Publications by authors named "Nicolas Girerd"

235 Publications

Lower is not always the better: A better understanding of loop diuretics in HF.

Eur J Heart Fail 2021 Apr 7. Epub 2021 Apr 7.

Duke Clinical Research Institute, Durham, North Carolina, USA.

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http://dx.doi.org/10.1002/ejhf.2182DOI Listing
April 2021

Spironolactone effect on the blood pressure of patients at risk of developing heart failure: an analysis from the HOMAGE trial.

Eur Heart J Cardiovasc Pharmacother 2021 Apr 2. Epub 2021 Apr 2.

Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, 1433, U1116, France.

Background: Uncontrolled blood pressure (BP) increases the risk of developing heart failure (HF). The effect of spironolactone on BP of patients at risk of developing HF is yet to be determined.

Aims: To evaluate the effect of spironolactone on the BP of patients at risk for HF and whether renin can predict spironolactone`s effect.

Methods: HOMAGE (Heart OMics in Aging) was a prospective multicenter randomized open-label blinded Endpoint (PROBE) trial including 527 patients at risk for developing HF randomly assigned to either spironolactone (25-50mg/day) or usual care alone for a maximum of 9 months. Sitting BP was assessed at baseline, month 1 and 9 (or last visit). Analysis of covariance (ANCOVA), mixed effects models, and structural modelling equations were used.

Results: The median (percentile25-75) age was 73 (69-79) years, 26% were female, and >75% had history of hypertension. Overall, the baseline BP was 142/78 mmHg. Patients with higher BP were older, more likely to have diabetes and less likely to have coronary artery disease, had greater left ventricular mass (LVM), and left atrial volume (LAV). Compared with usual care, by last visit, spironolactone changed SBP by -10.3 (-13.0 to -7.5)mmHg and DBP by -3.2 (-4.8 to -1.7)mmHg (p < 0.001 for both). A higher proportion of patients on spironolactone had controlled BP < 130/80 mmHg (36 vs. 26%; p = 0.014). Lower baseline renin levels predicted a greater response to spironolactone (interactionp=0.041).

Conclusion: Spironolactone had a clinically important BP-lowering effect. Spironolactone should be considered for lowering blood pressure in patients who are at risk of developing HF.
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http://dx.doi.org/10.1093/ehjcvp/pvab031DOI Listing
April 2021

Serum microRNAs and antifibrotic response to eplerenone in acute myocardial infarction complicated by systolic dysfunction.

Int J Cardiol 2021 Mar 5. Epub 2021 Mar 5.

Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France. Electronic address:

Background: After myocardial infarction (MI) complicated by heart failure (HF), eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of eplerenone as measured by a PICP and PIIINP decrease is unclear.

Methods: A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied.

Results: From the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to -0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of eplerenone on PICP and PIIINP changes.

Conclusion: Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.
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http://dx.doi.org/10.1016/j.ijcard.2021.02.088DOI Listing
March 2021

Risk stratification with echocardiographic biomarkers in heart failure with preserved ejection fraction: the media echo score.

ESC Heart Fail 2021 Mar 3. Epub 2021 Mar 3.

Inserm, Centre d'Investigations Cliniques-Plurithématique 1433, Inserm U1116, CHRU Nancy, Université de Lorraine, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.

Aims: Echocardiographic predictors of outcomes in heart failure with preserved ejection fraction (HFpEF) have not been systematically or independently validated. We aimed at identifying echocardiographic predictors of cardiovascular events in a large cohort of patients with HFpEF and to validate these in an independent large cohort.

Methods And Results: We assessed the association between echocardiographic parameters and cardiovascular outcomes in 515 patients with heart failure with preserved left ventricular (LV) ejection fraction (>50%) in the MEtabolic Road to DIAstolic Heart Failure (MEDIA) multicentre study. We validated out findings in 286 patients from the Karolinska-Rennes Prospective Study of HFpEF (KaRen). After multiple adjustments including N-terminal pro-brain natriuretic peptide (NT-proBNP), the significant predictors of death or cardiovascular hospitalization were pulmonary arterial systolic pressure > 40 mmHg, respiratory variation in inferior vena cava diameter > 0.5, E/e' > 9, and lateral mitral annular s' < 7 cm/s. The combination of these four variables differentiated patients with <10% vs. >35% 1 year risk. Adding these four echocardiographic variables on top of clinical variables and NT-proBNP yielded significant net reclassification improvement (33.8%, P < 0.0001) and increase in C-index (5.3%, a change from 72.2% to 77.5%, P = 0.015) of similar magnitude as the addition of NT-proBNP on top of clinical variables alone. In the KaRen cohort, these four variables yielded a similar improvement in net reclassification improvement (22.3%, P = 0.014) and C-index (4.0%, P = 0.029).

Conclusions: Use of four simple echocardiographic parameters (within the MEDIA echo score), indicative of pulmonary hypertension, elevated central venous pressure, LV diastolic dysfunction, and LV long-axis systolic dysfunction, independently predicted prognosis and improved risk stratification additionally to clinical variables and NT-proBNP in HFpEF. This finding was validated in an independent cohort.
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http://dx.doi.org/10.1002/ehf2.13251DOI Listing
March 2021

Clinical profile and midterm prognosis of left ventricular thrombus in heart failure.

ESC Heart Fail 2021 Apr 25;8(2):1333-1341. Epub 2021 Feb 25.

Université de Lorraine, Inserm, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU Nancy, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.

Aims: We documented the midterm prognosis of left ventricular thrombus (LVT) in heart failure (HF) patients with dilated cardiomyopathy (DCM) and ischaemic cardiomyopathy (ICM). We aimed to characterize patients with LVT in the context of HF with reduced (≤40%) left ventricular ejection fraction and evaluate their risk for death and/or embolic events, overall, and specifically in patients with ischaemic or non-ischaemic aetiology. We also intended to identify risk factors for LVT in patients with DCM.

