Search

Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor-neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptide-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions., (© 2023 Elsevier Inc and European Society of Cardiology. Published by Elsevier Inc and Wiley. All rights reserved.)

In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre-HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41-49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%., (© 2021 European Society of Cardiology and Elsevier, Inc.)

Aims: Plasma volume expansion is clinically and prognostically relevant in individuals with heart failure. Prior cohorts either excluded or had limited representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between calculated plasma volume status (PVS) and outcomes in HFpEF., Methods and Results: We included enrollees from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) with available haematocrit and weight data (n = 3414). Plasma volume was derived from the Hakim formula and compared to estimates of ideal plasma volume to generate a relative PVS. Multivariable Cox proportional hazards models tested the association of PVS with clinical outcomes. The median PVS was -11.9% (25th-75th percentile: -17.2% to -6.4%) and the majority (91.1%) had PVS consistent with relative volume contraction (PVS ≤ 0%) as opposed to volume expansion (8.9%, PVS > 0%). After multivariable adjustment, each 5% increment in PVS was associated with a ∼11%, 14%, and 12% higher risk for the primary composite endpoint, all-cause death, and heart failure hospitalization, respectively (P < 0.002 for all), but not cardiovascular death (P = 0.051). After additional adjustment for natriuretic peptides, PVS only remained associated with heart failure hospitalization (HR 1.10, 95% confidence interval 1.001-1.21, P = 0.047). There were no significant interactions between spironolactone use and the PVS-risk relationship for any endpoint (P > 0.1 for all)., Conclusion: Higher calculated estimates of PVS were independently associated with a higher risk of long-term clinical outcomes in HFpEF, and particularly, heart failure hospitalization., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Aims: Prior cohorts demonstrating the importance of serum chloride levels in heart failure either excluded or had partial representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between serum chloride concentration and outcomes in HFpEF., Methods and Results: We included participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) who met the following criteria: met inclusion by the natriuretic peptide stratum, had recorded serum chloride levels, and were from the Americas (n = 942). Multivariable Cox proportional hazards models tested the association of serum chloride with clinical outcomes, and mixed effects modelling tested the association of spironolactone or loop diuretic on serial serum chloride levels. The median serum chloride level was 102 [25th-75th percentile 100-105 mmol/L (range 84-114 mmol/L)]. After multivariable adjustment, every standard deviation decrease in serum chloride (4.05 mmol/L) was associated with ∼50% increased risk for cardiovascular death [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.11-2.06, P = 0.008] and ∼30% increased risk for all-cause death (HR 1.29, 95% CI 1.02-1.62, P = 0.04), but not with the primary composite endpoint or heart failure hospitalization (P > 0.3 for both). There were no significant interactions between spironolactone use and the serum chloride-risk relationship (P > 0.1) for each endpoint. Spironolactone was not (P = 0.33) but loop diuretic use was associated with lower serial serum chloride levels (P < 0.001)., Conclusion: Lower serum chloride was independently associated with increased risk of cardiovascular and all-cause death in HFpEF. Loop diuretic use, but not spironolactone, lead to a decrease in serum chloride levels over time., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Aims: Mechanical ultrafiltration (UF) involves the removal of an iso-osmotic filtrate from the blood. Its benefit in acute decompensated heart failure, however, remains inconclusive. We sought to better understand the direct effects of UF in comparison to an aggressive, urine output-guided pharmacological protocol for decongestion on fluid loss, renal function, and neurohormonal activation., Methods and Results: A per-protocol analysis of the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trial (n = 188) was performed. Participants were included if randomized to UF and had UF output collected, or if randomized to the pharmacological arm and had urine but not UF output collected. Using these definitions, there were 163 participants at 24 h, 156 at 48 h, 129 at 72 h, and 106 at 96 h. UF was associated with higher cumulative fluid loss (P = 0.003), net fluid loss (P = 0.001), and relative reduction in weight (P = 0.02). UF was also associated with higher serum creatinine and blood urea nitrogen by 72 h (P-interaction <0.05 for both), lower serum sodium by 48 h (P-interaction <0.01) and increased plasma renin activity by 96 h (P = 0.04). The pharmacological arm was associated with higher serum bicarbonate after 24 h (P-interaction <0.002). There were no differences in 60-day outcomes between the UF and pharmacological arms., Conclusions: Ultrafiltration vs. pharmacological therapy was associated with more fluid removal but also rise in serum creatinine and neurohormonal activation. Additionally, loop diuretic use vs. UF was associated with an increase in serum bicarbonate despite less decongestion, data which question the commonly held conception of a 'contraction alkalosis'., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Patients with acute heart failure (AHF) require urgent in-hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre-discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre-discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present.

