Search

International audience; Aims: Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all etiologies.Methods and results: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. "Active cancer" was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72 vs 52%, p=0.005 and norepinephrine-dobutamine combination 64.7 vs 44.5%, p=0.005), but had less mechanical circulatory support (5.9 vs 19.5%, p=0.016). They presented similar 30-day mortality rate (29 vs 26%) but a significantly higher mortality at one-year (70.6 vs 45.2%, p

No abstract available.

BACKGROUND Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODS In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTS During a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P

Drugs that inhibit the sodium–glucose co‐transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new‐onset heart failure events by ≈30%. In addition, in the EMPA‐REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti‐hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR‐Reduced trial is enrolling ≈3600 patients with heart failure and a reduced left ventricular ejection fraction (≤ 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin–angiotensin system and neprilysin, beta‐blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time‐to‐first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all‐cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high‐risk patients. A large proportion of the participants is expected to have an ejection fraction

AIMS: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). METHODS AND RESULTS: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46). CONCLUSIONS: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02661217. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons peerReviewed

© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology, Aims: Congestion is a central feature of acute heart failure (HF) and its assessment is important for clinical decisions (e.g. tailoring decongestive treatments). It remains uncertain whether patients with acute HF with preserved ejection fraction (HFpEF) are comparably congested as in acute HF with reduced EF (HFrEF). This study assessed congestion, right ventricular (RV) and renal dysfunction in acute HFpEF, HFrEF and non-cardiac dyspnoea. Methods and results: We compared echocardiographic and circulating biomarkers of congestion in 146 patients from the MEDIA-DHF study: 101 with acute HF (38 HFpEF, 41 HFrEF, 22 HF with mid-range ejection fraction) and 45 with non-cardiac dyspnoea. Compared with non-cardiac dyspnoea, patients with acute HF had larger left and right atria, higher E/e’, pulmonary artery systolic pressure and inferior vena cava (IVC) diameter at rest, and lower IVC variability (all P 0.05) compared with HFrEF. Conclusion: In acute conditions, HFpEF and HFrEF presented in a comparable state of venous congestion, with similarly altered RV and kidney function, despite higher BNP in HFrEF., L.N.L.V.A. is supported by a training grant from the European Society of Cardiology (2015; Sophia Antipolis, France) and a travelling award from the International Society for Heart and Lung Transplantation (August 2015 and 2016; Addison, TX, USA). L.N.L.V.A. gratefully acknowledges the financial support from the Belgian Fund for Cardiac Surgery through the Jacqueline Bernheim prize 2015 (Brussels, Belgium). M.A. is recipient of a fellowship of the Collège de Médecine des Hôpitaux de Paris (Paris, France). M.F.S. received a grant from the Ligue Française contre la Cardiomyopathie (Montboissier, France). E.A. is supported by a research fellowship from the Japan Heart Foundation (Tokyo, Japan). This study is supported by a grant from the European Union (FP7-HEALTH-2010-MEDIA; Luxembourg) to F.Z., P.R., A.M

International audience; Agents with vasodilator properties (AVDs) are frequently used in the treatment of acute heart failure (AHF). AVDs rapidly reduce preload and afterload, improve left ventricle to aorta and right ventricle to pulmonary artery coupling, and may improve symptoms. Early biomarker changes after AVD administration have suggested potentially beneficial effects on cardiac stretch, vascular tone, and renal function. AVDs that reduce haemodynamic congestion without causing hypoperfusion might be effective in preventing worsening organ dysfunction. Existing AVDs have been associated with different results on outcomes in randomized clinical trials, and observational studies have suggested that AVDs may be associated with a clinical outcome benefit. Lessons have been learned from past AVD trials in AHF regarding preventing hypotension, selecting the optimal endpoint, refining dyspnoea measurements, and achieving early randomization and treatment initiation. These lessons have been applied to the design of ongoing pivotal clinical trials, which aim to ascertain if AVDs improve clinical outcomes. The developing body of evidence suggests that AVDs may be a clinically effective therapy to reduce symptoms, but more importantly to prevent end-organ damage and improve clinical outcomes for specific patients with AHF. The results of ongoing trials will provide more clarity on the role of AVDs in the treatment of AHF.

