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Background Several studies have shown that heart rate control with selective beta-1 blockers in septic shock is safe. In these trials, esmolol was administered 24 h after onset of septic shock in patients who remained tachycardic. While an earlier use of beta-blockers might be beneficial, such use remains challenging due to the difficulty in distinguishing between compensatory and non-compensatory tachycardia. Therefore, the Esmosepsis study was designed to study the effects of esmolol aimed at reducing the heart rate by 20% after the initial resuscitation process in hyperkinetic septic shock patients on (1) cardiac index and (2) systemic and regional hemodynamics as well as inflammatory patterns. Methods Nine consecutive stabilized tachycardic hyperkinetic septic shock patients treated with norepinephrine for a minimum of 6 h were included. Esmolol was infused during 6 h in order to decrease the heart rate by 20%. The following data were recorded at hours H0 (before esmolol administration), H1–H6 (esmolol administration) and 1 h after esmolol cessation (H7): systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, central venous pressure, heart rate, PICCO transpulmonary thermodilution, sublingual and musculo-cutaneous microcirculation, indocyanine green clearance and echocardiographic parameters, diuresis, lactate, and arterial and venous blood gases. Results Esmolol was infused 9 (6.4–11.6) hours after norepinephrine introduction. Esmolol was ceased early in 3 out of 9 patients due to a marked increase in norepinephrine requirement associated with a picture of persistent cardiac failure at the lowest esmolol dose. For the global group, during esmolol infusion, norepinephrine infusion increased from 0.49 (0.34–0.83) to 0.78 (0.3–1.11) µg/min/kg. The use of esmolol was associated with a significant decrease in heart rate from 115 (110–125) to 100 (92–103) beats/min and a decrease in cardiac index from 4.2 (3.1–4.4) to 2.9 (2.5–3.7) l/min/m −2 . Indexed stroke volume remained unchanged. Cardiac function index and global ejection fraction also markedly decreased. Using echocardiography, systolic, diastolic as well as left and right ventricular function parameters worsened. After esmolol cessation, all parameters returned to baseline values. Lactate and microcirculatory parameters did not change while the majority of pro-inflammatory proteins decreased in all patients. Conclusion In the very early phase of septic shock, heart rate reduction using fast esmolol titration is associated with an increased risk of hypotension and decreased cardiac index despite maintained adequate tissue perfusion (NCT02068287).

BackgroundMyeloperoxidase (MPO), a neutrophil-derived enzyme, is associated with oxidative stress and inflammation, which contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Bioactive MPO causes vascular dysfunction and accumulation of serum uric acid (SUA). We investigated the association of plasma MPO and SUA with echocardiographic variables in a populational setting.MethodsThis was a cross-sectional analysis of the fourth visit of the STANISLAS cohort (N=1677 participants, age 49±14 years, 48% male), a population of initially healthy individuals. Participants were divided into four groups according to median plasma MPO and SUA levels. Adjusted linear regression models were used to assess the relationship of plasma MPO and SUA with echocardiographic markers.ResultsParticipants with high MPO and high SUA were older, had more diabetes, a higher body mass index, lower estimated glomerular filtration rate and higher systolic blood pressure. In multivariable regression analyses, compared with patients with low MPO and low SUA, they had decreased left atrial reservoir strain (mean±SE=−1.43±0.62, p=0.022), decreased mitral annular e’ velocity (mean±SE=−0.60±0.16, p<0.001) and more impaired left ventricular systolic global longitudinal strain (mean±SE=0.50±0.23, p=0.029). In contrast, high MPO with low SUA was not associated with impaired diastolic function.ConclusionsIn a population setting, high MPO and SUA, indicative of high bioactive MPO, were associated with early markers of diastolic dysfunction, suggesting a potential role of the MPO pathway in the early development of HFpEF.

BackgroundDiagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, particularly in older adults. While the Heart Failure Association (HFA)-PEFF and H2FPEF Scores offer structured diagnostic approaches, their clinical utility is still debated. This study aims to compare the diagnostic accuracy of HFpEF Scores versus inclusion criteria used in sodium-glucose cotransporter-2 inhibitors (SGLT2i) trials, age-adjusted N-terminal pro B-type natriuretic peptide (NT-proBNP) thresholds and the universal definition of heart failure (HF).MethodsDiagnostic tools were assessed using sex-weighted and age-weighted propensity score adjustment in individuals aged 60–80 years from two established HFpEF cohorts (MEtabolic Road to DIAstolic Heart Failure (MEDIA), n=297; Karolinska-Rennes (KaRen), n=174) and two community-based cohorts without HF (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS), n=461; Malmö, n=1030).ResultsHFA-PEFF and H2FPEF Scores classified a large proportion of participants in both community-based cohorts (up to 81% in Malmö) and HFpEF cohorts (up to 75% in MEDIA) in the intermediate-likelihood category, requiring further diagnostic evaluation. Their diagnostic discrimination ranged from moderate to good. The universal definition of HF, SGLT2i trial criteria and NT-proBNP age-adjusted thresholds showed diagnostic performance comparable to HFA-PEFF Scores in the HFpEF cohorts and correctly excluded almost all individuals in the community cohorts. The universal definition of HF demonstrated a diagnostic discrimination higher than H2FPEF and comparable to HFA-PEFF, with the most balanced performance in terms of sensitivity and specificity.ConclusionsUsing scores, a substantial proportion of HFpEF individuals fall into the intermediate likelihood category, highlighting diagnostic uncertainty. Simpler tools, such as the universal definition of HF, demonstrate comparable or even superior diagnostic and rule-out performances for HFpEF, emphasising the need for more practical and reliable approaches to HFpEF diagnosis.

