patients is linked to worse outcomes in death and hospital stay length. Evidence supports CA125-guided therapy in acute HF, but its role in managing chronic volume overload is still uncertain. We aim to assess the relationship between CA125 levels and estimated plasma volume (ePV). Method A retrospective unicentric observational study was conducted between June 2022, and April 17, 2023, at the Renocardiac clinic of a tertiary hospital. Clinical data were extracted from electronic patient records. CKD staging was determined following the Kidney Disease Improving Global Outcomes (KDIGO) classification. ePV was calculated using the Kaplan-Hakim formula. CA125 and ePV were assessed for the same patient in 2 different visits and their variation was calculated. The correlation between CA125 and ePV, as well as CA125 and ePV variation, was evaluated using Spearman's rank correlation coefficient for bivariate analysis, conducted with IBM SPSS®. Results This study comprised 65 patients, totaling 124 hospital visits. The patient demographic was 67.7% male, with a mean age of 76.4 (±12.47) years. In terms of CKD staging, 48.5% were classified as KDIGO 5, 40.6% as KDIGO 4, 9.4% as KDIGO 3, and 1.5% as KDIGO 2. HF etiology distribution included 59% ischemic, 9.8% hypertensive, 6.5% valvular, and 24.5% other causes. The mean ejection fraction was 37.35 (±12.36)% and 19% had preserved ejection fraction; 75% of them were treated with prognostic-modifying medication, including SGLT2 inhibitors. This proportion was lower (19%) in patients with reduced ejection fraction, receiving ACE/angiotensin ± neprilysin inhibitor + mineralocorticoid receptor inhibitor + beta-blocker + SGLT2 inhibitor. During the follow-up period, 13 hospitalizations, 1 major adverse cardiovascular event (MACE), and 5 deaths were recorded. The mean CA125 level was 193.98 (±154.55) U/mL, and patients had a mean ePV of 2.41 (±1.19) L. A significant positive correlation was found between CA125 levels and ePV (r = 0.355, p = 0.000). However, there was no significant correlation between the variation of CA125 and ePV levels between visits (p = 0.535). Conclusion This study focuses on a population with limited implementation of disease-modifying therapy due to advanced CKD, complicating the clinical management of volume status, kidney function, potassium levels, and long-term prognosis in both CKD and HF. CA125 shows potential clinical utility as a marker of congestion, aiding clinicians in assessing volume status by correlating with plasma volume. However, this study found no correlation between CA125 variation and changes in plasma volume. The outpatient nature of the studied population, typically euvolemic, may hinder assessing the relationship between CA125 and ePV changes. Future studies with larger sample sizes are essential to clarify this relationship and potentially identify volume-expanded patients early.

Titration of Medications After Acute Heart Failure Is Safe, Tolerated, and Effective Regardless of Risk

BackgroundGuideline-directed medical therapy (GDMT) decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF (Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure), high-intensity care (HIC) in the form of rapid uptitration of heart failure (HF) GDMT was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses. ObjectivesThe authors sought to assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable MAGGIC (Meta-Analysis Global Group in Chronic) HF risk score. MethodsIn STRONG-HF, 1,078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) vs usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable. ResultsAmong 1,062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC vs UC group and did not differ by MAGGIC risk score tertiles (interaction nonsignificant). The incidence of all-cause death or HF readmission at day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1, 2, and 3. The HIC arm was at lower risk of all-cause death or HF readmission at day 180 (HR: 0.66; 95% CI: 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR: 0.51; 95% CI: 0.62-0.68 in tertiles 1, 2, and 3; interaction nonsignificant) for all comparisons and continuous (interaction nonsignificant) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction nonsignificant). ConclusionsHIC led to better use of GDMT and lower HF-related morbidity and mortality compared with UC, regardless of the underlying HF risk profile. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies [STRONG-HF]; NCT03412201)

Spot urinary sodium guided titration of intravenous diuretic therapy in acute heart failure: A pilot randomised controlled trial.

Spot urinary sodium concentration (UNa) is advocated in guidelines to assess diuretic response and titrate dosage in acute heart failure (AHF). However, no randomised controlled trial data exists to support this approach. We performed a prospective pilot trial to investigate the feasibility of this approach. 60 patients with AHF (n=30 in each arm) were randomly assigned to titration of loop diuretics for the first 48 hours of admission according to UNa levels (intervention arm) or based on clinical signs and symptoms of congestion (standard care arm). Diuretic insufficiency was defined as UNa<50mmol/L. Endpoints relating to diuretic efficacy, safety and AHF outcomes were evaluated. UNa-guided therapy patients experienced less acute kidney injury (20%vs 50%, p=0.01) and a tendency towards less hypokalaemia (serum K+<3.5mmol, 7%vs 27%, p=0.04), with greater weight loss (3.3kg vs 2.1kg, p=0.01). They reported a greater reduction in the clinical congestion score (-4.7vs -2.6, p<0.01) and were more likely to report marked symptom improvement (40%vs 13.3%, p=0.04) at 48 hours. There was no difference in the length of hospital stay (median LOS: 8 days in both groups, p=0.98), 30-day mortality or readmission rate. UNa-guided titration of diuretic therapy in AHF is feasible and safer than titration based on clinical signs and symptoms of congestion, with more effective decongestion at 48 hours. Further large-scale trials are needed to determine if the superiority of this approach translates into improved patient outcomes.