Methods And Results: We included all HF patients (N = 105, age 56 ± 13) admitted from 2005 to 2018 in our institution for LVT without significant valve disease/prosthesis, heart transplant/left ventricular assist device, congenital heart disease, or acute myocardial infarction. Our primary endpoint was the 1 year risk of the composite of all-cause mortality (ACM) and symptomatic embolic events. Mean left ventricular ejection fraction was 23 ± 9%, and median BNP was 1795 pg/mL. Most (97%) patients were treated with vitamin K anticoagulants, and 64% had ICM. Symptomatic embolic events and/or ACM occurred in 20% of the population [embolic events (all within 30 days of LVT diagnosis) 15% and ACM 6%] and was similarly frequent in DCM or ICM (P > 0.05). Suspected/transient embolic events were more frequent in DCM (overall 13%; 29% in DCM vs. 5% in ICM, P < 0.01). Major bleeding occurred in 5% of patients. Left ventricular reverse remodelling occurred in 65% of patients, more frequently in DCM (86% in DCM vs. 65% in ICM, P = 0.02). In a case-control analysis matching DCM patients, BNP level was the only factor significantly associated with LVT (2447 pg/mL in LVT vs. 347 pg/mL, P < 0.001).

Conclusions: Patients with LVT have markedly high natriuretic peptides and experience a 20% 1 year risk for embolic events and/or death following diagnosis despite anticoagulant treatment. Most patients have favourable remodelling/recovery. As all symptomatic embolic events occurred within 30 days of LVT diagnosis, a very careful initial management is warranted.
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http://dx.doi.org/10.1002/ehf2.13211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006720PMC
April 2021

Non-fatal cardiovascular events preceding sudden cardiac death in patients with an acute myocardial infarction complicated by heart failure: insights from the high-risk myocardial infarction database.

Eur Heart J Acute Cardiovasc Care 2021 Apr;10(2):127-131

National Institute of Health and Medical Research Center for Clinical Multidisciplinary Research, INSERM U1116, Université de Lorraine, Inserm, Centre d'Investigations cliniques-plurithématique 1433, Inserm U1116; CHRU Nancy; F-CRIN INI-CRCT network, Nancy, France.

Aims: Among patients with acute myocardial infarction (AMI) complicated by heart failure [HF; clinical HF or left ventricular (LV) systolic dysfunction], we explored the probability of subsequent non-fatal cardiovascular (CV) events and sudden cardiac death (SCD).

Methods And Results: The high-risk myocardial infarction (HRMI) database contains 28 771 patients with signs of HF or reduced LV ejection fraction (<40%) after AMI. We evaluated the temporal association between SCD with preceding non-fatal CV event [HF hospitalization, recurrent myocardial infarction (MI), or stroke]. Median follow-up was 1.9 years. Mean age was 65.0 ± 11.5 years and 70% were male. The incidence of CV death was 7.9 per 100 patient-years and for SCD was 3.1 per patient-years (40% of CV deaths). The incidence of SCD preceded by HF hospitalization was greater than SCD without preceding HF hospitalization (P < 0.05). However, overall, SCD was less likely to be preceded by a non-fatal CV event compared to other causes of death: 9.6% of SCD events were preceded by an MI (vs. 46.6% for non-sudden CV death); 17.0% of SCD events were preceded with an HF hospitalization (vs. 25.4% for non-sudden CV death); and 2.7% of SCD events were preceded by stroke (vs.12.9% for non-sudden CV death).

Conclusion: Among patients with AMI complicated by HF, SCD, compared with other causes of death, was less likely to be preceded by a non-fatal CV event. As patients are less likely to have preceding non-fatal CV events to alert the healthcare team of a possible impending SCD event, additional strategies for risk stratification for SCD are needed.
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http://dx.doi.org/10.1093/ehjacc/zuaa012DOI Listing
April 2021

Head-to-head comparison of clustering methods for heterogeneous data: a simulation-driven benchmark.

Sci Rep 2021 Feb 18;11(1):4202. Epub 2021 Feb 18.

Centre d'Investigations Cliniques Plurithématique 1433, INSERM 1116, CHRU de Nancy, Université de Lorraine, Nancy, France.

The choice of the most appropriate unsupervised machine-learning method for "heterogeneous" or "mixed" data, i.e. with both continuous and categorical variables, can be challenging. Our aim was to examine the performance of various clustering strategies for mixed data using both simulated and real-life data. We conducted a benchmark analysis of "ready-to-use" tools in R comparing 4 model-based (Kamila algorithm, Latent Class Analysis, Latent Class Model [LCM] and Clustering by Mixture Modeling) and 5 distance/dissimilarity-based (Gower distance or Unsupervised Extra Trees dissimilarity followed by hierarchical clustering or Partitioning Around Medoids, K-prototypes) clustering methods. Clustering performances were assessed by Adjusted Rand Index (ARI) on 1000 generated virtual populations consisting of mixed variables using 7 scenarios with varying population sizes, number of clusters, number of continuous and categorical variables, proportions of relevant (non-noisy) variables and degree of variable relevance (low, mild, high). Clustering methods were then applied on the EPHESUS randomized clinical trial data (a heart failure trial evaluating the effect of eplerenone) allowing to illustrate the differences between different clustering techniques. The simulations revealed the dominance of K-prototypes, Kamila and LCM models over all other methods. Overall, methods using dissimilarity matrices in classical algorithms such as Partitioning Around Medoids and Hierarchical Clustering had a lower ARI compared to model-based methods in all scenarios. When applying clustering methods to a real-life clinical dataset, LCM showed promising results with regard to differences in (1) clinical profiles across clusters, (2) prognostic performance (highest C-index) and (3) identification of patient subgroups with substantial treatment benefit. The present findings suggest key differences in clustering performance between the tested algorithms (limited to tools readily available in R). In most of the tested scenarios, model-based methods (in particular the Kamila and LCM packages) and K-prototypes typically performed best in the setting of heterogeneous data.
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http://dx.doi.org/10.1038/s41598-021-83340-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892576PMC
February 2021

Circulating multimarker approach to identify patients with preclinical left ventricular remodelling and/or diastolic dysfunction.

