Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper

Peer reviewe

Fibroblast growth factor 23 is related to profiles indicating volume overload, poor therapy optimization and prognosis in patients with new-onset and worsening heart failure

Background: Fibroblast growth factor (FGF) 23 is a hormone that increases urinary phosphate excretion and regulates renal sodium reabsorption and plasma volume. We studied the role of plasma FGF23 in therapy optimization and outcomes in patients with new-onset and worsening heart failure (HF). Methods: We measured plasma C-terminal FGF23 levels at baseline in 2399 of the 2516 patients included in the BIOlogy Study to Tailored Treatment in Chronic HF (BIOSTAT-CHF) trial. The association between FGF23 and outcome was evaluated by Cox regression analysis adjusted for potential confounders. Results: Median FGF23 was 218.0 [IQR: 117.1–579.3] RU/ml; patients with higher FGF23 levels had a worse NYHA class, more signs of congestion, and were less likely to use an ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARBs) at baseline (all P < 0.01). Higher FGF23 levels were independently associated with higher BNP, lower eGFR, the presence of oedema and atrial fibrillation (all P < 0.001). In addition, higher FGF23 was independently associated with impaired uptitration of ACEi/ARBs after 3 months, but not of beta-blockers. In multivariable Cox regression analysis, FGF23 was independently associated with all-cause mortality (hazard ratio: 1.17 (1.09–1.26) per log increase, P < 0.001), and the combined endpoint of all-cause mortality and HF hospitalization (1.15 (1.08–1.22) per log increase, P < 0.001). Conclusions: In patients with new-onset and worsening HF, higher plasma FGF23 levels were independently associated with volume overload, less successful uptitration of ACEi/ARBs and an increased risk of all-cause mortality and HF hospitalization

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Continuous aortic flow augmentation - A pilot study of hemodynamic and renal responses to a novel percutaneous intervention in decompensated heart failure

Background - Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation ( CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy. Methods and Results - We studied 24 patients ( 12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA ( mean +/- SD 1.34 +/- 0.12 L/min) was achieved through percutaneous ( n = 19) or surgical ( n = 5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413 +/- 453 to 1136 +/- 381 dyne (.) s (.) cm(-5) at 72 hours ( P = 0.0008). Pulmonary capillary wedge pressure decreased from 28.5 +/- 4.9 to 19.8 +/- 7.0 mm Hg ( P < 0.0001), and cardiac index ( excluding augmented aortic flow) increased from 1.97 +/- 0.44 to 2.27 +/- 0.43 L (.) min(-1) (.) m(-2) ( P = 0.0013). Serum creatinine trended downward during treatment ( overall P = 0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation. Conclusions - In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial