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Aims: The impact of mitral regurgitation (MR) in patients hospitalized for acute heart failure (AHF) is not well established. We assessed the role of MR in patients enrolled in the Relaxin in Acute Heart Failure 2 (RELAX-AHF-2) trial. Methods and results: Patients enrolled in RELAX-AHF-2 with available data regarding MR status were included in this analysis. Baseline characteristics, in-hospital data, and clinical outcomes through 180-day follow-up were evaluated. The impact of moderate/severe MR was assessed. Among 6420 AHF patients with known MR status, 1810 patients (28.2%) had moderate/severe MR. Compared to patients with no/mild MR, those with moderate/severe MR were more likely to have history of heart failure (HF), prior HF hospitalization, more comorbidities, symptoms/signs of HF, lower left ventricular ejection fraction and higher N-terminal pro-B-type natriuretic peptide levels. Moderate/severe MR was associated with longer length of hospital stay, higher rates of residual dyspnoea, increased jugular venous pressure through the index hospitalization and a higher unadjusted risk of the composite of cardiovascular (CV) death or rehospitalization for HF/renal failure (RF) through 180 days (crude hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.03–1.27, p = 0.01). The association between moderate/severe MR and poorer outcomes was not maintained in a multivariable model including several covariates of interest (adjusted HR 1.03, 95% CI 0.91–1.17, p = 0.65). Similar findings were observed for HF/RF rehospitalization alone. Conclusions: In patients with AHF, moderate/severe MR was associated with a worse clinical profile but did not have an independent prognostic impact on clinical outcomes.

Previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) is a novel yet readily evaluable inflammatory biomarker that may be useful for determining cardiovascular prognosis during acute episodes. The study investigated the role of NLR in predicting cardiovascular (CV) outcomes in patients with acute heart failure (HF). Individual patient data from the BLAST-AHF (phase 2b study of the biased ligand of the angiotensin 2 type 1 receptor, TRV027), Pre-RELAX-AHF (phase 2b study of recombinant human relaxin-2, serelaxin), and RELAX-AHF (phase 3 study of serelaxin) randomized, placebo-controlled studies for patients with acute HF were pooled for analysis. Dyspnea visual analog scale area under the curve through day 5, worsening HF through day 5, 30-day all-cause mortality, 60-day HF/renal failure rehospitalizations or CV death, 180-day all-cause mortality, and 180-day CV death were assessed. There were several differences in the baseline characteristics of the patients divided by NLR tertile, with patients in the higher NLR having worse clinical characteristics. NLR was an independent predictor of 30-day all-cause mortality (adjusted hazard ratio [HR] per log2 NLR increment: 1.66 [1.22 to 2.25], p = 0.001), 60-day HF/renal failure rehospitalizations or CV death: 1.33 [1.12 to 1.57], p = 0.001), 180-day all-cause mortality (adjusted HR 1.27 [1.08 to 1.50], p = 0.003), and 180-day CV death (adjusted HR 1.24 [1.04 to 1.49], p = 0.018). NLR, a readily available inflammatory biomarker, was associated with independent risk for short- and long-term adverse outcomes in acute HF, surpassing traditional markers, such as natriuretic peptides.

Emergency department (ED) providers play a critical role in the stabilization and diagnostic evaluation of patients presenting with acute heart failure (AHF), and EDs are key areas for establishing current best practices and future considerations for the disposition of and decision making for patients with AHF. These elements include accurate risk assessment; response to initial treatment and shared decision making concerning optimal venue of care; reframing of physicians' risk perceptions for patients presenting with AHF; exploration of alternative venues of care beyond hospitalization; population-level changes in demographics, management and outcomes of HF patients; development and testing of data-driven pathways to assist with disposition decisions in the ED; and suggested outcomes for measuring success.

Background: We investigated the role of the dynamic changes of pulmonary congestion, as assessed by sonographic B-lines, as a tool to stratify prognosis in patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). Methods: In this multicenter, prospective study, lung ultrasound was performed at admission and before discharge by trained investigators, blinded to clinical findings. Results: We enrolled 208 consecutive patients (mean age 76 [95% confidence interval, 70–84] years), 125 with HFrEF, 83 with HFpEF (mean ejection fraction 32% and 57%, respectively). The primary composite endpoint of cardiovascular death or HF re-hospitalization occurred in 18% of patients within 6 months. In the overall population, independent predictors of the occurrence of the primary endpoint were the number of B-lines at discharge, NT-proBNP levels, moderate-to-severe mitral regurgitation, and inferior vena cava diameter on admission. B-lines at discharge were the only independent predictor in both HFrEF and HFpEF subgroups. A cut-off of B-lines > 15 at discharge displayed the highest accuracy in predicting the primary endpoint (AUC = 0.80, p < 0.0001). Halving B-lines during hospitalization further improved event classification (continuous net reclassification improvement = 22.8%, p = 0.04). Conclusions: The presence of residual subclinical sonographic pulmonary congestion at discharge predicts 6-month clinical outcomes across the whole spectrum of acute HF patients, independent of conventional biohumoral and echocardiographic parameters. Achieving effective pulmonary decongestion during hospitalization is associated with better outcomes.

Background and aims STRONG-HF showed that rapid up-titration of guideline-recommended medical therapy (GRMT), in a high intensity care (HIC) strategy, was associated with better outcomes compared to usual care (UC). The aim of this study was to assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and its changes early during up-titration. Methods A total of 1077 patients hospitalized for acute heart failure (HF) and with a >10% NT-proBNP decrease from screening (i.e. admission) to randomization (i.e. pre-discharge), were included. Patients in HIC were stratified by further NT-proBNP changes from randomization to 1 week later as decreased (≥30% decrease), stable (10% increase). The primary endpoint was 180-day HF readmission or death. Results The effect of HIC vs. UC was independent of baseline NT-proBNP. Patients in the HIC group with stable or increased NT-proBNP were older, with more severe acute HF and worse renal and liver function. Per protocol, patients with increased NT-proBNP received more diuretics and were up-titrated more slowly during the first weeks after discharge. However, by 6 months they reached 70.4% optimal GRMT doses, compared with 80.3% for those with NT-proBNP decrease. As a result, the primary endpoint at 60 and 90 days occurred in 8.3% and 11.1% of patients with increased NT-proBNP vs 2.2% and 4.0% in those with decreased NT-proBNP (p=0.039 and p=0.045, respectively). However, no difference in outcome was found at 180 days (13.5% vs. 13.2%; p=0.93). Conclusions Among patients with acute HF enrolled in STRONG-HF, HIC reduced 180-day HF readmission or death regardless of baseline NT-proBNP. GRMT up-titration early post-discharge utilizing increased NT-proBNP as guidance to increase diuretic therapy and reduce the GRMT up-titration rate resulted in the same 180-day outcomes regardless of early post-discharge NT-proBNP change.

OBJECTIVES: The aim of this study was to investigate the association between systolic blood pressure (SBP) drop, worsening renal function (WRF), and prognosis in patients with acute heart failure (AHF).BACKGROUND: A large drop in SBP early after hospital admission for AHF might be associated with increased risk for WRF and prognosis. However, there is a paucity of data regarding the interaction between WRF and a drop in SBP on clinical outcomes.METHODS: A post hoc analysis among 6,544 patients with AHF enrolled in the RELAX-AHF-2 (Relaxin in Acute Heart Failure-2) trial was performed. Blood pressure was uniformly and repetitively measured. Peak SBP drop was defined as the difference between baseline SBP and lowest SBP documented during the first 48 hours. WRF was defined by an increase in serum creatinine of ≥0.3 mg/dL from baseline to day 5.RESULTS: Peak SBP drop was independently associated with a higher risk for WRF (HR: 1.11 per 10 mm Hg SBP drop; P < 0.001), 5-day worsening heart failure (HR: 1.12 per 10 mm Hg SBP drop; P = 0.006), and 180-day cardiovascular death (HR: 1.09 per 10 mm Hg SBP drop; P = 0.026) after adjustment for potential confounders including baseline SBP. There was no interaction between the prognostic value of early SBP drop according to the presence or absence of WRF.CONCLUSIONS: In patients hospitalized for AHF, a greater early drop in SBP was associated with a higher incidence of WRF, worsening heart failure, and an increased risk for 180-day cardiovascular death. However, the association between SBP drop and prognosis was not influenced by WRF. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778).

Objectives The goal of this study was to determine whether a 6-hour lung ultrasound (LUS)-guided strategy-of-care improves pulmonary congestion over usual management in the emergency department (ED) setting. A secondary goal was to explore whether early targeted intervention leads to improved outcomes. Background Targeting pulmonary congestion in acute heart failure remains a key goal of care. LUS B-lines are a semi-quantitative assessment of pulmonary congestion. Whether B-lines decrease in patients with acute heart failure by targeting therapy is not well known. Methods A multicenter, single-blind, ED-based, pilot trial randomized 130 patients to receive a 6-hour LUS-guided treatment strategy versus structured usual care. Patients were followed up throughout hospitalization and 90 days’ postdischarge. B-lines ≤15 at 6 h was the primary outcome, and days alive and out of hospital (DAOOH) at 30 days was the main exploratory outcome. Results No significant difference in the proportion of patients with B-lines ≤15 at 6 hours (25.0% LUS vs 27.5% usual care; P = 0.83) or the number of B-lines at 6 hours (35.4 ± 26.8 LUS vs 34.3 ± 26.2 usual care; P = 0.82) was observed between groups. There were also no differences in DAOOH (21.3 ± 6.6 LUS vs 21.3 ± 7.1 usual care; P = 0.99). However, a significantly greater reduction in the number of B-lines was observed in LUS-guided patients compared with those receiving usual structured care during the first 48 hours (P = 0.04). Conclusions In this pilot trial, ED use of LUS to target pulmonary congestion conferred no benefit compared with usual care in reducing the number of B-lines at 6 hours or in 30 days DAOOH. However, LUS-guided patients had faster resolution of congestion during the initial 48 hours. (B-lines Lung Ultrasound–Guided ED Management of Acute Heart Failure Pilot Trial; NCT03136198 )

Aims Lung ultrasound B‐lines are the sonographic sign of pulmonary congestion and can be used in the differential diagnosis of dyspnoea to rule in or rule out acute heart failure (AHF). Our aim was to assess the prognostic value of B‐lines, integrated with echocardiography, in patients admitted to a cardiology department, independently of the initial clinical presentation, thus in patients with and without AHF, and in AHF with reduced and preserved ejection fraction (HFrEF and HFpEF). Methods and results We enrolled consecutive patients admitted for various cardiac conditions. Patients were classified into three groups: (i) acute HFrEF; (ii) acute HFpEF; and (iii) non‐AHF. All patients underwent an echocardiogram coupled with lung ultrasound at admission, according to standardized protocols. We followed up 1021 consecutive inpatients (69 ± 12 years) for a median of 14.4 months (interquartile range 4.6–24.3) for death and rehospitalization for AHF. During the follow‐up, 126 events occurred. Admission B‐lines > 30, ejection fraction 2.8 m/s, and tricuspid annular plane systolic excursion 30 had a strong predictive value in HFpEF and non‐AHF, but not in HFrEF. Conclusions Ultrasound B‐lines can detect subclinical pulmonary interstitial oedema in patients thought to be free of congestion and provide useful information not only for the diagnosis but also for the prognosis in different cardiac conditions. Their added prognostic value among standard echocardiographic parameters is more robust in patients with HFpEF compared with HFrEF.

