Advances in Congestion Assessment in Decompensated Heart Failure.

Article, see p 1671 Heart failure (HF) hospitalization presents a substantial burden to patients, hospitals, and payors. Hospitals face competing incentives from government payors because prolonged lengths of stay risk unreimbursed costs beyond the fixed reimbursement, whereas premature discharge increases the risk of 30-day readmission, for which hospitals can be penalized on a much broader scale. Clinicians have struggled to define the objective criteria regarding readiness for discharge from a HF hospitalization, which should address not only relief of congestion, but also evaluation of etiology, enhancement of guideline-directed therapies, review of disease trajectory, and consolidation of outpatient management. Once gaps in the transition process have been closed, the major cause of readmission is recurrent congestion. Regardless of how congestion is documented,1–3 patients who go home “wet” are likely to return “wetter”. Quality improvement and cost containment efforts are converging to design care pathways that begin early during hospitalization to ensure adequate decongestion by discharge. Employment of brain natriuretic peptide (BNP) levels as targets for therapy arose naturally from the robust predictive value of BNP levels and changes in levels, further supported by their close relationship with elevated cardiac filling pressures4,5 and recognized as a hemodynamic determinant of outcomes. Utility of a biomarker as a target for therapy requires not only clinical relevance, but also timely responsiveness to the therapy titration, and unique information beyond usual clinical assessments. Multiple trials have used natriuretic peptides as targets for adjustment of chronic outpatient therapy with neurohormonal antagonists6–10 (Figure). When uptitration was aggressive in response to persistently high levels of natriuretic peptides, outcomes were better than without such uptitration.9 However, when the design encouraged vigorous …

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated substantial cardiovascular benefits in chronic heart failure. However, the optimal timing of initiation during acute decompensated heart failure (ADHF) hospitalization and its impact on short-term and intermediate-term clinical outcomes remain insufficiently characterized. This study aimed to evaluate the effect of early in-hospital SGLT2 inhibitor initiation on all-cause mortality and heart failure rehospitalization in patients admitted with ADHF. Methods: A retrospective cohort study was conducted across two tertiary cardiac centers. A total of 742 patients hospitalized with ADHF were included: 318 who received SGLT2 inhibitors within 48 hours of admission (early initiation group) and 424 who received standard heart failure therapy without SGLT2 inhibitors during hospitalization (standard care group). The primary composite endpoint was all-cause mortality or first heart failure rehospitalization at 180 days. Secondary endpoints included individual components of the composite, in-hospital worsening heart failure events, change in N-terminal pro-B-type natriuretic peptide (NT-proBNP), length of hospital stay, and renal safety outcomes. Results: The primary composite endpoint occurred in 22.3% of the early initiation group versus 33.5% of the standard care group (hazard ratio [HR] 0.61, 95% CI 0.47–0.79, p < 0.001). All-cause mortality at 180 days was 8.2% versus 13.4% (HR 0.58, 95% CI 0.38–0.89, p = 0.012). Heart failure rehospitalization occurred in 16.4% versus 24.3% (HR 0.63, 95% CI 0.47–0.85, p = 0.002). The early initiation group demonstrated significantly greater NT-proBNP reduction at discharge (−48.2 ± 22.6% vs. −34.7 ± 24.1%, p < 0.001) and shorter median length of stay (6.3 ± 2.8 vs. 7.9 ± 3.4 days, p < 0.001). No significant differences in acute kidney injury, diabetic ketoacidosis, or urinary tract infections were observed between groups. Conclusion: Early in-hospital initiation of SGLT2 inhibitors within 48 hours of admission for ADHF was associated with significantly reduced all-cause mortality, lower heart failure rehospitalization rates, and greater neurohormonal decongestion without increased adverse events. These findings support the paradigm of prompt SGLT2 inhibitor initiation during acute heart failure hospitalization.

Erythroferrone can Diagnose Acute Decompensated Heart Failure in Patients Presenting With Breathlessness

Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P=0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6-27.7]; P=0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P=0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P=0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P=0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (-1861 versus -727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83-0.95]; P<0.001). There were no differences in the incidence of safety events between groups. Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure. URL: https://www. gov; Unique identifier: NCT04049045.