ESC Heart Fail 2021 Apr 12;8(2):1700-1705. Epub 2021 Feb 12.

Université de Lorraine, Centre d'Investigations Cliniques-Plurithématique, Inserm1433, CHRU Nancy, Inserm DCAC, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM CHU de Nancy, Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu, 4 Rue du Morvan, 54500 Vandoeuvre lès, Nancy, France.

Aims: Biomarkers reflecting myocardial fibrosis and inflammation have been individually associated with left ventricular hypertrophy (LVH) and diastolic dysfunction (DD). However, the added value of a fibrosis-inflammation multimarker approach in a populational setting is yet to be studied. We evaluated the value of a multimarker approach to detect LVH and DD in a large population-based cohort.

Methods And Results: In a prespecified analysis (BioSe-PreIC study) of the 4th visit of the STANISLAS cohort (1705 subjects, 47 ± 14 years, 47.4% men), we evaluated the ability of brain natriuretic peptide (BNP), Galectin-3 (GAL3), N-terminal propeptide of procollagen type III (P3NP), and soluble ST2 to predict LVH (LV mass > 116/100 g/m for men/women) and DD using discrimination (C-index) and reclassification analysis (NRI). Participants with LVH and/or DD had significantly higher levels of BNP, GAL3, and ST2. Overall, the predictive value of clinical variables for LVH and/or DD was good (C-index ranging from 0.76 to 0.82) and the addition of BNP, Gal3, P3NP, and ST2 moderately but significantly improved predictive value (delta C-index = 0.03, P = 0.03 for LVH and 0.01, P = 0.01 for DD) and reclassification (NRI = 25.3, P = 0.02 for LVH and NRI = 32.7 for DD, P < 0.0001). Gal3, P3NP, and ST2 significantly improved predictive value (delta C-index = 0.01, P = 0.01) and reclassification (NRI = 31.3, P < 0.0001) for DD of top of clinical variables and BNP.

Conclusions: As the measurement of Gal3, P3NP, and ST2 results in marginal (even if significant) increase in the prediction of DD/LVH on top of routine evaluation, their systematic use should not be promoted in unselected healthy individuals to screen for preclinical DD. Further research is needed to determine whether a more personalized medicine approach combing proteomic and clinical scoring can amplify the added value of biomarkers to identify preclinical DD.
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http://dx.doi.org/10.1002/ehf2.13203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006620PMC
April 2021

Proteomic and Mechanistic Analysis of Spironolactone in Patients at Risk for HF.

JACC Heart Fail 2021 Apr 3;9(4):268-277. Epub 2021 Feb 3.

Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique 1433, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France. Electronic address:

Objectives: This study sought to further understand the mechanisms underlying effect of spironolactone and assessed its impact on multiple plasma protein biomarkers and their respective underlying biologic pathways.

Background: In addition to their beneficial effects in established heart failure (HF), mineralocorticoid receptor antagonists may act upstream on mechanisms, preventing incident HF. In people at risk for developing HF, the HOMAGE (Heart OMics in AGEing) trial showed that spironolactone treatment could provide antifibrotic and antiremodeling effects, potentially slowing the progression to HF.

Methods: Baseline, 1-month, and 9-month (or last visit) plasma samples of HOMAGE participants were measured for protein biomarkers (n = 276) by using Olink Proseek-Multiplex cardiovascular and inflammation panels (Olink, Uppsala, Sweden). The effect of spironolactone on biomarkers was assessed by analysis of covariance and explored by knowledge-based network analysis.

Results: A total of 527 participants were enrolled; 265 were randomized to spironolactone (25 to 50 mg/day) and 262 to standard care ("control"). The median (interquartile range) age was 73 years (69 to 79 years), and 26% were female. Spironolactone reduced biomarkers of collagen metabolism (e.g., COL1A1, MMP-2); brain natriuretic peptide; and biomarkers related to metabolic processes (e.g., PAPPA), inflammation, and thrombosis (e.g., IL17A, VEGF, and urokinase). Spironolactone increased biomarkers that reflect the blockade of the mineralocorticoid receptor (e.g., renin) and increased the levels of adipokines involved in the anti-inflammatory response (e.g., RARRES2) and biomarkers of hemostasis maintenance (e.g., tPA, UPAR), myelosuppressive activity (e.g., CCL16), insulin suppression (e.g., RETN), and inflammatory regulation (e.g., IL-12B).

Conclusions: Proteomic analyses suggest that spironolactone exerts pleiotropic effects including reduction in fibrosis, inflammation, thrombosis, congestion, and vascular function improvement, all of which may mediate cardiovascular protective effects, potentially slowing progression toward heart failure. (HOMAGE [Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure]; NCT02556450).
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http://dx.doi.org/10.1016/j.jchf.2020.11.010DOI Listing
April 2021

Intravenous Mineralocorticoid Receptor Antagonist Use in Acutely Decompensated Heart Failure with Diuretic Resistance.

Int Heart J 2021 Jan 16;62(1):193-196. Epub 2021 Jan 16.

Université de Lorraine, INSERM, Centre d'Investigations Cliniques 1433, CHRU de Nancy, Inserm 1116 and INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network.

