No abstract

Aim Echo-derived haemodynamic classification, based on forward-flow and left ventricular (LV) filling pressure (LVFP) correlates, has been proposed to phenotype patients with heart failure and reduced ejection fraction (HFrEF). To assess the prognostic relevance of baseline echocardiographically defined haemodynamic profile in ambulatory HFrEF patients before starting sacubitril/valsartan. Methods and resultsIn our multicentre, open-label study, HFrEF outpatients were classified into 4 groups according to the combination of forward flow (cardiac index; CI:< or ≥2.0 L/min/m 2 ) and early transmitral Doppler velocity/early diastolic annular velocity ratio (E/e′: ≥ or <15): Profile-A: normal-flow, normal-pressure; Profile-B: low-flow, normal-pressure; Profile-C: normal-flow, high-pressure; Profile-D: low-flow, high-pressure. Patients were started on sacubitril/valsartan and followed-up for 12.3 months (median). Rates of the composite of death/HF-hospitalization were assessed by multivariable Cox proportional-hazards models. Twelve sites enrolled 727 patients (64 ± 12 year old; LVEF: 29.8 ± 6.2%). Profile-D had more comorbidities and worse renal and LV function. Target dose of sacubitril/valsartan (97/103 mg BID) was more likely reached in Profile-A (34%) than other profiles (B: 32%, C: 24%, D: 28%, P < 0.001). Event-rate (per 100 patients per year) progressively increased from Profile-A to Profile-D (12.0%, 16.4%, 22.9%, and 35.2%, respectively, P < 0.0001). By covariateadjusted Cox model, profiles with low forward-flow (B and D) remained associated with poor outcome (P < 0.01). Adding this categorization to MAGGIC-score and natriuretic peptides, provided significant continuous net reclassification improvement (0.329; P < 0.001). Intermediate and high-dose sacubitril/valsartan reduced the event's risk independently of haemodynamic profile. Conclusions Echocardiographically-derived haemodynamic classification identifies ambulatory HFrEF patients with different risk profiles. In real-world HFrEF outpatients, sacubitril/valsartan is effective in improving outcome across different haemodynamic profiles.

Background: Despite the fact that loop diuretics are a landmark in acute heart failure (AHF) treatment, few trials exist that evaluate whether the duration and timing of their administration and drug amount affect outcome. In this study, we sought to evaluate different loop diuretic infusion doses in relation to outcome and to diuretic response (DR), which was serially measured during hospitalization. Methods: This is a post-hoc analysis of a DIUR-HF trial. We divided our sample on the basis of intravenous diuretic dose during hospitalization. Patients taking less than 125 mg of intravenous furosemide (median value) were included in the low dose group (LD), patients with a diuretic amount above this threshold were inserted in the high dose group (HD). The DR formula was defined as weight loss/40 mg daily of furosemide and it was measured during the first 24 h, 72 h, and over the whole infusion period. Outcome was considered as death due to cardiovascular causes or heart failure hospitalization. Results: One hundred and twenty-one AHF patients with reduced ejection fractions (EF) were evaluated. The cardiovascular (CV) death/heart failure (HF) re-hospitalization rate was significantly higher in the HD group compared to the LD group (75% vs. 22%; p < 0.001). Both low DR, measured during the entire infusion period (HR 3.25 (CI: 1.92–5.50); p < 0.001) and the intravenous diuretic HD (HR 5.43 [CI: 2.82–10.45]; p < 0.001) were related to outcome occurrence. Multivariable analysis showed that DR (HR 3.01 (1.36–6.65); p = 0.006), intravenous diuretic HD (HR 2.83 (1.24–6.42); p=0.01) and worsening renal function (WRF) (HR 2.21 (1.14–4.28); p = 0.01) were related to poor prognosis. Conclusions: HD intravenous loop diuretic administration is associated with poor prognosis and less DR. Low DR measured during the whole intravenous administration better predicts outcome compared to DR measured in the early phases. ClinicalTrials.gov Acronym and Identifier Number: DIUR-HF; NCT01441245; registered on 23 September 2011.