Brain (B-type) natriuretic peptide (BNP) is a 32 amino acid peptide that is synthesized and released predominantly from ventricular myocardium in response to myocyte stretch. Like atrial natriuretic peptide (ANP), BNP seems to have almost exclusively beneficial physiological properties, including balanced vasodilation, natriuresis, and inhibition of both the sympathetic nervous system and the renin-angiotensin-aldosterone axis. Attempts to exploit these properties for therapeutic benefit has led to the development of recombinant human BNP (nesiritide) for the acute treatment of decompensated heart failure, and also of novel compounds that inhibit neutral endopeptidase, an enzyme that is partially responsible for BNP degradation. See p 2913 In patients with heart failure, the cardiac neurohormonal system is activated, and circulating plasma levels of ANP, BNP, and the N-terminal fragments of their prohormones (N-proANP and N-proBNP) are elevated. Compared with ANP and N-proANP, BNP and N-proBNP undergo a greater proportional rise in disease states (ie, higher “signal-to-noise” ratio), and thus have emerged as the preferred biomarkers for clinical development. With commercially available assays now available, measurement of BNP or N-proBNP can be integrated readily into the care of patients with suspected heart failure. Although data are limited, BNP and N-proBNP seem to provide qualitatively similar information, and for purposes of this editorial, will be referred to interchangeably. Incorporation of BNP measurement into the clinical evaluation facilitates the diagnosis of heart failure due to either left ventricular (LV) systolic or diastolic dysfunction; a normal BNP level virtually rules out the diagnosis of decompensated heart failure, whereas a markedly elevated BNP has a high positive predictive value for heart failure.1 Although BNP levels are correlated with age, sex, intracardiac filling pressures, LV mass and ejection fraction (LVEF), renal function, and symptoms, BNP provides prognostic information in patients with heart failure that is independent of these variables.2 …

Acute Kidney Function Declines in the Context of Decongestion in Acute Decompensated Heart Failure

HeartLogic Performs as Well as NT-proBNP to Rule out Acute Heart Failure at Point of Care

Cardiorenal Syndrome in Critical Care: The Acute Cardiorenal and Renocardiac Syndromes

Background: Dapagliflozin and sodium–glucose cotransporter 2 inhibitors reduce the risk of cardiac death and hospitalization for heart failure (HF), regardless of the patient’s status with type 2 diabetes mellitus (T2D). Further investigation is required to ascertain the impact of these drugs on patients suffering from acute myocardial infarction (AMI) complicated by acute decompensated heart failure (ADHF). Methods: In retrospective research comprising 371 patients with AMI complicated by ADHF of Killip class II–IV and left ventricular ejection fraction ≤40%, the effectiveness of dapagliflozin at a dosage of 10 mg once a day was compared to standard of care alone. The main results consisted of a primary composite outcome, which encompassed either cardiovascular (CV) mortality or hospitalization due to HF. Additional clinical outcomes assessed were CV mortality, hospitalization due to HF, and changes in laboratory measurements, including glycosylated hemoglobin, N-terminal prohormone B-type natriuretic peptide, and estimated glomerular filtration rate (eGFR). Results: In the group that received dapagliflozin, 10.7% of patients experienced a primary composite outcome event, while in the group that did not receive dapagliflozin, 24.9% of patients experienced one. The median follow-up period was 12.4 months, and the hazard ratio for CV death or hospitalization for HF was 0.67 (95% confidence interval [CI], 0.65–0.86; P &lt; 0.001). Hazard ratio, 0.68; 95% CI, 0.55–0.69; P &lt; 0.001), the group given dapagliflozin had fewer HF hospitalizations overall than the group given a placebo. Dapagliflozin decreased the likelihood of serious kidney outcomes and decelerated the yearly decline in the eGFR (2.1% vs. 7.6%; P &lt; 0.001). Conclusions: Patients with AMI complicated by ADHF who received dapagliflozin had a lower risk of CV death or HF hospitalization, regardless of their T2D status.