Intravenous mineralocorticoid receptor antagonists (MRAs) have been used in some centers for decades to reduce the risk of hypokalemia and boost diuresis in acutely decompensated heart failure (ADHF). We report the well-tolerated use of intravenous MRAs as a rescue procedure in 3 patients admitted for ADHF with important diuretic resistance. Undertaking trials evaluating the effect of this therapeutic strategy in ADHF could represent a promising avenue.
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http://dx.doi.org/10.1536/ihj.20-442DOI Listing
January 2021

Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study.

Crit Care 2021 01 7;25(1):21. Epub 2021 Jan 7.

INSERM CIC1433, Nancy University Hospital, 54000, Nancy, France.

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. 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).
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http://dx.doi.org/10.1186/s13054-020-03445-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791811PMC
January 2021

Estimated plasma volume status in heart failure: clinical implications and future directions.

Clin Res Cardiol 2021 Jan 6. Epub 2021 Jan 6.

Centre d'Investigations Cliniques Plurithématique, INSERM 1433, CHRU de Nancy, Inserm 1116 and INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network, Université de Lorraine, Nancy, France.

Congestion is one of the main predictors of poor outcome in patients with heart failure (HF). Assessing and monitoring congestion is essential for optimizing HF therapy. Among the various available methods, serial measurements of estimated plasma volume (ePVS) using routine blood count and/or body weight (e.g., the Strauss, Duarte, Hakim formulas) may be useful in HF management. Further prospective study is warranted to determine whether ePVS can help optimize decongestion therapy (loop diuretics, mineralocorticoid receptor antagonists, SGLT2i) in various HF settings. This narrative review summarizes the recent evidence supporting the association of ePVS with clinical congestion and outcome(s) and discusses future directions for monitoring ePVS in HF.
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http://dx.doi.org/10.1007/s00392-020-01794-8DOI Listing
January 2021

Cardiovascular imaging "guidelines" - High time for a paradigm shift.

Int J Cardiol 2021 Apr 31;329:246-248. Epub 2020 Dec 31.

Inserm Centre d'Investigations Cliniques-1433, Inserm DCAC, F-CRIN INI-CRCT, CHRU Nancy, Université de Lorraine, Nancy, France.

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http://dx.doi.org/10.1016/j.ijcard.2020.12.030DOI Listing
April 2021

Pre-Hospital Management of Critically Ill Patients with SARS-CoV-2 Infection: A Retrospective Multicenter Study.

J Clin Med 2020 Nov 21;9(11). Epub 2020 Nov 21.

Emergency Department, University Hospital of Nancy, 29 Avenue du Maréchal de Lattre de Tassigny, 54035 Nancy, France.

Introduction: The COVID-19 outbreak had a major impact on healthcare systems worldwide. Our study aims to describe the characteristics and therapeutic emergency mobile service (EMS) management of patients with vital distress due to COVID-19, their in-hospital care pathway and their in-hospital outcome.

Methods: This retrospective and multicentric study was conducted in the six main centers of the French Greater East region, an area heavily impacted by the pandemic. All patients requiring EMS dispatch and who were admitted straight to the intensive care unit (ICU) were included. Clinical data from their pre-hospital and hospital management were retrieved.

Results: We included a total of 103 patients (78.6% male, median age 68). In the initial stage, patients were in a critical condition (median oxygen saturation was 72% (60-80%)). In the field, 77.7% (CI 95%: 71.8-88.3%) were intubated. Almost half of our population (45.6%, CI 95%: 37.1-56.9%) had clinical Phenotype 1 (silent hypoxemia), while the remaining half presented Phenotype 2 (acute respiratory failure). In the ICU, a great number had ARDS (77.7%, CI 95% 71.8-88.3% with a PaO/FiO < 200). In-hospital mortality was 33% (CI 95%: 24.6-43.3%). The two phenotypes showed clinical and radiological differences (respiratory rate, OR = 0.98, = 0.02; CT scan lesion extension >50%, OR = 0.76, < 0.03). However, no difference was found in terms of overall in-hospital mortality (OR = 1.07, = 0.74).

Conclusion: The clinical phenotypes appear to be very distinguishable in the pre-hospital field, yet no difference was found in terms of mortality. This leads us to recommend an identical management in the initial phase, despite the two distinct presentations.
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http://dx.doi.org/10.3390/jcm9113744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700636PMC
November 2020

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial.

Eur Heart J 2021 Feb;42(6):684-696

Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique 1433, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, U1116, France.

Aims : To investigate the effects of spironolactone on fibrosis and cardiac function in people at increased risk of developing heart failure.

Methods And Results : Randomized, open-label, blinded-endpoint trial comparing spironolactone (50 mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma B-type natriuretic peptides. The primary endpoint was the interaction between baseline serum galectin-3 and changes in serum procollagen type-III N-terminal pro-peptide (PIIINP) in participants assigned to spironolactone or control. Procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), reflecting synthesis and degradation of type-I collagen, were also measured. In 527 participants (median age 73 years, 26% women), changes in PIIINP were similar for spironolactone and control [mean difference (mdiff): -0.15; 95% confidence interval (CI) -0.44 to 0.15 μg/L; P = 0.32] but those receiving spironolactone had greater reductions in PICP (mdiff: -8.1; 95% CI -11.9 to -4.3 μg/L; P < 0.0001) and PICP/CITP ratio (mdiff: -2.9; 95% CI -4.3 to -1.5; <0.0001). No interactions with serum galectin were observed. Systolic blood pressure (mdiff: -10; 95% CI -13 to -7 mmHg; P < 0.0001), left atrial volume (mdiff: -1; 95% CI -2 to 0 mL/m2; P = 0.010), and NT-proBNP (mdiff: -57; 95% CI -81 to -33 ng/L; P < 0.0001) were reduced in those assigned spironolactone.