Combinational Diuretics in Heart Failure.

Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy. Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted.

Effect Of Sglt2 Inhibitor Dapagliflozin On Sodium, Potassium And Creatinine Levels In Patients With Acute Heart Failure.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a new class of medication for the treatment of type 2 diabetes mellitus. Additionally, they have been found to have beneficial effects on heart failure outcomes, convincingly reducing the morbidity and mortality in heart failure. Although the medical data indicates SGLT2i to be safe and cardio-protective, very little attention has been given to the impact of these agents on electrolyte balance particularly in acute heart failure (AHF). We aimed to evaluate the effect of SGLT2i, and dapagliflozin on serum sodium, potassium and creatinine in AHF. Overall, 160 adult patients of either gender, admitted with AHF were selected for the study. Selected individuals were randomly assigned to receive dapagliflozin 10 mg orally added to standard medical treatment (n=80) or were in reception of standard medical therapy only (n=80). Serum electrolytes and serum creatinine were collected on admission and day 7 or on discharge whichever happened earlier. The mean level of serum electrolytes displayed insignificant differences among both groups on admission. The mean level of serum potassium was higher in the dapagliflozin group compared with the control group (p<0.001) on day 7/discharge. Mean serum sodium level was comparable and showed significant differences between the two groups following treatment (p-value=0.021). Significant higher levels of serum creatinine were observed following treatment in both groups. However, on intergroup comparison, they were statistically insignificant. Dapagliflozin is an effective treatment of heart failure and is not associated with deterioration of serum electrolyte levels and renal functioning when used as add-on therapy in AHF.

Cardiac resynchronization therapy in acute heart failure and left bundle-branch block in a real-life registry.

To determine the prevalence, characteristics, timing of implementation and prognosis of patients with left bundle branch block (LBBB) and acute heart failure (AHF) treated with cardiac resynchronization therapy (CRT) in a real-life registry. We analysed the characteristics of patients with AHF and LBBB at the time of inclusion in the EAHFE (Epidemiology Acute Heart Failure Emergency) cohort to determine the indication for CRT, the timing of implementation and its impact on 10-year all-cause mortality. 729 patients with a median age of 82 years and there was a high burden of comorbidities and functional dependence. The median left-ventricle ejection fraction (LVEF) was 40%. Forty-six (6%) patients were treated with CRT at some point during follow-up, with a median time of delay for CRT implementation of 960 (IQR=1,147 days) and at least 108 more untreated patients fulfilled criteria for CRT. Patients receiving CRT were younger, had different comorbidities, less functional dependence (higher Barthel index) and lower LVEF values. The median follow-up was 5.7 years (95% CI: 5.6-5.8) and CRT was not associated with changes in 10-year mortality (adjusted HR 1.33, 95% CI: 0.72-2.48; p-value 0.4). When compared with untreated patients fulfilling criteria for CRT, very similar results were observed (adjusted HR 1.34, 95% CI: 0.67-2.68). CRT implementation was delayed and underused in patients with AHF and LBBB. Under these circumstances, CRT is not associated with a reduction in all-cause mortality in the long term.

Timing for combined diuretic therapy in acute heart failure: should we continue waiting for the poor response?

Decongestion is an important primary goal in acute heart failure treatment. Loop diuretics remain a fundamental role in congestion management and symptom improvement in patients with acute heart failure. Diuretic combination contributes to achieving better diuretic efficacy. However, the optimal timing for diuretic combination in clinical practice has not been distinctly recommended in current guidelines.

Inferior vena cava and lung ultrasound-guided therapy in acute heart failure (CAVAL US-AHF study): a randomized controlled trial