BackgroundThe role of worsening renal function during acute heart failure (AHF) hospitalization is still debated. Very few studies have extensively evaluated the renal function (RF) trend during hospitalization by repetitive measurements.ObjectivesTo investigate the prognostic relevance of different RF trajectories together with the congestion status in hospitalized patients.MethodsThis is a post hoc analysis of a multi-center study including 467 patients admitted with AHF who were screened for the Diur-AHF Trial. We recognized five main RF trajectories based on serum creatinine and estimated glomerular filtration rate (eGFR) behavior. According to the RF trajectories our sample was divided into 1-stable (S), 2-transient improvement (TI), 3-permanent improvement (PI), 4-transient worsening (TW), and 5-persistent worsening (PW). The primary outcome was the combined endpoint of 180 days including all causes of mortality and re-hospitalization.ResultsWe recruited 467 subjects with a mean congestion score of 3.5±1.08 and a median creatinine value of 1.28 (1.00–1.70) mg/dl, eGFR 50 (37–65) ml/min/m2 and NTpro B-type natriuretic peptide (BNP) 7,000 (4,200–11,700) pg/ml. A univariate analysis of the RF pattern demonstrated that TI and PW patterns were significantly related to poor prognosis [HR: 2.71 (1.81–4.05); p &lt; 0.001; HR: 1.68 (1.15–2.45); p = 0.007, respectively]. Conversely, the TW pattern showed a significantly protective effect on outcome [HR:0.34 (0.19–0.60); p &lt; 0.001]. Persistence of congestion and BNP reduction ≥ 30% were significantly related to clinical outcome at univariate analysis [HR: 2.41 (1.81–3.21); p &lt; 0.001 and HR:0.47 (0.35–0.67); p &lt; 0.001]. A multivariable analysis confirmed the independently prognostic role of TI, PW patterns, persistence of congestion, and reduced BNP decrease at discharge.ConclusionsVarious RF patterns during AHF hospitalization are associated with different risk(s). PW and TI appear to be the two trajectories related to worse outcome. Current findings confirm the importance of RF evaluation during and after hospitalization.

Background Although loop diuretic is the cornerstone of treatment in acute heart failure (AHF) there is no consensus about the best modality and amount to be used during acute phase. Current Guidelines do not provide specific insights regarding timing course and target dose. Usually physicians double the oral domestic amount when they start intravenous infusion, but a precise algorithm does not exist. Aims To compare admission and pre discharge clinical congestion and BNP trend in relation to furosemide amount and modality administration; 2- to evaluate diuretic efficiency and renal function in the four arms and the potential effects on outcome. Methods This is a multicentre prospective Trial (DIUR-AHF) designed in order to clarify the correct loop diuretic target avoiding potential side effects. The study enrolled patients with AHF BNP level &gt;100 pg/ml and congestion signs. Patients were divided in four arms in accordance with modality administration: Continuous (Ci) vs Bolus (Bi) and dose administered Low (LD) vs High (HD) considering a cutoff 125 mg/die. All patients executed a clinical congestion evaluation and Chest radiography at admission and pre discharge, BNP sample and renal function were measured during the first 12 hours and before discharge. Diuretic efficiency (DE) defined as weight change per 40 mg of furosemide during infusional period. DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, Follow up were obtained by direct visit or phone contact at 30 and 60 days after discharge Results We included 268 hospitalized patients with a mean BNP level 987±440 pg /ml, mean congestion score (3.5±2) creatinine and GFR value were 1.6±0.7 mg/dl; and 48±20 ml/min/m2 respectively. At admission BNP and Creatinine were modestly increased in HD (P&lt;0.01) compared with all other groups. Pre discharge Congestion score were increased in Bi and HD groups (2.5±1 vs 1±1), similarly BNP levels were increased in Bi and HD with respect to Ci and LD (454±215 and 413±223 vs 288±170 and 312±248 p&lt;0.05). Whereas DE were significantly increased in Ci compared with the other arms (−1.23 vs −0.55 p&lt;0.01). In all groups, low DE, residual congestion and BNP reduction &lt;30% resulted in escalation of diuretic strategies and impaired outcome (HR 1.88 [1.16–204]; 2.1 [1.4–2.8]; 1.3 [0.88–2.1]). A significant correlation between poor DE and residual congestion was recruited (r=0.76). Worsening Renal function (WRF) occurred much more in HD and Ci compared to LD and Bi (HD 44%, Ci 35% vs LD 33% and Bi 23% p&lt;0.01) without significant effects on outcome. Conclusions HD and Bi of furosemide are both related with reduced congestion and invreased BNP level before discharge. In all groups low DE residual congestion and poor BNP reduction appear associated with higher rate of adverse events. Current data provide additional features for AHF patients during intravenous loop diuretic administration Funding Acknowledgement Type of funding source: None