Purpose Cardiogenic shock (CS) remains a critical condition with high mortality rates despite advances in treatment. This study aims to comprehensively evaluate both macrocirculatory and tissue perfusion variables over the initial 24 h post-admission to determine their impact on patient prognosis and identify potential hemodynamic thresholds for optimal outcomes. Secondary aims were to explore the correlation between macrocirculatory and tissue perfusion variables. Design This is a post hoc analysis of data from two prospective studies, OptimaCC (NCT01367743) and MicroShock (NCT03436641), involving only patients with CS. Both studies applied regular assessment of hemodynamic variables at specific time points (admission, 6, 12, and 24 h) to ensure consistency in data collection, enrolling 118 patients between September 2011 and July 2021, with similar inclusion criteria and care processes. Results The median age of the cohort was 69 years, 59% being male. The primary outcome, 30-day mortality, occurred in 37% of patients. Average macrocirculation variables over the first 24 h of CS such as mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), and cardiac power index (CPI) were significantly lower in patients meeting the primary outcome. Accordingly, average tissue perfusion variables (ΔPCO 2 and ΔPCO 2 /C(a-v)O 2 ) over the first 24 h of CS were also consistently impaired in patients meeting the primary outcome. The optimal clinically relevant thresholds of the first 24 h time course for poor outcomes, closely approximating the optimal values identified in the analysis, were: mean SAP < 95 mmHg, MAP < 70 mmHg, CO < 3.5 L/min, CI ≤ 1.8 L/min/m 2 , CPI < 0.27 W/m 2 , ScvO 2  < 70%, ΔPCO 2  ≥ 9 mmHg, and ΔPCO 2 /C(a-v)O 2  ≥ 1.5 mmHg/mL. Conclusions This study is the first to identify critical hemodynamic thresholds, encompassing both macrocirculatory and tissue perfusion variables, within the initial 24 h of CS that are associated with adverse outcomes. The identified thresholds suggest specific hemodynamic targets that may guide resuscitation strategies.

Congestion score index (CSI), a semiquantitative evaluation of congestion on chest radiography (CXR), is associated with outcome in patients with heart failure (HF). However, its diagnostic value in patients admitted for acute dyspnea has yet to be evaluated. The diagnostic value of CSI for acute HF (AHF; adjudicated from patients' discharge files) was studied in the Pathway of dyspneic patients in Emergency (PARADISE) cohort, including patients aged 18 years or older admitted for acute dyspnea in the emergency department (ED) of the Nancy University Hospital (France) between January 1, 2015 and December 31, 2015. CSI (ranging from 0 to 3) was evaluated using a semiquantitative method on CXR in consecutive patients admitted for acute dyspnea in the ED. Results were validated in independent cohorts (N = 224). Of 1,333 patients, mean (standard deviation [SD]) age was 72.0 (18.5) years, 686 (51.5%) were men, and mean (SD) CSI was 1.42 (0.79). Patients with higher CSI had more cardiovascular comorbidities, more severe congestion, higher b-type natriuretic peptide (BNP), poorer renal function, and more respiratory acidosis. AHF was diagnosed in 289 (21.7%) patients. CSI was significantly associated with AHF diagnosis (adjusted odds ratio [OR] for 0.1 unit CSI increase 1.19, 95% CI 1.16-1.22, p < 0.001) after adjustment for clinical-based diagnostic score including age, comorbidity burden, dyspnea, and clinical congestion. The diagnostic accuracy of CSI for AHF was >0.80, whether alone (area under the receiver operating characteristic curve [AUROC] 0.84, 95% CI 0.82-0.86) or in addition to the clinical model (AUROC 0.87, 95% CI 0.85-0.90). CSI improved diagnostic accuracy on top of clinical variables (net reclassification improvement [NRI] = 94.9%) and clinical variables plus BNP (NRI = 55.0%). Similar diagnostic accuracy was observed in the validation cohorts (AUROC 0.75, 95% CI 0.68-0.82). The key limitation of our derivation cohort was its single-center and retrospective nature, which was counterbalanced by the validation in the independent cohorts. In this study, we observed that a systematic semiquantified assessment of radiographic pulmonary congestion showed high diagnostic value for AHF in dyspneic patients. Better use of CXR may provide an inexpensive, widely, and readily available method for AHF triage in the ED.