Objective: Experts recommended that direct discharge without hospitalization (DDWH) for emergency departments (EDs) able to observe acute heart failure (AHF) patients should be 40%, and these discharged patients should fulfil the following outcome standards: 30-day all-cause mortality 40%. Considering DDWH patients altogether, outcomes A/C were above the recommended standards (4.3%/29.4%), while outcome B was nearly met (B = 10.1%). When analyzing individual EDs, 58.1% of them achieved the outcome B standard, while outcomes A/C standards were barely achieved (19.3%/9.7%). We observed clinically relevant linear/quadratic relationships between higher DDWH and worse outcomes B (weighted R-2 = 0.184/0.322) and C (weighted R-2 = 0.430/0.624), but not with outcome A (weighted R-2 = 0.002/0.022). Conclusions: The EDs of this nationwide cohort do not fulfil the standards for AHF patients with DDWH. High DDWH rates negatively impact ED revisit or hospitalization but not mortality. This may represent an opportunity for improvement in better selecting patients for early ED discharge and in ensuring early follow-up after ED discharge. (c) 2020 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.

Objectives The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events. Background Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF). Methods This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure Results In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro–B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation. Conclusions Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325 )

Objectives This study sought to better understand the discrepant results of 2 trials of serelaxin on acute heart failure (AHF) and short-term mortality after AHF by analyzing causes of death of patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF-2) trial. Background Patients with AHF continue to suffer significant short-term mortality, but limited systematic analyses of causes of death in this patient population are available. Methods Adjudicated cause of death of patients in RELAX-AHF-2, a randomized, double-blind, placebo-controlled trial of serelaxin in patients with AHF across the spectrum of ejection fraction (EF), was analyzed. Results By 180 days of follow-up, 11.5% of patients in RELAX-AHF-2 died, primarily due to heart failure (HF) (38% of all deaths). Unlike RELAX-AHF, there was no apparent effect of treatment with serelaxin on any category of cause of death. Older patients (≥75 years) had higher rates of mortality (14.2% vs. 8.8%) and noncardiovascular (CV) death (27% vs. 19%) compared to younger patients. Patients with preserved EF (≥50%) had lower rates of HF-related mortality (30% vs. 40%) but higher non-CV mortality (36% vs. 20%) compared to patients with reduced EF. Conclusions Despite previous data suggesting benefit of serelaxin in AHF, treatment with serelaxin was not found to improve overall mortality or have an effect on any category of cause of death in RELAX-AHF-2. Careful adjudication of events in the serelaxin trials showed that older patients and those with preserved EF had fewer deaths from HF or sudden death and more deaths from other CV causes and from noncardiac causes. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778 )

Aims: Whether risk of worsening renal function (WRF) during acute heart failure (AHF) hospitalization or the association between in-hospital WRF and post-discharge outcomes vary according to left ventricular ejection fraction (LVEF) is uncertain. We assessed incidence of WRF, factors related to its development and impact of WRF on post-discharge outcomes across the spectrum of LVEF in patients enrolled in RELAX-AHF-2.Methods and results: A total of 6112 patients who had LVEF measured on admission and renal function determined prospectively during hospitalization were included. WRF, defined as a rise in serum creatinine ≥0.3 mg/dL from baseline through day 5, occurred in 1722 patients (28.2%). Incidence increased progressively from lowest to highest LVEF quartile (P < 0.001). After baseline adjustment, WRF risk in Q4 (LVEF >50%) remained significantly greater than in Q1 (LVEF ≤29%; hazard ratio 1.2, 95% confidence interval 1–1.43; P = 0.050). Age and comorbidity burden including chronic kidney disease increased as LVEF increased. Neither admission haemodynamic abnormalities, extent of diuresis during hospitalization nor residual congestion explained the increased incidence of WRF in patients with higher LVEF. Serelaxin treatment and diuretic responsiveness were associated with reduced risk of WRF in all LVEF quartiles. WRF in patients in the upper three LVEF quartiles increased risk of post-discharge events.Conclusions: Worsening renal function incidence during AHF hospitalization increases progressively with LVEF. Greater susceptibility of patients with higher LVEF to WRF appears more related to their advanced age and worse underlying kidney function rather than haemodynamic or treatment effects. WRF is associated with increased risk of post-discharge events except in patients in the lowest LVEF quartile.

International audience; Aims: Over the last 30 years, many medicine development programmes in acute and chronic heart failure (HF) with preserved ejection fraction (HFpEF) have failed, in contrast to those in HF with reduced ejection fraction (HFrEF). We explore how the neutral results in larger HF trials may be attributable to chance and/or the dilution of statistical power.Methods and results: Using simulations, we examined the probability that a positive finding in a Phase 2 trial would result in the study of a truly effective medicine in a Phase 3 trial. We assessed the similarity of clinical trial and registry patient populations. We conducted a meta-analysis of paired Phase 2 and 3 trials in HFrEF and acute HF examining the associations of trial phase and size with placebo event rates and treatment effects for HF events and death. We estimated loss in trial power attributable to dilution with increasing trial size. Appropriately powered Phase 3 trials should have yielded ∼35% positive results. Patient populations in Phase 3 trials are similar to those in Phase 2 trials but both differ substantially from the populations of 'real-life' registries. We observed decreasing placebo event rates and smaller treatment effects with increasing trial size, especially for HF events (and less so for mortality). This was more pronounced in trials in acute HF patients.Conclusions: The selection of more positive Phase 2 trials for further development does not explain the failure of HFpEF and acute HF medicine development. Increasing sample size may lead to reduced event rates and smaller treatment effects, resulting in a high rate of neutral Phase 3 trials.

Background Heart failure (HF) necessitates frequent transport by emergency medical services (EMS), but few studies have been conducted to evaluate predictors of EMS use and of multiple EMS transports that are amenable to intervention. Objectives To characterize prehospital clinical status of community-dwelling adults with reported HF who used EMS across 8 years and to evaluate predictors of EMS use and multiple EMS transports. Methods Data were from a database in a large Midwestern county. Descriptive statistics, logistic and negative binomial regression were used for analysis. Results EMS transports were evaluated for 6582 adults with 16,905 transports. The most common chief complaints were respiratory problems, feeling sick, and chest pain. Shortness of breath, chest pain, level of consciousness, age, gender, race, and hospital site predicted multiple transports. Conclusions Clinicians need to educate patients with HF about ways to manage shortness of breath and chest pain and when to activate EMS.