Heart failure (HF) is highly prevalent disease, and prevalence increases with age. HF is generally discovered on presentation of an acute episode of decompensation (or insufficiency). Acute decompensated heart failure (ADHF) is very frequent in elderly subjects and is difficult to diagnose when the patient is admitted with acute dyspnoea. The advent of plasma biomarkers, such as BNP or NT-proBNP represents a major advancement in the diagnostic of ADHF. ADHF leads to high rates of re-admission and mortality. The objectives of this doctoral thesis were: (1) to describe the epidemiology of ADHF in France in a one-day observational study of admissions for ADHF in 170 French hospitals; (2) to evaluate the prognostic and diagnostic value of natriuretic peptides (NPs) in ADHF; (3) to describe the extent of post-transcriptional modifications in these NPs in ADHF; and (4) to search for new biomarkers.The comparison of the prognostic and diagnostic properties of NPs showed that the 4 commercially available NPs (namely BNP, NT-proBNP, proBNP and MR-proANP) overall have very similar prognostic and diagnostic abilities. However, proBNP and BNP seem to be more useful for diagnosis, while MR-proANP appears to be better for the association with 5-year mortality.Amongthe post-transcriptional modifications of BNP, we studied the impact of glycosylation of pro¬BNP. Threonin 71 0-glycosylation prevents cleavage of proBNP into BNP and NT-proBNP, resulting in the release of proBNP from the cell without being cleaved. Conversely, non-glycosylated proBNP is cleaved into BNP and NT-proBNP by corin or furin. We showed that non-glycosylation of proBNP and activation of furin are two important mechanisms in the acceleration of production of NPs during ADHF. We also showed that production of NT-proBNP was more closely linked to the rate of glycosylation of proBNP than to the production of BNP. Thus, our results strongly suggest that NT-proBNP should be used in future studies exploring the concept of "biomarker-guided therapy" in ADHF.To investigate new biomarkers, we explored plasma concentrations of 5 microRNAs (miR-l/-21/-23/-126/-423-5p), in patients with acute dyspnoea. None of these microRNAs were shown to have any diagnostic value. Conversely, miR-423-5p appears to be a prognostic marker for re-admission at 1 year. Secondly, we investigated the consequences of cardiac congestion on the liver. The hepatic markers studied were alkaline phosphatise and transaminases. Markers of cholestasis were associated with hepatic congestive while markers of cellular necrosis (transaminases) were related to arterial hypertension and low cardiac output. An increase in transaminases was associated with various criteria of excess mortality in the short term; L'insuffisance cardiaque (IC) est une maladie dont la prévalence est élevée, cette prévalence augmente avec l'âge. La découverte de la maladie se fait le plus souvent lors d'un épisode de décompensation (ou insuffisance) cardiaque aiguë (ICA). L'ICA est très fréquente chez les sujets âgés et est caractérisée par des difficultés diagnostiques quand le patient est admis avec une dyspnée aiguë. L'apport de biomarqueurs plasmatiques tels que le BNP ou le NT-proBNP a été majeur pour le diagnostic de l'ICA. La décompensation cardiaque aiguë est suivie d'un taux de réhospitalisations et d'une mortalité très élevés. Les objectifs de la thèse était 1- de préciser l'épidémiologie de l'ICA en France lors d'un observatoire d'une journée des hospitalisations pour ICA dans 170 hôpitaux français (OFICA), 2- d'identifier la puissance diagnostiques et pronostiques des peptides natriurétiques lors de l'ICA, 3-de définir l'importance des modifications post-transcriptionnelles de ces PNs lors de l'ICA, 4- de rechercher de nouveaux biomarqueurs.La comparaison des propriétés diagnostiques et pronostiques des peptides natriurétiques révèle que les 4 peptides natriurétiques commercialement accessibles (BNP, NT-proBNP, proBNP et MR-proANP) ont des qualités diagnostiques et pronostiques globalement très similaires. Néanmoins, proBNP et BNP semblent meilleurs pour le diagnostic tandis que MR-proANP apparaît meilleur pour son association avec la mortalité à 5 ans.Parmi les modifications post-transcriptionnelles du BNP, nous avons étudié l'impact de la glycosylation du pro-BNP. La O glycosylation en 71 inactive proBNP, qui est libéré hors de la cellule sans action préalable des enzymes de « cleavage » la corine ou la furine. En revanche, le proBNP non-glycosylé est scindé en BNP et NT-proBNP par la corine ou la furine. Nous avons pu montrer que la non-glycosylation du proBNP et l'activation de la furine étaient deux mécanismes très importants d'accélération de la production de peptides natriurétiques lors de l'ICA. On a pu également montrer que la production du NT-proBNP était beaucoup plus liée au niveau glycosylation du proBNP que ne l'est la production de BNP. Ainsi, nos résultats suggèrent fortement d'utiliser le NT-proBNP pour toute étude future souhaitant explorer le concept de « biomarker-guided therapy » dans l'ICA.Pour la recherche de nouveaux biomarqueurs, nous avons exploré 1-la concentration plasmatique de 5 microRNAs (miR-l/-21/-23/-126/-423-5p), chez des patients avec dyspnée aiguë. Aucun de ces miR n'a de valeur diagnostique, en revanche, le miR-423-5p apparaît être un marqueur pronostique de réhospitalisation à un an ; 2-les conséquences de la congestion cardiaque sur le foie. Les marqueurs hépatiques étudiés étaient la phosphatase alcaline et les transaminases : les marqueurs de la cholestase étaient associés à une congestion hépatique tandis que ceux de la nécrose cellulaires (transaminases) étaient liés à l'hypotension artérielle et au bas débit cardiaque. L'augmentation des transaminases a été associée à divers critères dont une surmortalité à court terme