IntroductionDyspnoea frequently leads to admissions in the Emergency Department (ED). Rapid and accurate diagnosis, specifically to distinguish acute heart failure from pneumonia and exacerbations of chronic obstructive pulmonary disease (COPD), is imperative to initiate appropriate therapy. This study aims to evaluate the feasibility and performance of the EMERgency ALgorithm efficiency for Dyspneic patient-UltraSound (EMERALD-US) algorithm using ultrasound (US) to diagnose the etiology of dyspnea in the ED-admitted patients.Method and analysis225 patients of 50 years and above, presenting with acute non-traumatic dyspnoea, across six participating EDs will be enrolled. Patients will undergo a lung, a simplified four-chamber cardiac and a venous US. A physician, blinded to any clinical data or previous results, will execute the algorithm. The algorithm’s performance will be assessed using a receiver operating characteristic (ROC) curve. Secondary objectives include an evaluation of the protocol’s feasibility in the ED, an assessment of the concordance between the EMERALD-US algorithm diagnoses and results from other diagnostic tests (including laboratory work and imaging), as well as an evaluation of the algorithm’s performance in diagnosing other causes of dyspnoea, such as pulmonary embolism or pleural effusion, and the 30-day mortality rate.Ethics and disseminationThe study protocol was approved by the French Committee for the Protection of Persons (CPP) (RCB n°2018-A02136-49). Misdiagnosis of dyspneic patients on ED admission has been associated with inappropriate treatment, prolonged hospital stays and increased mortality, particularly among elderly patients. The implementation of protocols like the EMERALD-US algorithm can help physicians in expedited decision-making and diagnosis without increasing ED visit durations.Trial registration numberNCT03691857.

BackgroundPlasma volume (PV) estimated from Duarte's formula (based on hemoglobin/hematocrit) has been associated with poor prognosis in patients with heart failure (HF). There are, however, limited data regarding the association of estimated PV status (ePVS) derived from hemoglobin/hematocrit with clinical profiles and study outcomes in patients with HF and preserved ejection fraction (HFpEF).Methods and resultsPatients from North and South America enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) with available hemoglobin/hematocrit data were studied. The association between ePVS (Duarte formula and Hakim formula) and the composite of cardiovascular mortality, HF hospitalization, or aborted cardiac arrest was assessed. Among 1747 patients (age 71.6 years; males 50.1%), mean ePVS derived from Duarte formula was 4.9 ± 1.0 mL/g. Higher Duarte-derived ePVS was associated with prior HF admission, diabetes, more severe congestion, poor renal function, higher natriuretic peptide level, and E/e'. After adjustment for potential covariates including natriuretic peptide, higher Duarte-derived ePVS was associated with an increased rate of the primary outcome [highest vs. lowest ePVS quartile: adjusted-HR (95%CI) = 1.79 (1.28–2.50), p < 0.001]. Duarte-derived ePVS improved prognostic performance on top of clinical and routine variables (including natriuretic peptides) (NRI = 11, p < 0.001), whereas Hakim-derived ePVS did not (p = 0.59). The prognostic value of Duarte-derived ePVS was not modified by renal function (P interaction > 0.10 for all outcomes).ConclusionePVS from Duarte’s formula was associated with congestion status and improved risk stratification regardless of renal function. Our findings suggest that Duarte-derived ePVS is a useful congestion variable in patients with HFpEF.Graphic abstract