Objective Intravenous push (IVP) diltiazem and metoprolol are commonly used for management of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). This study's objective was to determine if there was a significant difference in blood pressure reduction between agents. Methods This was a single-center, retrospective study of adult patients initially treated with IVP diltiazem or metoprolol in the ED from 2008 to 2018. Primary endpoint was mean reduction in systolic blood pressure (SBP) from baseline to nadir during the study period. Study period was defined as time from first dose of IVP intervention to 30 min after last dose of IVP intervention or first dose of maintenance therapy, whichever came first. Results A total of 63 diltiazem patients and 45 metoprolol patients met eligibility criteria. Baseline characteristics were similar except for initial ventricular rate (VR) and home beta-blocker use. Median dose of initial intervention was 10 [10−20] mg and 5 [5–5] mg for diltiazem and metoprolol respectively. Mean SBP reduction was 18 ± 22 mmHg for diltiazem compared to 14 ± 15 mmHg for metoprolol (p = .33). Clinically relevant hypotension was similar between groups 14% vs. 16% (p = .86). Rate control was achieved in 35 (56%) of the diltiazem group and 16 (36%) of the metoprolol group (p = .04). Conclusion IVP diltiazem and metoprolol caused similar SBP reduction and hypotension when used for initial management of AF with RVR in the ED. However, rate control was achieved more often with diltiazem.

Background Patients with heart failure (HF) with concomitant ischemic heart disease (IHD) have not been well characterized. We examined survival of patients with ischemic HF syndrome (IHFS), defined as presentation with acute HF and concomitant features suggestive of IHD. Methods Patients were included if they presented with acute HF to hospitals in Ontario, Canada. IHD was defined by any of the following criteria: angina/chest pain, prior myocardial infarction (MI), or troponin elevation that was above the upper limit of normal (mild) or suggestive of cardiac injury. Deaths were determined after hospital presentation. Results Of 5353 patients presenting with acute HF, 4088 (76.4%) exhibited features of IHFS. Patients with IHFS demonstrated a higher rate of 30-day (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.33-2.68) and 1-year death (HR, 1.16, 95% CI, 1.00-1.35) compared with those with nonischemic HF. Troponin elevation demonstrated the strongest association with mortality. Mildly elevated troponin was associated with increased hazard over 30-day (HR, 1.77; 95% CI, 1.12-2.81) and 1-year (HR, 1.63; 95% CI, 1.38-1.93) mortality. Troponins indicative of cardiac injury were associated with increased hazard of death over 30 days (HR, 2.33; 95% CI, 1.63-3.33) and 1 year (HR, 1.40; 95% CI, 1.21-1.61). The association between elevated troponin and higher mortality at 30 days was similar in left ventricular ejection fraction subcategories of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, or HF with preserved ejection fraction (P interaction = 0.588). After multivariable adjustment, prior MI and angina were not associated with higher mortality risk. Conclusions In acute HF, elevated troponin, but not prior MI or angina, was associated with a higher risk of 30-day and 1-year mortality irrespective of left ventricular ejection fraction. Resume Contexte Les patients presentant une insuffisance cardiaque et une cardiopathie ischemique (CI) concomitante ne sont pas bien caracterises. Nous avons examine les donnees sur la survie de patients atteints d’un syndrome d’insuffisance cardiaque ischemique (SICI), caracterise par la presence d’une insuffisance cardiaque aigue et de manifestations concomitantes evoquant une CI. Methodologie Les donnees examinees concernaient des patients atteints d’insuffisance cardiaque aigue recus en consultation dans des hopitaux de l’Ontario, au Canada. Un patient etait repute atteint de CI s’il repondait a l’un des criteres suivants : angine/douleur thoracique, antecedents d’infarctus du myocarde (IM) ou elevation de la concentration de troponine se situant au-dela de la limite superieure de la normale (cas leger) ou evoquant une lesion cardiaque. La determination des deces a ete effectuee en aval des consultations hospitalieres. Resultats Parmi 5 353 patients atteints d’insuffisance cardiaque aigue recus en consultation, 4 088 (76,4 %) presentaient des caracteristiques de SICI. Chez les patients atteints d’un SICI, un taux plus eleve de mortalite a 30 jours (rapport des risques instantanes [RRI] : 1,89, intervalle de confiance [IC] a 95 % : 1,33-2,68) et a 1 an (RRI : 1,16, IC a 95 % : 1,00-1,35) a ete note comparativement aux patients atteints d’insuffisance cardiaque non ischemique. L’elevation de la concentration de troponine presentait la plus forte association avec la mortalite. Une legere elevation de la concentration de troponine se trouvait associee a un risque accru de mortalite a 30 jours (RRI : 1,77, IC a 95 % : 1,12-2,81) et a 1 an (RRI : 1,63, IC a 95 % : 1,38-1,93). Les concentrations de troponine temoignant de lesions cardiaques etaient associees a une augmentation du risque de mortalite a 30 jours (RRI : 2,33, IC a 95 % : 1,63-3,33) et a 1 an (RRI : 1,40, IC a 95 % : 1,21-1,61). L’association entre une concentration elevee de troponine et une augmentation du taux de mortalite a 30 jours etait semblable dans les sous-categories d’insuffisance cardiaque avec fraction d’ejection ventriculaire gauche reduite, legerement reduite ou preservee (p = 0,588 pour l’interaction). Apres correction multivariee, les antecedents d’IM et d’angine n’etaient pas associes a un risque accru de mortalite. Conclusions Dans un contexte d’insuffisance cardiaque aigue, l’elevation de la concentration de troponine etait associee a un risque plus eleve de mortalite a 30 jours et a 1 an independamment de la fraction d’ejection ventriculaire gauche; les antecedents d’IM ou d’angine ne l’etaient toutefois pas.