Abstract Background The 90-day readmission rate for hospitalized patients with acute heart failure (AHF) ranges from 25% to 30%, mostly due to persistent congestion at discharge. Since the optimal assessment of decongestion has not been clearly defined, there is an opportunity to implement new tools to identify subclinical congestion to guide treatment. Purpose To evaluate whether inferior vena cava (IVC) and pulmonary ultrasound (CAVAL US)-guided therapy in patients with AHF reduces subclinical congestion at discharge. A secondary objective was to investigate whether CAVAL US-guided therapy leads to improved outcomes al 90 days. Methods In this single-center, single-blind, randomized controlled trial, adult patients with AHF were randomized within 24 hours of hospital admission to the CAVAL US-guided strategy or clinically-guided decongestive therapy. A quantitative ultrasound protocol was used and patients were stratified into 3 groups according to the degree of congestion. All patients underwent lung and IVC ultrasound and were blinded to group allocation. The treating medical team was blinded to the results of the ultrasound evaluation in the control group and adjusted the treatments in the intervention group according to an individualized therapeutic algorithm. The primary endpoint was the presence of more than 5 B-lines and/or an increase in IVC diameter with and without collapsibility at discharge. The secondary endpoints were the composite of HF readmission, unplanned visit for worsening HF or death at 90 days and pro-B-type natriuretic peptide (NT-proBNP) reduction at discharge in %. Results Sixty patients were randomized to CAVAL US (n=30) or control (n=30). The mean age was 76.7±13 years, 68.3% were male and the mean left ventricular ejection fraction was 44% ± 15. The primary outcome occurred in 4 patients (13.3%) in the CAVAL US group and 20 patients (66.6%) in the control group (p&amp;lt;.001). A reduction in HF readmission, unplanned visit for worsening HF or death at 90 days was seen in the CAVAL US group (13.3% vs 36.7%; log rank p=0.038). Other secondary endpoints such as NT-proBNP reduction at discharge showed a non-statistically significant reduction in the CAVAL US group (48% IQR 27-67 vs 37% -3-59; p=0.09). The mean hospital stay was 4.5±5 days in the CAVAL US group and 3.3±1.6 days in the control group (p=0.26), with a trend toward higher total furosemide use in the CAVAL US group (170 mg IQR 120-240 vs 120 mg IQR 80-200, p=0.08). Safety outcomes were similar in both groups (p&amp;gt;0.05). Conclusion IVC and lung ultrasound-guided therapy in AHF patients significantly reduced subclinical congestion at discharge. CAVAL US-AHF provides evidence for the use of a simple, safe and non-invasive technique to guide decongestive therapy during hospitalization for AHF, that reduced the risk of HF readmission, unplanned visit for worsening HF, or death at 90 days without prolonging hospital stay.Subclinical congestion at dischargeKM secondary endpoint

Acute heart failure: current pharmacological treatment and perspectives.

Acute heart failure (AHF) represents the most frequent cause of unplanned hospital admission in patients older than 65 years. Symptoms and clinical signs of AHF (e.g. dyspnoea, orthopnoea, oedema, jugular vein distension, and variation of body weight) are mostly related to systemic venous congestion secondary to various mechanisms including extracellular fluids, increased ventricular filling pressures, and/or auto-transfusion of blood from the splanchnic into the pulmonary circulation. Thus, the initial management of AHF patients should be mostly based on decongestive therapies on admission followed, before discharge, by rapid implementation of guideline-directed oral medical therapies for heart failure. The therapeutic management of AHF requires the identification and rapid diagnosis of the disease, the diagnosis of the cause (or triggering factor), the evaluation of severity, the presence of comorbidities, and, finally, the initiation of a rapid treatment. The most recent guidelines from ESC and ACC/AHA/HFSA have provided updated recommendations on AHF management. Recommended pharmacological treatment for AHF includes diuretic therapy aiming to relieve congestion and achieve optimal fluid status, early and rapid initiation of oral therapies before discharge combined with a close follow-up. Non-pharmacological AHF management requires risk stratification in the emergency department and non-invasive ventilation in case of respiratory failure. Vasodilators should be considered as initial therapy in AHF precipitated by hypertension. On the background of recent large randomized clinical trials and international guidelines, this state-of-the-art review describes current pharmacological treatments and potential directions for future research in AHF.

The effect of Dapagliflozin on renal functions in hospitalized patients with Acute Heart Failure.

To evaluate the influence of dapagliflozin on renal functions and diuretics use in patients with acute heart failure (AHF). This comparative analytical study was conducted at Armed Forces Institute of Cardiology, Rawalpindi from July 2022 to November 2022. Patients were distributed equally in two groups i.e. Dapagliflozin and Conventional Groups, where patients received dapagliflozin added to conventional therapy for AHF and, only conventional therapy for AHF respectively. Estimated glomerular filtration rate (eGFR), serum creatinine were measured and compared on admission, after 48 hours and on discharge. Weight loss during hospitalization, daily dose of furosemide and length of hospital stay was also recorded. Quantitative parameters were analyzed using t-test or Mann Whitney U test accordingly. There were no significant baseline differences in renal functions. A modest decline in eGFR was observed in both groups after 48 hours. However, the variation in values of eGFR remained similar among both groups after 48 hours (p-value 0.365) and on discharge (p-value 0.768). Whereas, patients subjected to dapagliflozin treatment exhibited a more profound diuretic response expressed as greater weight loss (p-value < 0.001), achieved at comparatively lower doses of loop diuretics. Moreover, they also had a shorter duration of hospital stay (six vs eight days, p-value <0.001). Institution of dapagliflozin did not cause any significant deterioration of renal functions, whereas; it was associated with improved diuretic response as depicted by more pronounced weight loss at comparatively lower doses of loop diuretics.

Urinary Sodium-Guided Intravenous Diuretic Therapy in Acute Heart Failure: Transitioning From Art to Science?

Urinary Sodium-Guided Intravenous Diuretic Therapy in Acute Heart Failure: Transitioning From Art to Science?