Background:Patients hospitalised for acute decompensated heart failure (ADHF) show reduced functional capacity, limited activities of daily living (ADL), and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP). The management of these patients focuses mainly on medical therapy with little consideration for in-patient cardiac rehabilitation. There has been a growing interest in evaluating the efficacy of early mobilisation, as the core for in-hospital rehabilitation, in ADHF patients in the last decade; however, the randomised trials on this topic are few.Objective:This randomised-controlled study, therefore, aimed to further test the hypothesis that early supervised mobilisation would have beneficial effects on functional capacity, ADL, and NT-proBNP in stabilised patients following ADHF.Methods:This is a single-centered, randomised-controlled, parallel-group trial in which 30 patients hospitalised for ADHF were randomly assigned to two groups; the study group ( years, ) and the control group ( years, =15). Inclusion criteria were ADHF on top of chronic heart failure independent of etiology or ejection fraction, clinical/hemodynamic stability, age from 40 to 60 years old, and both genders. Exclusion criteria were cardiogenic shock, acute coronary ischemia, or significant arrhythmia. Both groups received the usual medical care, but only the study group received an early structured mobilisation protocol within 3 days of hospital admission till discharge. The outcome measures were the 6-min walk distance (6-MWD) and the rating of perceived exertion (RPE) determined from the 6-min walk test at discharge, the Barthel index (BI), NT-proBNP, and the length of hospital stays (LOS).Results:The study group showed significantly greater improvements compared to the controls in the 6-MWD ( versus m, ), the RPE ( versus , ), and the LOS ( versus days, ) at discharge. Also, the study group showed significant improvements in the BI compared to baseline [100 (100–100) versus 41.87 (35–55), ] and the controls [100 (100–100) versus 92.5(85–95), ]. The mean value of NT-proBNP showed a significant reduction only compared to baseline ( versus pg/mL, ) following the intervention. The absolute mean change () of NT-proBNP showed an observed difference between groups in favor of the study group (i.e., pg/mL in the study group versus pg/mL in the control group, ).Conclusion:Early structured mobilisation under the supervision of a physiotherapist could be strongly suggested in combination with the usual medical care to help improve the functional capacity and daily living activities, reduce NT-proBNP levels, and shorten the hospital stay in stabilised patients following ADHF. Trial registration number: PACTR202202476383975.

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro–B-type natriuretic peptide levels: An individual patient data analysis

to study prognostic value of various biomarkers and their combinations in patients who survived decompensation of chronic heart failure. Patients (n=159) who were hospitalized with diagnosis of heart failure (HF) decompensation were included in a prospective single-center study. Examination on admission and the day of hospital discharge, included measurement of concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), copeptin, soluble suppression of tumorigenicity 2 (sST2), kopetin, neutrophil gelatinase-associated lipocalin (NGAL), and galectin-3. Te combined primary endpoint comprised cardiovascular (CV) death, frst hospitalization because of HF heart failure decompensation, episodes of HF deterioration which required additional i/v diuretics, and CV death with successful resuscitation. During one-year follow-up 56 pts (35.2%) reached the combined primary endpoint. Tere were 78 (49.1%) cardiovascular events. During hospitalization, patients with the decompensation of heart failure experienced a decrease of sST2, NT-proBNP, galectin-3, kopetin, hsTnT and an insignifcant increase of NGAL. ROC analysis identifed signifcant relation between concentrations of NT-proBNP, sST2, copeptin and, to a lesser degree, hsTnT, determined at hospital discharge, and risk of combined primary endpoint during 1-year follow-up: area under the curve (AUC) was 0.733 [95% CI 0.645-0.820], p&lt;0.0001, 0.772 [95% CI 0.688-0.856], p&lt;0.0001, 0.735 [95% CI 0.640-0.830], p&lt;0.0001, and 0.659 [95% CI 0.553-0.764], p=0.005, respectively. Patients who during hospitalization did not achieve cut-off values of NT-proBNP ≤1696 rg/ml, sST2≤37.8 hg/ml, copeptin≤28.31 rmol/L and hsTnT≤28.37 rg/ml, had higher risk of reaching adverse events during 1 year; OR and 95% CI were 2.96 [1.61, 5.42] p&lt;0.0001, 4.31 [2.34, 7.93] p&lt;0.0001, 3.06 [1.59, 5.89] and 2.19 [2.12, 4.27]), respectively. According to Cox regression analysis, risk of the combined primary end point was the highest in patients with 3 or more elevated markers (OR = 6.6 [3.584, 12.158], p&lt;0.0001), average in patients with 2 elevated markers (OR = 1.123 [0.51, 2.48]), p=0.7), and the lowest in patients with no markers increase or increase of only one marker (OR = 0.11 [0.049, 0.241], p&lt;0.0001). In the Kaplan-Mayer survival analysis all three groups were statistically different. In order to identify the most prognostically strong model, a reclassifcation analysis was performed. According to this analysis, the combination of sST2 and NT-proBNP concentrations determined at hospital discharge, exceeded one NT-proBNP (reclassifcation = -8.1%). At the same time, predictive value of only sST2 just insignifcantly less than value of sST2 and NT-proBNP combination (reclassifcation = -1.9%). Patients with three and more elevated markers at hospital discharge have high risk of adverse events. Te biggest prognostic value has combination of sST2 and NT-proBNP concentrations. In order to determine the long-term prognosis of a patient with HF decompensation, it is sufcient to measure concentrations of sST2 and NT-proBNP at hospital discharge. Alternatively, it is possible to limit to sST2 only, which is just insignifcantly inferior to the sST2 and NT-proBNP combination. Patients with concentrations of sST2 ≥37.8 hg/ml and NT-proBNP ≥1696 rg/ml at hospital discharge have maximal 1year risk of death due to recurrent HF decompensation.