Aims Concentrations of insulin‐like growth factor binding protein‐7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea. Methods and results In this pre‐specified subgroup analysis of the International Collaborative of N‐terminal pro‐B‐type Natriuretic Peptide Re‐evaluation of Acute Diagnostic Cut‐Offs in the Emergency Department (ICON‐RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r = 0.49, P

AIMS Although left ventricular ejection fraction (LVEF) is routinely used to categorize patients with heart failure (HF), whether it predicts outcomes after hospitalization for acute heart failure (AHF) is uncertain. Consequently, we assessed the relationship between LVEF and cardiovascular (CV) outcomes in a large, well characterized cohort of patients hospitalized for AHF. METHODS AND RESULTS The 6128 patients from the RELAX-AHF-2 trial who had LVEF measured during AHF hospitalization were separated into LVEF quartiles and the relationship between LVEF and a composite of CV mortality and rehospitalization for HF or renal failure through 180 days was assessed. We found progressively lower risk for this composite outcome as LVEF increased (hazard ratio 0.95, 95% confidence interval 0.93-0.98 per 5% LVEF increase, P

Background: There is a paucity of evidence for dose and pace of up-titration of guideline-directed medical therapies after admission to hospital for acute heart failure.Methods: In this multinational, open-label, randomised, parallel-group trial (STRONG-HF), patients aged 18–85 years admitted to hospital with acute heart failure, not treated with full doses of guideline-directed drug treatment, were recruited from 87 hospitals in 14 countries. Before discharge, eligible patients were randomly assigned (1:1), stratified by left ventricular ejection fraction (≤40% vs >40%) and country, with blocks of size 30 within strata and randomly ordered sub-blocks of 2, 4, and 6, to either usual care or high-intensity care. Usual care followed usual local practice, and high-intensity care involved the up-titration of treatments to 100% of recommended doses within 2 weeks of discharge and four scheduled outpatient visits over the 2 months after discharge that closely monitored clinical status, laboratory values, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations. The primary endpoint was 180-day readmission to hospital due to heart failure or all-cause death. Efficacy and safety were assessed in the intention-to-treat (ITT) population (ie, all patients validly randomly assigned to treatment). The primary endpoint was assessed in all patients enrolled at hospitals that followed up patients to day 180. Because of a protocol amendment to the primary endpoint, the results of patients enrolled on or before this amendment were down-weighted. This study is registered with ClinicalTrials.gov, NCT03412201, and is now complete.Findings: Between May 10, 2018, and Sept 23, 2022, 1641 patients were screened and 1078 were successfully randomly assigned to high-intensity care (n=542) or usual care (n=536; ITT population). Mean age was 63·0 years (SD 13·6), 416 (39%) of 1078 patients were female, 662 (61%) were male, 832 (77%) were White or Caucasian, 230 (21%) were Black, 12 (1%) were other races, one (Interpretation: An intensive treatment strategy of rapid up-titration of guideline-directed medication and close follow-up after an acute heart failure admission was readily accepted by patients because it reduced symptoms, improved quality of life, and reduced the risk of 180-day all-cause death or heart failure readmission compared with usual care.Funding: Roche Diagnostics.

Heart failure (HF) is a common condition leading to activation of emergency medical services (EMS).The aim of this study was to describe reasons given by persons with HF, family members, or other caregivers for requesting EMS activation during 911 calls.In this descriptive qualitative study, a content analysis was performed on transcribed audio files of 383 EMS requests involving 383 persons with HF in the community.One hundred forty-seven calls (38.4%) were placed by the family members, 75 (19.6%) were placed by the patients, 56 (14.6%) were placed by healthcare workers or personnel from living facilities, and the remaining calls (n = 105, 27.4%) were placed by others (eg, friends, neighbors, officers). Three broad categories of symptoms, signs, and events were identified as the reasons for an EMS request. Frequently reported symptoms were breathing problems (55.4%), chest pain (18.3%), and other pain (eg, head, extremities) (16.7%). Signs included decreased consciousness (15.4%), swelling (5.7%), and bleeding (5.0%). The reported events involved falls (8.1%), heart attack (6.3%), hypoxic episodes (6.0%), stroke (5.2%), and post-hospital-discharge complications (4.7%). In most calls (74.9%), multiple reasons were reported and a combination of symptoms, signs, and events were identified. Heart failure diagnosis was mentioned in fewer than 10% of the calls.Overall, symptoms and signs of HF exacerbation were common reasons to activate 911 calls. Falls were frequently reported. Under the duress of the emergent situations surrounding the 911 call, callers rarely mentioned the existence of HF. Interventions are needed to guide patients with HF and their family members to promote the management of HF to reduce EMS activation as well as to activate EMS quickly for acute changes in HF conditions.

Younger patients (18 to 65 years old) are often excluded from delirium outcome studies. We sought to determine if delirium was associated with short-term adverse outcomes in a diverse cohort of younger and older patients with acute heart failure (AHF). We conducted a multi-center prospective cohort study that included adult emergency department patients with confirmed AHF. Delirium was ascertained using the Brief Confusion Assessment Method (bCAM). The primary outcome was a composite outcome of 30-day all-cause death, 30-day all-cause rehospitalization, and prolonged index hospital length of stay. Multivariable logistic regression was performed, adjusting for demographics, cognitive impairment without delirium, and HF risk factors. Older age (≥ 65 years old)*delirium interaction was also incorporated into the model. Odds ratios (OR) with their 95% confidence intervals (95%CI) were reported. A total of 1044 patients with AHF were enrolled; 617 AHF patients were < 65 years old and 427 AHF patients were ≥ 65 years old, and 47 (7.6%) and 40 (9.4%) patients were delirious at enrollment, respectively. Delirium was significantly associated with the composite outcome (adjusted OR = 1.64, 95%CI: 1.02 to 2.64). The older age*delirium interaction p-value was 0.47. In conclusion, delirium was common in both younger and older patients with AHF and was associated with poorer short-term outcomes in both cohorts. Younger patients with acute heart failure should be included in future delirium outcome studies.