Acute-on-chronic heart failure (ACHF) currently represents the leading etiology of cardiogenic shock (CS). We aimed to assess the prognostic value of history of heart failure (HF) in patients with refractory CS as well as its effect on the benefit of moderate hypothermia (MH) (33–34 °C). Of the 334 patients included in the HYPO-ECMO trial, 321 (96 %) had available HF history information, among whom 65 (20 %) had prior HF. Inverse probability weighting (IPW) was used to compare ACHF patients and de-novo HF (DNHF) patients. Primary outcome was all-cause mortality at day 30. Main secondary outcomes were mortality and the composite of death, heart transplant, escalation to left ventricular assist device, or stroke up to day 180. At 30 days, 26 patients (40.0 %) died in the ACHF group versus 122 patients (47.7 %) in the DNHF group (crude risk difference (RD), −7.7 % [−21.0 to 5.7] p = 0.26; IPW RD, −11.6 % [−24.8 to 1.6] p = 0.084). Mortality (IPW RD, −13.7 % [−27.1 to −0.2], p = 0.047) and the composite outcome (IPW RD, −19.5 % [−32.9 to −6.1], p = 0.004) were significantly lower at day 180 in the ACHF group. Patients randomized to MH tended to have a lower risk for the primary outcome (RD -10.9 %, [−23.1 to 1.2], p = 0.078) and a significant reduction in composite outcome (p < 0.05 at each timepoint) in the DNHF group but not in the ACHF group, despite the absence of a significant interaction (p > 0.05). In VA-ECMO-treated CS, ACHF was associated with comparable 30-day survival but lower 180-day mortality and morbidity-mortality. In this exploratory post-hoc analysis, MH appeared to be associated with improved outcomes in DNHF patients only. ClinicalTrials.gov Identifier: NCT02754193 [Display omitted] •In refractory cardiogenic shock treated with VA-ECMO, prior heart failure (HF) was not associated to higher 30-day mortality.•Prior HF should not preclude the use of VA-ECMO in refractory cardiogenic shock patients.•Despite the absence of interaction with HF status, moderate hypothermia (MH) appeared to exclusively benefit patients with de-novo HF.•Further research is needed to identify patients who could benefit from MH in CS managed with VA-ECMO.

Abstract Background The use of intravenous (IV) diuretics in an outpatient setting may represent an alternative to conventional hospitalization. Our objective was to identify factors associated with diuretic response during ambulatory IV diuretic sessions in a population of advanced heart failure with no therapeutic project and a frequent flyer profile. Method All patients with 4-h IV diuretic sessions were analysed. An initial bolus followed a tailored protocol for continuous infusion based on the patient's baseline diuretic dose. Variables associated with diuresis and natriuresis following furosemide infusion were evaluated using mixed linear models. Results Seventy-six patients (mean age 75.4 years; LVEF 42.7%; eGFR 40.7 mL/min/1.73 m2) totalling 175 IV diuretic sessions were included. Mean diuresis was 1.0 L, natriuresis 92.6 mmol/L, and weight loss 610 grams. Baseline use of ACE inhibitors (+302 mL, P = 0.0005), eGFR (+160 mL per 10 mL/min/1.73 m2 increase, P < 0.0001), and addition of thiazide during the diuretic session (+238 mL, P = 0.0001) were associated with higher diuresis. Prior percutaneous mitral valve repair or chronic thiazide treatment was associated with lower diuresis. Baseline use of ACE inhibitors (+10.83 mmol/L, P = 0.018) was associated with higher natriuresis. Worsening renal function (>3 mg/L increase from baseline) and dyskalaemia 48 h after these sessions were uncommon (respectively 11% and 15%). Conclusions Ambulatory 4-h IV loop diuretic sessions induced a diuresis of approximately 1000 mL with a substantial sodium content, without causing significant complications. Addition of thiazide during the session increased diuresis and/or natriuresis, and could potentially be implemented to maximize the efficacy of ambulatory IV diuretic therapy.

BackgroundSystemic congestion, evaluated by estimated plasma volume status (ePVS), is associated with in-hospital mortality in acute heart failure (AHF). However, the diagnostic and prognostic value of ePVS in patients with acute dyspnea has been insufficiently studied.ObjectivesTo assess the association between the first ePVS calculated from blood samples on admission in the emergency department (ED) and discharge diagnosis of AHF and in-hospital mortality in patients admitted for acute dyspnea.MethodsThe study included 1369 patients admitted for dyspnea in the ED in 2015. ePVS was calculated from hematocrit and hemoglobin values at admission. Comparisons of baseline characteristics according to ePVS tertiles were carried out and then associations between ePVS and the two outcomes “AHF diagnosis” and “intra-hospital mortality” were assessed using a logistic regression model.Results36.6% had a BNP > 400 pg/mL and median ePVS was 4.58 dL/g [3.96–5.55]. Overall in-hospital mortality was 11.1% (n = 149). In multivariable analysis, the third ePVS tertile (> 5.12 dL/g) had a significantly increased risk of having AHF (OR = 1.64 [1.16–2.33], p = 0.005). In-hospital mortality rose across ePVS tertiles (8.4–13.8% p < 0.01). ePVS greater than the first or second tertile threshold (respectively, 4.17 dL/g and 5.12 dL/g) were both significantly associated with a higher risk of in-hospital mortality (OR for 2nd/3rd tertile = 2.06 [1.25–3.38], p = 0.004 and OR for 3rd tertile = 1.54 [1.01–2.36], p = 0.04).ConclusionHigher ePVS values determined from first blood sample at admission are associated with a higher probability of AHF and in-hospital mortality in patients admitted in the ED for acute dyspnea.