Left ventricular ejection fraction (EF) is used to assess patients with heart failure (HF); however, frequent measurements are not cost-effective. Impedance cardiography (ICG) is a low-cost, noninvasive test that measures systolic time intervals and may be a method for detecting impaired vs intact EF. This study evaluated the relationship between EF by echocardiography or gated nuclear ventriculography and systolic time ratio (STR) by ICG in outpatients with chronic HF. A retrospective chart review identified 52 patients with EF and STR measured within 2 weeks. There was an inverse correlation between STR and EF (r=-0.54; P<.001). The area under the receiver operating characteristic curve for STR to identify reduced EF was 0.86. An EF < or =50% and STR > or =0.50 demonstrated 93% sensitivity and 85% specificity. STR was able to distinguish intact (>50%) from impaired EF (< or =50%). STR by ICG has the potential to be a reliable method to monitor ventricular function in chronic HF.

African-American patients with heart failure treated at urban public hospitals are at high risk for adverse outcomes likely due to complex socioeconomic factors. While establishing a heart failure disease management program at Parkland Memorial Hospital in Dallas, TX, the authors completed two studies that address the high rates of heart failure hospitalizations seen in this population. The first study found high rates of adverse outcomes following emergency department discharge for heart failure. The second identified important deficiencies in dietary sodium knowledge. Both 90-day outcomes (return emergency department visit or heart failure hospitalization) following an index emergency department discharge and dietary sodium knowledge represent new potential measures of quality of care of heart failure. Studies of this high-risk population of heart failure patients may offer insights that lead to improved outcomes both in the urban setting and elsewhere.

The treatment of heart failure with angiotensin-converting enzyme inhibitors has resulted in substantial improvements in morbidity and mortality due to heart failure. Varying reports in the literature have suggested that African Americans respond less well to angiotensin-converting enzyme inhibitors, but careful reanalysis of major clinical trials in heart failure, especially the Studies of Left Ventricular Dysfunction (SOLVD), demonstrates a similar mortality benefit for African Americans as for whites. Morbidity, measured as hospitalizations, may not be as favorably impacted. African Americans do respond to angiotensin-converting enzyme inhibitors as a preemptive strategy to prevent heart failure, but the incidence of heart failure is still higher in this population. Mechanisms for these potential nuances in the response to angiotensin-converting enzyme inhibitors are not yet clear. The exaggerated benefit of nitrates and hydralazine implicates alterations in nitric oxide homeostasis. Race is an inadequate model to explain the observed differences. Careful translational research focusing on genetic patterns of disease may help resolve these outstanding questions.

The importance placed on the physical examination in the assessment of patients with cardiovascular disorders appears to be declining, perhaps in part due to a paucity of data showing its value in the modern era. To determine whether the physical examination provides important prognostic information in patients with chronic heart failure, the authors performed a post-hoc analysis of 2479 participants from the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial. The presence of elevated jugular venous pressure and a third heart sound at baseline were each associated with subsequent heart failure hospitalization, the composite end point of death or heart failure hospitalization, and pump-failure death, independently of many other markers of disease severity. The subgroup of patients with at least one of these two physical examination findings was at increased risk for all-cause mortality. The authors believe that additional studies assessing the prognostic value of the physical examination should be conducted and, if favorable, likely would lead to a renewed interest in the physical examination.