BackgroundNon-invasive finger-cuff monitors measuring cardiac index and vascular tone (SVRI) classify emergency department (ED) patients with acute heart failure (AHF) into three otherwise-indistinguishable subgroups. Our goals were to validate these “hemodynamic profiles” in an external cohort and assess their association with clinical outcomes.MethodsAHF patients (n=257) from five EDs were prospectively enrolled in the validation cohort (VC). Cardiac index and SVRI were measured with a ClearSight finger-cuff monitor (formerly NexFin, Edwards Lifesciences) as in a previous study (derivation cohort, DC, n=127). A control cohort (CC, n=127) of ED patients with sepsis was drawn from the same study as the DC. K-means cluster analysis previously derived two-dimensional (cardiac index and SVRI) hemodynamic profiles in the DC and CC (k=3 profiles each). The VC was subgroupedde novointo three analogous profiles by unsupervised K-means consensus clustering. PERMANOVA tested whether VC profiles 1-3 differed from profiles 1-3 in the DC and CC, by multivariate group composition of cardiac index and vascular tone.Profiles in the VC were compared by a primary outcome of 90-day mortality and a 30-day ranked composite secondary outcome (death, mechanical cardiac support, intubation, new/emergent dialysis, coronary intervention/surgery) as time-to-event (survival analysis) and binary events (odds ratio, OR). Descriptive statistics were used to compare profiles by two validated risk scores for the primary outcome, and one validated score for the secondary outcome.ResultsThe VC had median age 60 years (interquartile range {49-67}), and was 45% (n=116) female. Multivariate profile composition by cardiac index and vascular tone differed significantly between VC profiles 1-3 and CC profiles 1-3 (p=0.001, R2=0.159). A difference was not detected between profiles in the VC vs. the DC (p=0.59, R2=0.016).VC profile 3 had worse 90-day survival than profiles 1 or 2 (HR = 4.8, 95%CI 1.4-17.1). The ranked secondary outcome was more likely in profile 1 (OR = 10.0, 1.2-81.2) and profile 3 (12.8, 1.7-97.9) compared to profile 2. Diabetes prevalence and blood urea nitrogen were lower in the high-risk profile 3 (pConclusionsHemodynamic profiles in ED patients with AHF, by non-invasive finger-cuff monitoring of cardiac index and vascular tone, were replicatedde novoin an external cohort. Profiles showed significantly different risks of clinically-important adverse patient outcomes.

Background: For patients with acute heart failure (AHF), a substantial diuresis after administration of loop diuretics is generally associated with better clinical outcomes but may cause creatinine to rise, suggesting a decline in renal function. We investigated the interaction between diuretic response and worsening renal function (WRF) on clinical outcomes in patients with AHF. Methods: In two cohorts of patients with AHF (PROTECT, n=1,698 and RELAX-AHF-2, n=5,586 in current analysis), the prognostic impact of WRF (creatinine ≥0.3 mg/dL increase baseline-day 4, sensitivity analyses were performed incorporating baseline renal function) by diuretic response (kg weight loss per 40 mg furosemide equivalent from baseline-day 4) was investigated with regards to (CV) death or cardiovascular/renal hospitalisation using subpopulation treatment effect pattern (STEPP) plots and survival analyses. Results: WRF occurred in 286 (16.8%) patients in PROTECT and 1,031 (18.5%) patients in RELAX-AHF-2. Patients with WRF had higher left ventricular ejection fraction and lower estimated glomerular filtration rate at baseline (P Conclusion: In two large cohorts of patients with AHF, WRF in the first 4 days was not associated with worse outcomes when patients had a good diuretic response. The occurrence of WRF in patients with AHF should therefore be considered in the context of diuretic response.

BackgroundFor patients with acute heart failure (AHF), substantial diuresis after administration of loop diuretics is generally associated with better clinical outcomes but may cause creatinine to rise, suggesting renal function decline. We investigated the interaction between diuretic response and worsening renal function (WRF) on clinical outcomes in patients with AHF.Methods and resultsIn two AHF cohorts (PROTECT, n= 1698 and RELAX-AHF-2, n= 5586 in current analysis), the prognostic impact of WRF (creatinine ≥0.3mg/dl increase baseline-day 4; sensitivity analyses incorporated baseline renal function) by diuretic response (kg weight loss/40 mg furosemide equivalent baseline-day 4) was investigated with regard to (cardiovascular) death or cardiovascular/renal hospitalization using subpopulation treatment effect pattern plots (STEPP) and survival analyses. WRF occurred in 286 (16.8%) and 1031 (18.5%) patients in PROTECT and RELAX-AHF-2, respectively. Patients with WRF had higher left ventricular ejection fraction and lower estimated glomerular filtration rate at baseline (p&nbsp

Background: We conducted a secondary analysis of changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 over 30 days in a randomized trial of self-care coaching versus structured usual care in patients with acute heart failure who were discharged from the emergency department. Methods: Patients in 15 emergency departments completed the KCCQ-12 at emergency department discharge and at 30 days. We compared change in KCCQ-12 scores between the intervention and usual care arms, adjusted for enrollment KCCQ-12 and demographic characteristics. We used linear regression to describe changes in KCCQ-12 summary scores and logistic regression to characterize clinically meaningful KCCQ-12 subdomain changes at 30 days. Results: There were 350 patients with both enrollment and 30-day KCCQ summary scores available; 166 allocated to usual care and 184 to the intervention arm. Median age was 64 years (interquartile range, 55–70), 37% were female participants, 63% were Black, median KCCQ-12 summary score at enrollment was 47 (interquartile range, 33–64). Self-care coaching resulted in significantly greater improvement in health status compared with structured usual care (5.4-point greater improvement, 95% CI, 1.12–9.68; P =0.01). Improvements in health status in the intervention arm were driven by improvements within the symptom frequency (adjusted odds ratio, 1.62 [95% CI, 1.01–2.59]) and quality of life (adjusted odds ratio, 2.39 [95% CI, 1.46–3.90]) subdomains. Conclusions: In this secondary analysis, patients with acute heart failure who received a tailored, self-care intervention after emergency department discharge had clinically significant improvements in health status at 30 days compared with structured usual care largely due to improvements within the symptom frequency and quality of life subdomains of the KCCQ-12. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02519283.