Conclusions : Galectin-3 did not identify greater reductions in serum concentrations of collagen biomarkers in response to spironolactone. However, spironolactone may influence type-I collagen metabolism. Whether spironolactone can delay or prevent progression to symptomatic heart failure should be investigated.
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http://dx.doi.org/10.1093/eurheartj/ehaa758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878013PMC
February 2021

Diagnostic performance of congestion score index evaluated from chest radiography for acute heart failure in the emergency department: A retrospective analysis from the PARADISE cohort.

PLoS Med 2020 11 11;17(11):e1003419. Epub 2020 Nov 11.

Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm, CHRU Nancy, F-CRIN INI-CRCT, Nancy, France.

Background: 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.

Methods And Findings: 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.

Conclusions: 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.
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http://dx.doi.org/10.1371/journal.pmed.1003419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657510PMC
November 2020

Prognostic value for long-term graft survival of estimated glomerular filtration rate and proteinuria quantified at 3 months after kidney transplantation.

Clin Kidney J 2020 Oct 26;13(5):791-802. Epub 2020 Apr 26.

Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Vandoeuvre-lès-Nancy, France.

Background: The estimated glomerular filtration rate (eGFR) measured at 1 year is the usual benchmark applied in kidney transplantation (KT). However, acting on earlier eGFR values could help in managing KT during the first post-operative year. We aimed to assess the prognostic value for long-term graft survival of the early (3 months) quantification of eGFR and proteinuria following KT.

Methods: The 3-, 6- and 12-month eGFR using the Modified Diet in Renal Disease equation (eGFR) was determined and proteinuria was measured in 754 patients who underwent their first KT between 2000 and 2010 (with a mean follow-up of 8.3 years) in our centre. Adjusted associations with graft survival were estimated using a multivariable Cox model. The predictive accuracy was estimated using the C-index and net reclassification index. These same analyses were measured in a multicentre validation cohort of 1936 patients.

Results: Both 3-month eGFR and proteinuria were independent predictors of return to dialysis (all P < 0.05) and there was a strong correlation between eGFR at 3 and 12 months (Spearman's ρ = 0.76). The predictive accuracy of the 3-month eGFR was within a similar range and did not differ significantly from the 12-month eGFR in either the derivation cohort [C-index 62.6 (range 57.2-68.1) versus 66.0 (range 60.1-71.9), P = 0.41] or the validation cohort [C-index 69.3 (range 66.4-72.1) versus 71.7 (range 68.7-74.6), P = 0.25].

Conclusion: The 3-month eGFR was a valuable predictor of the long-term return to dialysis whose predictive accuracy was not significantly less than that of the 12-month eGFR in multicentre cohorts totalling >2500 patients. Three-month outcomes may be useful in randomized controlled trials targeting early therapeutic interventions.
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http://dx.doi.org/10.1093/ckj/sfaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577768PMC
October 2020

Ultrasound imaging of congestion in heart failure: examinations beyond the heart.

Eur J Heart Fail 2020 Oct 29. Epub 2020 Oct 29.

Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique, INSERM 1433, CHRU de Nancy, Institut Lorrain du Coeur et des Vaisseaux, Nancy, France.

Congestion, related to pressure and/or fluid overload, plays a central role in the pathophysiology, presentation and prognosis of heart failure and is an important therapeutic target. While symptoms and physical signs of fluid overload are required to make a clinical diagnosis of heart failure, they lack both sensitivity and specificity, which might lead to diagnostic delay and uncertainty. Over the last decades, new ultrasound methods for the detection of elevated intracardiac pressures and/or fluid overload have been developed that are more sensitive and specific, thereby enabling earlier and more accurate diagnosis and facilitating treatment strategies. Accordingly, we considered that a state-of-the-art review of ultrasound methods for the detection and quantification of congestion was timely, including imaging of the heart, lungs (B-lines), kidneys (intrarenal venous flow), and venous system (inferior vena cava and internal jugular vein diameter).
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http://dx.doi.org/10.1002/ejhf.2032DOI Listing
October 2020

Dyskalemia: a management problem for students.

Fundam Clin Pharmacol 2021 Apr 3;35(2):473-484. Epub 2020 Dec 3.

Inserm, Centre d'Investigations Cliniques- Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Vandoeuvre, France.

Background: Although dyskalemia is common, its management can be problematic for students and general practitioners, especially when it occurs in patients with heart and renal failure. The basic academic knowledge of general medicine students, who have often not yet encountered clinical situations of dyskalemia, remains unclear in this regard.

Objectives: The purpose of this study was to evaluate the knowledge and reflexive practices of general medicine students in regard to dyskalemia.

Methods: A cross-sectional survey, based on a self-questionnaire, of all of the students enrolled in general medicine studies at the Faculty of Medicine at the University of Nancy (France) at the end of their degree. The students were asked questions pertaining to specific clinical situations. The answers were compared to the information provided in the medical curriculum as well as to the relevant European guidelines.

Results: We collected 290 of the questionnaires (participation rate: 81.2%). The hyper- and hypokalemia thresholds considered pathological (3.5-5.0 mmol/L) were known by 78% and 67% of the students, respectively. The perception of danger in case of severe hypokalemia was underestimated by 62.7% of them. In most cases, the proposed management of hyperkalemia in heart and renal failure did not comply with the relevant guidelines. The students tended to favor permanent discontinuation of the administration of converting enzyme inhibitors (ACE) and/or mineralocorticoid receptor antagonists (MRA) without considering the need for their reintroduction (51.6%). Sodium polystyrene sulfate was frequently seen as an appropriate first-line treatment for hyperkalemia (45%).