The value of natriuretic peptides, both B-type natriuretic peptide (BNP) and N-terminal prohormone brain natriuretic peptide (NTproBNP), for determining diagnosis, severity, and prognosis of emergency department (ED) patients with acute decompensated heart failure (ADHF) has been well documented. Emerging data support the hypothesis that repeated natriuretic peptide determinations in the acute phase of ADHF may assist in confirming the diagnosis, monitoring drug therapy, and evaluating the adequacy of patient stabilization. Data from the authors' group demonstrate that in patients admitted to the ED for acute dyspnea, serial NTproBNP measurement at admission and 4, 12, and 24 hours later was useful in confirming the diagnosis of ADHF compared with patients with chronic obstructive pulmonary disease. Moreover, in the same patients receiving intensive intravenous diuretic therapy, there was a progressive reduction of NTproBNP blood levels from hospitalization to discharge (P<.001), accompanied by clinical improvement and stabilization of heart failure. More recently, the authors also demonstrated that in ADHF patients improving with diuretics, a progressive reduction in BNP levels was observed, starting 24 hours after ED admission and continuing until discharge. Comparing BNP and NTproBNP, there was a significant correlation between NTproBNP and BNP levels but not between NTproBNP's and BNP's percent variation compared with baseline. In ADHF, serial ED measurements of BNP are useful for monitoring the effects of treatment. A reduction in BNP from admission to discharge is indicative of clinical improvement.

NT-proBNP-Guided Preemptive Treatment of Outpatients with Chronic Heart Failure Followed in a Out Hospital Clinic

AimsThe Registry to Evaluate Early and Long‐Term PAH Disease Management (REVEAL) risk scores differentiate survivals in patients with pulmonary arterial hypertension (PAH). However, measurements of N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) in the peripheral blood may not adequately reflect early‐stage decompensated heart failure (HF). Given that right heart catheterization (RHC) can facilitate measurements of intracardiac NT‐proBNP, in this study our aim was to evaluate the predictive role of right ventricular (RV) NT‐proBNP measurements in patients with PAH.Methods and resultsWe prospectively collected intracardiac blood samples for NT‐proBNP measurements from patients diagnosed with World Health Organization Group I PAH during RHC. Clinical information including the aetiology of PAH (idiopathic, connective tissue disease, or congenital heart disease) and REVEAL scores were recorded. The primary endpoint was hospitalization for decompensated HF; median duration of follow‐up was 28 months. Among the 62 patients evaluated, 12 reached the designated endpoint. REVEAL risk scores were higher among patients hospitalized for HF. We detected no significant differences in plasma NT‐proBNP levels in peripheral circulation, in the right atrium, or in pulmonary arterial blood; however, significantly higher levels of NT‐proBNP were detected in the RV in patients diagnosed with PAH. RV NT‐proBNP was a sensitive predictor (cut‐off value 1500 pg/mL) of subsequent hospitalization for HF. Our findings indicate that RV NT‐proBNP levels add predictive value to REVEAL scores with respect to future hospitalization due to HF.ConclusionsRight ventricular NT‐proBNP levels combined with REVEAL 2.0 could predict the development of subsequent HF in patients with PAH and may be a potential biomarker.