Background Community paramedicine (CP) leverages trained emergency medical services personnel outside of emergency response as an innovative model of health care delivery. Often used to bridge local gaps in healthcare delivery, the CP model has existed for decades. Recently, the number of programs has increased. However, the level of robust data to support this model is less well known. Objective To describe the evidence supporting community paramedicine practice. Data sources OVID, PubMed, SCOPUS, EMBASE, Google Scholar-WorldCat, OpenGrey. Study appraisal and synthesis methods Three people independently reviewed each abstract and subsequently eligible manuscript using prespecified criteria. A narrative synthesis of the findings from the included studies, structured around the type of intervention, target population characteristics, type of outcome and intervention content is presented. Results A total of 1098 titles/abstracts were identified. Of these 21 manuscripts met our eligibility criteria for full manuscript review. After full manuscript review, only 6 ultimately met all eligibility criteria. Given the heterogeneity of study design and outcomes, we report a description of each study. Overall, this review suggests CP is effective at reducing acute care utilization. Limitations The small number of available manuscripts, combined with the lack of robust study designs (only one randomized controlled trial) limits our findings. Conclusions Initial studies suggest benefits of the CP model; however, notable evidence gaps remain.

Background Acute decompensated heart failure (ADHF) is the most common presenting phenotype of acute heart failure (AHF). The main goal of this article was to review the contemporary management strategies in these patients and to describe how future clinical trials may address unmet clinical needs. Areas of uncertainty The current pathophysiologic understanding of AHF is incomplete. The guideline recommendations for the management of ADHF are based only on algorithms provided by expert consensus guided by blood pressure and/or clinical signs of congestion or hypoperfusion. The lack of adequately conducted trials to address the unmet need for evidence therapy in AHF has not yet been surpassed, and at this time, there is no evidence-based strategy for targeted decongestive therapy to improve outcomes. The precise time point for initiation of guideline-directed medical therapies (GDMTs), as respect to moment of decompensation, is also unknown. Data sources The available data informing current management of patients with ADHF are based on randomized controlled trials, observational studies, and administrative databases. Therapeutic advances A major step-forward in the management of ADHF patients is recognizing congestion, either clinical or hemodynamic, as a major trigger for heart failure (HF) hospitalization and most important target for therapy. However, a strategy based exclusively on congestion is not sufficient, and at present, comprehensive assessment during hospitalization of cardiac and noncardiovascular substrate with identification of potential therapeutic targets represents "the corner-stone" of ADHF management. In the last years, substantial data have emerged to support the continuation of GDMTs during hospitalization for HF decompensation. Recently, several clinical trials raised hypothesis of "moving to the left" concept that argues for very early implementation of GDMTs as potential strategy to improve outcomes. Conclusions The management of ADHF is still based on expert consensus documents. Further research is required to identify novel therapeutic targets, to establish the precise time point to initiate GDMTs, and to identify patients at risk of recurrent hospitalization.

Vasodilators are commonly recommended to treat acute heart failure (AHF), yet they are infrequently used. This review aims to evaluate the clinical utility of traditional, historical, and novel vasodilators in the treatment of AHF. No traditional vasodilator (i.e., nitroglycerin) therapy definitely improves short- or long-term outcomes. Despite repeated efforts to develop new pharmacologic treatments, no novel therapy outperforms traditional management. At the present time, we continue to recommend traditional vasodilators, such as nitroglycerin. The use of select vasodilators in the treatment of AHF improves hemodynamics and provides short-term relief; however, data regarding long-term benefits is lacking.

Acute heart failure accounts for over one million hospital discharges annually. Current guidelines suggest treatments for AHF should begin “without delay” but this time interval has not been clearly defined. Data suggest that certain treatments such as earlier treatment with diuretics and vasodilators may improve patient symptom relief, morbidity, and mortality. Secondary analyses of clinical trials of novel treatments under development have not shown similar results. The data are equivocal regarding the impact of early treatment in AHF on in-hospital and long-term morbidity and mortality. Improved clinical trial designs will help answer when and if “early” treatment should begin and whether it impacts short- and long-term outcomes in AHF.

Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown.Concentrations of NT-proBNP, high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 were analyzed in 1448 patients presenting with acute dyspnea from the prospective, multicenter International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all 3 biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in 2 biomarkers (18.8%, 44 of 234), 1 biomarker (3.8%, 10 of 260), or no elevated biomarkers (0.4%, 2 of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite end point of mortality and HF rehospitalization. In adjusted models, patients with one, 2, and 3 elevated biomarkers had 3.74 (95% confidence interval [CI], 1.26-11.1, P = .017), 12.3 (95% CI, 4.60-32.9, P.001), and 12.6 (95% CI, 4.54-35.0, P.001) fold increased risk of 180-day mortality or HF rehospitalization.A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic, and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization.

To review the key clinical and research questions regarding blood pressure (BP) reduction with vasodilators in the early management of hypertensive acute heart failure (H-AHF). Despite numerous AHF vasodilator clinical trials in the past two decades, virtually none has studied a population where vasoconstriction is the predominant physiology, and with the agents and doses most commonly used in contemporary practice. AHF patients are remarkably heterogenous by vascular tone, and this heterogeneity is not always discernible through BP or clinical exam. Emerging data suggest that diastolic BP may be a stronger correlate of vascular tone in AHF than systolic BP, despite the latter historically serving as a key inclusion criterion for vasodilator clinical trials. Existing data are limited. A clinical trial that evaluates vasodilators in a manner of use consistent with contemporary practice, specifically within the subpopulation of patients with true H-AHF, is greatly needed. Until then, observational data supports long-standing vasodilators such as nitroglycerin, administered by IV bolus, and with goal reduction of SBP ≤25% as a safe first-line approach for patients with severe H-AHF presentations.