The aim of this study was to assess the prevalence of abnormal liver function tests (LFTs) and the associated clinical profile and outcome(s) in acute decompensated heart failure (ADHF) patients. Alteration in LFTs is a recognized feature of ADHF, but prevalence and outcomes data from a broad contemporary cohort of ADHF are scarce and the mechanism(s) of ADHF-induced cholestasis is unknown. We conducted a post hoc analysis of SURVIVE, a large clinical trial including ADHF patients treated with levosimendan or dobutamine. All LFTs were available in 1134 patients at baseline. Abnormal LFTs were seen in 46 of ADHF patients: isolated abnormal alkaline phosphatase (AP) was noted in 11, isolated abnormal transaminases in 26, and a combination of abnormal AP and transaminases in 9. Abnormal AP was associated with marked signs of systemic congestion and elevated right-sided filling pressure. Abnormal AP had no relationship with 31-day mortality but was associated with worse 180-day mortality (23.5 vs. 34.9, P 0.001 vs. patients with normal AP). Abnormal transaminases were associated with clinical signs of hypoperfusion and with greater 31-day and 180-day mortality compared with normal transaminase profiles (17.6 vs. 8.4 and 31.6 vs. 22.4, respectively; both P 0.001). There was no additive value of abnormal AP plus abnormal transaminase on a long-term outcome. Abnormal LFTs were present in about a half of patients presenting with ADHF treated with inotropes. Abnormal AP and abnormal transaminases were associated with specific clinical, biological, and prognostic features, including a short-term overmortality with increased transaminases but not with biological signs of cholestasis, in ADHF patients.

Aims: EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials. Methods and results: EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 �� 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41���50%. The mean LVEF (54 �� 9%) was slightly lower while the median NT-proBNP [974 (499���1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor���neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists. Conclusion: When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.

WOS: 000316128800011, PubMed ID: 23091203, The aim of this study was to assess the prevalence of abnormal liver function tests (LFTs) and the associated clinical profile and outcome(s) in acute decompensated heart failure (ADHF) patients. Alteration in LFTs is a recognized feature of ADHF, but prevalence and outcomes data from a broad contemporary cohort of ADHF are scarce and the mechanism(s) of ADHF-induced cholestasis is unknown. We conducted a post hoc analysis of SURVIVE, a large clinical trial including ADHF patients treated with levosimendan or dobutamine. All LFTs were available in 1134 patients at baseline. Abnormal LFTs were seen in 46 of ADHF patients: isolated abnormal alkaline phosphatase (AP) was noted in 11, isolated abnormal transaminases in 26, and a combination of abnormal AP and transaminases in 9. Abnormal AP was associated with marked signs of systemic congestion and elevated right-sided filling pressure. Abnormal AP had no relationship with 31-day mortality but was associated with worse 180-day mortality (23.5 vs. 34.9, P 0.001 vs. patients with normal AP). Abnormal transaminases were associated with clinical signs of hypoperfusion and with greater 31-day and 180-day mortality compared with normal transaminase profiles (17.6 vs. 8.4 and 31.6 vs. 22.4, respectively; both P 0.001). There was no additive value of abnormal AP plus abnormal transaminase on a long-term outcome. Abnormal LFTs were present in about a half of patients presenting with ADHF treated with inotropes. Abnormal AP and abnormal transaminases were associated with specific clinical, biological, and prognostic features, including a short-term overmortality with increased transaminases but not with biological signs of cholestasis, in ADHF patients., Abbott; Orion Pharma, SURVIVE study was sponsored by Abbott and Orion Pharma.