Conclusions: The knowledge and competence of general medicine students appear to be lacking for hyperkalemia in heart and renal failure, and they are long way from full compliance with the relevant European guidelines. Exposure to complex clinical situations as part of the medical curriculum, therefore, seems essential to improve the way dyskalemia is managed in France.
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http://dx.doi.org/10.1111/fcp.12621DOI Listing
April 2021

Subclinical ventricular dysfunction in rheumatoid arthritis.

Int J Cardiovasc Imaging 2021 Mar 14;37(3):847-859. Epub 2020 Oct 14.

Department of Surgery and Physiology, Cardiovascular Research and Development Center, Faculty of Medicine, University of Porto, Porto, Portugal.

Patients with rheumatoid arthritis (RA) are at higher risk for having underdiagnosed heart failure, however there are no recommendations regarding echocardiographic screening. We aimed to determine the prevalence of subclinical ventricular dysfunction in RA applying current echocardiographic guidelines, its association with patients' characteristics, biomarkers and prognostic parameters and compare the 2016 guidelines to the recommendations from 2009. Prospective study of RA patients without known heart disease, categorized as preserved ventricular function (PVF), systolic dysfunction (SD), isolated diastolic dysfunction (DD) or indeterminate diastolic function (IDF) as per the 2016 echocardiography guidelines-or any ventricular dysfunction (AVD) comprehending the last 3. The median age was 58 years and 78% were females. The majority had PVF (73%), followed by DD (13%), IDF (11%) and SD (4%). Concordance with the 2009 echocardiographic guidelines was low. Compared with PVF, AVD patients were older (65 vs 55 years, p < 0.001), had a higher prevalence of hypertension and dyslipidaemia (56% vs 38%, p = 0.003 and 60% vs 41%, p = 0.002, respectively). In multivariable analysis, age (particularly > 57 years) was the only independent predictor of AVD or DD. AVD was significantly associated with higher NT-proBNP and lower distance in 6-min walk test. There were no significant independent associations between characteristics of RA disease and ventricular function. A total of 17% of RA patients without known cardiovascular disease presented subclinical systolic or diastolic dysfunction, which was associated with older age. The echocardiographic screening may have clinical value in identifying subclinical ventricular dysfunction, especially in older RA patients.
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http://dx.doi.org/10.1007/s10554-020-02057-3DOI Listing
March 2021

Plasma Volume Status and Its Association With In-Hospital and Postdischarge Outcomes in Decompensated Heart Failure.

J Card Fail 2021 Mar 7;27(3):297-308. Epub 2020 Oct 7.

Duke Clinical Research Institute, Durham, North Carolina; Division of Cardiology, Duke University Medical Center, Durham, North Carolina. Electronic address:

Background: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial.

Methods And Results: The KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00-1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97-1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62-0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98-1.12, P = .139).

Conclusions: Baseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.
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http://dx.doi.org/10.1016/j.cardfail.2020.09.478DOI Listing
March 2021

Multiple Arterial Thrombosis in a 78-Year-Old Patient: Catastrophic Thrombotic Syndrome in COVID-19.

CJC Open 2021 Feb 2;3(2):198-200. Epub 2020 Oct 2.

CHRU-Nancy, Regional Competence Center For Marfan Syndrome, Vascular Medicine Division, Nancy, France.

We describe a patient with coronavirus disease 2019 (COVID-19) and multiple concomitant thromboses occurring on the 9th day of hospital stay. Thromboses were found in distinct zones of the aorta, as well as in the renal, humeral, and pulmonary arteries. The extensive biological workup performed following this catastrophic thrombotic syndrome found no evidence for underlying prothrombotic disease. In light of current evidence regarding endothelium abnormalities related to COVID-19, this extreme case of catastrophic thrombotic syndrome suggests that COVID-19 can induce severe arterial thrombosis following intense endothelial activation.
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http://dx.doi.org/10.1016/j.cjco.2020.09.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529607PMC
February 2021

Sex differences in circulating proteins in heart failure with preserved ejection fraction.

Biol Sex Differ 2020 08 24;11(1):47. Epub 2020 Aug 24.

Université de Lorraine, INSERM, Centre d'Investigation Clinique et Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.

Background: Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce.

Methods: A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models.

Results: We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83-2.63), p = 0.18.

Conclusion: In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.
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http://dx.doi.org/10.1186/s13293-020-00322-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444077PMC
August 2020

Association between right-sided cardiac function and ultrasound-based pulmonary congestion on acutely decompensated heart failure: findings from a pooled analysis of four cohort studies.

Clin Res Cardiol 2020 Aug 8. Epub 2020 Aug 8.

INSERM, Centre d'Investigations Cliniques 1433, CHRU de Nancy, Inserm 1116 and INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network, Institut Lorrain du cœur et des, Université de Lorraine, 4, rue du Morvan, Vandoeuvre-Les-Nancy, 54500, Nancy, France.

Background: Right ventricular (RV) dysfunction and RV-pulmonary artery (PA) uncoupling are associated with the development of pulmonary congestion during exercise. However, there is limited information regarding the association between these right-sided cardiac parameters and pulmonary congestion in acutely decompensated heart failure (HF).

Methods: We performed an individual patient meta-analysis from four cohort studies of hospitalized patients with HF who had available lung ultrasound (B-lines) data on admission and/or at discharge. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE), RV-PA coupling was defined as the ratio of TAPSE to PA systolic pressure (PASP).

Results: Admission and discharge cohort included 319 patients (75.8 ± 10.1 years, 46% women) and 221 patients (77.9 ± 9.0 years, 47% women), respectively. Overall, higher TAPSE was associated with higher ejection fraction, lower PASP, b-type natriuretic peptide and B-line counts. By multivariable analysis, worse RV function or RV-PA coupling was associated with higher B-line counts on admission and at discharge, and with a less reduction in B-line counts from admission to discharge. Higher B-line counts at discharge were associated with a higher risk of the composite of all-cause mortality and/or HF re-hospitalization [adjusted-HR 1.13 (1.09-1.16), p < 0.001]. Furthermore, the absolute risk increase related to high B-line counts at discharge was higher in patients with lower TAPSE.