Aims Our aim was to assess the dynamic changes of pulmonary congestion (PC) through variations of sonographic B-lines, in addition to conventional clinical, biohumoral and echocardiographic findings, to improve prognostic stratification of patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). Methods In this multicenter, prospective, observational study, lung ultrasound was performed in all patients at admission and before discharge by trained investigators, blinded to clinical findings and outcomes. Results We enrolled 208 consecutive patients admitted for acute heart failure (125 HFrEF, 83 HFpEF, mean age 75.9±11.7 years, 36% females, mean ejection fraction 38%). After 180-day follow-up, 38 composite endpoint events occurred (cardiovascular deaths or HF re-hospitalisations). In a multivariate model, B-lines at discharge had independent prognostic value in the overall population together with NT-proBNP, moderate-to-severe mitral regurgitation (MR) and inferior vena cava diameter at admission. When dividing the population in HFrEF and HFpEF, B-lines at discharge was the only independent parameter to predict events in all subgroups. At ROC analysis, a cut-off of B-lines>15 at discharge displayed the highest accuracy in predicting adverse events (AUC=0.80, p15 at discharge, improved event classification (integrated discrimination improvement=4%, p=0.01; continuous net reclassification improvement=22.8%, p=0.04). Conclusions The presence of residual subclinical sonographic PC at discharge predicts adverse events in the whole spectrum of acute HF patients, independently of conventional biohumoral and echocardiographic parameters. The dynamic evaluation of pulmonary decongestion during hospital stay can further improve patient risk stratification. Funding Acknowledgement Type of funding source: None

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices, transplantation capabilities, and specialists in advanced heart failure, cardiothoracic surgery, cardiac pathology, immunology, and infectious disease. Education of frontline providers who are most likely to encounter FM first is essential to increase timely access to appropriately resourced facilities, to prevent multiorgan system failure, and to tailor disease-specific therapy as early as possible in the disease process.

Aims The goal of this study was to determine the number of scans needed for novice learners to attain proficiency in B‐line quantification compared with expert interpretation. Methods and results This was a prospective, multicentre observational study of novice learners, physicians and non‐physicians from three academic institutions. Learners received a 2 h lung ultrasound (LUS) training session on B‐line assessment, including lecture, video review to practice counting and hands‐on patient scanning. Learners quantified B‐lines using an eight‐zone scanning protocol in patients with suspected acute heart failure. Ultrasound (US) machine settings were standardized to a depth of 18 cm and clip length of 6 s, and tissue harmonics and multibeam former were deactivated. For quantification, the intercostal space with the greatest number of B‐lines within each zone was used for scoring. Each zone was given a score of 0–20 based on the maximum number of B‐lines counted during one respiratory cycle. The B‐line score was determined by multiplying the percentage of the intercostal space filled with B‐lines by 20. We compared learner B‐line counts with a blinded expert reviewer (five US fellowship‐trained faculty with > 5 years of clinical experience) for each lung zone scanned; proficiency was defined as an intraclass correlation of > 0.7. Learning curves for each learner were constructed using cumulative sum method for statistical analysis. The Wilcoxon rank‐sum test was used to compare the number of scans required to reach proficiency between different learner types. Twenty‐nine learners (21 research associates, 5 residents and 3 non‐US‐trained emergency medicine faculty) scanned 2629 lung zones with acute pulmonary oedema. After a mean of 10.8 (standard deviation 14.0) LUS zones scanned, learners reached the predefined proficiency standard. The number of scanned zones required to reach proficiency was not significantly different between physicians and non‐physicians (P = 0.26), learners with no prior US experience vs. > 25 prior patient scans (P = 0.64) and no prior vs. some prior LUS experience (P = 0.59). The overall intraclass correlation for agreement between learners and experts was 0.74 and 0.80 between experts. Conclusions Our results show that after a short, structured training, novice learners are able to achieve proficiency for quantifying B‐lines on LUS after scanning 11 zones. These findings support the use of LUS for B‐line quantification by non‐physicians in clinical and research applications.

Introduction: Several landmark studies, which enrolled heart failure (HF) patients who were ambulatory at the time of inclusion, identified iron deficiency (ID) as an important therapeutic target: intravenous iron administration with ferric carboxymaltose (FCM) improves morbidity, exercise capacity, and quality of life in patients with HF and reduced EF (HFrEF). However, there is still limited knowledge about ID prevalence during hospitalization for Worsening Chronic HF (WCHF) and about the relationship between ID during hospitalization and post-discharge outcomes. Although previous studies documented ID as an independent risk factor for poor outcomes in HFrEF, its prognostic significance in HF patients with EF>40% remains unclear. Method and Results: The FERIC-RO study is a prospective, multicenter, observational study with longitudinal follow up, conducted in 9 Romanian hospitals that will include 200 consecutive patients admitted for worsening HF. A comprehensive description of the Iron metabolism biomarkers will be performed on discharge and 1-month follow up. The primary endpoint is defined as the prevalence of ID on discharge and 1-month post-discharge, and the secondary endpoints include: all-cause re-hospitalization and all-cause-mortality at 1 and 3 months follow up, and quality of life on discharge and 1-month. Conclusions: FERIC-RO will provide new evidence about the prevalence and the predictors of ID in patients hospitalized for WCHF regardless of LVEF. Furthermore, the study will explore the relationship between in-hospital ID and post-discharge outcomes. The results of FERIC-RO will thus be highly relevant to the management of patients hospitalized for AHF.