Conclusions: In patients with acutely decompensated HF, impaired RV function and RV-PA coupling were associated with severe pulmonary congestion on admission, and less resolution of pulmonary congestion during hospital stay. Worse prognosis related to residual pulmonary congestion was enhanced in patients with RV dysfunction. TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure.
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http://dx.doi.org/10.1007/s00392-020-01724-8DOI Listing
August 2020

Improved cardiovascular risk prediction in patients with end-stage renal disease on hemodialysis using machine learning modeling and circulating microribonucleic acids.

Theranostics 2020 9;10(19):8665-8676. Epub 2020 Jul 9.

Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.

To test whether novel biomarkers, such as microribonucleic acids (miRNAs), and nonstandard predictive models, such as decision tree learning, provide useful information for medical decision-making in patients on hemodialysis (HD). Samples from patients with end-stage renal disease receiving HD included in the AURORA trial were investigated (n=810). The study included two independent phases: phase I (matched cases and controls, n=410) and phase II (unmatched cases and controls, n=400). The composite endpoint was cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. miRNA quantification was performed using miRNA sequencing and RT-qPCR. The CART algorithm was used to construct regression tree models. A bagging-based procedure was used for validation. In phase I, miRNA sequencing in a subset of samples (n=20) revealed miR-632 as a candidate (fold change=2.9). miR-632 was associated with the endpoint, even after adjusting for confounding factors (HR from 1.43 to 1.53). These findings were not reproduced in phase II. Regression tree models identified eight patient subgroups with specific risk patterns. miR-186-5p and miR-632 entered the tree by redefining two risk groups: patients older than 64 years and with hsCRP<0.827 mg/L and diabetic patients younger than 64 years. miRNAs improved the discrimination accuracy at the beginning of the follow-up (24 months) compared to the models without miRNAs (integrated AUC [iAUC]=0.71). The circulating miRNA profile complements conventional risk factors to identify specific cardiovascular risk patterns among patients receiving maintenance HD.
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http://dx.doi.org/10.7150/thno.46123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392028PMC
July 2020

Hypokalemia is frequent and has prognostic implications in stable patients attending the emergency department.

PLoS One 2020 4;15(8):e0236934. Epub 2020 Aug 4.

Université de Lorraine, Inserm, Centre d'Investigations Cliniques- Plurithématique 1433, and Inserm U1116, CHRU, Nancy, France.

Background: Potassium disturbances are associated with adverse prognosis in patients with chronic conditions. Its prognostic implications in stable patients attending the emergency department (ED) is poorly described.

Aims: This study aimed to assess the prevalence of dyskalemia, describe its predisposing factors and prognostic associations in a population presenting the ED without unstable medical illness.

Methods: Post-hoc analysis of a prospective, cross-sectional, multicenter study in the ED of 11 French academic hospitals over a period of 8 weeks. All adults presenting to the ED during this period were included, except instances of self-drug poisoning, inability to complete self-medication questionnaire, presence of an unstable medical illness and decline to participate in the study. All-cause hospitalization or deaths were assessed.

Results: A total of 1242 patients were included. The mean age was 57.2±22.3 years, 51% were female. The distribution according to potassium concentrations was: hypokalemia<4mmol/L(n = 620, 49.9%), normokalemia 4-5mmol/L(n = 549, 44.2%) and hyperkalemia >5mmol/L(n = 73, 0,6%). The proportion of patients with a kalemia<3.5mmol/L was 8% (n = 101). Renal insufficiency (OR [95% CI] = 3.56[1.94-6.52], p-value <0.001) and hemoglobin <12g/dl (OR [95% CI] = 2.62[1.50-4.60], p-value = 0.001) were associated with hyperkalemia. Female sex (OR [95% CI] = 1.31[1.03-1.66], p-value = 0.029), age <45years (OR [95% CI] = 1.69 [1.20-2.37], p-value = 0.002) and the use of thiazide diuretics (OR [95% CI] = 2.04 [1.28-3.32], p-value = 0.003), were associated with hypokalemia<4mmol/l. Two patients died in the ED and 629 (52.7%) were hospitalized. Hypokalemia <3.5mmol/L was independently associated with increased odds of hospitalization or death (OR [95% CI] = 1.47 [1.00-2.15], p-value = 0.048).

Conclusions: Hypokalemia is frequently found in the ED and was associated with worse outcomes in a low-risk ED population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236934PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402484PMC
October 2020

Practical management of worsening renal function in outpatients with heart failure and reduced ejection fraction: Statement from a panel of multidisciplinary experts and the Heart Failure Working Group of the French Society of Cardiology.

Arch Cardiovasc Dis 2020 Oct 11;113(10):660-670. Epub 2020 Jul 11.

Centre d'Investigations Cliniques Plurithématique 1433, inserm 1116, CHRU de Nancy, Université de Lorraine, F-CRIN INI-CRCT, 54500 Vandoeuvre-lès-Nancy, France. Electronic address:

Renal function is often affected in patients with chronic heart failure with reduced ejection fraction (HFrEF). The complex interplay between heart and renal dysfunction makes renal function and potassium monitoring mandatory. Renin-angiotensin-aldosterone system (RAAS) blockers are a life-saving treatment for patients with HFrEF, regardless of worsening renal function. Uptitration to the maximum-tolerated dose should be a constant goal. This simple fact is all too often forgotten (only 30% of patients with heart failure receive the target dosage of RAAS blockers), and the RAAS blocker effect on renal function is sometimes misunderstood. RAAS blockers are not nephrotoxic drugs as they only have a functional effect on renal function. In many routine clinical cases, RAAS blockers are withheld or stopped because of this misunderstanding, combined with suboptimal assessment of the clinical situation and underestimation of the life-saving effect of RAAS blockers despite worsening renal function. In this expert panel, which includes heart failure specialists, geriatricians and nephrologists, we propose therapeutic management algorithms for worsening renal function for physicians in charge of outpatients with chronic heart failure. Firstly, the essential variables to take into consideration before changing treatment are the presence of concomitant disorders that could alter renal function status (e.g. infection, diarrhoea, hyperthermia), congestion/dehydration status, blood pressure and intake of nephrotoxic drugs. Secondly, physicians are invited to adapt medication according to four clinical scenarios (patient with congestion, dehydration, hypotension or hyperkalaemia). Close biological monitoring after treatment modification is mandatory. We believe that this practical clinically minded management algorithm can help to optimize HFrEF treatment in routine clinical practice.
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http://dx.doi.org/10.1016/j.acvd.2020.03.018DOI Listing
October 2020

Hyperkalaemia and hypokalaemia outpatient management: a survey of 500 French general practitioners.

ESC Heart Fail 2020 10 29;7(5):2042-2050. Epub 2020 Jun 29.

Université de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithématique 1433, and Inserm 1116 DCAC, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.

Aims: How general practitioners (GPs) manage dyskalaemia is currently unknown. This study aimed at describing GP practices regarding hypokalaemia or hyperkalaemia diagnosis and management in their outpatients.

Methods And Results: A telephone survey was conducted among French GPs with a 20-item questionnaire (16 closed-ended questions and 12 open-ended questions) regarding their usual management of hypokalaemia or hyperkalaemia patients, both broadly and more specifically in patients with heart failure and/or chronic kidney disease and/or in patients treated with angiotensin-converting enzyme/angiotensin receptor blockers or mineralocorticoid receptor antagonists. We aimed to interview 500 GPs spread geographically throughout France. This descriptive survey results are presented as mean ± standard deviation (if normally distributed or as median and inter-quartile range if the distribution was skewed). Categorical variables are expressed as frequencies and proportions (%). A total of 500 GPs participated in the study. Dyskalaemia thresholds (for diagnosis and intervention) and management patterns were highly heterogeneous. The mean ± SD (range) potassium level leading to 'intervene' was 5.32 ± 0.34 mmol/L (4.5-6.5) for hyperkalaemia and 3.23 ± 0.34 mmol/L (2.0-6.5) for hypokalaemia. Potassium levels leading to refer the patient to the emergency department (ED) were 6.14 ± 0.55 (4.5-10) and 2.69 ± 0.42 mmol/L (1-4), respectively. Potassium binders (51-65%) or potassium supplements (67-74%) were frequently used to manage hyperkalaemia or hypokalaemia. GPs uncommonly referred their dyskalaemic patients to cardiologists or nephrologists (or to the emergency department, if the latter was deemed necessary owing to the severity of the dyskalaemia). We identified an association between the close vicinity of GP office from an ED and 'referring a heart failure patient' (19.2% with ED vs. 8.6% without ED) and referring a heart failure and chronic kidney disease patient on mineralocorticoid receptor antagonist (16.7% with ED vs. 9.3% without ED). Although the majority (67%) of GPs had an electrocardiogram on hand, it was rarely used (14%) in dyskalaemic patients. Subgroup analyses considering gender, age of the participating GPs, and high-income/low-income regions did not identify specific patterns regarding the multidimensional aspect of dyskalaemia management.

Conclusions: Owing to the considerable heterogeneity of French GP practices toward dyskalaemia diagnosis and management approaches, there is a likely need to standardize (potentially enabled by therapeutic algorithms) practices.
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http://dx.doi.org/10.1002/ehf2.12834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524073PMC
October 2020

Left ventricular myocardial deformation pattern, mechanical dispersion, and their relation with electrocardiogram markers in the large population-based STANISLAS cohort: insights into electromechanical coupling.

Eur Heart J Cardiovasc Imaging 2020 10;21(11):1237-1245

Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, CHRU de Nancy, Inserm U1116, Rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.

Aims: Mechanical alterations in patients with electrical conduction abnormalities are reported to have prognostic value in patients with left ventricular asynchrony or long QT syndrome beyond electrocardiogram (ECG) variables. Whether conduction and repolarization patterns derived from ECG are associated with speckle tracking echocardiography parameters in subjects without overt cardiac disease is yet to be investigated. To report ranges of longitudinal deformation according to conduction and repolarization values in a population-based cohort.

Methods And Results: One thousand, one hundred, and forty subjects (48.6 ± 14.0 years, 47.7% men) enrolled in the fourth visit of the STANISLAS cohort (Lorraine, France) were studied. Echocardiography strain was performed in all subjects. RR, PR, QRS, and QT intervals were retrieved from digitalized 12-lead ECG. Echocardiographic data were stratified according to quartiles of QRS and QTc duration values. Full-wall global longitudinal strain (GLS) was -21.1 ± 2.5% with a mechanical dispersion (MD) value of 34 ± 12 ms. Absolute GLS value was lower in the longest QRS quartile and shortest QTc quartile (both P < 0.001). Time-to-peak of strain was not significantly different according to QRS duration although significantly higher in patients with higher QTc (P < 0.001). MD was significantly greater in patients with longer QTc (32 ± 12 ms for QTc < 396 ms vs. 36 ± 12 ms for QTc > 421 ms; P = 0.002).

Conclusion: Longer QTc is related to increased MD and better longitudinal strain values. In a population-based setting, QRS is not associated with MD, suggesting that echocardiography-based dyssynchrony does not largely overlap with ECG-based dyssynchrony.
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http://dx.doi.org/10.1093/ehjci/jeaa148DOI Listing
October 2020